PATHOLOGY: Implications for the Physical Therapist

MEDICAL MANAGEMENT

DIAGNOSIS AND TREATMENT.

Diagnosis of these benign lesions is based on physical examination, mammography, and biopsy. Because benign disease and fibroadenoma are often indistinguishable from carcinomas, biopsy is often used to confirm the diagnosis. More advanced ultrasonography now allows for the differentiation of cystic (fluid-filled) masses from solid masses. The presence of nodularities does not predispose a woman to cancer but may make diagnosis of cancerous lumps more difficult.

Treatment for these conditions is often palliative and includes aspirin, mild analgesics, and local heat or cold. Dietary changes are often recommended such as avoiding coffee, colas, chocolate, and tea (foods and drinks that contain xanthines). Women are encouraged to wear a brassiere that provides adequate support. For women in severe pain, danazol may be given. Surgery is performed if a suspicious mass that is deemed not to be malignant on cytologic examination does not resolve over several months.

Breast Cancer

Overview

Breast cancer is the most common malignancy of females in the United States and accounts for one-third of all cancers diagnosed in American women. Breast cancer begins in the lobules (20%), which are the milkproducing glands of the breast, or in the ducts (80%), which bring the milk to the nipple (Fig. 20-11). Most breast carcinomas are adenocarcinomas originating in the single layer of epithelial cells that line the ductal and lobular systems of all milk ducts.

Figure 20-11 Breast anatomy. The breast is composed of glandular tissue; fibrous tissue, including suspensory ligaments; and adipose tissue. Glandular tissue contains 15 to 20 lobes radiating from the nipple and composed of lobules. Within each lobe are clusters of alveoli that produce milk. Each lobe is embedded in adipose tissue and empties into a lactiferous duct. There are 15 to 20 lactiferous ducts that form a collecting duct system converging toward the nipple. These ducts form ampullae or lactiferous sinuses behind the nipple, which are reservoirs for storing milk. The lobules and ducts are surrounded by fatty and connective tissue, nerves, blood vessels, and lymphatic vessels. The suspensory ligaments (Cooper’s ligaments) are fibrous bands extending vertically from the surface attaching to the chest wall muscle. These support the breast tissue and become contracted in cancer of the breast, producing pits or dimples in the overlying skin. (From Jarvis C: Physical examination and health assessment, ed 4, Philadelphia, 2004, WB Saunders.)

Not all breast cancers are the same; different characteristics in gene expression profiles result in differential clinical behavior. Gene profiling assays aid in documenting different subtypes of breast cancer.¹⁵³ For now, clinical practice recognizes six types of breast cancer: (1) ductal CIS (DCIS); (2) invasive (infiltrating) ductal carcinoma (IDC); (3) invasive (infiltrating) lobular carcinoma; (4) medullary, tubular, and mucinous carcinoma; (5) inflammatory breast cancer (IBC); and (6) Paget’s disease of the breast.

DCIS (sometimes called intraductal cancer), the most common type of in situ cancer, occurs in 20% to 30% of newly diagnosed breast cancer cases and develops at several points along a duct, appearing as a cluster of calcifications or white flecks on a mammogram. DCIS accounts for about 10% of breast cancers in men. This is a precancerous change in breast tissue (abnormal but not malignant cells and highly curable) with a broad continuum from slow-growing cells with little potential to be transformed into cancer to life-threatening aggressive types of cancer that will invade the duct wall and grow beyond it.

IDC is the most common of the invasive breast cancers, beginning in a duct, breaking through the duct wall, and invading fatty tissue of the breast with further metastasis possible via lymphatic invasion. IDC is usually detected as a mass on a mammogram or as a palpable lump during a breast examination. From 80% to 90% of breast cancer cases in men are caused by IDC.

Invasive lobular carcinoma makes up 10% to 15% of invasive cancers. This type grows through the wall of the lobule and spreads via the lymphatic or circulatory system.

Medullary, tubular, and mucinous carcinomas are less common types of ductal carcinoma, together accounting for less than 10% of breast cancers. Medullary carcinoma and tubular carcinoma are both invasive but have better outcomes than invasive ductal or invasive lobular carcinomas.

IBC, a less common form of invasive ductal cancer, is a rare and very aggressive form of breast cancer that presents much like an infection with warmth, redness of the skin, and lymphatic blockage. It is often missed or misdiagnosed as a breast infection because of its appearance and because there may not be a distinct lump or tumor; it is not usually detected by ultrasound or mammography. Although most common in young women, it has been reported in men as well. When the symptoms last longer than a week after starting antibiotics for a breast “infection,” then a biopsy is strongly recommended.

Paget’s disease of the breast is a rare form of ductal carcinoma arising in the ducts near the nipple, with itching, redness and flaking of the nipple, and occasionally bleeding (Fig. 20-12).¹²⁵ This condition occurs in conjunction with a ductal adenocarcinoma of the breast, which has frequently metastasized to the axillary lymph nodes.

Figure 20-12 Paget’s disease of the breast. An erythematous plaque surrounds the nipple. (From Bolognia JL: Dermatology, St. Louis, 2003, Mosby.)

Breast cancer appears biologically similar in both genders, although it is often diagnosed at later stages in older men. Men and women develop the same types of breast cancer, although lobular carcinoma is rare in men because of the absence of lobules in the male breast. Most breast cancers in men are carcinomas, most commonly IDC.

Incidence

In recent years the statistical picture of breast cancer has brightened, thanks to early detection and advances in treatment. More tumors are found at an earlier stage. This fact, combined with a slowing in the rise in incidence, has dropped the death rate. Even so, breast carcinomas still account for approximately 30% of all the female cancers in the United States. In addition, breast cancer is the number two cause of female cancer deaths in the United States, second only to lung cancer.

Estimated new breast cancer cases in 2007 were 2030 (up from 1500 in the year 2002) for men and 178,480 for women (down from 203,500 in 2002). Approximately 450 men and 40,460 women died as a result of breast cancer in 2007.¹⁴⁸ This is up from 400 for men and 39,600 for women in 2002.

The cumulative lifetime risk of developing breast cancer for white women in the United States is 1 in 8 based on a woman living 95+ years, but it should be kept in mind that a woman’s risk at age 25 years is 1 in 21,441, with increasing risk as she ages.⁹¹

Approximately 70% of all breast cancer occurs in women over age 50 years. Demographics suggest that in the next 2 decades, women over the age of 65 years will become the most prevalent patient cohort in the breast cancer population. The number of complicating comorbidities will likely be a complicating factor in the diagnosis and treatment in this age group.¹³³

Female breast cancer incidence rates vary by race and ethnicity. Cases remain highest in white women followed by African Americans. Incidence of breast cancer in African Americans has stabilized for women age 50 years and older and decreasing for women younger than 50 years. Death rates in African-American women remain 37% higher than in whites, despite lower incidence rates.²⁸⁴

According to a new analysis of breast cancer rates, overall breast cancer rates may be decreasing, possibly as a result of the decline in use of HRT. For women of all ages and all breast cancer types, the incidence of breast cancer dropped by 7% in 2003. This is the first reported decrease in incidence since 1980, possibly reflecting the saturation of mammography utilization and reduction in the use of HRT.¹⁴⁸

One proposed possibility for the decline in breast cancer incidence rates in younger (premenopausal) women is the increasing prevalence of obesity. The mechanism is thought to be through anovulatory menstrual cycles and lower levels of circulating steroid hormones.²⁸⁴

Etiologic Factors

The cause of breast cancer is unknown, although there are some genetic bases, expression of which will vary in different ethnic groups. A known genetic mutation in two genes, BRCA1 and BRCA2 (the “breast cancer” genes), has been identified and may be responsible for most inherited cancers (accounting for 10% of all cases).

BRCA1 and BRCA2 are tumor suppressor genes. Everyone has two copies of each gene, and when working properly, they produce proteins that keep cell growth in check. Mutations can render these genes inactive, increasing the risk for developing breast, ovarian, and certain other cancers.

Risk Factors

Female gender, age, ethnicity, family history, medical history, menstrual history (early onset of menstruation with greater exposure to estrogen), nulliparity or infertility (greater number of menstrual cycles with hormonal exposures), and geography are all factors linked to breast cancer (Box 20-6).

Box 20-6 RISK FACTORS FOR BREAST CANCER IN WOMEN

Key Risk Factors

• Gender (female)

• Age 60 years or older

• Age at menarche (first menstruation <12 years = greater risk), especially when combined with late menopause (>55 years)

• Age at first live birth (>35 years = greater risk)

• Two or more first-degree relatives (mother, sisters, or daughters) with breast or ovarian cancer

• Male relative with breast cancer

• Number of previous breast biopsies (whether positive or negative)

• At least one biopsy with atypical (ductal or lobular) hyperplasia or radial stars

• Previous personal history of breast cancer

Additional Risk Factors^*

• History of benign breast disease

• Ethnicity (whites: greater incidence; blacks: more deaths)

• Late menopause (>50 years)

• Nulliparity, infertility; first child born after age 30 years

• DES exposure

• Alcohol (≥2 drinks/day of beer, wine, hard liquor)

• Postmenopausal weight gain (20 to 30 lb or more since age 18 years); obesity

• High doses of chest radiation before age 30 years (e.g., Hodgkin’s disease)

• Environmental exposures (under investigation)

• High-fat diet

• Long-term use of first-generation oral contraceptives before 1975 (high doses, e.g., EstrAval) or recent (last 5 years) combined HRT

• High bone density (postmenopausal women); circulating estrogen promotes bone formation

DES, Diethylstilbestrol; HRT, hormone replacement therapy.

^*These risk factors are not included in the National Cancer Institute’s Breast Cancer Risk Assessment tool for two reasons: either (1) evidence is not conclusive or (2) researchers cannot accurately determine how much these factors contribute to the calculation of risk for an individual. Nevertheless, these additional risk factors are known to contribute to the increased risk of breast cancer. For more information about risk assessment, see http://www.yourcancerrisk.harvard.edu or visit the National Cancer Institute’s Breast Cancer Risk Assessment tool at http://www.cancer.gov/bcrisktool/

Gender and Hormone Exposure.: Gender (female) is the most significant risk factor associated with this disease. Although women have many more breast cells than men, the primary reason they develop breast cancer more often is because breast cells are constantly exposed to the growth-promoting effects of the female hormones estrogen and progesterone. New evidence indicates that estrogen exposures throughout life including in utero may have an effect on breast cancer risk. Over half of all women diagnosed with breast cancer will have estrogen receptor–positive (ER-positive), lymph node–negative breast cancer.²²⁹ Tumors that are ER-positive have estrogen receptors and are stimulated to grow by estrogen. Tumors that do not have estrogen receptors are called ER-negative and are not influenced by the hormone.

Previous history of first-generation hormonal contraceptive use (higher dose formulations before 1975) and recent (last 5 years) prolonged use of combined HRT have been linked with increased risk of breast cancer, often found at a more advanced stage.

The established role of estrogen in the development and progression of breast cancer raises questions concerning a potential contribution from the many chemicals in the environment with estrogenic activity that can enter the human breast. A range of organochlorine pesticides and polychlorinated biphenyls possess estrogen-mimicking properties that have been measured in human breast adipose tissue and in human milk. These may enter the breast from contamination of food, water, and air.⁶⁵

Fewer than 1% of breast cancers occur in males. In men, age (>60 years) and heredity are the most common risk factors, but more than one-half have no known risk factors. Other factors associated with an increased risk of breast cancer in men include chest radiation exposure, liver disease, treatment with estrogen, treatment with immunosuppressants after organ transplantation, BRCA2 gene mutations, Klinefelter’s syndrome, history of benign breast disease or gynecomastia, and history of testicular pathology.

Weight Gain and Obesity.: Many studies show that weight gain is a risk factor for breast cancer, especially for women after menopause. The ACS reports that women who gain 20 to 30 lb (or more) during adulthood (after age 18) are 40% more likely to develop breast cancer after menopause compared with women who gain no more than 5 lb and compared to women who have been overweight since childhood.^9,79

Estrogen stored in fat keeps the hormone circulating even when ovarian production stops at menopause. There is evidence to suggest think that fat cells in different parts of the body metabolize differently. For example, excess fat in the waist area may affect risk more than the same amount of fat in the hips and thighs. Obesity at the time of diagnosis is also thought to be significant as a poor prognostic factor.⁴³

Age.: Age is the second most significant risk factor; the incidence of breast cancer increases with advancing age. For example, the 10-year risk of developing breast cancer jumps from 1 in 48 at age 40 years to 1 in 26 at age 60 years. The median and mean ages of women with breast cancer are between 60 and 61 years. Women with a personal or family history (personal history of breast, ovarian, or uterine cancer or family history of breast cancer among first-degree relatives) have a significantly increased risk of developing breast cancer.

Personal or Family History and Heredity.: A personal history of breast cancer in one breast increases a woman’s risk of developing a new cancer in the other breast or in another part of the same breast threefold to fourfold. This is not the same as a cancer recurrence of the first cancer. About 5% to 10% of breast cancer cases are hereditary as a result of gene mutations, most commonly affecting the BRCA1 and BRCA2 genes. Normally, these genes help prevent cancer by making proteins that keep cells from growing abnormally. Inheriting either mutated gene from a parent increases the risk of breast cancer.⁵²

Women with an inherited BRCA1 or BRCA2 mutation have up to an 80% chance of developing breast cancer during their lifetime and at a younger age than women who do not have these gene mutations. Women with these inherited mutations are also at increased risk for developing ovarian cancer. Other genes that might also lead to inherited breast cancer (e.g., ataxia-telangiectasia mutation [ATM] and CHEK2 gene) are under investigation.⁹

Although only a small percentage of breast cancer cases are hereditary, about 20% to 30% of women with breast cancer have a family member with this disease. Having one first-degree relative with breast cancer doubles a woman’s risk; breast cancer in two or more first-degree relatives (mother, sister, daughter) increases the risk fivefold.⁹

Breast cancer before age 50 years in a relative on either side of the family also increases the risk; the risk is higher if the mother or sister has a history of breast cancer. Although the exact risk is not known, women with a family history of breast cancer in a father or brother also have an increased risk of breast cancer.⁹

In addition, a history of benign breast disease, when accompanied by proliferative changes, papillomatosis, or atypical epithelial hyperplasia, increases the risk of cancer. Even with all these potential risk factors, the majority of women with breast cancer do not have any apparent risk factors.

Race/Ethnicity.: White women are slightly more likely to develop breast cancer than are African-American women but African-American women are more likely to die of this cancer, possibly because of more aggressive tumors in African-American women. Black men are at almost twice the risk of white men. Asian, Hispanic, and Native American women have a lower risk of developing and dying from breast cancer.⁹

Ashkenazi Jews who have a mutation in either BRCA gene have an 80% risk of developing breast cancer by age 80 years. This is compared to a 13% risk for the average 80-year old woman who does not have an Ashkenazi heritage.

Alcohol.: Alcohol intake is also associated with an increase in risk, particularly for women whose intake of folate is low.¹⁷ Folate is a vitamin that helps prevent birth defects and has been linked to cancer prevention. The exact mechanism between alcohol consumption and breast cancer remains unknown, but alcohol may interfere with the body’s ability to use folate.¹⁷⁶

It is also possible some individuals are more susceptible to the harmful effects of alcohol intake because of differences in alcohol metabolism. How much daily alcohol makes the difference remains under investigation; for now, research overwhelmingly agrees that risk increases with the amount of alcohol consumed and that even moderate alcohol consumption (two drinks or 20 g/day) increases breast cancer risk by at least 1.5 times.^301,339

Factors in Question.: Scientists thus far have been unable to establish a direct link between breast cancer and tobacco smoke; electromagnetic fields; silicone breast implants; abortion or miscarriage^23,32,299; work at night; or the chemicals used in pesticides, plastics, herbicides, or hair colorings.^9,125,230 The role of estrogenic chemicals applied as antiperspirants, deodorants, or cosmetics to the underarm and breast areas remains hotly debated. Evidence in support of a functional role for the combined interactions of cosmetic chemicals with environmental estrogens, pharmacologic estrogens, phytoestrogens, and physiologic estrogens has been presented^63,65 along with evidence to refute the role of antiperspirants in breast cancer.²⁰⁸

Although scientists have found chemicals from antiperspirants and deodorants in breast tumors, the concentrations were far lower than the amount of estrogen naturally circulating in the body. The chemicals may be present in normal breast tissue, too, but this has not been studied yet.⁶⁴

Breast cancer is the most common solid tumor among women treated for Hodgkin’s disease. Radiotherapy of the mediastinum has been implicated. The secondary cancer risk to females seems to increase 10 years after the initial diagnosis and treatment of Hodgkin’s disease. Whereas there is a fifteenfold increase in risk for a second malignancy, the risk of breast cancer for females who had childhood Hodgkin’s disease is 45 times greater than for those who did not have childhood Hodgkin’s.^266,300

Pathogenesis

The pathogenesis of breast cancer is unknown, but estrogen is believed to be a key factor in promoting (rather than initiating) breast cancer. It may not trigger the series of genetic changes that are required to transform normal breast cells into malignant ones, but it may spur the proliferation of transformed cells, increasing the likelihood that they will develop into cancer. The development of invasive breast cancer involves epithelial hyperplasia, premalignant change, in situ carcinoma, and invasive carcinoma.

These progressive alterations in the structure of the mammary epithelium are accompanied by a reorganization in the composition of the epithelial, periductal, and stromal extracellular matrix (ECM). This observation is important because ECM proteins (elastin, collagens, proteoglycans, and glycoproteins) not only provide a physical support for cells within developing and mature tissues but also act as an informational system.

These proteins detect and coordinate signals originating from the tissue microenvironment and adjacent cells. Networks of ECM interact with transmembrane receptors called integrins to transmit signals from the ECM to the cell interior. It is hypothesized that modifications in the mammary ECM that occur during tumor formation or a failure to respond appropriately to the preexisting ECM may result in aberrant cell behavior. Studies show that changes in cell adhesion play a major part in the development and progression of breast cancer.¹⁵⁰

Biologists collecting and recording salivary estrogen levels have recognized patterns of low feminine fertility correlated with famine. Estrogen samples from the mouths of hungry women are found to be about one-half of estrogen levels in the saliva of well-nourished women, a difference that can account for the drop in pregnancy rate in lean women.

Improved nutrition in developed countries, such as the United States, has led to increased exposure to estrogen over a lifetime. This variable combined with the resulting earlier age of menarche, delayed and decreased childbearing, increased prevalence of obesity, and the increase in exposure to environmental toxins all may contribute to more and prolonged estrogen exposure, possibly resulting in genetic mutations, loss of suppressor genes, and cell proliferation or cell growth.

An older but still unproved theory is the environmental exposure hypothesis that prolonged and cumulative exposure to hormonally active synthetic chemicals contributes to the rising incidence of breast cancer. Synthetic chemicals may do this directly by acting as estrogen, altering the way the body produces or metabolizes estrogen; they can work bifunctionally, through genetic or hormonal paths, depending on the periods and extent of exposure.⁶⁹

Prenatal exposure to estrogens may predispose a woman to breast cancer later in life through an “imprinting” process that sensitizes her to estrogen exposure. One way that synthetic chemicals may increase breast cancer risk is to alter the way the body processes its own estrogen. This theory is the basis for the use of indoles (phytochemicals found in vegetables) shown to reduce cancer risk.

Most carcinomas develop in the glandular epithelium of the terminal duct lobular unit. In the normal breast, the milk ducts and lobules are neatly lined with epithelial cells. Over time, some extra (noncancerous) cells may grow within the duct (hyperplasia) and begin to look odd (atypia); this condition is atypical ductal hyperplasia.

When cancer cells multiply but remain contained within the duct, the condition is called DCIS. A stromal invasion by malignant cells usually results in fibroblastic proliferation. A palpable mass within the breast tissue will typically develop. IDC occurs when cancer cells break through the duct wall and enter other tissues.

Breast cancer has a propensity for metastases to the bone, possibly related to a small protein found in the bone marrow (osteonectin) that both attracts breast (and prostate) cancer cells to bone and once attracted, stimulates the cells to invade the bone. Researchers suggest that metastasis of breast cancer cells to the bone is mediated by the ability of osteonectin to promote migration, protease activity, and invasion.¹⁴⁶

Clinical Manifestations

The most common initial presenting sign of breast cancer is a palpable lump or nodule. Approximately 90% of breast masses are discovered by the woman herself; for men, the lump is usually in the center behind the areola and for women, either centrally behind the areola or in the upper, outer quadrant, although neoplasm can occur anywhere in the breast tissue (Fig. 20-13).

Figure 20-13 The distribution of breast carcinoma and the pathway of lymphatic metastases. Most tumors in women are found in the upper lateral quadrant and behind the nipple (areola) and for men, behind the nipple. (From Damjanov I: Pathology for the health-related professions, ed 3, Philadelphia, 2006, Saunders.)

The mass tends to be firm and irregular if it is a carcinoma versus smooth and rubbery if it is benign. The mass is typically not painful if it is cancer. Fixation of the breast to the underlying pectoral muscles and chest wall can cause significant asymmetry (Fig. 20-14).

Figure 20-14 Fixation. Asymmetry, distortion, or decreased motility is observed in the woman’s right breast as she lifts her arms. As cancer becomes invasive, fibrosis can fix the breast to the underlying pectoral muscle. Although at first glance, it looks as if the woman’s left breast is enlarged compared to the right, in fact, the woman’s right breast is held against the chest wall. (From Mansel R: Color atlas of breast diseases, London, 1995, Mosby.)

Other manifestations include a change in breast contour or texture, nipple discharge and retraction or inversion, local skin dimpling (Fig. 20-15), erythema, and a local rash or ulceration. Lymphadenopathy may also be the initial presentation of this disease. Most local breast cancer recurrence occurs along the incision line.

Figure 20-15 Dimpling. The shallow dimple above and slightly to the right of the nipple as viewed in this photograph shows signs of skin retraction or skin tethering. Cancer causes fibrosis, which contracts the suspensory ligaments of the breast, resulting in this clinical change in the breast tissue. The dimpling may be visible at rest, with compression, or with lifting of the arms. The fibrosis can also pull the nipple as seen by the distortion of the areola here. (From Evans AJ: Atlas of breast disease management: 50 illustrative cases, Philadelphia, 1998, WB Saunders.)

IBC is characterized by one breast becoming larger than the other. Warmth, redness, swelling, itching, pain, skin dimpling called peau d’orange, and nipple changes (e.g., retraction or flattening) are just some of the many symptoms of IBC. Some women report it looks like a bug bite on their breast. They may also report a bruise on the breast that does not go away.

Metastases

Local metastases by direct extension of the primary disease site may involve the chest wall, ribs, pleura, pulmonary parenchyma, or bronchi and may erode the first and second ribs and associated vertebrae.²⁰⁰ Symptoms associated with metastases can include upper extremity edema, bone pain, jaundice, or weight loss. These findings are rarely the initial complaint.

If not diagnosed and treated early, the cancer can spread to the regional lymph nodes, including the axillary, internal mammary, and supraclavicular nodes. As the disease progresses, the cancer commonly spreads to the lungs, liver, bone, adrenals, skin, and brain.

Signs and symptoms of the affected system may be the first clinical indication of a problem. For example, lung lesions may present as vague, aching chest pain, hemoptysis, or unexplained dyspnea. Metastases to the liver may present as fatigue, jaundice, CTS, or skin changes.

Bone metastases is especially common affecting the vertebrae, pelvis, ribs, hip, femur, and humerus (see Table 9-2); metastatic spread from breast cancer rarely presents in locations below the elbows and knees. Bone pain and fracture are the most common symptoms of bone metastases.

Paraneoplastic Syndrome

A rare neurologic paraneoplastic syndrome associated with breast cancer in women called stiff-man syndrome has been reported with increasing frequency.^145,232,245 Paraneoplastic stiff-person syndrome is characterized by progressive symptoms of neuropathy or myelopathy with increased muscle tone and rigidity in the spine and lower extremities, especially the ankle dorsiflexors with loss of ankle motion. See further discussion on Paraneoplastic Syndrome in Chapter 9.²¹⁸

MEDICAL MANAGEMENT

PREVENTION.

Healthy People 2010 has identified the reduction of the breast cancer death rate by 20% as its primary objective related to breast cancer. The ACS’s 2015 Challenge Goals and Nationwide Objectives include a reduction of 15% in the age-adjusted incidence rate of the disease and a 45% reduction in the age-adjusted mortality rate. By the year 2008, the ACS hopes that 90% of women 40 year of age or older will undergo breast cancer screening that is consistent with their guidelines.^36,334 Additionally, by 2008, the ACS’s goal is to increase to 90% the portion of breast cancers diagnosed at a local stage or earlier.

Risk factor modification is advocated, including moderate-to-vigorous physical activity (45 to 60 minutes on 5 or more days per week), weight control and minimal lifetime weight gain, alcohol restriction (avoid alcohol if at high risk for breast cancer), and chemopreventive agents to reduce exposure to estrogen.

Controlling weight, anytime after age 18 but especially in middle age, may help in preventing breast cancer, the recurrence of breast cancer, and death from breast cancer.⁴³ Fat tissue contains an enzyme that converts adrenal gland hormones to estrogen. The extra estrogen in overweight women acts as a nutrient and aids the growth of precancerous or abnormal cancerous cells in the breast.

Data from the Nurses’ Health Study show a clear benefit for postmenopausal women from engaging in some form of exercise. Postmenopausal women who get at least 1 hour of physical activity per day are 15% to 20% less likely to develop breast cancer than sedentary women.²⁵⁸

Restricting alcohol is a proven risk reducer. Excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.^17,340 The effects of diet and nutrition (low fat and rich in fruits and vegetables) remain under investigation.

Evidence to support a link between antiperspirants or deodorants and breast cancer remains controversial. Many women choose to avoid these products as a means of preventing breast cancer until proved otherwise.

Other preventive steps may include exposure to the sun needed by the skin to manufacture vitamin D and increased vitamin D intake (food or supplementation).¹⁴⁹ Vitamin D receptor (VDR) in mammary cells has a role in signaling proliferation, differentiation, and survival of normal mammary epithelial cells. However, whether calcium or vitamin D intake modifies risk by genotype has not been fully investigated.^37,197

Prophylactic mastectomy (also referred to as risk-reduction mastectomy) for women with a BRCA1 or BRCA2 mutation and positive family history has proved extremely effective, but there is still a risk of breast cancer even after any kind of mastectomy. There is a need for research to better guide high-risk women in the decision-making process.^179,290 Numerous reputable books are available on the trade market specifically addressing ways to reduce risk and prevent breast cancer.

EARLY DETECTION.

The hallmark of effective intervention in cases of breast cancer is early detection using a combination of three tools: monthly self-breast examination (SBE), clinical breast examination (CBE), and mammography (Box 20-7). Women should start examining their breasts in their twenties so they are comfortable doing it and familiar with the way their breasts feel from month to month. The same is true for women with breast implants. Additional mammogram screening, called an implant displacement view, may be requested.

Box 20-7 AMERICAN CANCER SOCIETY RECOMMENDATIONS FOR BREAST CANCER SCREENING

The American Cancer Society (ACS) recommendations for breast cancer screening are presented below in abbreviated form. Readers should refer to the original full text guideline document to see the complete recommendations, along with the rationale and summary of the evidence.

Clinical breast examination (CBE) should be part of periodic health examinations, at least every 3 years for women in their 20s and 30s; asymptomatic women age 40 and older should have an annual CBE by a qualified health care professional.

Mammography should be done annually beginning at age 40. Women should be educated about the benefits, limitations, and potential harms associated with regular mammography.

Additional screening (e.g., starting annual mammography at a younger age and/or at closer intervals, or adding magnetic resonance imaging or ultrasound examination to mammography screening) may be recommended for women with any of the following:

• Previous personal history of breast cancer

• History of chest wall radiation

• Documented genetic mutation (BRCA or other genes)

• Strong positive family history without genetic mutation

• High-risk benign pathology (e.g., lobular carcinoma in situ or atypical hyperplasia)

• Very dense breast tissue on mammography

Summary of New ACS Guidelines

• CBE every 3 years for women ages 20-39

• Annual CBE every year for asymptomatic women ages 40+

• SBE occasionally or not at all

• Women ages 20+ should be educated about the benefits and limitations of the SBE

• Mammogram annually from age 40

Data from American Cancer Society (ACS): ACS News Center: Updated breast cancer screening guidelines

http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Updated_Breast_Cancer_Screening_Guidelines_Released.asp, May 2003. Accessed January 24, 2007.

Clinical Breast Examination (CBE).

The ACS makes the following screening recommendations for asymptomatic women at average risk: beginning at age 20, CBE and counseling to raise awareness of breast symptoms; for women ages 20 to 39 years, a CBE every 3 years and annual mammogram after age 40 years.

Self-Breast Examination (SBE).

The ACS no longer recommends that all women conduct regular SBE, but women should be informed about the potential benefits and limitations associated with SBE.²⁸⁵ This change in the recommendation came about as a result of a large study of female factory workers in China (referred to as the Shanghai Study). The women were taught how to do SBE with follow-up to see if the number of deaths from breast cancer was reduced. Although the rate of breast cancer was not reduced, the authors of the study clearly note that the women were not asked if or how often they performed the SBE. Without the availability of mammography, when women did find a cancerous lump, the cancer was more advanced with a much worse prognosis.³⁰⁴

There is still much controversy over the methodology and results of this study. Many experts still advocate monthly SBE performed 1 week after the cessation of bleeding from the menstrual cycle or in the postmenopausal woman consistently perhaps on the same day each month. The American College of Obstetricians and Gynecologists (ACOG) advocates performing BSE as one way to increase a woman’s breast cancer awareness. If a woman chooses to perform BSE, she should learn the correct procedure from a qualified health care professional (including physical therapists)^106,107 who can evaluate her technique.

One of the striking changes in the presentation of breast cancer in the United States over the past 25 years is the reduction in the size of lumps discovered by women themselves.¹²³ There is also case-control evidence that excellent BSE may reduce mortality.¹²⁷ For a discussion of the relative merits and disadvantages of the study, see the American Cancer Center News Center: Do breast self-exams make a difference? available at http://www.cancer.org/docroot/nws/content/nws_1_1x_do_breast_self-exams_make_a_difference.asp. The Susan G. Komen Foundation also offers step-by-step BSE instructions in English and Spanish (see www.komen.org/bse).

Mammography.

Screening mammography can reduce mortality from breast cancer by approximately 20% to 35% in women aged 50 to 69 years and approximately 20% in women aged 40 to 49 years.^81,92 Approximately 11% of all mammography studies are abnormal and 3% of those “abnormals” are actually diagnosed as breast cancer.¹⁶²

The term screening mammography implies the mammogram is done when there is no palpable lump or anything else indicating cancer. Until 1997 the ACS recommended the first screening mammogram by age 40 years, whereas the National Cancer Institute stopped advocating routine mammograms for women between the ages of 40 and 50 years²²⁷; and in the rest of the world, screening mammograms were not recommended until age 50 years.

Much controversy and debate centered around screening mammography for this particular age group (40 to 49 years); but in 1997, based on data presented at the NIH conference on breast cancer screening establishing the effectiveness of mammography in women younger than 50 years, the NIH began recommending breast cancer screening to women in their forties.^227,286

Organizations, including the American Medical Association (AMA), ACOG, and the ACS, support mammography screening beginning at age 40 years, although these groups vary in their recommendations regarding intervals for rescreening.²⁶⁵ The U.S. Preventive Services Task Force, an independent panel of private-sector experts in prevention and primary care, recommends that women aged 40 years and older be screened for breast cancer with mammograms every 1 to 2 years.^311a

At present, data are insufficient to recommend a specific surveillance strategy for high-risk women. Earlier initiation of screening, screening at shorter intervals, and screening with additional modalities, such as ultrasound and MRI, may be advised.²⁸⁵

The cost-effectiveness and efficacy of screening mammography in women age 70 years and older have come under examination. It has been suggested that the small gain in life expectancy is a variable that must be factored in when a woman decides about screening.¹⁶³

Some experts suggest that screening, including mammography, should be continued as long the woman’s life expectancy is more than 5 years. The challenge remains for the physician to accurately estimate and older person’s life expectancy based on individual health status, including concomitant comorbidity.¹³³

Genetic Testing.

Inherited mutations of BRCA1 and BRCA2 do increase the lifetime risk of breast (and ovarian) cancer, but genetic testing is not advised for everyone. Having an inherited gene mutation does not mean breast cancer is inevitable. Women who have a positive family history of breast cancer before the age of 40 years should seek genetic counseling. Testing may be advised for anyone with a family history described previously in the section on Risk Factors for this disease.

There are many considerations when considering genetic testing. A negative test for a mutation may be dif ficult to interpret if the family history is unknown. Coping with the results if they are positive and weighing all the options can be challenging. Although most states have genetic privacy laws to prevent discrimination by health insurers, the guidelines do not always apply to life or disability insurance. Testing is done by a simple blood test, but the test may be expensive and is not always covered by insurance.

DIAGNOSIS.

Clinical examination, mammography, and ultrasonography are all used to detect breast abnormalities. Tissue biopsy is the standard for a definitive diagnosis, and sentinel lymph node mapping to identify micrometastases has become standard practice to identify and remove only the first node or nodes that cancer cells reach after leaving the breast. This eliminates unnecessary dissection (see discussion of biopsy technique in the section on Diagnosis in Chapter 9). Only women whose sentinel nodes indicate the spread of cancer will need to undergo more extensive biopsy.

Imaging Technology.

As mentioned, mammography is an important tool for the detection of a lesion before the mass (cancerous or benign) is large enough to be palpable but is not a substitute for biopsy because by itself it is not diagnostic and it may not detect cancer in very dense breast tissue.

Digital Mammography.: Updated technology, such as digital mammography (computerized x-rays), may improve early detection of breast cancer. With the added capability of transmitting results electronically to specialists worldwide for consultation, this technology may reduce further misdiagnosis and unnecessary surgery. Mammography does not detect all breast cancers, and it cannot distinguish well among the various kinds of breast cancer. A more precise, noninvasive screening technique that does not involve the use of radiation is the ultimate goal of investigators developing improved breast cancer screening. Breast cancer can remain dormant for years before becoming clinically apparent, so long-term follow-up is mandatory for all women, especially anyone with a previous history of breast cancer.³⁵

Ductal lavage is another new method to detect early changes in ductal cells for women at high risk for developing breast cancer. Epithelial cells that line the ductal and lobular system of all milk ducts are collected using a microcatheter inserted into the milk ducts through the nipple surface. Results of this test may be able to diagnose abnormal ductal cells before cancer becomes evident on a mammogram or in a physical examination.^72,86

Magnetic Resonance Imaging.: Scientists are adapting MRI and positron emission tomography (PET) scanning, two imaging technologies that are good at distinguishing malignant from benign tissue, for use in breast cancer diagnosis (staging), although these remain too costly to use in general screening programs. MRI scans do find cancers that mammograms miss, especially in high-risk women, perhaps because breast cancer occurs in these women at a younger age when breast tissue is denser. About 3% of new cases of breast cancer have malignant tumors in the contralateral breast that can only be detected by MRI. The cost of MRI prohibits its use as a screening tool, but it is cost-effective and recommended for use to improve the detection of cancer in women already diagnosed.^177a

New guidelines from the ACS recommend MRI scans and mammograms once a year starting at age 30 for high-risk women. High risk is defined as a 20% to 25% or higher chance of developing breast cancer over the course of a lifetime. The average lifetime risk for women in the United States is 12% to 13%.

The high-risk group includes women who had radiation treatment to the chest between ages 10 and 30 years (e.g., for Hodgkin’s disease); women who are prone to breast cancer because of the presence of genetic mutations, such as BRCA1 or BRCA2; or those whose mothers, sisters, or daughters carry those mutations.

Ultrasound.: Ultrasonography is primarily used to differentiate a cystic from a solid lesion. Real-time elastography (elastogram), an experimental ultrasound technique, is on the horizon. This technology distinguishes harmless lumps from malignancy and provides results in minutes. The technique was pioneered at the University of Texas Medical School at Houston in the 1990s.⁹⁸

Ultrasound elastography is capable of imaging tissue strain even before tissue stiffness associated with pathologic change occurs. Some areas that appear as shadows on sonograms show up as discrete masses on elastograms. The technique may be able to replace tissue biopsy in the diagnostic process.^303,323

Biomarkers.

The protein (oncogene) c-erbB-2, also known as HER2/neu, is a prognostic breast cancer marker assayed in tissue biopsy specimens from women diagnosed with malignant tumors. Current studies suggest that soluble fragments of this oncogene may be released from the cell surface and become detectable in the saliva of men and women with the recurrence of breast cancer.²⁹⁴ Other biomarkers are under investigation, including one ECM component called tenascin-C. Expression of this large glycoprotein is suppressed in the normal adult mammary gland but is induced in breast cancer and is present in preinvasive cancer, as well as invasive breast cancer.¹⁰⁴ Researchers are investigating the use of minimally invasive tests to seek out biologic markers in blood or other fluids before a tumor develops.

Staging.

Once the diagnosis is established, the clinical stage is ascertained in order to determine optimal management, including selection of candidates for adjuvant systemic therapies (Table 20-3). Staging is done most often using sentinel lymph node biopsy (SLNB), which consists of the removal of one to three nodes; the removal of more than three nodes is considered a dissection.

Table 20-3

Stages of Breast Cancer and Prognosis

DCIS, Ductal carcinoma in situ; LCIS, lobular carcinoma in situ.

^*Survival rates for IIIC breast cancer are unavailable; this stage was only defined a few years ago.

Data from American Cancer Society and the Health Alliance Cancer Services, 2007.

Stage 0 (preinvasive cancer), referred to as in situ, means that the cancer remains “in place” and has not spread from its point of origin. Stage I disease is marked by a tumor 2 cm in size or smaller. Stage II disease is marked by a tumor between 2 and 5 cm in size without nodal metastases or a tumor less than 5 cm with homolateral axillary lymphatic metastases (the nodes are movable). A tumor larger than 5 cm is classified as stage III, as is a tumor fixed to the pectoral muscle or fascia or if the diseased axillary lymph nodes are fixed to adjacent tissues. Stage IV disease is a tumor fixed to the chest wall or skin or any tumor with metastases to the homolateral infraclavicular or supraclavicular nodes, with upper extremity edema, or with any distant metastasis.

The TNM classification of breast cancer has been revised and changed considerably, based on important developments that have occurred in breast cancer diagnosis and management. For example, the average size of breast tumors when first detected has decreased significantly. Immunohistochemical (IHC) staging and molecular biology techniques (e.g., reverse-transcriptase polymerase chain reaction [RT-PCR]), increasing knowledge of the importance of total positive axillary lymph nodes, and new information about clinical outcomes associated with metastases have led to greater refinement in TNM staging.²⁸³

TREATMENT.

Once the diagnosis of breast cancer is made, most of the treatment is the same for men as for women. The treatment plan depends on the type of cancer, stage at diagnosis (early or advanced), hormonal sensitivity (ER-positive or progesterone receptor–positive [PR-positive]), and presence of the growth-promoting protein Her-2/Neu, which appears to produce tamoxifen resistance. Treatment options include surgery, chemotherapy, radiation therapy, and hormonal manipulation.

The NCCN publishes an annual update of its original 1996 NCCN Breast Cancer Treatment Guidelines. The Guidelines address the treatment of all stages of breast cancer. With constant changes in the adjuvant therapy for breast cancer, a supplement to the Guidelines from the NCCN Breast Cancer Adjuvant Therapy Task Force is available.⁴²

Radical mastectomy was the most commonly employed procedure until the 1970s. This technique included removal of the entire breast, pectoral muscles, axillary lymph nodes, and some additional skin. Postsurgical problems included lymphedema, restricted shoulder mobility, impaired muscle function, and paresthesia.

Likewise, axillary node dissection is no longer performed routinely since it has been shown that the therapeutic benefit of a complete dissection has no effect on survival rate or risk of metastasis but only local control of the tumor. Instead, intraoperative lymphatic mapping and sentinel lymph node dissection are replacing complete lymph node dissection as the preferred procedure for the management of early-stage disease.¹³⁷

Breast-Conserving Therapy.

More recent treatment recommendations for women with stage I or II breast cancer include breast-conserving surgery (BCT), or lumpectomy to remove only the tumor and a surrounding margin of normal tissue with preservation of the breast, and radiation therapy (Fig. 20-16). Lumpectomy may be an option for women with larger tumors who have neoadjuvant chemotherapy (before surgery) to shrink the tumor.

Figure 20-16 Breast-conserving therapy (BCT). A, Incisions to remove malignant tumors are made directly over the tumor without tunneling. A transverse incision in the low axilla is used for either the sentinel node biopsy or the axillary dissection. The inset shows the excision cavity of the lumpectomy; no attempt is made to approximate the sides of the cavity, which will fill with serous fluid and gradually shrink. B, In the sentinel node biopsy, a similar transverse incision is made and extended through the clavipectoral fascia and the true axilla entered. The sentinel node is located by virtue of its staining with dye or radioactivity, or both, and dissected free as a single specimen. (From Townsend CM: Sabiston textbook of surgery, ed 17, Philadelphia, 2004, WB Saunders.)

Up to 50% of women with early breast cancer in the United States are now treated with BCT. In some geographic areas, modified radical mastectomy, which spares the pectoralis major muscle, is also a commonly used procedure with the primary advantage being avoidance of radiation therapy. However, radiotherapy, now an integral part of BCT, should not be withheld.^95,138

BCT may not be appropriate for women whose breasts are so small a simple lumpectomy would be too disfiguring, making a simple mastectomy the more feasible option. Breast conservation is not appropriate when there are multiple areas of cancer, a tumor too large to excise, and previous history of radiation to the breast.^199a

Mastectomy is usually reserved for women with more extensive disease; although the surgeon may recommend mastectomy for some women with early breast cancer if, for example, cancer is found in more than one location in the breast. Some women choose mastectomy to avoid radiation or for greater peace of mind.

Breast reconstruction with an implant is an option for women who have mastectomies. This is a two-stage process; first, a balloonlike tissue expander is placed under the chest wall muscle. Every 2 or 3 weeks for several months, saline is injected into the expander to gradually stretch the overlying chest wall muscles and skin.

The expander is replaced in a second surgery with a permanent saline implant. Although silicone implants were banned in 1992, after reviewing years of evidence and research concerning silicone gel-filled breast implants, the Institute of Medicine (IOM) has not found any increased risk of adverse health outcomes. The use of silicone-based implants has been reinstated once again.

Silicone breast implants may be contraindicated or used with caution in women with existing malignant or premalignant cancer of the breast. Silicone gel-filled breast implants have not been clinically tested in women who have had radiation to the breast after implantation. For a complete discussion of this topic, the reader is referred to the IOM’s publications.^144,144a

Alternately, muscle-flap procedures use tissue from the back or abdomen to either form a breast or create a pocket for an implant. The most popular flap procedures are the latissimus dorsi (back) flap, the transverse rectus abdominis muscle (TRAM) flap (Fig. 20-17), and the free flap. Free flaps use little or no muscle; a plastic surgeon trained in microvascular technique is needed for this procedure.

Figure 20-17 Transverse rectus abdominis myocutaneous (TRAM) flap. A, After mastectomy of the involved breast, (B) a breast is reconstructed using the lower abdominal skin and fatty tissue. In a pedicled TRAM, the tissue’s own blood supply remains attached and the lower abdominal tissue is rotated into position on the chest. The tissue is tunneled under the skin to the chest area, where it is brought through the mastectomy incision. The reconstructed tissue is shaped to form a matching breast and placed in the mastectomy skin pocket. A free TRAM flap refers to using skin and tissue that are completely disconnected from their own blood supply, moved from the abdomen to the new site, and then reconnected to different blood vessels. A nipple and areola can be tattooed on later after healing has taken place.

More recently a new procedure, the deep inferior epigastric perforator (DIEP) flap, uses skin and fatty tissue from the abdomen to reconstruct the breast without sacrificing the underlying abdominal muscles. Blood vessels (deep inferior epigastric artery) harvested to supply the new breast tissue do not travel within the abdominal muscles. Less disruption of the abdominal tissue results in far fewer abdominal impairments.^47,109,110

A similar procedure, the gluteal artery perforator (GAP) flap, allows transfer of tissue from the buttock, also with minimal donor-site morbidity. Like the DIEP, the superficial inferior epigastric artery (SIEA) flap transfers the same tissue from the abdomen to the chest for breast reconstruction as the TRAM flap without sacrificing the rectus muscle or fascia (Fig. 20-18).^109,110

Figure 20-18 Vascular territories of the abdominal wall provided by unilateral transverse rectus abdominis myocutaneous (TRAM) flap. Studies show that the most reliable cutaneous portion is directly overlying muscle zone I, followed by zones III, II, and IV, respectively. A deep inferior epigastric perforator flap (DIEP) is an alternative procedure to the TRAM. The rectus abdominis muscle is dissected to harvest the blood vessels, but the muscle is preserved because no muscle or overlying muscle fascia is used. The DIEP flap relies on blood vessels that perforate the rectus abdominis muscle (e.g., deep inferior epigastric artery and vein). (From Townsend CM: Sabiston textbook of surgery, ed 17, Philadelphia, 2004, WB Saunders.)

After surgery, the treatment plan may include radiation therapy, chemotherapy, hormone therapy, or a combination of these approaches. Chemotherapy is used when a tumor is larger than 1 cm or when smaller tumors have spread to the lymph nodes. The primary objective of these treatments is to reduce the odds of occult metastases developing into disease.

Chemotherapy.

Women with harder to treat ERnegative breast tumors benefit much more from chemotherapy than do women with ER-positive tumors. Almost all women with ER-negative breast tumors should receive chemotherapy, whereas women with ER-positive tumors are better served by hormonal therapy; chemotherapy adds little additional improvement for ER-positive women.²⁵

Increased disease-free survival time after combination chemotherapy has been noted consistently in premenopausal women with metastases to the axillary lymph nodes. Combination chemotherapy combines two or more drugs and is given in multiple courses over 3 to 6 months. The addition of hormone therapy or ovarian ablation for premenopausal women to stop estrogen production is more effective than chemotherapy alone in women whose tumors contain estrogen receptors.

The majority of women with early-stage breast cancer are advised to receive chemotherapy in addition to radiation and hormonal therapy, yet research has not demonstrated that chemotherapy benefits everyone equally. The development of molecular profiling tests (a technique that examines many genes simultaneously) may be able to spare women unnecessary treatment if chemotherapy is not likely to be of benefit to them.^153,207

Gene Profiling.: Testing, or Trial Assigning IndividuaLized Options for Treatment (TAILORx), is underway to determine the most effective current approach to cancer treatment with the fewest side effects for women with early-stage breast cancer using gene profiling assays. Two such diagnostic tests now available for gauging a woman’s risk of breast cancer recurrence are Oncotype DX and MammaPrint gene profiling tests.

The Oncotype DX test can be performed in women of all ages with early-stage node-negative, ER-positive tumors. The MammaPrint assay is used only for women 55 years or younger who have early ER-positive or ER-negative tumors. Using this test to obtain characteristic genetic information, called a genetic signature, about the tumor can predict rate of metastasis and disease-free survival.

Researchers have found that women classified as high risk by the Oncotype DX test gain substantially from chemotherapy with a 90% 10-year disease-free survival rate when treated with chemotherapy compared to 65% with tamoxifen alone.²³⁷ Neither test is intended for use in women with either carcinoma in situ (precancerous) or metastatic breast cancer; the tests are not 100% accurate or fool-proof.

Radiation Therapy.

Most women receive radiation therapy after a lumpectomy to eradicate any cancer cells that may remain in the affected breast or nearby lymph nodes. Usually, radiation is delivered to the whole breast once a day, 5 days a week, for about 6 weeks (Fig. 20-19).

Figure 20-19 The standard radiation field configuration for breast cancer. Two tangentially directed fields encompass the breast with a minimal amount of underlying lung tissue. The contralateral breast and all of the critical structures are avoided. (From Abeloff MD: Clinical oncology, ed 3, Philadelphia, 2004, Churchill Livingstone.)

Software algorithms used to produce discriminating radiation fields conform the radiation to the breast, chest wall, and/or regional lymph nodes to achieve a homog- enous dose to the breast and decrease or avoid doses to the ribs, lung, and heart. This technology has allowed greater adaptation to a variety of breast and chest wall shapes.³⁵

Women who have a mastectomy may also be treated with radiation if the tumor is more than 8 cm or if the tumor is close to the rib cage or chest wall, or if there were many positive axillary lymph nodes.

The use of partial-breast radiation to target the tissue immediately around the tumor where cancer is most likely to recur is on the rise. Radiation beams can be targeted at the tumor site instead of the breast, cutting down the usual 6-week treatment to 5 days (Fig. 20-20). Studies are underway to determine who is the best candidate for this treatment and what treatment protocol works best. A 1-day method that permanently implants radiation seeds inside the breast to kill stray cancer cells is also in use. The pellets emit radiation for about 2 months until they run out; the implant remains under the skin with no further effects.^158,244

Figure 20-20 Balloon brachytherapy. The MammoSite device approved for partial breast radiation in the treatment of early-stage breast cancer. A single-balloon catheter is inserted in the breast to deliver a site-specific, prescribed dose of radiation. The deflated balloon is placed inside the lumpectomy cavity (the space left after the tumor is removed). A tiny radioactive source (seed) is placed within the balloon by a computer-controlled machine. Because the radiation source is inside the balloon, radiation is delivered to the area of the breast where cancer is most likely to recur. Radiation exposure to the rest of the breast, skin, ribs, lungs, and heart is minimized. Once it has emitted the prescribed dose of radiation, the source is removed. When used as primary therapy (i.e., the only form of radiation after a lumpectomy) treatments are twice a day for up to 5 days. The applicator shaft, a tube connected to the balloon, remains outside the breast. After 10 sessions in 5 days, the balloon is deflated and the catheter is then removed.

Stem Cell Transplantation.

In 1998, breast cancer was the most common indication for stem cell transplant in North America, accounting for nearly one-third of all transplants. However, subsequent reports have concluded that high-dose chemotherapy plus autologous bone marrow transplantation does not improve survival in women with metastatic breast cancer.^24,288 Thus a gentler approach using trastuzumab (Herceptin) was developed with better outcomes and fewer side effects.

Hormonal Therapy.

Knowing that estrogen promotes the growth of ER-positive breast cancers, several methods are used to block the effect of estrogen or to lower estrogen levels. Antiestrogens prevent estrogen from causing the growth of cancer cells by binding directly to and blocking the estrogen receptor. Hormonal therapies, such as tamoxifen and the newer aromatase inhibitors, help prevent the growth, spread, or recurrence of ER-positive tumors by preventing estrogen from reaching them. Women with ER-positive tumors may benefit from hormonal therapy without needing chemotherapy. Hormonal therapy does not work against ER-negative tumors.

Tamoxifen (Nolvadex) has been the definitive standard of antiestrogen hormonal therapies for the last 30 years because of its documented efficacy in preventing ER-positive breast cancers from coming back and its reasonable safety profile. Tamoxifen prevents estrogen from entering cells, whereas some newer antiestrogens, such as fulvestrant (Faslodex), work by reducing the number of estrogen receptors. Tamoxifen is typically used as a chemopreventive agent to reduce the risk of recurrence. It is administered for 5 years after surgery for premenopausal and postmenopausal women with early-stage breast cancer. It has a proven track record when administered postoperatively in stages I and II disease of a 50% or more reduction of invasive and noninvasive breast cancer in all age groups and all categories of estrogen-sensitive breast cancer.

Tamoxifen is a preferred drug used to prevent breast cancer recurrence in premenopausal women. Some women over age 70 years with ER-positive breast cancer who choose hormonal therapy may be able to avoid radiation therapy after lumpectomy. Tamoxifen is used to reduce the risk that the tumor will recur locally or metastasize after the woman has completed local surgical and/or radiation treatment. It is also used to treat metastatic breast cancer. There are some disadvantages to this treatment such as cancer resistance and toxicities (e.g., endometrial carcinoma, thromboembolism, hot flashes, and vaginal/urinary symptoms).¹⁸⁸

One major drawback to the use of tamoxifen is the increased rate of endometrial cancer. Weight gain is a significant side effect for some women. Giving the drug for more than 5 years failed to enhance its effect; more studies are under way to determine the optimal duration of tamoxifen administration, especially in relation to the concomitant development of endometrial cancer in some women.

Tamoxifen does not appear to benefit women with tumors that can grow without estrogen and progesterone as they are unresponsive to hormonal blockers. More study is needed to develop chemotherapeutic agents that target progesterone receptors similar to how tamoxifen is used to treat ER-positive tumors by blocking the estrogen pathway.

The use of raloxifene, a SERM drug approved for women at risk of osteoporosis that shows promise in breast cancer prevention, is also under investigation. Like tamoxifen, raloxifene blocks the effect of estrogen on breast tissue and breast cancer. Initial results of the Study of Tamoxifen and Raloxifene (STAR) showed that raloxifene works as well as tamoxifen with the added benefit of fewer uterine cancers and fewer overall serious side effects (e.g., cataracts, deep vein thrombosis, or pulmonary embolism).^175,228,318

A large number of other chemopreventive agents under investigation include other SERMs, cyclooxygenase-2 inhibitors, aromatase inactivators/Gn-RH agonists, isoflavones, and vitamin D derivatives.^87,179 Aromatase inhibitors (AIs) are a new class of endocrine agents that block an enzyme necessary to convert other hormones to estrogen in the breast. AIs cannot stop the ovaries of premenopausal women from making estrogen, so they are only effective in postmenopausal women.

Third-generation drugs (e.g., letrozole [Femara], anastrozole [Arimidex], and exemestane [Aromasin]) in this group have also been approved for first-line treatment based on studies that show at least a 90% estrogen suppression effect. Some researchers are investigating the use of several aromatase inhibitors in women with mild symptoms and slow disease progression.^33,297 Exemestane after tamoxifen reduces breast cancer recurrence by about half.¹⁸⁸

Biologic Therapy.

Trastuzumab (Herceptin) is highly effective in treating breast tumors that produce too much HER2, a protein that spurs the growth of cancer cells. Herceptin is a humanized IgG monoclonal antibody, and the first biologic therapy approved for use that attacks cancer at its genetic roots. It targets a defective growth-promoting oncogene, known as HER2/neu, found in about 30% of women with aggressive breast cancer.

HER2/neu is a protein that often appears on the surface of breast cancer cells. HER2-positive tumors are like a car with the accelerator stuck to the floor with constant signaling to grow contributing to cell proliferation. After the antibody attaches to the protein, it is taken into the cell, where it interferes with basic cell function and eventually kills the cells but spares other fast-growing cells. HER2-positive breast cancers are more aggressive and less likely to respond to conventional therapies.

When administered to women with metastatic breast cancer along with standard chemotherapy, trastuzumab delays the progression of the disease for several months and produces a greater regression in existing tumors without additional side effects. Unfortunately, Herceptin eventually stops working for many women with advanced breast cancer. Its use also has been linked with heart failure and is not recommended for women with impaired heart function.

There is another drug, lapatinib (Tykerb) under investigation that targets tumors without killing healthy cells. Like Herceptin, Tykerb targets the protein HER2/neu. Herceptin blocks the protein on the cell surface; Tykerb blocks it inside the cell and blocks another abnormal protein as well.¹⁰²

Bevacizumab (Avastin), a targeted drug that cuts off the blood supply to cancer cells, has been approved to treat advanced colorectal cancer and may be helpful in late-stage breast cancer when given in combination with paclitaxel (Taxol). At the time of this writing, Avastin had not yet been approved by the FDA for use in breast cancer. All of these targeted drugs are very expensive (up to $100,000 per year).

The role of cannabis (specifically, δ⁹-tetrahydrocannabinol [THC] in marijuana) in the treatment of breast cancer is also under investigation. Studies in mice have shown an inhibition of breast cancer when exposed to THC.¹⁸⁰ THC exhibits antitumor effects on various cancer cell types, but its use in chemotherapy is limited by its psychotropic activity.

Uncertainties remain about how to treat node-negative women, particularly when the tumor is small; how to treat DCIS; who should receive preoperative systemic therapy; and who should be given tamoxifen. Despite these unresolved issues, medical advances have saved the lives of many people and will continue to progress with further reduction in morbidity and mortality.

Ovarian Ablation.

Removing estrogens from premenopausal women by surgically removing the ovaries is another effective way of treating ER-positive breast cancer. Drugs can be injected monthly as an alternate (nonsurgical) method of stopping ovary function without removing the organ.

PROGNOSIS.

Prognosis is dependent on when the lump is discovered, how large it is, and the involvement of lymph nodes. This is true for men and women, although some studies have found lower survival rates for men with advanced breast cancer. This may be the result of older age, coexisting diseases, and lower life expectancy of men at the time of diagnosis. When cancer stage and grade are matched, survival rates for men and women with breast cancer are equal.

The presence of three or more comorbid conditions has been associated with a fourfold higher rate of all- cause mortality at 3 years for women compared to women with primary breast cancer with no comorbid conditions. Similar comparisons have not been made for men.²⁶⁹

Cancer prognosis and risk of recurrence is dependent on the age of the client, stage of disease, menopausal status, race/ethnicity (blacks and Hispanics are often diagnosed at later stages), activity level (sedentary has a poorer prognosis), and body mass index (BMI; risk is increased when BMI is greater than 30).

The status of the axillary nodes is an important prognostic factor in breast cancer and determines the selection of treatment. Breast tumors that lack estrogen responsiveness have had a poor prognosis because of the cancer’s poor response to current treatment available.¹⁷⁴ However, for the 70,000 U.S. women diagnosed each year with nonhormonal cancer, advances in conventional IV chemotherapy have improved survival rates.²⁵

Pathologic characteristics of the primary tumor are also prognostic (e.g., high grade, aneuploid DNA content, presence of tumor necrosis factor [TNF], negative estrogen (ER-negative and PR levels, and Her2/neu overexpression).¹⁹⁸ Newer findings offer more evidence that a tumor’s “personality characteristics” are more important than size and how much the cancer has spread. Whether the tumor is fueled by estrogen is also a factor in how fast it grows and spreads, affecting outcomes.

If detected early before metastases, breast cancer is curable. There has been a reduction in mortality of 1% to 2% annually in the United States and other industrialized countries, possibly related to changes in lifestyle (e.g., diet, exercise, and reproductive behavior), early diagnosis, and improved success of treatment.⁷¹ More than one-half of all cases reported are diagnosed as stage 0 or I disease.

The 5-year survival rate for localized tumors is 92%; survival rate drops considerably if there is nodal involvement; and metastatic disease is incurable and results in an overwhelming death rate.¹¹² Ten-year survival rate for stage I disease is 85%, for stage II 66%, for stage III 36%, and for stage IV 7%.²⁸

Negative prognostic indicators for bone metastases include aggressive nature of primary lesion (i.e., advanced breast cancer that is poorly differentiated), lytic or multiple bone lesions, metastases to multiple systems, high tumor markers, overall poor health of the individual, and a short period of cancer-free status.²⁰⁰

Advancements in technology make early detection possible with a higher survival rate; even so, more than 40,000 women died from this disease in the last year. Many women experience secondary complications of the disease and its treatments, including decreased quality of life, weight gain, sleep disturbances, poor body image, fatigue, increased risk for osteoporosis, cardiovascular disease, premature menopause, and lymphedema.²⁶

RECURRENCE.

Breast cancer recurs in 20% to 25% of women deemed by current tests to be at low risk. The probability of recurrence is higher with histologically positive axillary nodes and increases with each additional positive node. Other risk factors for recurrent disease include premenopausal status, estrogen status, tumor size (>2 cm), high grade, and other histopathology.¹

Despite treatment with chemopreventive drugs like tamoxifen, some women have recurrences because the cancer cells develop resistance to the drug. It may be possible to switch from one drug to another to increase the odds of long-term survival for women at risk for recurrence. Herceptin has been shown to cut the risk of relapse by 50% for women with aggressive breast cancer when used in the early stages of disease.^243,260

Patterns of recurrence and metastases are similar for men and women, usually occurring within 2 years of the initial diagnosis and treatment. For example, DCIS in stage 0 at the time of diagnosis is usually considered cured after treatment. Even though the highest risk of recurrence is in the first 2 years, small stage I cancers can reappear years later in a more lethal form. Stage IV breast cancer has the poorest prognosis; tumors have spread to other parts of the body.

Molecular profiling studying the genetic characteristics of breast cancer will help identify women at greatest risk of breast cancer recurrence. Genomic testing will help identify women as low-, medium-, or high-risk of cancer recurrence with a high degree of accuracy. Treatment and surveillance for these individuals will likely be more aggressive. Microarray technology may make it possible to examine the genomic profile of the primary tumor, identify the presence of micrometastatic cells, and determine the best drug to elicit a positive response based on pharmacogenetic data.^116,142

Men are less likely than women to develop cancer in the opposite breast, but recurrence of cancer does happen. Local recurrence is treated with surgical excision or radiotherapy combined with chemotherapy, especially if hormonal therapy has failed. A key to recognizing women whose cancer is most likely to recur might be a tumor-suppressing protein called maspin, produced by cells in the breast and an effective inhibitor of angiogenesis. Women who have high levels of maspin in the bone marrow tend to remain disease-free for 2 years, whereas those with low concentrations are more likely to have a recurrence.^184,338 The most powerful predictor of recurrence remains whether or not the cancer has spread to the lymph nodes, although 20% of women whose nodes are clear still relapse.

New drugs on the market, such as letrozole (Femara) an anti-aromatase agent, have also been found to reduce the risk of relapse in older or postmenopausal women. Letrozole, like tamoxifen, works by interfering with estrogen. Whereas tamoxifen blocks estrogen receptors on the cells, letrozole inhibits the creation of estrogen.

20-11 SPECIAL IMPLICATIONS FOR THE THERAPIST

Breast Cancer

PREFERRED PRACTICE PATTERNS

4B:

Impaired Posture

4C:

Impaired Muscle Performance

6H:

Impaired Circulation and Anthropometric Dimensions Associated with Lymphatic System Disorders

There are many considerations for the therapist working with men and women who report upper quadrant symptoms of unknown origin or who have been diagnosed with breast cancer, both before and after treatment. Besides the considerations discussed in this section, limited literature evaluating physical therapy and breast cancer is available.^117,143,201 See also the section on Lymphedema in Chapter 13.

Screening for Disease and Cancer Recurrence

When treating a woman with a history of breast cancer, an awareness of the symptoms and signs associated with breast cancer is important. Local and distant metastases occur most frequently within 3 years of the initial diagnosis. Typical sites of metastasis in women with breast cancer are lymph nodes, bone, lung, liver, and brain.¹⁴⁸

Approximately 10% of women with breast cancer will develop cancer in the opposite breast. After surgical removal of all malignant breast tissue, there is still a risk of breast cancer recurrence in the breast and along the chest wall. In 40% of the cases, cancer recurs at the original location of the primary tumor.²⁰⁰

A local recurrence of breast cancer will present most commonly as a new lump or mass. A lump that is painless, hard, and with irregular edges is very suspicious and must be evaluated. Palpation of a lump or mass in these areas or new onset of edema or swelling in the upper quadrant should raise concern on the therapist’s part and lead to further questioning regarding the clinical findings.²⁰⁰

Therapists examining the shoulder and shoulder girdle region need to be aware of the nonmusculature structures (including breast tissue and regional lymph nodes) located in these areas. The upper, outer quadrant of the breast can extend up toward the glenohumeral joint, and more cancerous masses occur in this area of the breast than in any other part of the breast.

In addition, approximately 50% of women with breast cancer have metastasis to the axillary nodes at the time the diagnosis is made. Breast tumor metastases to lymph nodes can involve the axillary, supraclavicular, and mediastinal lymph nodes. Disease spread to these lymph nodes groups may cause compression of adjacent structures, resulting in referred pain to the shoulder, upper extremity, and/or chest wall.^110a,200

If the mass lies in the pectoralis major muscle, the mass should change during palpation when the muscle is actively contracting. Metastases to the thorax are common in breast cancer, and pulmonary symptoms can be very similar to pulmonary abnormalities that occur after radiotherapy. If the therapist is in doubt regarding any reported or observed manifestations, the client should be evaluated by a physician (see the section on Lymphedema in Chapter 13).

Bone metastases occur in up to 70% of women with advanced breast cancer.²⁶¹ The humerus is the most common upper extremity site for bone metastasis, and pathologic fractures can occur. The femur is the most common lower extremity site. Any report of new (or increased) bone pain, especially at night and/or with weight-bearing activities, should be carefully assessed. Other common sites for breast cancer metastases include brain, liver, lymph nodes, bone marrow, and lungs.

The therapist must remain aware of and monitor for risk factors for bone metastases for individuals with breast cancer. Positive nodal status, large tumor size, ER-positive status, and age under 35 years are significant risk factors for bone metastases in this population. Individuals who use tobacco, have a poor diet and nutrition, report decreased physical activity, and engage in alcohol abuse are much more likely to develop metastases.^57,88

Preoperative Considerations

Preoperative evaluation is recommended for all women undergoing surgical intervention for breast cancer whether the intervention is axillary node dissection, lumpectomy, or mastectomy of any kind. Therapists have a great amount of work to do to provide evidence-based research supporting the role of the physical therapist in preoperative assessment and education. Educating surgeons, radiation oncologists, and medical oncologists regarding the benefits of mobility and soft tissue mobility is essential.

Upper quadrant motion, posture, joint range of motion (including accessory motions), flexibility, and soft tissue movement should be assessed. Identification of current physical activity level and exercise regimen is important. Preoperative education is included to teach safe movement and exercise techniques to be used in the early postoperative phase. Lymphedema precautions are also important (see Table 13-2).

Starting with the preoperative diagnosis and throughout the recovery process the therapist can guide women into physical activity and exercise routines that help them maintain endurance, function, flexibility, and strength; reduce pain and fatigue; and prevent musculoskeletal injury or debilitation, especially during adjuvant treatment such as chemotherapy or radiation. Helping women cope with the emotional challenges of living with a life-threatening and body-altering disease is integral to the healing and recovery process.

If BCT or reconstruction has not been discussed with the woman, the therapist may want to encourage the woman to discuss this with her surgeon before the scheduled procedure. A recent study has shown that only about 25% of general surgeons refer most of their clients with breast cancer for a reconstructive surgery consultation at the time of treatment planning. A multidisciplinary approach involving clinicians in different specialties is needed to help women understand all of their surgical options.^104a

Side Effects of Treatment

Women receiving adjuvant therapy (chemotherapy, radiation therapy, or hormonal therapy) may experience numerous side effects that could interfere with rehabilitation (see Chapters 5 and 9). Potential side effects of therapy are listed in Table 9-8; see also Tables 5-7 and 5-8).

There has been an increased frequency of rheumatoid symptoms reported after breast cancer treatment. Significant joint pain and swelling of the upper extremity, morning stiffness lasting less than 1 hour (41%) or more than 1 hour (26%), and prolonged joint pain and stiffness have been documented.¹⁰

CHEMOTHERAPY

Women receiving chemotherapy will likely be fatigued and experience flulike symptoms. This has been minimized to some extent with erythropoietin (EPO) used to treat anemia by stimulating bone marrow production of red blood cells. For the individual with low nadir (lowest point of blood cell production after neutrophil and platelet count have been depressed by chemotherapy) and/or anemia, the timing of scheduled therapy visits is important to maximize productivity during the session.

Exercises and functional activities may have to be paced or therapy visits shortened to accommodate the woman’s energy level. An exercise program to improve endurance in order to perform activities of daily living is important.

RADIOTHERAPY

Radiotherapy to the left breast is associated with higher rates of chest pain, coronary artery disease, and myocardial infarction. Cardiotoxic drugs such as Adriamycin and Herceptin may compound the problem. The therapist can screen women treated for breast cancer for cardiac symptoms and risk factors such as blood pressure and smoking. Regular cardiac surveillance is important for all breast cancer survivors regardless of whether they had radiation therapy because of the increased risk of cardiac disease with aging.¹²²

HORMONAL THERAPY

Although tamoxifen has a protective effect on bone mineral density, the majority of AIs have been linked with an increase in osteoporosis. Future reports may bear out a significant difference in fractures as well.¹⁷² To date there are no standard guidelines on the prevention and management of osteoporosis for these clients. The therapist must be alert to the need for referral for baseline studies, use of bisphosphonates, and preventive exercise in these individuals.¹⁷² All of the clinical trials using adjuvant AIs have shown an increase in arthralgias and myalgias. Symptoms are usually mild and include joint pain and muscle aches that seem to respond to antiinflammatories.¹⁷²

Postoperative Considerations

Breast surgery (lumpectomy, modified regional mastectomy, breast conserving mastectomy, or breast reconstruction) combined with radiation therapy and chemotherapy are common treatment interventions that can contribute to postoperative problems such as pain, decreased range of motion, weakness, movement impairment, swelling, neuropathy, radiation fibrosis, fatigue, and lymphatic cording.^278a,335

Recovery after each individual surgical procedure may vary. Differences exist even among the different choices for reconstruction (e.g., pedicled TRAM flap, free TRAM flap, or DIEP free flap). Every woman is different in her recovery, depending on the total treatment process. Most centers have postoperative protocols for each procedure available for review.¹⁷⁰

BREAST CONSERVING THERAPY

BCT usually does not affect the pectoralis major or overlying fascia, but the therapist should read the operative report to be certain; lobular breast cancer can go deep to the chest wall requiring deep resection. Keep in mind that the muscles are not spared by radiation therapy.

MASTECTOMY

Mastectomy without reconstruction will be different from mastectomy with reconstruction. Women who have undergone mastectomy should be instructed postoperatively and assisted with breathing and coughing exercises to prevent pulmonary complications. In addition, lower extremity exercises are also important to prevent thromboemboli. More specific rehabilitation recommendations based on specific oncologic treatment are available.¹⁰¹

About 40% of women undergoing mastectomy or level 1 and 2 lymph node removal with nerve resection experience a neuropathic pain phenomenon called postmastectomy pain syndrome (PMPS) or postbreast therapy pain syndrome (PBTPS). PMPS/PBTPS is thought to arise from damage to the axillary nerves during surgery, specifically the intercostobrachial nerve, a peripheral nerve with tributaries that branch into the armpit and upper arm.²⁹⁵

The pain occurs at the incision site, axilla, arm, or shoulder and is experienced as burning, numbness, tingling, or stabbing. Severity ranges from mild to extremely distressing; onset and frequency are highly variable (immediate to after 3 months or continuous, daily, weekly, and monthly). Because PMPS/PBTPS seems to be on the rise, it is important to ask about postmastectomy pain. Prognostic risk factors that predispose an individual to PMPS/PBTPS are unknown, with the possible exception of age (more common in women younger than 30 years).^44,287 In addition to medications for pain, a program to prevent loss of mobility and to prevent adhesive capsulitis must be initiated.

Sensory stimulation to the skin with a variety of techniques (e.g., deep pressure, light touch, and sharp or vibratory stimulation) and nerve gliding techniques may be helpful. For the person who cannot tolerate the touch of clothing against the skin, medications (e.g., Neurontin or Elavil) may be considered. Some women have relief from symptoms with the application of Lidocaine patches to the nerve root region while waiting for nerve regeneration to take place.

BREAST RECONSTRUCTION

The TRAM flap has an incision that runs laterally from hip to hip and may weaken the abdominal wall. Women with chronic back problems are usually not good candidates for this procedure without adequate preoperative rehabilitation. Other complications of TRAM include failed vasculature of the breast and fat necrosis (small areas of scar tissue formed by necrotic fatty nodules), abdominal wall hernias, and flap failure.

Risk factors for postoperative complications include smoking and peripheral vascular disease for a higher incidence of wound infection and preoperative radiation therapy for increased rates of seroma.²⁷⁷ A postoperative strengthening program is essential to prevent further back-related musculoskeletal complications. Although uncommon (occurring in 1% to 5% of cases), the most serious complication of the flap procedure is a loss of blood circulation to the transferred tissue, leading to necrosis and the loss of all or part of the reconstructed breast.

BREAST IMPLANTS

Women who receive breast implants for reconstruction after mastectomies may experience surgical complications caused by tissue damage from the cancer surgery and follow-up chemotherapy and radiation to the surrounding tissue. These alterations in tissue may prevent the implant from being fit in where the breast tissue was excised, thus affecting the way scar tissue forms around the implant. Scar-tissue formation that deforms or hardens the implant, called capsular contraction, is the most common complication, followed by implant rupture or malfunction, bruising, infection, and chronic pain.⁹⁶

AXILLARY NODE DISSECTION

Numbness under the arm (axillary area) is often a clue that axillary node dissection was done; many times, the woman does not know how many nodes were removed. The therapist must read the pathology report to assess the level of risk for lymphedema and other complications. Postoperative deficits following axillary lymph node dissection can become chronic conditions for many breast cancer survivors.¹¹⁸ Most of these problems develop within 3 months of surgery and have not resolved up to 2 years later.¹⁹⁶

Lymphatic cording, also known as axillary web syndrome (AWS) associated with surgical removal of axillary lymph nodes is not uncommon. Lymphatic cording is described as a visible and palpable web or fibrous cord of subcutaneous tissue extending from the axilla into the medial arm (Fig. 20-21). The network of cords usually extends to the cubital space and even below with occasional cording to the base of the thumb.²⁴⁷

Figure 20-21 Axillary web syndrome (AWS) 2 weeks after initiation of physical therapy intervention. The cording is less prominent but still visible as the skin is pulled back by the cord. This effect can make the arm look swollen as if there is some swelling from lymphedema. Edema can also accompany cording. (Courtesy Jane Kepics, MS, PT, CLT-LANA, Phoenixville Hospital, Phoenixville, PA.)

The cords are most visible in the axilla when the shoulder is abducted or in the antecubital space when the elbow is extended (Fig. 20-22). Radiating pain down the arm during shoulder abduction and limitation of shoulder abduction and/or elbow extension are the most common symptoms.

Figure 20-22 Photo shows a pretreatment axillary cord that limits shoulder abduction. This client had a biopsy of a swollen axillary lymph node. The biopsy was benign, but the woman had pain and limited range of motion for about 6 weeks. (Courtesy Jane Kepics, MS, PT, CLT-LANA, Phoenixville Hospital, Phoenixville, PA.)

Typically there are two or three palpable cords under the skin that are hard and painful but not erythematic. It is usually self-limiting, often resolving within 3 months’ time.²⁴⁶ However, some women do report persistent discomfort in the chest wall or axillary for a long time after surgery and may not continue to report this to their physicians because they have been told it will go away or to “live with it.”

The physical therapist may be very instrumental in finding out about unreported or unresolved AWS. Physical therapy intervention may have a role in reducing the length of time clients suffer from this condition, especially for women for whom the condition persists beyond the expected time due to concurrent cancer care.³³⁵ Clinicians report good success with myofascial release and soft tissue mobilization techniques directly to the cords and to the surrounding tissues. Increased range of motion and decreased discomfort can be attained quickly in most cases. An individual’s low tolerance for pain may require additional time and intervention to resolve.

This condition is thought to occur from lymphatic disruption after breast or axillary surgery. The exact mechanism is unknown but may be attributed to lymphovenous injury (e.g., lymph vein rupture, superficially dilated veins with thrombi inside, or lymphatic outflow obstruction) from prolonged positioning during surgery or lymphovenous stasis from removal of nodes in the axilla. The cords may represent thrombosed lymphatics after an inflammatory phase with thickening of the vessels, temporary shortening, and tightening, which later remits.^161,178,215

It is important to differentiate articular or postoperative muscular shortening, as well as the fear-avoidance behavior (i.e., fear of pain from movement), from AWS. The woman usually has a good postoperative course but begins to report intense pain along with limited range of motion, especially shoulder abduction (less than 90 degrees in 74% of cases).^215,247

SHOULDER/UPPER EXTREMITY

Of those who have surgery, seven out of eight experience some ongoing problems with shoulder/arm function; most women present with more than one symptom such as arm and breast swelling, shoulder stiffness, weakness, movement impairment, axillary and/or chest wall pain, and numbness.^196,295 The impact of impairments on activity limitations 6 months and 12 months after breast cancer surgery were reported for a group of 96 women. The most common impairments 6 months after surgery were breast and axillary scar tightness, axillary edema, and neck-shoulder pain. Breast scar tightness and edema were reduced by 12 months, but limb ache increased significantly. Lifting, carrying, and reaching were limited; impairments and their impact on activities were frequent and constant.¹⁵⁶

The risk of postoperative adhesive capsulitis may be decreased with current treatment protocols, such as preoperative physical therapy, and postoperative limitations in shoulder range of motion until 5 days after the drain is removed. Too much movement while the drain is in can cause increased drainage. The downside of this situation is that women are advised to limit their motion so they can get stiff throughout the entire upper quadrant on the affected side. Scarring with facial tightness complicates the therapist’s treatment intervention.

Releasing cording associated with AWS may also be preventive but this statement is made on the basis of clinical observation rather than evidence-based clinical studies. A home program of stretching and encouraging functional tasks may help to maintain range of motion in preparation for radiation with its known effects on soft tissue. Some therapists have observed increased adhesive capsulitis with the use of hormonal therapy with anastrozole, but this has not been reported in the literature to date.

There is a great need for a functional assessment tool and rehabilitation protocols specific to breast cancer survivors. The use of functional scales adapted for the breast cancer client, including the visual analogue scale (VAS) and Scale for Breast Cancer Patients (based on the Oswestry Low Back Pain Disability Questionnaire), has been documented.¹⁵⁶

Subtle changes in upper extremity function are difficult to quantify, potentially leading to an underreporting of functional deficits.²⁰⁵ Many of the problems unique to this population are not captured by standard functional scales (e.g., the Penn Shoulder Score, the disabilities of the arm, shoulder and hand [DASH] questionnaire, and the functional assessment of cancer therapy for breast cancer [FACT-B]) used with other diagnoses.

A newly developed upper limb lift test (ULLT) modified from a previous study¹²⁴ has been pilot tested in women newly diagnosed with breast cancer before medical treatment. Weight used was scaled to the participant’s body weight to avoid fatigue. The ULLT appears to be a promising test of gross motor upper extremity function that may provide a quantitative measure of function to guide rehabilitation of women during and after breast cancer treatment.²⁴¹

LYMPHEDEMA

Secondary arm lymphedema remains a chronic and distressing condition for some women after breast cancer treatment. Conservative therapies, such as complex physical therapy, compression bandaging and garments, and exercise, have proved effective in reducing fluid volume and improving subjective arm symptoms and quality of life.²¹⁴ Lymphedema and its treatment are presented in depth in Chapter 13.

Low-level laser treatment has recently been approved by the FDA for the treatment of postmastectomy lymphedema. The laser-beam pulses produce photochemical reactions at the cellular level, thereby influencing the course of metabolic processes and reducing the volume of the affected arm, extracellular fluid, and tissue hardness.⁴¹

The use of low-level laser over areas where carcinoma was originally found has not been investigated. Manufacturers of laser equipment suggest that a history of carcinoma is a contraindication for the use of class 3 laser. Information is lacking regarding the use of class 1 laser. If we consider the method of action of the laser (increased transport across the mitochondrial barrier), prior carcinoma remains a contraindication in the use of laser.⁹⁰ Research in this area is needed. FDA has approved laser for lymphedema treatment.

Exercise and Breast Cancer

Throughout this text, the benefits of exercise in relation to various diseases, disorders, and conditions have been discussed, including (pertinent to the diagnosis of breast cancer) exercise and immunology (see Chapter 7), exercise and cancer from a variety of viewpoints (see Chapter 9), exercise and the cardiovascular system (see Chapter 12), and exercise and the lymphatic system (see Chapter 13).

Many observational studies show exercise to be inversely associated with risk for breast cancer; the mechanisms by which exercise may alter breast cancer remain under investigation. Studies show a modest protective effect of strenuous leisure time physical activity (intense enough to make the woman break a sweat) among postmenopausal women who are consistently active throughout their lifetime.⁷⁵

Several theories have been proposed, including reduction of excess body weight, excess body fat, elevated fasting insulin, insulin resistance, and alterations in plasma levels of insulin-like growth factor (IGF). If these factors are part of the biologic basis for breast cancer and they can be improved by exercise training, then breast cancer risk could be modified with exercise.²⁷²

Three separate considerations regarding exercise and breast cancer are presented in this section: the effect of exercise in the prevention of breast cancer, the effect of exercise in the prevention or exacerbation of clinical symptoms associated with breast cancer and/or its treatment (e.g., lymphedema or fatigue), and the effect of exercise on breast cancer recurrence.

EXERCISE IN THE PREVENTION OF BREAST CANCER

A clear relationship between physical activity and exercise and breast cancer prevention has been established.^{31,257,258,306} These studies have all been of white women; there are limited data on black women or women of other ethnic groups, but findings suggest that strenuous physical activity in early adulthood is associated with a reduced risk of breast cancer in black women as well.²

Prescriptive exercise (preventive or otherwise) usually includes type of exercise, intensity, duration, and frequency since these parameters are carefully matched to the underlying pathologic process and clinical presentation. The association of physical activity and exercise to overall and site-specific cancer risk is under investigation, especially in relation to whether any dose-response correlation has been observed.

A review of 41 studies, including 108,031 breast cancer cases, identified an observed inverse association with a dose-response relationship between physical activity and breast cancer. Moderate activity (defined as >4.5 metabolic equivalents [MET]/week) was shown to have a protective effect against breast cancer in premenopausal and postmenopausal women.³⁰⁷

Physical activity corresponding to 15 MET/week or higher at age 10 to 24 years has been shown to significantly reduce breast cancer at age 51 to 60 years in a small number of women.¹³⁰ Women who consistently exercise even minimally have a 35% lower risk of developing breast cancer in situ; this does not apply to women with a family history of breast cancer.²³⁹

Other investigators reviewed number of hours per week, suggesting that breast cancer rates were 20% lower among women who exercise an average of 1 hour per day (or more), compared with those who exercised less than 1 hour per week.²⁵⁸ Much more investigation in this area is both warranted and under way.

EFFECT OF EXERCISE DURING BREAST CANCER TREATMENT

Exercise during adjuvant treatment for breast cancer is regarded by some as a supportive self-care intervention that results in improved physical fitness and thus the capacity to perform activities of daily living, which might otherwise be impaired due to inactivity during treatment.¹⁹⁰ Benefits of exercise for clients with breast cancer include but are not limited to the following²⁵²:

• Increased functional capacity

• Improved mood and coping

• Decreased nausea

• Increased self-esteem and self-efficacy

• Increased natural killer cell activity

• Improved body image

• Decreased fatigue

The therapist should keep in mind that exercise interventions for sedentary individuals requires behavior change, which can be a significant challenge when prescribing appropriate exercise for the individual.

The impact of all types of aerobic exercise is significant in maintaining functional ability and reducing fatigue in women with breast cancer receiving chemotherapy or radiation therapy.^167,274 Moderate-intensity aerobic exercise has been shown effective during radiation for breast cancer to increase peak VO₂ and therefore aerobic capacity reserves. Improved physical function, decreased fatigue, and improved psychologic factors are the final outcomes.⁷⁶

Exercise for women with or at risk for breast cancer–related lymphedema has also been studied. Previous results suggested the recommendation to avoid vigorous or strenuous exercise and upper extremity resistance training for women with breast cancer. Preliminary results of other studies have challenged this contraindication and suggest such exercise may be safe and effective. In other words, aerobic or strenuous exercise may not initiate or exacerbate lymphedema.^26,196 Limitations in study size and methods require further research. Long-term results are needed before there is a definitive answer regarding the total effect of exercise in this population.

Supervised exercise in women with breast cancer not receiving chemotherapy increases aerobic capacity and reduces body weight.²⁷⁶ For those who are postoperative, research indicates that range of motion exercises can be delayed immediately after surgery without significant long-term consequences to range of motion/pain. Delaying exercises until the Jackson-Pratt (JP) drain comes out (7 to 10 days) reduces infection and seroma rates.^{93,168,182,282} See also the section on Exercise During and After Chemotherapy in Chapter 9.

EFFECT OF EXERCISE ON BREAST CANCER RECURRENCE

It has been proposed that the extent to which breast cancer survivors can improve body composition, insulin, and IGF axis proteins through exercise intervention may result in reduced cancer recurrence and improved survival.²⁷² In a study of nearly 3000 women with breast cancer, women who exercised 3 MET hours/week after diagnosis were less likely to die of their disease.¹³⁴ Twice-weekly weight training has been shown effective in increasing muscle mass and decreasing body fat, which may have implications in preventing cancer recurrence. Weight training may have some advantages over aerobic exercise because it has been shown to positively alter body composition, glucose/insulin dynamics, and IGF axis proteins. Adherence to exercise interventions may be more likely with this type of exercise.²⁷²

Concerns that upper body resistance activity may increase the risk of lymphedema have not been proved. Investigations thus far support the use of this type of supervised exercise program even for breast cancer survivors. Further study is needed to determine whether exercise leads to physiologic change of lymphatic structure and/or function, as well as timing between exercise and change in lymphedema.⁵

Personality factors as they relate to exercise participation across the breast cancer experience have come under scrutiny. Personality may be an important determinant of exercise after breast cancer diagnosis.²⁴⁸ Women with outgoing personalities who are conscientious and have low scores of neuroticism were better able to discriminate when and how to exercise during and after cancer treatment, as well as better able to recognize changes in exercise stage across the cancer experience (prediagnosis through treatment to posttreatment).²⁴⁹

Women with high scores of neuroticism especially engaged in maladaptive exercise patterns.²⁴⁹ In addition, unsatisfactory coping and defending mechanisms are linked with increased breast cancer risk.²³⁴ This type of information can be potentially helpful to the therapist when assessing the individual woman’s needs and abilities as they relate to designing an effective interventional prescriptive program of exercise.

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Clinical Manifestations

MEDICAL MANAGEMENT

TREATMENT.

BREAST DISEASE

Benign Breast Disease and Fibroadenoma

Incidence and Risk Factors

Etiologic Factors and Pathogenesis

Clinical Manifestations

MEDICAL MANAGEMENT

Breast Cancer

Incidence

Etiologic Factors

Risk Factors

Pathogenesis

Clinical Manifestations

Metastases

Paraneoplastic Syndrome

MEDICAL MANAGEMENT

EARLY DETECTION.

Clinical Breast Examination (CBE).

Self-Breast Examination (SBE).

Mammography.

Genetic Testing.

DIAGNOSIS.

Imaging Technology.

Biomarkers.

Staging.

TREATMENT.

Breast-Conserving Therapy.

Chemotherapy.

Radiation Therapy.

Stem Cell Transplantation.

Hormonal Therapy.

Biologic Therapy.

Ovarian Ablation.

PROGNOSIS.

RECURRENCE.

References