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Breast Cancer

Breast cancer accounts for approximately one third of all cancers in women and is second only to lung cancer as the leading cause of cancer deaths among women. Breast cancer, however, has the highest incidence rate of all cancers. According to statistics from the American Cancer Society, 213,000 new cases of invasive breast cancer, as well as nearly 62,000 cases of in situ cancers, will be diagnosed during 2006 in the United States, with 41,000 women succumbing to the disease during the same period (1). Over the past 50 years, the incidence of breast cancer in the United States has increased significantly; currently one in every seven women will develop the disease during her lifetime. Fortunately, the mortality rate has declined since 1990.

Predisposing Factors

Fewer than 1% of breast cancers occur in women younger than 25 years of age. After age 30, however, there is a sharp increase in the incidence of breast cancer. Except for a short plateau between the ages of 45 and 50 years, the incidence increases steadily with age (2).

Family History

Of women who develop breast cancer, 20% to 30% have a family history of the disease. Although any family history of breast cancer increases the overall relative risk (3), this risk is not significantly increased if the disease was diagnosed postmenopausally in a first degree or more distant relative. If a woman's mother or sister had unilateral breast cancer premenopausally, her lifetime risk of developing the disease approaches 30%, whereas a woman whose mother or sister had bilateral breast cancers premenopausally has at least a 40% to 50% lifetime risk. The increased incidence in these women is probably due to inherited oncogenes.

Approximately 5% to 10% of breast cancers have an inherited basis. All inherited genes are autosomal dominant but have variable penetrance. Men carry the gene 50% of the time. The most common mutations are the BRCA1 (chromosome 17q21) and BRCA2 (chromosome 13q12–13) gene deletions. Carriers of these germline mutations have up to a 4%-per-year risk of developing breast cancer and a lifetime risk that ranges from 35% to 85% (4). In addition, these individuals have up to a 65% risk of developing a contralateral breast cancer. The BRCA1 mutation also is associated with an increased risk of ovarian and prostate cancer, whereas BRCA2 carriers, although less common, demonstrate increased risks of male breast and prostate cancers. Both mutations are rare in the general public (0.1%) but are more commonly identified in Jews of Ashkenazi descent (1%–2.3%) (5). Genetic testing is available and should be considered if there is a high likelihood that results will be positive and will be used to influence decisions regarding the clinical management of the care of the patient and her family.

Diet, Obesity, and Alcohol

There are marked geographic differences in the incidence of breast cancer that may be related to diet. A recent meta-analysis demonstrated an association between higher intakes of total fat and an increased risk of breast cancer (6). Although a definitive relationship between total alcohol consumption and an increased risk of breast cancer has yet to be determined, high wine intake has been shown to be associated with elevated risk (7).

Reproductive and Hormonal Factors

The risk of breast cancer increases with the length of a woman's reproductive phase (8). Although early menarche has been reported among breast cancer patients, early menopause appears to protect against the development of the disease, with artificial menopause from oophorectomy lowering the risk more than early natural menopause (9). There is no clear association between the risk of breast cancer and menstrual irregularity and the duration of menses. Although lactation does not affect the incidence of breast cancer, women who have never been pregnant have a higher risk of breast cancer than those who are multiparous. Also, women who give birth to their first child later in life have a higher incidence of breast cancer than do younger primigravida women (10).

An historic well-controlled study from the Centers for Disease Control and Prevention showed that oral contraceptive use does not increase the risk of breast cancer, regardless of duration of use, family history, or coexistence of benign breast disease (11). However, a more recent pooled analysis from 54 epidemiologic studies showed current users of oral contraceptives had a small but significant increased risk when compared with nonusers. Ten years after discontinuation, the risk of past users declined to that of the normal population (12).

Although it was previously reported that short-term estrogen treatment for menopausal symptoms did not increase the risk of breast cancer, this belief was refuted by publication of the results of the Women's Health Initiative randomized trial. This prospective trial, involving 16,000 postmenopausal women randomly assigned to receive estrogen plus progesterone or placebo, revealed an association between hormone therapy use and the development of breast cancer. In addition, when invasive breast cancer did develop, it was diagnosed at a more advanced stage compared with tumors that developed among placebo users. Based on interim analysis, the trial was stopped early and the investigators concluded that even relatively short-term use of combined estrogen–progesterone therapy increases the development of invasive breast cancer (13). The risk demonstrated by this study must be considered when postmenopausal hormone therapy is used to treat conditions such as hot flashes and osteoporosis.

History of Cancer

Women with a history of breast cancer have a 50% risk of developing microscopic cancer and a 20% to 25% risk of developing clinically apparent cancer in the contralateral breast, which occurs at a rate of 1% to 2% per year (14). Lobular carcinoma has a higher incidence of bilaterality than does ductal carcinoma. A history of endometrial, ovarian, or colon cancer also is associated with an increased risk of subsequent breast cancer, as is a history of radiation therapy for Hodgkin's lymphoma.

Diagnosis

Breast cancer most commonly arises in the upper outer quadrant, where there is proportionally more breast tissue. Masses are most often discovered by the patient and less frequently by the physician during routine breast examination. The increasing use of screening mammography has enhanced the ability to detect nonpalpable breast abnormalities. Metastatic breast cancer is found as an axillary mass without obvious malignancy in less the 1% of cases.

The standard screening modalities of mammography and physical examination are complementary. Approximately 10% to 50% of cancers detected mammographically are not palpable, whereas physical examination detects 10% to 20% of cancers not seen radiographically (15). The purpose of screening is to detect tumors when they are small (less than 1 cm) and have the highest potential for surgical cure. Most trials have shown a 20% to 30% reduction in breast cancer mortality for women age 50 and older who undergo annual screening mammography. Data on screening women younger than 40 years have been more controversial. Results from the Gothenburg screening trial showed a 45% reduction in mortality for women screened between the ages of 40 and 49 (16). Because of these findings, it is recommended that all women undergo yearly screening mammography starting at age 40, along with clinical breast examination and breast self-examination. No other tests, including ultrasonography, computed tomography (CT) scans, sestamibi scans, positron emission tomography (PET) scans, or serum blood markers, have been shown to be effective screening modalities. Screening guidelines recommended by the American College of Radiology and the American Cancer Society are presented in Table 38.1. Recently, MRI was identified as a valuable adjunct to screening mammography for women with either a familial or genetic predisposition to breast cancer, although exact guidelines for its implementation have yet to be defined (17).

Unfortunately, although breast MRI is exceptionally sensitive in the detection of breast abnormalities, the technology is currently not specific enough for this imaging modality to be used for routine screening.

Masses are easier to palpate in older women with fatty breasts than in younger women with dense, nodular breasts. An area of thickening amid normal nodularity may be the only clue to an underlying malignancy. Skin dimpling, nipple retraction, or skin erosion, while obvious, are later-stage disease signs. Algorithms for the evaluation of breast masses in premenopausal and postmenopausal women are presented in Chapter 19.

When a dominant breast mass is identified, the presence of a carcinoma must be considered, and biopsy should be performed to establish a tissue diagnosis. About 30% to 40% of lesions believed clinically to be malignant will be benign on histologic examination (18). Conversely, 25% of clinically benign-appearing lesions will be malignant when biopsied (19).

Biopsy Techniques

In rare cases, it may be reasonable to perform frozen section analysis on a biopsy specimen immediately before mastectomy or other definitive surgical treatment. It is preferable, however, for the patient to be involved in the planning of her therapy. In most instances, initial biopsy is better followed by definitive treatment at a later date. This approach allows the physician to discuss alternative forms of surgical therapy with the patient who has a malignancy. It also gives the patient an opportunity to obtain a second opinion before undergoing definitive treatment.

Fine-needle Aspiration Cytology

Fine-needle aspiration cytology (FNAC) is usually pe