Breast Cancer Health Article

BREAST CANCER

Breast cancer is the most common malignancy in American women, accounting for approximately 30 percent of their new cancer cases. It is the second leading cause of cancer death in women, following lung cancer. In the year 2000, it was estimated that there were more than 180,000 new cases of breast cancer diagnosed, and over 41,000 breast cancer deaths in the United States. Breast cancer incidence rates were steady through the 1990s, although the number of breast cancer deaths declined, decreasing an average of 1.8 percent per year between 1990 and 1996.

Breast cancer can be divided into invasive and noninvasive forms. Noninvasive breast cancer is almost always cured through local control measures (surgery and radiation therapy). Tamoxifen (a selective estrogen-receptor modulator), is used to reduce the risk of a local recurrence in patients treated with breast conservation. Early-stage invasive disease is limited to the breast and axillary lymph nodes, while metastatic disease includes tumors that have spread outside the breast and local lymph nodes. Early-stage invasive breast cancer is curable, although less so than noninvasive disease.

The first step in the management of early-stage breast cancer is surgical removal of the tumor. This can be accomplished by lumpectomy (removal of the tumor and a margin of surrounding normal breast tissue) or mastectomy (removal of the entire affected breast). Following lumpectomy, patients should receive radiation to the remaining breast tissue to decrease the risk of recurrence. Studies have shown that patients with small tumors who are treated with breast conservation therapy (lumpectomy and radiation) have equivalent survival rates to patients treated with mastectomy. Ipsilateral axillary lymph nodes are removed in order to determine whether the tumor has spread via the lymphatic drainage. Involvement of the ipsilateral lymph nodes is a marker for increased risk of later distant spread of the tumor.

Once the tumor is removed, the size of the tumor, hormonal status (estrogen and progesterone receptor), and lymph node involvement is considered in aggregate to determine the overall risk of distant spread of disease. Patients at high risk for recurrent disease can be given systemic therapy in order to decrease the odds of relapse. Systematic therapy circulates throughout the entire body in order to kill microscopic tumor cells. Conventionally this therapy can consist of chemotherapy, hormonal therapy (if the tumor is estrogen- or progesterone-receptor positive), or both. Chemotherapy is typically given to patients with invasive tumors greater than 1 centimeter in largest diameter or with involved (positive) lymph nodes. Patients with hormone receptor—positive tumors or tumors in which the receptor status is unknown benefit from treatment with tamoxifen for five years. Both of these interventions have been shown to decrease both the patient's annual risk of recurrence and the risk of mortality from breast cancer. Tamoxifen also decreases the risk of a second primary breast cancer in the preserved contralateral breast.

Breast cancer can metastasize to other organs in the body. Once breast cancer has been detected in distant sites, it is no longer curable. At that stage, the goal of the treatment is to prolong survival while maintaining quality of life. Patients with hormone receptor—positive tumors who are minimally symptomatic and who have predominantly bone disease can frequently be treated with hormonal therapy. This treatment is taken orally and is generally well tolerated. Patients who have hormone receptor—negative tumors, those who have failed hormone therapy, and those who have symptomatic or rapidly progressive disease are frequently treated with chemotherapy. The specific decisions regarding hormone therapy, chemotherapy, and supportive measures require skill, compassion, and a detailed understanding of the numerous treatment options.

Established risk factors for breast cancer include older age (women over fifty have a 6.5 times higher risk of developing breast cancer than younger women), a family history of breast cancer (especially the presence of a documented genetic abnormality), early age of menarche (less than 12 versus equal to or greater than 14), late age of menopause (equal to or greater than 55 versus less than 55), age at first live birth (greater than 30 versus less than 20), history of benign breast disease, and a history of hormone replacement use. Some studies also suggest an increased breast-cancer risk associated with increased alcohol and dietary fat intake, excess body weight, and limited exercise. Further studies are needed to establish the benefit of lifestyle modification in the prevention of breast cancer.

Randomized trials have shown the benefit of chemoprevention in reducing the risk of breast cancer for women at increased risk. The National Surgical Adjuvant Breast and Bowel Project Tamoxifen Prevention Trial (NSABP-1) evaluated the benefits of tamoxifen in the prevention of breast cancer. More than three thousand women at increased risk for breast cancer (defined as a five-year risk of breast cancer of 1.66 percent or more) were followed for approximately four years. Treatment with tamoxifen reduced the overall odds of developing both invasive and noninvasive breast cancer by approximately 50 percent. This decrease in breast cancer risk was seen across all age groups. Side effects of tamoxifen include hot flashes, an increased risk of thromboembolic events, and increased risk of endometrial cancer.

Newer antiestrogens, such as raloxifene, may have fewer side effects than tamoxifen. The MORE (Multiple Outcomes of Raloxifene Evaluation) trial was a trial of 7,705 postmenopausal women who received raloxifene for the treatment of osteoporosis. Raloxifene was found to reduce the risk of invasive breast cancer by 76 percent, with no increased risk of endometrial cancer. Raloxifene is being compared directly to tamoxifen for prevention in high-risk patients in the STAR (Study of Tamoxifen and Raloxifene) trial.

CLIFFORD HUDIS

ARTI HURRIA

(SEE ALSO: Breast Cancer Screening; Breast Self-Examination; Cancer; Clinical Breast Examination; Gender and Health; Mammography; Tamoxifen)