Breast Cancer

Explanation
The incidence of breast cancer in the United States increased steadily from World War II to the turn of the 21st century. Multiple risk factors for its development have been identified. Chief among the risk factors are advancing age and family history. The incidence increases with age, and about 75% of breast cancer cases in the United States are diagnosed in women older than 50 years. The diagnosis of breast cancer in first-degree relatives younger than 50 years is associated with a threefold to fourfold increased risk. Approximately 5% to 8% of cases of breast cancer occur in high-risk families. Several familial breast cancer syndromes and their associated molecular abnormalities have been identified. Reproductive risk factors include early menarche, late menopause, late first pregnancy, and nulliparity. The common thread in all of these is presumed to be prolonged exposure of the breast to estrogen. Careful study has demonstrated that certain types of breast pathology, such as atypical hyperplasia and lobular carcinoma in situ, are also associated with increased risk. Furthermore, certain environmental factors increase the risk of breast cancer. These factors include exposure to ionizing radiation during adolescence, prolonged use of hormone replacement therapy (but not estrogen replacement therapy), ongoing use of oral contraceptives, and consumption of alcohol.

Explanation
There has been much interest in the development of breast cancer prevention strategies. Pharmacologic approaches are the most developed at this time. The nonsteroidal selective estrogen receptor modulator (SERM) tamoxifen, a mainstay in the management of breast cancer, has also been tested as a chemopreventive agent. In a large United States trial, use of tamoxifen was associated with a reduction in the diagnosis of breast cancer of about 50%. On the basis of data from this trial, the Food and Drug Administration approved the use of tamoxifen to reduce the occurrence of breast cancer in women at high risk, as defined by the eligibility requirements for this prevention trial. A meta-analysis demonstrated a 38% reduction in invasive breast cancer with tamoxifen. Prevention strategies that involve alterations in lifestyle have been suggested. The Women's Health Initiative did not show a clear advantage for a low-fat diet as a means of breast cancer prevention.

Explanation
Screening strategies for breast cancer include the triad of BSE, clinical breast examination by a health care professional, and screening mammography. Although widely touted as an important component of early detection, BSE is of uncertain value. A large randomized trial that compared conventional BSE with observation in over 260,000 female Chinese textile workers failed to show any clinical advantage with BSE. As a consequence, some experts, including the American Cancer Society, now promote breast awareness rather than regular BSE. In contrast, regular screening by mammography and clinical breast examination appear to decrease mortality from breast cancer by 25% to 30% in women older than 50 years. Considerable controversy continues over the value of screening mammography and clinical breast examination in women 40 to 50 years of age. Currently, the American Cancer Society and the National Cancer Institute recommend annual screening mammography for women older than 40 years who are at standard risk for breast cancer. There have been no trials of mammographic strategies directed explicitly at high-risk women, particularly those with BRCA1 and BRCA2 mutations. In the absence of relevant data, a reasonable approach is to begin mammographic screening either at 25 years of age or 5 years earlier than the age of the person with the earliest diagnosis of breast cancer in the immediate or extended family.

Explanation
Many cases of early, clinically occult breast cancer are diagnosed on the basis of architectural changes or microcalcification seen on a mammogram. Women with clinically evident breast cancer generally present with breast-specific complaints, such as a palpable mass, a change in breast contour, or skin or nipple changes. For both clinically occult and clinically apparent cancer, pathologic evaluation is mandatory to establish a diagnosis. In the past, incisional or excisional biopsies were routinely employed for this purpose. Today, fine-needle aspiration and core-needle biopsy are the standard diagnostic modalities. These procedures can be performed in the office in patients with suspicious palpable lesions. For women with nonpalpable lesions, biopsies guided by mammography, ultrasonography, or magnetic resonance imaging are now routine. These technologies permit an accurate diagnosis, which can be followed by definitive treatment planning; consequently, only a single surgical procedure is required. Alternatively, women whose diagnoses are unequivocally negative can be spared an open surgical biopsy. However, it is axiomatic that further evaluation be undertaken for suspicious lesions that yield an equivocal diagnosis after needle aspiration or core biopsy. In addition, bilateral breast imaging is required to identify any unsuspected lesions in the contralateral breast that may also mandate further evaluation.

Explanation
Most women with breast cancer present with stage I or II breast cancer and receive appropriate local and systemic therapy. A critical issue is how longitudinal follow-up should be conducted in these patients. Two randomized trials have addressed this issue. Both compared a schedule of physician visits and regular laboratory testing (i.e., chest x-ray, bone scanning, and blood studies) with a program of physician visits and laboratory testing that was restricted to the evaluation of symptoms. Together, they showed that routine laboratory screening did not enhance survival or quality of life when compared with a program of careful clinical examination with testing tailored for symptoms and physical findings. About 70% of metastases were first detected by the patients themselves, even in the group undergoing physician and laboratory evaluation every 3 months. On the basis of these and other studies, the American Society of Clinical Oncology has recommended annual mammography, as well as other measures, for the surveillance of asymptomatic survivors of early breast cancer. Annual complete blood count and CT scan of the chest, abdomen, and pelvis were not recommended.