Benign breast disease and the risk of developing invasive malignancy

VG Vogel, MD, MHS

University of Pittsburgh Cancer Institute/Magee-Womens Hospital, Pittsburgh, PA 15213

Benign breast disease (BBD) includes chronic cystic mastitis, fibroadenoma, fibrocystic disease, and related lesions. Sclerosing adenosis increases the risk of breast cancer by approximately 70%. The most informative classification schema is based on histopathology. Proliferative disease accounts for between one-fourth and one-third of all biopsies for BBD, and 5% to 10% of proliferative lesions show cellular atypia which increases the risk of breast cancer by 5-fold. A family history of breast cancer in first-degree relatives has an additive effect on the subsequent risk of breast cancer. Increasing use of mammographic screening has led to increased identification of women with proliferative lesions of the breast. Fewer than 5% of women without proliferative changes on biopsy develop breast cancer over the subsequent 25 years, but nearly 40% of women with a family history of breast cancer and atypical hyperplasia subsequently develop breast cancer. Biopsy before the age of 50 to 55 years is associated with a five- to six-fold increase in the risk of breast cancer, while biopsy at older ages is associated with only half this risk. Development of breast cancer can be predicted by the presence of atypical hyperplasia in histologic biopsies or fine-needle aspirates (FNA) of the breast plus the Gail model probability of developing breast cancer. The Gail model prediction of risk that incorporates biopsy for BBD has been evaluated prospectively and shown to be valid. Among women with normal findings on clinical examination, bilateral FNA of all four breast quadrants yields cytological evidence of proliferative breast disease in 30% to 40% of patients who have two or more first-degree relatives with breast cancer, compared with only 13% of women without a family history of breast cancer. These changes may serve as intermediate biological endpoints in clinical prevention trials that enroll these women as subjects, but this strategy has not been evaluated prospectively. Expression of EGFR, estrogen receptor, p53, and HER2/NEU is associated with atypical hyperplasia but does not predict the development of breast cancer. Ductal lavage may be a useful technique in the evaluation and follow-up of BBD: 24% of subjects had abnormal cells that were mildly (17%) or markedly (6%) atypical or malignant (<1%) in one published study. Confirmatory studies are required. Tamoxifen reduces the risk of subsequent invasive breast cancer within 5 years by >80% in women with atypical hyperplasia and by 55% in women with LCIS. Tamoxifen also reduces the incidence of biopsies for benign disease among women at increased risk for breast cancer. Estrogen replacement therapy lowers the risk of breast cancer in women with proliferative benign breast disease with or without atypia, and a history of proliferative benign breast disease is not, therefore, a contraindication to estrogen replacement therapy. Identification of women with BBD can improve the management of women at increased risk for breast cancer and may lower morbidity and mortality from breast cancer through the application of risk reduction strategies.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Risk Assessment & Prognosis.