HEREDITARY BREAST CANCER

Maren T. Scheuner, M.D., M.P.H

Medical Director, GenRISK Prevention Program

Cedars-Sinai Medical Center

8700 Beverly Blvd., SSB-378

Los Angeles, CA 90048

e-mail: mscheuner@mailgate.csmc.edu

 

Introduction

Breast cancer is the leading cause of cancer among women in the United States with more than 180,000 new cases expected annually, and it is second only to lung cancer as a cause of cancer death (about 45,000 deaths per year) (1). Fortunately, better detection and treatment modalities have improved a woman’s chance of surviving breast cancer; if breast cancer is found before it spreads, the five-year survival rate is greater than 90% (1).

Breast cancer is typically a disease which occurs with advancing age (Table A).

Only 1 in 622 women will develop breast cancer by age 35, compared to 1 in 9 by age 85 (2). Ethnic variations in breast cancer incidence are also observed. In U.S. women, breast cancer most commonly is reported in whites, followed by blacks, Hispanics and Asians (3). Important breast cancer risk factors include some forms of benign breast disease, early menarche, late menopause, lengthy exposure to cyclic estrogen, never having children, or having the first live birth at a later age (4). The underlying mechanism for most of these risk factors may be an endogenous hormonal milieu that promotes an estrogenic carcinogenic environment, as estrogens and their metabolites may cause both proliferative effects as well as damage to DNA (5).

One of the most significant risk factors for breast cancer is a family history of breast cancer (Table B).

Women with an affected mother or sister have a two to three fold increase in breast cancer risk. This risk increases with early ages of cancer onset and if the disease is bilateral. For example, if a sister is diagnosed with breast cancer before age 40 and also has bilateral disease, a woman's risk is increased 9-fold over the population risk (6). Empiric risk estimates provide an alternative method of quantifying the magnitude of risk associated with a family history of breast cancer. These estimates are derived from mathematical models that use population-based family history data (7). Empiric risks describe the cumulative risks for breast cancer incidence by a particular age given a particular family history (Table C). These risk figures are usually more meaningful to most women and are used in genetic counseling.

The increased breast cancer risk associated with a family history may reflect shared environmental carcinogenic factors among family members such as diet, exposure to infection or tobacco smoke, and it may reflect shared genetic factors. Gaining an appreciation of the role of each breast cancer risk factor may ultimately lead to improved therapies and preventive strategies.