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INTRODUCTION

Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast. In the year 2017, ~247,000 cases of invasive and 61,000 cases of in situ breast cancer and 41,000 deaths will occur in the United States. In addition, ~2000 men will be diagnosed with breast cancer. Epithelial malignancies of the breast are the most common cause of cancer in women (excluding skin cancer), accounting for about one-third of all cancer in women. As a result of improved treatment and earlier detection, the mortality rate from breast cancer has begun to decrease very substantially in the United States. This chapter does not consider rare malignancies presenting in the breast, such as sarcomas and lymphomas, but focuses on the epithelial cancers.

EPIDEMIOLOGY AND RISK FACTORS

Breast cancer is principally a disease of older women. Seventy-five percent of all breast cancers occur in women aged >50 years. The female-to-male ratio is ~150:1. It is also a hormone-dependent disease. Women without functioning ovaries, or who experience an early menopause, and who never receive combination estrogen/progesterone replacement therapy, are much less likely to develop breast cancer than those who have a normal menstrual history. A log-log plot of incidence versus age for breast cancer shows two components: a straight-line increase with age but with a decrease in slope beginning at the age of menopause. Length of menstrual life—particularly the fraction occurring before first full-term pregnancy—is a substantial component of the total risk of breast cancer. Breast cancer risk is increased in women with early menarche, late first full-term pregnancy, and late menopause. These three factors account for 70–80% of the variation in breast cancer frequency in different countries. Also, duration of maternal nursing correlates with substantial risk reduction independent of either parity or age at first full-term pregnancy.

International variation and immigration statistics of incidence provide insight into hormonal carcinogenesis. A woman living to age 80 years in North America has one chance in nine of developing invasive breast cancer. Asian women have traditionally had only 1/5th to 1/10th the risk of breast cancer of women in North America or Western Europe. However, with shifts from agrarian to industrialized economic systems, and in immigrant populations, Asian women living in modern, Western-style environments have risks identical to those of their Western counterparts.

Presumably, these differences are secondary to menstrual, and associated intrinsic estrogen exposure, histories. However, differences in diets have also been implicated, although the role of diet in breast cancer etiology is controversial. While there are associative links between total caloric and fat intake and breast cancer risk, the exact role of fat in the diet is unproven and may actually intersect with menstrual history and estrogenic exposure.

Central obesity is both a risk factor for occurrence and recurrence of breast cancer. Moderate alcohol intake also increases the risk by an unknown mechanism. Folic acid ...

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