Background

Incidence and mortality

In the United States, a cumulative risk by age 90 years of being diagnosed with breast cancer is one in eight.[1] With an estimated 192,370 cases expected, breast cancer will be the most frequently diagnosed nonskin malignancy in U.S. women in 2009.[2] In the same year, breast cancer will kill an estimated 40,170 women, second only to lung cancer as a cause of cancer mortality in women. Breast cancer also occurs in men, and it is estimated that 1,910 new cases will be diagnosed in 2009.[2] Despite a prior long-term trend of gradually increasing breast cancer incidence, data from the Surveillance, Epidemiology, and End Results Program show a decrease in breast cancer mortality of 2.3% per year from 1990 to 2001.[3]

Screening for breast cancer decreases mortality by identifying and treating cases at an earlier stage. Screening also identifies more cases than would become symptomatic in a woman's lifetime, so breast cancer incidence is higher in screened populations.

The incidence of breast cancer is lower in patients using selective estrogen receptor modifiers. Whether this will translate into reduced breast cancer mortality is not known, and these agents have side effects.

Etiology and pathogenesis of breast cancer

Genetic, epidemiologic, and laboratory studies support a stochastic model of breast cancer development in which a series of genetic changes contribute to the dynamic process known as carcinogenesis.[4] An accumulation of genetic changes is thought to correspond to the phenotypic changes associated with the evolution of malignancy. The carcinogenesis sequence is viewed histologically as starting with tissue of normal appearance followed by changes that lead to hyperplasia and dysplasia, the most severe forms of which are difficult to distinguish from carcinoma in situ.[5]

The concept that breast cancer may be preventable is supported by the wide international variation in breast cancer rates, which is an indicator that there are potentially modifiable environmental and lifestyle determinants of breast cancer. Migration studies reinforce this premise; for example, it has been observed that Japanese immigrants to the United States increase their breast cancer risk from Japanese to American levels within two generations.[6,7,8]

Endogenous estrogen

Many of the risk factors for breast cancer, including age at menarche, first birth, and menopause, suggest hormonal influences for the development of the disease. Estrogen and progestin cause growth and proliferation of breast cells that may work through growth factors such as transforming growth factor (TGF)-alpha.[9] Women who develop breast cancer tend to have higher endogenous estrogen and androgen levels.[10]

The role of ovarian hormones in the development of breast cancer is demonstrated by studies of artificial menopause. Following ovarian ablation, breast cancer risk may be reduced as much as 75% depending on age, weight, and parity, with the greatest reduction for young, thin, nulliparous women.[11,12,13,14] The removal of one ovary also reduces the risk of breast cancer, but to a lesser degree than the removal of both ovaries.[15]