Incidence and mortality
With an estimated 232,340 cases expected, breast cancer will be the most frequently diagnosed nonskin malignancy in U.S. women in 2013. In the same year, breast cancer will kill an estimated 39,620 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 2,240 new cases will be diagnosed in 2013. 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 1.9% per year from 1998 to 2007.
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.
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. 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.
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.[5,6,7]
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. Women who develop breast cancer tend to have higher endogenous estrogen and androgen levels.
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.[10,11,12,13] The removal of one ovary also reduces the risk of breast cancer, but to a lesser degree than the removal of both ovaries.
Other hormonal changes also influence breast cancer risk. Childbirth is followed by a transient increase in risk and then a long-term reduction in risk, which is greater for younger women.[13,15,16] In one study, women who experienced a first full-term pregnancy before age 20 years were half as likely to develop breast cancer as nulliparous women or women who underwent a first full-term pregnancy at age 35 years or older.[17,18] Age at menarche also affects breast cancer risk. Women who experienced menarche at age 11 years or younger have about a 20% greater chance of developing breast cancer than women who experienced menarche at age 14 years or older. Women who experience late menopause also have increased risk. Reproductive risk factors may interact with more predisposing genotypes. In the Nurses' Health Study, the associations between age at first birth, menarche, and menopause and the development of breast cancer were observed only among women without a family history of breast cancer in a mother or sister. Breast-feeding is associated with a decreased risk of breast cancer.[21,22]