question. As understanding grows of how the genetic, epigenetic, cellular, and tissue changes in the breast during development and over the life course influence susceptibility to breast carcinogenesis, researchers have continuing and increased appreciation for the potential for timing of exposure to make a difference in the effects of environmental agents on breast cancer risk. The committee sees the need to direct attention to the accumulating evidence that environmental exposures may have a differential impact, depending on their timing during the life course.

ENVIRONMENTAL EXPOSURES OVER THE LIFE COURSE AS DETERMINANTS OF BREAST CANCER RISK

The female breast is not static; it changes in structure and function over the life course. Breast development begins in utero and continues into adulthood, with further differentiation occurring with pregnancy and lactation and involution occurring with menopause (Russo and Russo, 2004; Polyak and Kalluri, 2010). Most breast cancers arise in and spread from the ducts or the lobules, which are the breast’s main functional components (Figure 5-1).

The sections that follow consider the major life stages for women and the state of breast tissue during each stage, with indications of the potential for exposures during each stage to alter risk for breast cancer. Although evidence from human studies is limited, studies in animal models strongly indicate the potential for timing of environmental exposures to alter risk for developing cancer. Box 5-1 lists the life stages discussed by the committee and mechanisms of carcinogenesis likely to be of particular relevance or importance to breast cancer.

Early Life Exposures and Breast Cancer Risk

Preconceptional and Periconceptional Exposure

Preconception studies focus on parental exposure to environmental agents before the conception of offspring. There is no standard definition for the preconceptional period, and the term is used rather loosely. Some studies combine the time before conception with early pregnancy as the periconceptional period (Van Maele-Fabry et al., 2010). Studies examining pre- or periconceptional exposures may consider paternal or maternal exposure, or both.

To date, epidemiologic studies have not addressed parental exposure before conception and subsequent risk of breast cancer in offspring. However, childhood cancers, such as leukemia and brain tumors, have been linked to prenatal exposures such as maternal smoking, ionizing radiation,



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