Mammographic density, lobular involution, and risk of breast cancer

Abstract

In this review, we propose that age-related changes in mammographic density and breast tissue involution are closely related phenomena, and consider their potential relevance to the aetiology of breast cancer. We propose that the reduction in mammographic density that occurs with increasing age, parity and menopause reflects the involution of breast tissue. We further propose that age-related changes in both mammographic density and breast tissue composition are observable and measurable phenomena that resemble Pike's theoretical construct of 'breast tissue ageing'. Extensive mammographic density and delayed breast involution are both associated with an increased risk of breast cancer and are consistent with the hypothesis of the Pike model that cumulative exposure of breast tissue to hormones and growth factors that stimulate cell division, as well as the accumulation of genetic damage in breast cells, are major determinants of breast cancer incidence.

Figure 1

Percent mammographic density vs age. (A) Baseline percentage mammographic density in women from three mammographic screening programmes. Reproduced with kind permission of BioMed Central from Martin and Boyd, 2008. (B) Unadjusted mean percent density as a function of age group and case status. Reproduced with kind permission of American Association for Cancer Research from Maskarinec et al, 2006.

Figure 2

Breast tissue ageing (A) and the age-specific incidence of breast cancer (B). Reproduced with kind permission of Nature Publishing Group from Pike et al, 1983.

Figure 3

Boxplots of histological measures vs age (left hand panels); and histological measures vs percent density (right hand panels), data from Boyd and colleagues (unpublished).