Determinants of breast cancer risk : focusing on mammographic density

Abstract: Breast cancer is the most common cancer and also one of the leading causes of cancer death among women worldwide. Since most known factors associated with breast cancer risk are difficult to influence, the potential of lifestyle factors, which are modifiable, in breast cancer prevention has recently been emphasised. Studies have shown a reduced risk of breast cancer among women who are more physically active, and an increased risk among women with higher alcohol consumption or cigarette smoking. These lifestyle factors have been hypothesised to influence breast cancer risk through a mechanism that involves mammographic density, one of the strongest risk factors of the disease. Moreover, whether such associations might be modified by the women’s background risk of breast cancer is unclear. We therefore used data from the KARMA (KARolinska MAmmography) study to investigate the potential influence of background breast cancer risk on the association between physical activity (Study I, n = 38,913), alcohol consumption (Study II, n = 53,060), and cigarette smoking (Study III, n = 53,728) and mammographic density. These lifestyle factors were assessed using self-administrated web-based questionnaires. Mammographic density was estimated using the fully-automated volumetric Volpara method and expressed as absolute dense volume, non-dense volume, and per cent dense volume. The Tyrer-Cuzick (TC) prediction model was used to estimate the individual background risk of developing breast cancer in the next 10 years. In Study I, higher levels of physical activity were associated with a lower absolute dense breast volume and non-dense (adipose) breast volume, but a higher per cent dense breast volume among all women. After taking the TC 10-year risk of breast cancer into consideration, an association with lower absolute density was seen for all types of physical activity among women at low (< 3.0%) TC risk, for total and vigorous activities among women at moderate (3.0-4.9%) TC risk, and only for vigorous activity among women at high (≥ 5.0%) TC risk. In Study II, among all women we found an overall association between alcohol consumption and absolute and per cent dense breast volumes. Furthermore, alcohol consumption was only associated with a higher absolute dense volume among high-risk women. In Study III, current cigarette smoking was associated with lower absolute and per cent dense volumes, and this association was not found to be modified by TC 10-year background breast cancer risk. However, with respect to breast cancer risk, this finding should be viewed in light of the carcinogenic effects of cigarette smoking. In the last study, we used prospective cohort data of 58,441 Swedish women of whom 522 developed invasive breast cancer. Overall, women with higher alcohol consumption had an increased risk of breast cancer compared to those with no alcohol consumption. After taking the TC background 10-year risk of breast cancer into account, alcohol consumption was only associated with breast cancer risk among women at moderate background risk.