Subtype-specific risk factors for postmenopausal breast cancer: findings from the PLCO trial

Objective The aim of this analysis is to evaluate the relative weight of different epidemiological risk factors on the development of different breast cancer subtypes (i.e. luminal, Her2+ overexpressed or triple negative). Methods De-identified datasets of female participants recruited within the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial were accessed. Multivariate Cox regression analysis was utilized to assess factors affecting the development of breast cancer (regardless of subtype). Additional multivariate analyses were conducted to assess factors affecting the development of the three principal subtypes of breast cancer (ER+/Her2- breast cancer; Her2 overexpressed breast cancer and ER-/Her2- breast cancer). Results A total of 73,570 eligible participants were evaluated in the current analysis of which 2370 participants subsequently developed breast cancer. The following factors were associated with a higher risk of ER+/Her2- breast cancer: white race (P < 0.001), nulliparity (P < 0.001), higher body mass index (P = 0.003), prior exposure to hormone treatment (P = 0.004) and breast cancer in first-degree female relatives (P < 0.001). The following factors were associated with a higher risk of Her2 overexpressed breast cancer: prior exposure to hormone treatment (P = 0.002) and breast cancer in first-degree female relatives (P = 0.001). The following factors were associated with a higher risk of ER-/Her2- breast cancer: black race (P = 0.013), younger age (P = 0.017) and breast cancer in first-degree female relatives (P 0.023). Conclusions There is considerable heterogeneity in risk factors among patients with different subtypes of breast cancer. In particular, factors associated with high estrogen levels seem to be associated with luminal breast cancer rather than other breast cancer subtypes.