Qualitative age-interactions in breast cancer: a tale of two diseases?

A qualitative age-interaction is defined as the reversal of relative risks or rates according to age at onset. Once thought rare, qualitative age-interactions are commonly reported in studies that examine the etiology, prognosis, and treatment of breast cancer. Thus, nulliparity, obesity, and oral contraceptives decrease breast cancer risk in younger women but increase risk in older women. High-risk tumors are more common in younger women, whereas low-risk tumors are more common among the elderly, with bimodal peak frequencies at ages 50 and 70, respectively. Curves depicting the annual hazard of breast cancer death for women with high-risk (early-onset) and low-risk (late-onset) tumors are shaped differently and move in opposite directions. Additionally, mammography screening and neo-adjuvant chemotherapy seem to have opposing effects in women with early and late-onset tumors. Taken together, these qualitative age-interactions may indicate that early and late-onset breast cancers are different diseases, derived from different pathways.