Attribution to Heterogeneous Risk Factors for Breast Cancer Subtypes Based on Hormone Receptor and Human Epidermal Growth Factor 2 Receptor Expression in Korea

Abstract

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Parity, hormones and breast cancer subtypes - results from a large nested case-control study in a national screening program

“…This is consistent with a systematic review and [47] and two recent studies [8, 49]. However, age at first birth was only statistically significantly associated with luminal A cancer, whereas in the current study age at first birth was significantly associated with luminal A-like and luminal B-like HER2-negative subtypes.…”

“…Our observation of an inverse association between parity and luminal A-like breast cancer is consistent with the vast majority of studies as summarized in the recent systematic review of 38 studies [47] and the more recent studies that were not included in the review [7, 8, 10, 48–51]. The results for luminal B breast cancer have been less clear, with studies finding a protective or increased effect, or no effect of parity [47–50].…”

“…In the current study, a non-statistically significant positive association was observed between late age at first birth (31 years or older), and both HER2-positive and triple-negative breast cancer. This is consistent with the Nurses’ Health Study [49], and inconsistent with the case-control study from Korea [8]. In the latter study, the majority of women were premenopausal, whereas the current study included mainly postmenopausal women.…”

“…The overall published evidence [7, 8, 10, 47–50] seems to be consistent with luminal A-like cancers having a hormonal etiology, but the association between hormonal factors and other subtypes, in particular luminal B-like disease, HER2-positive disease, and triple-negative cancer, is less clear. Specifically, reproductive factors such as parity and early age at first birth have been associated with reduced risk of luminal A-like disease.…”

“…There is less evidence of a protective effect of parity on luminal B-like and HER2-positive cancers and parity has consistently been found not to protect against triple-negative disease [7, 47–50]. There is some, albeit inconsistent, evidence that older age at menarche and breastfeeding may protect against all subtypes [7, 8, 47, 49–52] suggesting that these protective effects may work through non-hormonal mechanisms. The use of menopausal hormone therapy has been consistently associated with an increased risk of luminal A-like breast cancer, but the evidence is less clear for risk of luminal B-like, HER2-positive and triple-negative breast cancer [10, 47, 49].…”