Associations of parity-related reproductive histories with ER± and HER2± receptor-specific breast cancer aetiology

TY - JOUR

T1 - Associations of parity-related reproductive histories with ER± and HER2± receptor-specific breast cancer aetiology

AU - Anderson, William F

AU - Pfeiffer, Ruth M

AU - Wohlfahrt, Jan

AU - Ejlertsen, Bent

AU - Jensen, Maj-Britt

AU - Kroman, Niels

N1 - Published by Oxford University Press on behalf of the International Epidemiological Association 2016. This work is written by US Government employees and is in the public domain in the US.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background: Associations of reproductive history with breast cancer risk differ by oestrogen receptor (ER6) status and possibly by the joint expression of ER and the human epidermal growth factor receptor-2 (ERplusmn;/HER2plusmn;). However, large sample sizes are needed to establish ER-specific risks by HER2plusmn; expression. Methods: We linked a cancer registry covering nearly 95% of the primary breast cancer diagnoses in Denmark with a research parity database to assess associations for parity, number of live births and age at first live birth (AFLB) with receptor-specific risk. Relative risks (RRs) for associations were estimated with Poisson regression models. Results: With nearly 31 million women-years of follow-up, 45 786 Danish women aged 20-84 years developed invasive breast cancer during 1992-2011. ER6 expression was available for the entire study period and HER2plusmn; after 2006. Of the breast cancers with known ER expression, 79% were ER+. Most breast cancers with known ER and HER2 were HER2- (90% of ER+ cancers and 65% of ER- cancers). RRs differed by ER± expression for all reproductive variables (p-homogeneity < 0.001). Associations were stronger for ER+ than ER- cancers and for those diagnosed before age 50. Parity and early [not later] AFLB showed a protective association with ER+/HER2- and risk association with ER-/HER2- cancers. Conclusion: Associations of reproductive history with breast cancer risk varied among Danish women by ER6 and ER6/HER2plusmn; expression and age-at-diagnosis, consistent with receptor-specific and age-related etiological heterogeneity. Further stratification by HER2 status demonstrated dual (or opposite) effects for ER+/HER2- and ER-/HER2- cancers.

AB - Background: Associations of reproductive history with breast cancer risk differ by oestrogen receptor (ER6) status and possibly by the joint expression of ER and the human epidermal growth factor receptor-2 (ERplusmn;/HER2plusmn;). However, large sample sizes are needed to establish ER-specific risks by HER2plusmn; expression. Methods: We linked a cancer registry covering nearly 95% of the primary breast cancer diagnoses in Denmark with a research parity database to assess associations for parity, number of live births and age at first live birth (AFLB) with receptor-specific risk. Relative risks (RRs) for associations were estimated with Poisson regression models. Results: With nearly 31 million women-years of follow-up, 45 786 Danish women aged 20-84 years developed invasive breast cancer during 1992-2011. ER6 expression was available for the entire study period and HER2plusmn; after 2006. Of the breast cancers with known ER expression, 79% were ER+. Most breast cancers with known ER and HER2 were HER2- (90% of ER+ cancers and 65% of ER- cancers). RRs differed by ER± expression for all reproductive variables (p-homogeneity < 0.001). Associations were stronger for ER+ than ER- cancers and for those diagnosed before age 50. Parity and early [not later] AFLB showed a protective association with ER+/HER2- and risk association with ER-/HER2- cancers. Conclusion: Associations of reproductive history with breast cancer risk varied among Danish women by ER6 and ER6/HER2plusmn; expression and age-at-diagnosis, consistent with receptor-specific and age-related etiological heterogeneity. Further stratification by HER2 status demonstrated dual (or opposite) effects for ER+/HER2- and ER-/HER2- cancers.

UR - https://academic.oup.com/ije/article/46/1/373/3093407

U2 - 10.1093/ije/dyw286

DO - 10.1093/ije/dyw286

M3 - Journal article

C2 - 27818374

SN - 0300-5771

VL - 46

SP - 86

EP - 95

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 1

ER -