Associations of parity-related reproductive histories with ER± and HER2± receptor-specific breast cancer aetiology.
Associations of reproductive history with breast cancer risk differ by oestrogen receptor (ER±) status and possibly by the joint expression of ER and the human epidermal growth factor receptor-2 (ER±/HER2±). However, large sample sizes are needed to establish ER-specific risks by HER2± expression.



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.



With nearly 31 million women-years of follow-up, 45 786 Danish women aged 20-84 years developed invasive breast cancer during 1992-2011. ER± expression was available for the entire study period and HER2± 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.



Associations of reproductive history with breast cancer risk varied among Danish women by ER± and ER±/HER2± 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.
DHHS/NIH/National Cancer Institute/Division of Cancer Epidemiology and Genetics/Biostatistics Branch, Bethesda, MD, USA.
William F
WF
Anderson
DHHS/NIH/National Cancer Institute/Division of Cancer Epidemiology and Genetics/Biostatistics Branch, Bethesda, MD, USA.
Ruth M
RM
Pfeiffer
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Jan
J
Wohlfahrt
Danish Breast Cancer Group (DBCG), Copenhagen, Denmark.
Bent
B
Ejlertsen
Danish Breast Cancer Group (DBCG), Copenhagen, Denmark.
Maj-Britt
MB
Jensen
Department of Breast Surgery, Rigshopitalet, Copenhagen, Denmark.
Niels
N
Kroman
D000328:Adult; D017677:Age Distribution; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010298:Parity; D011247:Pregnancy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D012042:Registries; D012044:Regression Analysis; D017584:Reproductive History; D012307:Risk Factors; D055815:Young Adult
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
breast cancer aetiology; breast cancer subtype; human epidermal growth factor receptor-2; oestrogen receptor; reproductive history