Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women.
OBJECTIVE
Breast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes.


METHODS
We investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2-) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype.


RESULTS
We found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype.


CONCLUSIONS
The results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.
Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Julie.Horn@ntnu.no.
Julie
J
Horn
Signe
S
Opdahl
Monica J
MJ
Engstrøm
Pål R
PR
Romundstad
Steinar
S
Tretli
Olav A
OA
Haugen
Anna M
AM
Bofin
Lars J
LJ
Vatten
Bjørn Olav
BO
Åsvold
D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D016016:Proportional Hazards Models; D017584:Reproductive History; D046888:Tissue Array Analysis