Cancer Causes & Control

, Volume 25, Issue 7, pp 881–889 | Cite as

Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women

  • Julie HornEmail author
  • Signe Opdahl
  • Monica J. Engstrøm
  • Pål R. Romundstad
  • Steinar Tretli
  • Olav A. Haugen
  • Anna M. Bofin
  • Lars J. Vatten
  • Bjørn Olav Åsvold
Original paper



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.


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.


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.


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.


Breast cancer Molecular subtype Reproductive factors Epidemiology 



This study was funded by The Norwegian Cancer Society.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Julie Horn
    • 1
    • 2
    Email author
  • Signe Opdahl
    • 1
  • Monica J. Engstrøm
    • 3
  • Pål R. Romundstad
    • 1
  • Steinar Tretli
    • 1
    • 4
  • Olav A. Haugen
    • 3
  • Anna M. Bofin
    • 3
  • Lars J. Vatten
    • 1
  • Bjørn Olav Åsvold
    • 1
    • 5
  1. 1.Department of Public HealthNorwegian University of Science and TechnologyTrondheimNorway
  2. 2.Department of Gynecology and Obstetrics, Levanger HospitalHealth Trust Nord-TrøndelagLevangerNorway
  3. 3.Department of Laboratory Medicine, Children’s and Women’s HealthNorwegian University of Science and TechnologyTrondheimNorway
  4. 4.Cancer Registry of NorwayInstitute of Population-based Cancer ResearchOsloNorway
  5. 5.Department of Endocrinology, St. Olavs HospitalTrondheim University HospitalTrondheimNorway

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