Reproductive risk factor associations with lobular and ductal carcinoma in the Carolina Breast Cancer Study

Lindsay A. Williams, Hazel B. Nichols, Katherine A. Hoadley, Chiu Kit Tse, Joseph Geradts, Mary Elizabeth Bell, Charles M. Perou, Michael I. Love, Andrew F. Olshan, Melissa A. Troester

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Background: Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype. Methods: Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal–lobular (n = 473)] in the Carolina Breast Cancer Study (1993–2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER−/PR−/HER2-), and HER2+ (ER−/PR−/HER2+). Results: In case–case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33–2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03–1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08–3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype. Conclusions: Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalCancer Causes and Control
Issue number1
StatePublished - Jan 1 2018

Bibliographical note

Publisher Copyright:
© 2017, Springer International Publishing AG, part of Springer Nature.


  • Breast cancer
  • Breast cancer subtype
  • Histology
  • Reproductive risk factors


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