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. 2016 May 15;138(10):2346-56.
doi: 10.1002/ijc.29968. Epub 2016 Feb 8.

Reproductive risk factors in relation to molecular subtypes of breast cancer: Results from the nurses' health studies

Julia S Sisti  1   2   3 , Laura C Collins  4 , Andrew H Beck  4 , Rulla M Tamimi  1   2 , Bernard A Rosner  2 , A Heather Eliassen  1   2
Affiliations

Reproductive risk factors in relation to molecular subtypes of breast cancer: Results from the nurses' health studies

Julia S Sisti et al. Int J Cancer. .

Abstract

Several intrinsic breast cancer subtypes, possibly representing unique etiologic processes, have been identified by gene expression profiles. Evidence suggests that associations with reproductive risk factors may vary by breast cancer subtype. In the Nurses' Health Studies, we prospectively examined associations of reproductive factors with breast cancer subtypes defined using immunohistochemical staining of tissue microarrays. Multivariate-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over follow-up, we identified 2,063 luminal A, 1,008 luminal B, 209 HER2-enriched, 378 basal-like and 110 unclassified tumors. Many factors appeared associated with luminal A tumors, including ages at menarche (p(heterogeneity) = 0.65) and menopause (p(heterogeneity) = 0.05), and current HT use (p(heterogeneity) = 0.33). Increasing parity was not associated with any subtype (p(heterogeneity) = 0.76), though age at first birth was associated with luminal A tumors only (per 1-year increase HR = 1.03 95%CI (1.02-1.05), p(heterogeneity) = 0.04). Though heterogeneity was not observed, duration of lactation was inversely associated with risk of basal-like tumors only (7+ months vs. never HR = 0.65 95%CI (0.49-0.87), ptrend = 0.02), p(heterogeneity) = 0.27). Years between menarche and first birth was strongly positively associated with luminal A and non-luminal subtypes (e.g. 22-year interval vs. nulliparous HR = 1.80, 95%CI (1.08-3.00) for basal-like tumors; p(heterogeneity) = 0.003), and evidence of effect modification by breastfeeding was observed. In summary, many reproductive risk factors for breast cancer appeared most strongly associated with the luminal A subtype. Our results support previous reports that lactation is protective against basal-like tumors, representing a potential modifiable risk factor for this aggressive subtype.

Keywords: breast cancer; lactation; molecular subtypes; pregnancy; reproductive risk factors.

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References

    1. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000;406:747–52. - PubMed
    1. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74. - PMC - PubMed
    1. Sørlie T, Wang Y, Xiao C, Johnsen H, Naume B, Samaha RR, Børresen-Dale A-L. Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms. BMC Genomics. 2006;7:127. - PMC - PubMed
    1. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn, Perou CM. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74. - PubMed
    1. Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS, Perou CM, Ellis MJ, Nielsen TO. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50. - PMC - PubMed

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