Postmenopausal serum sex steroids and risk of hormone receptor-positive and -negative breast cancer: A nested case-control study

Rebecca E. James, Annekatrin Lukanova, Laure Dossus, Susen Becker, Sabina Rinaldi, Anne Tjønneland, Anja Olsen, Kim Overvad, Sylvie Mesrine, Pierre Engel, Françoise Clavel-Chapelon, Jenny Chang-Claude, Alina Vrieling, Heiner Boeing, Madlen Schütze, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Vittorio KroghSalvatore Panico, Rosario Tumino, Carlotta Sacerdote, Laudina Rodríguez, Genevieve Buckland, Maria José Sánchez, Pilar Amiano, Eva Ardanaz, Bas Bueno-de-Mesquita, Martine M. Ros, Carla H. Van Gils, Petra H. Peeters, Kay Tee Khaw, Nick Wareham, Timothy J. Key, Naomi E. Allen, Isabelle Romieu, Afshan Siddiq, David Cox, Elio Riboli, Rudolf Kaaks

Research output: Contribution to journalArticlepeer-review

Abstract

Prediagnostic endogenous sex steroid hormone levels have well established associations with overall risk of breast cancer. While evidence toward the existence of distinct subtypes of breast cancer accumulates, few studies have investigated the associations of sex steroid hormone levels with risk of hormone receptor [estrogen receptor (ER) and/or progesterone receptor (PR)] defined breast cancer. In a case-control study nested within the EPIC cohort (European Prospective Investigation into Cancer and Nutrition), estradiol, testosterone, and sex hormone-binding globulin levels were measured in prediagnostic serum samples from postmenopausal women not using hormone replacement therapy at blood donation. A total of 554 women who developed invasive breast cancer with information on receptor status were matched with 821 control subjects. Conditional logistic regression models estimated breast cancer risk with hormone concentrations according to hormone receptor status of the tumor. Sex steroid hormones were associated with risks of not only ER+PR+ breast cancer [estradiol OR for highest vs. lowest tertile = 2.91 (95% CI: 1.62-5.23), P trend = 0.002; testosterone OR = 2.27 (95% CI: 1.35-3.81), P trend = 0.002] but also of ER-PR- breast cancer [estradiol OR = 2.11 (95% CI: 1.00-4.46), P trend = 0.05; testosterone OR = 2.06 (95% CI: 0.95-4.46), P trend = 0.03], with associations appearing somewhat stronger in the receptor-positive disease. Serum androgens and estrogens are associated with risks of both hormone receptor-negative as well as receptor-positive breast tumors. Further research is needed to establish through which molecular pathways, and during which evolutionary stages of development, androgens and estrogens can promote the occurrence of both receptor-positive and -negative clinical breast tumors.

Original languageEnglish
Pages (from-to)1626-1635
Number of pages10
JournalCancer Prevention Research
Volume4
Issue number10
DOIs
Publication statusPublished - Oct 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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