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

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.

• Authors: 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 Krogh, Salvatore 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
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 4 Issue 10 Pg. 1626-35 (Oct 2011) ISSN: 1940-6215 [Electronic] United States
• PMID: 21813404 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Gonadal Steroid Hormones
• Receptors, Estrogen
• Receptors, Progesterone

Topics

• Adult
• Aged
• Breast Neoplasms (blood, etiology)
• Case-Control Studies
• Cohort Studies
• Female
• Follow-Up Studies
• Gonadal Steroid Hormones (blood)
• Humans
• Middle Aged
• Odds Ratio
• Postmenopause
• Prognosis
• Prospective Studies
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Risk Factors