TY - JOUR
T1 - Sex hormone levels, breast cancer risk, and cancer receptor status in postmenopausal women
T2 - The ORDET cohort
AU - Sieri, Sabina
AU - Krogh, Vittorio
AU - Bolelli, Gianfranco
AU - Abagnato, Carlo Alberto
AU - Grioni, Sara
AU - Pala, Valeria
AU - Evangelista, Alberto
AU - Allemani, Claudia
AU - Micheli, Andrea
AU - Tagliabue, Giovanna
AU - Schunemann, Holger J.
AU - Menard, Sylvie
AU - Berrino, Franco
AU - Muti, Paola
PY - 2009/1
Y1 - 2009/1
N2 - Background: Endogenous sex hormone levels have been associated with increased breast cancer risk in postmenopausal women in several prospective studies. However, it remains unclear to what extent serum hormone-breast cancer associations differ with receptor status. Methods: Associations between serum sex hormone levels and breast cancer risk were assessed in a nested case-control study on postmenopausal women of the ORDET cohort. After a median follow-up of 13.5 years, 165 women developed breast cancer. Relative risks of developing breast cancer were estimated by conditional logistic regression. Results: Total and free testosterone levels were directly associated with breast cancer risk [relative risk, 3.28 (95% confidence interval, 1.93-5.55) and 2.86 (95% confidence interval, 1.66-4.94), respectively, for highest versus lowest quartile]. When relations between hormone level and risk of breast cancer expressing various receptor combinations were assessed, high total testosterone was significantly associated with increased risk of estrogen receptor-positive cancers, irrespective of progesterone receptor status. High total testosterone was also associated with increased risk of both human epidermal growth factor receptor 2 (HER2)-negative (HER2-) and HER2+ cancers. High estradiol tended to be associated with increased risk of HER2- cancer and inversely associated with HER2+ cancer, with significant (P = 0.027) heterogeneity between HER2+ and HER2- cancers. However, there were relatively few HER2+ cases. Conclusions: This study provides further evidence that high levels of circulating testosterone increase the risk of developing breast cancer in postmenopausal women. The cancers that develop are mainly estrogen receptor positive. Although HER2 + and HER2- breast cancers were both associated with high total testosterone, they showed opposing associations with estrogen.
AB - Background: Endogenous sex hormone levels have been associated with increased breast cancer risk in postmenopausal women in several prospective studies. However, it remains unclear to what extent serum hormone-breast cancer associations differ with receptor status. Methods: Associations between serum sex hormone levels and breast cancer risk were assessed in a nested case-control study on postmenopausal women of the ORDET cohort. After a median follow-up of 13.5 years, 165 women developed breast cancer. Relative risks of developing breast cancer were estimated by conditional logistic regression. Results: Total and free testosterone levels were directly associated with breast cancer risk [relative risk, 3.28 (95% confidence interval, 1.93-5.55) and 2.86 (95% confidence interval, 1.66-4.94), respectively, for highest versus lowest quartile]. When relations between hormone level and risk of breast cancer expressing various receptor combinations were assessed, high total testosterone was significantly associated with increased risk of estrogen receptor-positive cancers, irrespective of progesterone receptor status. High total testosterone was also associated with increased risk of both human epidermal growth factor receptor 2 (HER2)-negative (HER2-) and HER2+ cancers. High estradiol tended to be associated with increased risk of HER2- cancer and inversely associated with HER2+ cancer, with significant (P = 0.027) heterogeneity between HER2+ and HER2- cancers. However, there were relatively few HER2+ cases. Conclusions: This study provides further evidence that high levels of circulating testosterone increase the risk of developing breast cancer in postmenopausal women. The cancers that develop are mainly estrogen receptor positive. Although HER2 + and HER2- breast cancers were both associated with high total testosterone, they showed opposing associations with estrogen.
UR - http://www.scopus.com/inward/record.url?scp=58349115858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58349115858&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-08-0808
DO - 10.1158/1055-9965.EPI-08-0808
M3 - Article
C2 - 19124495
AN - SCOPUS:58349115858
VL - 18
SP - 169
EP - 176
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 1
ER -