Sex hormone levels, breast cancer risk, and cancer receptor status in postmenopausal women: the ORDET cohort.
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.
Sieri
Sabina
S
Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, I-20133 Milan, Italy.
Krogh
Vittorio
V
Bolelli
Gianfranco
G
Abagnato
Carlo Alberto
CA
Grioni
Sara
S
Pala
Valeria
V
Evangelista
Alberto
A
Allemani
Claudia
C
Micheli
Andrea
A
Tagliabue
Giovanna
G
Schunemann
Holger J
HJ
Menard
Sylvie
S
Berrino
Franco
F
Muti
Paola
P
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000378:metabolism*; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012306:Risk; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D004958:Estradiol; D012739:Gonadal Steroid Hormones; D018719:Erb-b2 Receptor Tyrosine Kinases; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone