Abstract
Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1 = 1.56 (95% CI 1.15-2.13), ptrend = 0.02 for testosterone and ORQ4-Q1 = 1.33 (95% CI 0.99-1.79), ptrend = 0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1 = 1.32 (95% CI 0.87-2.01), ptrend = 0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1 = 0.94 (95% CI 0.60-1.47), ptrend = 0.34, phet = 0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen. What's new? Sex hormones have often been connected with the development of breast cancer, and estrogens have clear pro-proliferative effects on breast cancer cells. In this large prospective study, the authors underscore a direct association of premenopausal levels of testosterone with subsequent breast cancer risk. By contrast, no direct relationship between premenopausal estrogen and progesterone levels with increased breast cancer risk was observed although a weak association between higher estradiol levels and increased risk for tumors diagnosed before age 50 was noted. The authors point to the possibility that a conversion from androgen to estrogen might take place in the breast that may mechanistically explain the increased risk in breast cancer development when androgens are high.
| Original language | English |
|---|---|
| Pages (from-to) | 1947-1957 |
| Number of pages | 11 |
| Journal | International Journal of Cancer |
| Volume | 134 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Apr 15 2014 |
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Keywords
- breast cancer
- EPIC
- estrogen receptor
- prospective cohort
- sex hormones
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status - Results from the EPIC cohort. / Kaaks, Rudolf; Tikk, Kaja; Sookthai, Disorn; Schock, Helena; Johnson, Theron; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Clavel-Chapelon, Françoise; Dossus, Laure; Baglietto, Laura; Rinaldi, Sabina; Chajes, Veronique; Romieu, Isabelle; Boeing, Heiner; Schütze, Madlen; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Ricceri, Fulvio; Mattiello, Amalia; Buckland, Genevieve; Ramón Quirós, Jose; Sánchez, María José; Amiano, Pilar; Chirlaque, Maria Dolores; Barricarte, Aurelio; Bas Bueno-De-Mesquita, H.; Van Gils, Carla H.; Peeters, Petra H.; Andersson, Anne; Sund, Malin; Weiderpass, Elisabete; Khaw, Kay Tee; Wareham, Nick; Key, Timothy J.; Travis, Ruth C.; Merritt, Melissa A.; Gunter, Marc J.; Riboli, Elio; Lukanova, Annekatrin.
In: International Journal of Cancer, Vol. 134, No. 8, 15.04.2014, p. 1947-1957.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status - Results from the EPIC cohort
AU - Kaaks, Rudolf
AU - Tikk, Kaja
AU - Sookthai, Disorn
AU - Schock, Helena
AU - Johnson, Theron
AU - Tjønneland, Anne
AU - Olsen, Anja
AU - Overvad, Kim
AU - Clavel-Chapelon, Françoise
AU - Dossus, Laure
AU - Baglietto, Laura
AU - Rinaldi, Sabina
AU - Chajes, Veronique
AU - Romieu, Isabelle
AU - Boeing, Heiner
AU - Schütze, Madlen
AU - Trichopoulou, Antonia
AU - Lagiou, Pagona
AU - Trichopoulos, Dimitrios
AU - Palli, Domenico
AU - Sieri, Sabina
AU - Tumino, Rosario
AU - Ricceri, Fulvio
AU - Mattiello, Amalia
AU - Buckland, Genevieve
AU - Ramón Quirós, Jose
AU - Sánchez, María José
AU - Amiano, Pilar
AU - Chirlaque, Maria Dolores
AU - Barricarte, Aurelio
AU - Bas Bueno-De-Mesquita, H.
AU - Van Gils, Carla H.
AU - Peeters, Petra H.
AU - Andersson, Anne
AU - Sund, Malin
AU - Weiderpass, Elisabete
AU - Khaw, Kay Tee
AU - Wareham, Nick
AU - Key, Timothy J.
AU - Travis, Ruth C.
AU - Merritt, Melissa A.
AU - Gunter, Marc J.
AU - Riboli, Elio
AU - Lukanova, Annekatrin
PY - 2014/4/15
Y1 - 2014/4/15
N2 - Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1 = 1.56 (95% CI 1.15-2.13), ptrend = 0.02 for testosterone and ORQ4-Q1 = 1.33 (95% CI 0.99-1.79), ptrend = 0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1 = 1.32 (95% CI 0.87-2.01), ptrend = 0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1 = 0.94 (95% CI 0.60-1.47), ptrend = 0.34, phet = 0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen. What's new? Sex hormones have often been connected with the development of breast cancer, and estrogens have clear pro-proliferative effects on breast cancer cells. In this large prospective study, the authors underscore a direct association of premenopausal levels of testosterone with subsequent breast cancer risk. By contrast, no direct relationship between premenopausal estrogen and progesterone levels with increased breast cancer risk was observed although a weak association between higher estradiol levels and increased risk for tumors diagnosed before age 50 was noted. The authors point to the possibility that a conversion from androgen to estrogen might take place in the breast that may mechanistically explain the increased risk in breast cancer development when androgens are high.
AB - Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1 = 1.56 (95% CI 1.15-2.13), ptrend = 0.02 for testosterone and ORQ4-Q1 = 1.33 (95% CI 0.99-1.79), ptrend = 0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1 = 1.32 (95% CI 0.87-2.01), ptrend = 0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1 = 0.94 (95% CI 0.60-1.47), ptrend = 0.34, phet = 0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen. What's new? Sex hormones have often been connected with the development of breast cancer, and estrogens have clear pro-proliferative effects on breast cancer cells. In this large prospective study, the authors underscore a direct association of premenopausal levels of testosterone with subsequent breast cancer risk. By contrast, no direct relationship between premenopausal estrogen and progesterone levels with increased breast cancer risk was observed although a weak association between higher estradiol levels and increased risk for tumors diagnosed before age 50 was noted. The authors point to the possibility that a conversion from androgen to estrogen might take place in the breast that may mechanistically explain the increased risk in breast cancer development when androgens are high.
KW - breast cancer
KW - EPIC
KW - estrogen receptor
KW - prospective cohort
KW - sex hormones
UR - http://www.scopus.com/inward/record.url?scp=84893719571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893719571&partnerID=8YFLogxK
U2 - 10.1002/ijc.28528
DO - 10.1002/ijc.28528
M3 - Article
C2 - 24155248
AN - SCOPUS:84893719571
VL - 134
SP - 1947
EP - 1957
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 8
ER -