The Combined Influence of Multiple Sex and Growth Hormones on Risk of Postmenopausal Breast Cancer: a Nested Case-control Study

Overview

Journal Breast Cancer Res

Specialty Oncology

Date 2011 Oct 25

PMID 22017816

Citations 19

Authors

Shelley S Tworoger

Bernard A Rosner

Walter C Willett

Susan E Hankinson

Affiliations

Soon will be listed here.

Abstract

Introduction: Sex and growth hormones are positively associated with postmenopausal breast cancer risk. However, few studies have evaluated the influence of multiple hormones simultaneously.

Methods: We considered the roles of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate and prolactin and, secondarily, insulin-like growth factor 1 (IGF-1) and c-peptide in postmenopausal breast cancer risk among 265 cases and 541 controls in the prospective Nurses' Health Study. We created several hormone scores, including ranking women by the number of hormones above the age- and batch-adjusted geometric mean and weighting hormone values by their individual associations with breast cancer risk.

Results: Women in the top versus bottom quintile of individual estrogen or androgen levels had approximately a doubling of postmenopausal breast cancer risk. Having seven or eight compared to zero hormones above the geometric mean level was associated with total (RR = 2.7, 95% CI = 1.3 to 5.7, P trend < 0.001) and estrogen receptor (ER)-positive (RR = 3.4, 95% CI = 1.3 to 9.4, P trend < 0.001) breast cancer risk. When comparing the top versus bottom quintiles of the score weighted by individual hormone associations, the RR for total breast cancer was 3.0 (95% CI = 1.8 to 5.0, P trend < 0.001) and the RR for ER-positive disease was 3.9 (95% CI = 2.0 to 7.5, P trend < 0.001). The risk further increased when IGF-1 and c-peptide were included in the scores. The results did not change with adjustment for body mass index.

Conclusions: Overall, the results of our study suggest that multiple hormones with high circulating levels substantially increase the risk of breast cancer, particularly ER-positive disease. Additional research should consider the potential impact of developing risk prediction scores that incorporate multiple hormones.

Citing Articles

Investigating the Link between Early Life and Breast Anomalies.

Christopoulos P, Matsas A, Eleftheriades M, Kotsira G, Eleftheriades A, Vlahos N Children (Basel). 2023; 10(3).

PMID: 36980159 PMC: 10047184. DOI: 10.3390/children10030601.

Linking Physical Activity to Breast Cancer Risk via the Insulin/Insulin-like Growth Factor Signaling System, Part 2: The Effect of Insulin/Insulin-like Growth Factor Signaling on Breast Cancer Risk.

Drummond A, Swain C, Milne R, English D, Brown K, Skinner T Cancer Epidemiol Biomarkers Prev. 2022; 31(12):2116-2125.

PMID: 36464995 PMC: 7613928. DOI: 10.1158/1055-9965.EPI-22-0505.

Sex steroid hormones and risk of breast cancer: a two-sample Mendelian randomization study.

Nounu A, Kar S, Relton C, Richmond R Breast Cancer Res. 2022; 24(1):66.

PMID: 36209141 PMC: 9548139. DOI: 10.1186/s13058-022-01553-9.

Linking Physical Activity to Breast Cancer via Sex Steroid Hormones, Part 2: The Effect of Sex Steroid Hormones on Breast Cancer Risk.

Drummond A, Swain C, Brown K, Dixon-Suen S, Boing L, van Roekel E Cancer Epidemiol Biomarkers Prev. 2021; 31(1):28-37.

PMID: 34670801 PMC: 7612577. DOI: 10.1158/1055-9965.EPI-21-0438.

Pre-diagnostic sex hormone levels and survival among breast cancer patients.

Kensler K, Eliassen A, Rosner B, Hankinson S, Brown M, Tamimi R Breast Cancer Res Treat. 2019; 174(3):749-758.

PMID: 30604001 PMC: 6446911. DOI: 10.1007/s10549-018-05121-8.

References

Kaaks R, Rinaldi S, Key T, Berrino F, Peeters P, Biessy C . Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer. 2005; 12(4):1071-82. DOI: 10.1677/erc.1.01038. View

Zeleniuch-Jacquotte A, Shore R, Koenig K, Akhmedkhanov A, Afanasyeva Y, Kato I . Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study. Br J Cancer. 2004; 90(1):153-9. PMC: 2395327. DOI: 10.1038/sj.bjc.6601517. View

Kiss R, de Launoit Y, Wouters W, Deslypere J, Lescrainier J, Paridaens R . Inhibitory action of androstenedione on the proliferation and cell cycle kinetics of aromatase-free MXT and MCF-7 mammary tumour cell lines. Eur J Cancer Clin Oncol. 1989; 25(5):837-43. DOI: 10.1016/0277-5379(89)90129-6. View

Stewart A, Johnson M, May F, Westley B . Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells. J Biol Chem. 1990; 265(34):21172-8. View

Henderson B, Feigelson H . Hormonal carcinogenesis. Carcinogenesis. 2000; 21(3):427-33. DOI: 10.1093/carcin/21.3.427. View

Jozan S, Moure C, Gillois M, Bayard F . Effects of estrone on cell proliferation of a human breast cancer (MCF-7) in long term tissue culture. J Steroid Biochem. 1979; 10(3):341-2. DOI: 10.1016/0022-4731(79)90263-2. View

Billich A, Nussbaumer P, LEHR P . Stimulation of MCF-7 breast cancer cell proliferation by estrone sulfate and dehydroepiandrosterone sulfate: inhibition by novel non-steroidal steroid sulfatase inhibitors. J Steroid Biochem Mol Biol. 2000; 73(5):225-35. DOI: 10.1016/s0960-0760(00)00077-7. View

Buehring G . Effect of hormones on growth rates of malignant and nonmalignant human mammary epithelia in cell culture. In Vitro. 1980; 16(6):491-501. DOI: 10.1007/BF02626462. View

Santner S, Ohlsson-Wilhelm B, Santen R . Estrone sulfate promotes human breast cancer cell replication and nuclear uptake of estradiol in MCF-7 cell cultures. Int J Cancer. 1993; 54(1):119-24. DOI: 10.1002/ijc.2910540119. View

10.

Biswas R, Vonderhaar B . Role of serum in the prolactin responsiveness of MCF-7 human breast cancer cells in long-term tissue culture. Cancer Res. 1987; 47(13):3509-14. View

11.

Reddel R, Sutherland R . Effects of pharmacological concentrations of estrogens on proliferation and cell cycle kinetics of human breast cancer cell lines in vitro. Cancer Res. 1987; 47(20):5323-9. View

12.

Tworoger S, Hankinson S . Prolactin and breast cancer risk. Cancer Lett. 2006; 243(2):160-9. DOI: 10.1016/j.canlet.2006.01.032. View

13.

Andersen H, Andersson A, Arnold S, Autrup H, Barfoed M, Beresford N . Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals. Environ Health Perspect. 1999; 107 Suppl 1:89-108. PMC: 1566352. DOI: 10.1289/ehp.99107s189. View

14.

Key T, Appleby P, Barnes I, Reeves G . Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 2002; 94(8):606-16. DOI: 10.1093/jnci/94.8.606. View

15.

Gayosso V, Montano L, Lopez-Marure R . DHEA-induced antiproliferative effect in MCF-7 cells is androgen- and estrogen receptor-independent. Cancer J. 2006; 12(2):160-5. View

16.

Tworoger S, Eliassen A, Sluss P, Hankinson S . A prospective study of plasma prolactin concentrations and risk of premenopausal and postmenopausal breast cancer. J Clin Oncol. 2007; 25(12):1482-8. DOI: 10.1200/JCO.2006.07.6356. View

17.

Ando S, De Amicis F, Rago V, Carpino A, Maggiolini M, Panno M . Breast cancer: from estrogen to androgen receptor. Mol Cell Endocrinol. 2002; 193(1-2):121-8. DOI: 10.1016/s0303-7207(02)00105-3. View

18.

Hankinson S, Willett W, Colditz G, Hunter D, Michaud D, Deroo B . Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998; 351(9113):1393-6. DOI: 10.1016/S0140-6736(97)10384-1. View

19.

Shi R, Yu H, Mclarty J, Glass J . IGF-I and breast cancer: a meta-analysis. Int J Cancer. 2004; 111(3):418-23. DOI: 10.1002/ijc.20233. View

20.

Yu H, Shu X, Li B, Dai Q, Gao Y, Jin F . Joint effect of insulin-like growth factors and sex steroids on breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2003; 12(10):1067-73. View