Skip to main content

Advertisement

SpringerLink
Log in

Polycystic ovarian syndrome (PCOS), related symptoms/sequelae, and breast cancer risk in a population-based case–control study

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

Despite the overlap between the clinical symptoms/sequelae of polycystic ovarian syndrome (PCOS) and many known reproductive risk factors for breast cancer, the relationship between PCOS and breast cancer remains unclear, possibly because of the complex heterogeneity and challenges in diagnosing PCOS over time. We hypothesized that PCOS, specific PCOS-related symptoms/sequelae, or clusters of PCOS-related symptoms/sequelae may be differentially associated with pre- versus postmenopausal breast cancer risk.

Materials and methods

Cases were 1,508 women newly diagnosed with a first primary in situ or invasive breast, and the 1,556 population-based controls were frequency-matched by age.

Results

History of physician-diagnosed PCOS was reported by 2.2 % (n = 67), among whom oral contraceptive (OC) use, irregular menstruation, and infertility due to ovulatory dysfunction were common. Using unconditional logistic regression, adjusted odds ratios (95 % CI) for PCOS were increased for premenopausal [2.74 (1.13, 6.63)], but not postmenopausal breast cancer [0.87 (0.44, 1.71)]. We used cluster analysis to investigate whether risk among all women varied by PCOS-related symptoms/sequelae, such as reproductive irregularities, OC use, and components of insulin resistance. In the cluster analysis, odds ratios were elevated among premenopausal women who had a history of OC use and no ovulatory dysfunction [1.39 (1.03, 1.88)], compared to those with fewer number of PCOS-related symptoms/sequelae.

Conclusion

PCOS and associated PCOS-related symptoms/sequelae including OC use may play a role in the development of premenopausal breast cancer. Our findings require confirmation in studies with a larger number of premenopausal women with systematically applied diagnostic criteria for PCOS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ (2010) The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 25:544–551

    Article  PubMed  Google Scholar 

  2. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO (2004) The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 89:2745–2749

    Article  CAS  PubMed  Google Scholar 

  3. Norman RJ, Dewailly D, Legro RS, Hickey TE (2007) Polycystic ovary syndrome. Lancet 370:685–697

    Article  CAS  PubMed  Google Scholar 

  4. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R (2011) Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7:219–231

    Article  CAS  PubMed  Google Scholar 

  5. Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR et al (2008) The metabolic syndrome. Endocr Rev 29:777–822

    Article  CAS  PubMed  Google Scholar 

  6. Garruti G, Depalo R, Vita MG, Lorusso F, Giampetruzzi F, Damato AB et al (2009) Adipose tissue, metabolic syndrome and polycystic ovary syndrome: from pathophysiology to treatment. Reprod Biomed Online 19:552–563

    Article  CAS  PubMed  Google Scholar 

  7. Gammon MD, Thompson WD (1991) Polycystic ovaries and the risk of breast cancer. Am J Epidemiol 134:818–824

    CAS  PubMed  Google Scholar 

  8. Anderson KE, Sellers TA, Chen PL, Rich SS, Hong CP, Folsom AR (1997) Association of Stein-Leventhal syndrome with the incidence of postmenopausal breast carcinoma in a large prospective study of women in Iowa. Cancer 79:494–499

    Article  CAS  PubMed  Google Scholar 

  9. Gottschau M, Kjaer SK, Jensen A, Munk C, Mellemkjaer L (2015) Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study. Gynecol Oncol 136:99–103

    Article  PubMed  Google Scholar 

  10. Brinton LA, Moghissi KS, Westhoff CL, Lamb EJ, Scoccia B (2010) Cancer risk among infertile women with androgen excess or menstrual disorders (including polycystic ovary syndrome). Fertil Steril 94:1787–1792

    Article  PubMed Central  PubMed  Google Scholar 

  11. Wild S, Pierpoint T, Jacobs H, McKeigue P (2000) Long-term consequences of polycystic ovary syndrome: results of a 31 year follow-up study. Hum Fertil (Camb) 3:101–105

    Article  Google Scholar 

  12. Barry JA, Azizia MM, Hardiman PJ (2014) Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 20:748–758

    Article  PubMed Central  PubMed  Google Scholar 

  13. Goldenberg N, Glueck C (2008) Medical therapy in women with polycystic ovarian syndrome before and during pregnancy and lactation. Minerva Ginecol 60:63–75

    CAS  PubMed  Google Scholar 

  14. Collaborative Group on Hormonal Factors in Breast Cancer (1996) Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Lancet 347:1713–1727

    Article  Google Scholar 

  15. Willett WC, Tamimi R, Hankinson SE, Hazra A, Eliassen AH, Colditz GA (2014) Chapter 18: nongenetic factors in the causation of breast cancer. In: Harris JR, Lippman ME, Morrow M, Osborne CK (eds) Diseases of the Breast, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 211–267

    Google Scholar 

  16. Anderson KN, Schwab RB, Martinez ME (2014) Reproductive risk factors and breast cancer subtypes: a review of the literature. Breast Cancer Res Treat 144:1–10

    Article  PubMed Central  PubMed  Google Scholar 

  17. McCullough LE, Eng SM, Bradshaw PT, Cleveland RJ, Teitelbaum SL, Neugut AI et al (2012) Fat or fit: the joint effects of physical activity, weight gain, and body size on breast cancer risk. Cancer 118:4860–4868

    Article  PubMed Central  PubMed  Google Scholar 

  18. Wright CE, Zborowski JV, Talbott EO, McHugh-Pemu K, Youk A (2004) Dietary intake, physical activity, and obesity in women with polycystic ovary syndrome. Int J Obes Relat Metab Disord 28:1026–1032

    Article  CAS  PubMed  Google Scholar 

  19. Lin AW, Lujan ME (2014) Comparison of dietary intake and physical activity between women with and without polycystic ovary syndrome: a review. Adv Nutr 5:486–496

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE et al (2009) Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 101:48–60

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Glintborg D, Altinok ML, Mumm H, Hermann AP, Ravn P, Andersen M (2014) Body composition is improved during 12 months treatment with metformin alone or combined with oral contraceptives compared to treatment with oral contraceptives in polycystic ovary syndrome. J Clin Endocrinol Metab 99:2584–2591

    Article  CAS  PubMed  Google Scholar 

  22. Cogliano V, Grosse Y, Baan R, Straif K, Secretan B, ElGhissassi F, WHO International Agency for Research on Cancer (2005) Carcinogenicity of combined oestrogen–progestagen contraceptives and menopausal treatment. Lancet Oncol 6:552–553

    Article  PubMed  Google Scholar 

  23. Cowan LD, Gordis L, Tonascia JA, Jones GS (1981) Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol 114:209–217

    CAS  PubMed  Google Scholar 

  24. Chittenden BG, Fullerton G, Maheshwari A, Bhattacharya S (2009) Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review. Reprod Biomed Online 19:398–405

    Article  CAS  PubMed  Google Scholar 

  25. Micheli A, Muti P, Secreto G, Krogh V, Meneghini E, Venturelli E et al (2004) Endogenous sex hormones and subsequent breast cancer in premenopausal women. Int J Cancer 112:312–318

    Article  CAS  PubMed  Google Scholar 

  26. Clavel-Chapelon F (2002) Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women. Br J Cancer 86:723–727

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Clavel-Chapelon F, Gerber M (2002) Reproductive factors and breast cancer risk. Do they differ according to age at diagnosis? Breast Cancer Res Treat 72:107–115

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Gammon MD, Neugut AI, Santella RM, Teitelbaum SL, Britton JA, Terry MB et al (2002) The Long Island Breast Cancer Study Project: description of a multi-institutional collaboration to identify environmental risk factors for breast cancer. Breast Cancer Res Treat 74:235–254

    Article  CAS  PubMed  Google Scholar 

  29. Shantakumar S, Terry MB, Teitelbaum SL, Britton JA, Millikan RC, Moorman PG et al (2007) Reproductive factors and breast cancer risk among older women. Breast Cancer Res Treat 102:365–374

    Article  PubMed  Google Scholar 

  30. Shantakumar S, Terry MB, Paykin A, Teitelbaum SL, Britton JA, Moorman PG et al (2007) Age and menopausal effects of hormonal birth control and hormone replacement therapy in relation to breast cancer risk. Am J Epidemiol 165:1187–1198

    Article  PubMed  Google Scholar 

  31. Terry MB, Zhang FF, Kabat G, Britton JA, Teitelbaum SL, Neugut AI et al (2006) Lifetime alcohol intake and breast cancer risk. Ann Epidemiol 16:230–240

    Article  PubMed  Google Scholar 

  32. Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA et al (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 291:2433–2440

    Article  CAS  PubMed  Google Scholar 

  33. Eng SM, Gammon MD, Terry MB, Kushi LH, Teitelbaum SL, Britton JA et al (2005) Body size changes in relation to postmenopausal breast cancer among women on Long Island, New York. Am J Epidemiol 162:229–237

    Article  PubMed  Google Scholar 

  34. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47

    Article  Google Scholar 

  35. Jamil AS, Alalaf SK, Al-Tawil NG, Al-Shawaf T (2015) Comparison of clinical and hormonal characteristics among four phenotypes of polycystic ovary syndrome based on the Rotterdam criteria. Arch Gynecol Obstet 293:447–456

    Article  PubMed  Google Scholar 

  36. Shen J, Terry MB, Gammon MD, Gaudet MM, Teitelbaum SL, Eng SM et al (2005) MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk. Carcinogenesis 26:2131–2137

    Article  CAS  PubMed  Google Scholar 

  37. Greenland S (1989) Modeling and variable selection in epidemiologic analysis. Am J Public Health 79:340–349

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Selvin S (1996) Statistical analysis of epidemiologic data. Oxford University Press, New York

    Google Scholar 

  39. Shrier I, Platt RW (2008) Reducing bias through directed acyclic graphs. BMC Med Res Methodol 8:70

    Article  PubMed Central  PubMed  Google Scholar 

  40. Breslow NE, Day NE (1980) Statistical methods in cancer research. Volume I—the analysis of case–control studies. IARC Sci Publ, Lyon, pp 5–338

    Google Scholar 

  41. Rothman KJ, Greenland S, Lask TL (2012) Modern epidemiology. Williams and Wilkins, Linppincott

    Google Scholar 

  42. Cleveland RJ, North KE, Stevens J, Teitelbaum SL, Neugut AI, Gammon MD (2012) The association of diabetes with breast cancer incidence and mortality in the Long Island Breast Cancer Study Project. Cancer Causes Control 23:1193–1203

    Article  PubMed Central  PubMed  Google Scholar 

  43. Milligan G (1988) A study of standardization of variables in cluster analysis. J Classif 5:181–204

    Article  Google Scholar 

  44. Barry JA, Azizia MM, Hardiman PJ (2014) Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 20(5):748–758

    Article  PubMed Central  PubMed  Google Scholar 

  45. Schisterman EF, Cole SR, Platt RW (2009) Overadjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology 20:488–495

    Article  PubMed Central  PubMed  Google Scholar 

  46. Lange T, Rasmussen M, Thygesen LC (2013) Assessing natural direct and indirect effects through multiple pathways. Am J Epidemiol 179:513–518

    Article  PubMed  Google Scholar 

  47. Bonnier P, Romain S, Charpin C, Lejeune C, Tubiana N, Martin PM, Piana L (1995) Age as a prognostic factor in breast cancer: relationship to pathologic and biologic features. Int J Cancer 62(2):138–144

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported in part by grants from the National Institutes of Health (CA/ES 66572, and 5TL1CA133837-05).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, 596 Nonhyun-ro, Gangnam-gu, Seoul, 135-907, South Korea

    Jayeon Kim

  2. Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA

    Jayeon Kim, Nikhil Khankari, Lauren E. McCullough & Marilie D. Gammon

  3. Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA

    Jayeon Kim & Jennifer E. Mersereau

  4. Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA

    Patrick T. Bradshaw

  5. Department of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Rebecca Cleveland

  6. Glaxo-Smith-Kline, Inc., Singapore, Singapore

    Sumitra Shantakumar

  7. Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Susan L. Teitelbuam

  8. Department of Medicine, Columbia University, New York, NY, USA

    Alfred I. Neugut

  9. Department of Epidemiology, Columbia University, New York, NY, USA

    Ruby T. Senie

Authors
  1. Jayeon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer E. Mersereau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nikhil Khankari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrick T. Bradshaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lauren E. McCullough
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rebecca Cleveland
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sumitra Shantakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Susan L. Teitelbuam
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alfred I. Neugut
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ruby T. Senie
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Marilie D. Gammon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jayeon Kim.

Ethics declarations

Conflict of interest

The authors report no financial or nonfinancial conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, J., Mersereau, J.E., Khankari, N. et al. Polycystic ovarian syndrome (PCOS), related symptoms/sequelae, and breast cancer risk in a population-based case–control study. Cancer Causes Control 27, 403–414 (2016). https://doi.org/10.1007/s10552-016-0716-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-016-0716-7

Keywords

Search

Navigation