title: Polycystic ovarian syndrome (PCOS), related symptoms/sequelae, and breast cancer risk in a population-based case-control study.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, 596 Nonhyun-ro, Gangnam-gu, Seoul, 135-907, South Korea. dr.jykim76@gmail.com.|Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. dr.jykim76@gmail.com.|Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA. dr.jykim76@gmail.com.
authors.forename: Jayeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Mersereau
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Khankari
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Bradshaw
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: McCullough
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cleveland
authors.affiliation: Glaxo-Smith-Kline, Inc., Singapore, Singapore.
authors.forename: Sumitra
authors.initials: S
authors.lastname: Shantakumar
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbuam
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY, USA.
authors.forename: Ruby T
authors.initials: RT
authors.lastname: Senie
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000453:epidemiology*; D012307:Risk Factors
keywords: Breast cancer; Oral contraceptives; Polycystic ovarian syndrome; Premenopausal