The Impact of Hormonal Contraceptives on Breast Cancer Pathology
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This retrospective case series study, using data obtained through questionnaires and histopathological diagnoses from 656 patients enrolled in the Department of Defense (DoD) Clinical Breast Care Project (CBCP), evaluated associations between hormonal contraceptive use and breast cancer pathology including benign breast pathologies. Three combination hormonal contraceptive agents (COCs) Lo Ovral (LO), Ortho Novum (ON), and Ortho Tri-Cyclen (OTC) were evaluated as they represented the most commonly used hormonal contraceptives in our cohort. The results of this study suggest that the ever use of LO + ON + OTC does not influence the overall incidence of benign breast condition or malignant disease compared to other COCs; however, patients that have used OTC had an association with a diagnosis of benign or luminal A pathologies whereas ON was associated with a diagnosis of benign and DCIS; LO showed no association with any diagnosis—benign or malignant. Patients that have used LO or ON were more likely to be diagnosed with breast cancer at age ≥ 40 years whereas patients that had ever used OTC were likely to be diagnosed before the age of 40. Caucasians were less likely to have used OTC and more likely to have used ON; however, use of either hormonal agent positively correlated with premenopausal status at diagnosis and having a benign condition. Age at diagnosis, ethnicity, BMI, family history, menstruation status, and duration of use were all independent predictors of different histopathological subtypes. We conclude that patient-specific variables should be considered when deciding on which type of hormonal contraceptive to use to minimize the risk of developing breast cancer or a breast-related pathology.
We thank all patients for their participation in the CBCP. We thank Jianfang Liu, Nicholas Costantino, and Brad Mosteller for their guidance on statistical analysis and Deepika Rao and Khalid Kamal especially for their help on the multivariate analyses.
Designed and researched topic, drafted IRB requests at Duquesne, evaluated and extracted data from CBCP query searches, and analyzed data: JAD, JLG. Drafted and wrote the manuscript: JAD, JLG, and PAW-E. Contributed to statistical analysis, specifically multinomial logistical regression: SM. Participated in CBCP query searches: BD. Marc Purazo: preliminary statistics. Critically reviewed the manuscript and provided input: SS, JI, HH, PAW-E, JC, CDS, AD. Supervisors for this study: SS, PAW-E.
Compliance with Ethical Standards
Appropriate IRB approval was obtained for the Clinical Breast Care Project (CBCP) from the study sites at the Walter Reed National Military Medical Center and Windber Research Institute/Windber Medical Center. IRB approval was also obtained from Duquesne University School of Pharmacy and Division of Pharmaceutical, Administrative and Social Sciences.
The identification of specific products, scientific instrumentation, or organization is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the authors, Department of Defense, or any component agency. The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or US Government.
- 1.American Cancer Society. Cancer facts & figures 2016. 2016. Journal. http://www.cancer.org/acs/groups/content/@research/documents/document/acspc047079.pdf
- 2.Centers for Disease Control and Prevention: Cancer among women. 2015. Journal . http://www.cdc.gov/cancer/dcpc/data/women.htm
- 7.Dorgan JF, Klifa C, Deshmukh S, Egleston BL, Shepherd JA, Kwiterovich PO, van Horn L, Snetselaar LG, Stevens VJ, Robson AM, Lasser NL, Hylton NM (2013) Menstrual and reproductive characteristics and breast density in young women. Cancer Causes Control 24(11):1973–1983CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Lu, Yani, Ma, Huiyan, Malone, Kathleen E, Norman, Sandra A, et al. (2011) Oral contraceptive use and survival in women with invasive breast cancer. Cancer Epidemiology and Prevention BiomarkersGoogle Scholar
- 10.Moorman PG, Havrilesky LJ, Gierisch JM, Coeytaux RR, Lowery WJ, Peragallo Urrutia R, Dinan M, McBroom AJ, Hasselblad V, Sanders GD, Myers ER (2013) Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. J Clin Oncol 31(33):4188–4198CrossRefPubMedGoogle Scholar
- 14.World contraceptive patterns 2013. New York: United Nations, Department of Economic and Social Affairs Journal .(http://www.un.org/en/development/desa/population/publications/family/contraceptive-wallchart-2013.shtml)
- 15.Current contraceptive status among women aged 15–44: United States, 2011–2013. 2014. Journal (Issue)Google Scholar
- 23.Marchbanks PA, Curtis KM, Mandel MG, Wilson HG, Jeng G, Folger SG, McDonald JA, Daling JR, Bernstein L, Malone KE, Wingo PA, Simon MS, Norman SA, Strom BL, Ursin G, Weiss LK, Burkman RT, Spirtas R (2012) Oral contraceptive formulation and risk of breast cancer. Contraception 85(4):342–350CrossRefPubMedGoogle Scholar
- 24.Kumle M, Weiderpass E, Braaten T, Persson I et al (2002) Use of oral contraceptives and breast cancer risk. Cancer Epidemiology and Prevention Biomarkers 11(11):1375–1381Google Scholar
- 35.Hunter, David J, Colditz, Graham A, Hankinson, Susan E, Malspeis, Susan, et al., 2010, Oral contraceptive use and breast cancer: a prospective study of young women. Cancer Epidemiology and Prevention Biomarkers: p. cebp. 0747.2010Google Scholar
- 38.Lanfranchi, Angela (2014) Normal breast physiology: the reasons hormonal contraceptives and induced abortion increase breast-cancer risk. Issues L. & Med. 29: p. 135Google Scholar
- 39.North American Menopause Society: The 2012 hormone therapy position statement of the North American Menopause Society. 2012. Journal. 19: p. 257Google Scholar
- 40.Pup D, Lino B, Massimiliano DF, Raffaele C, Carla, et al. (2014) Nomegestrol acetate/estradiol hormonal oral contraceptive and breast cancer risk. Anti-Cancer Drugs 25(7):745–750Google Scholar
- 43.Fournier A, Bernio F, Clavel-Chapelon F (2008) Unequal risks for BC associated with different hormone replacement therapies: results from the E3N cohort study. BC Res Treat 107(1):101–111Google Scholar
- 45.Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, Lane DS, Hubbell FA, Assaf AR, Sarto GE, Schenken RS, Yasmeen S, Lessin L, Chlebowski RT (2006) Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 295(14):1647–1657CrossRefPubMedGoogle Scholar
- 47.Beaber, Elisabeth F, Malone, Kathleen E, Tang, Mei-Tzu Chen, Barlow, William E, et al. (2014) Oral contraceptives and breast cancer risk overall and by molecular subtype among young women. Cancer Epidemiology and Prevention BiomarkersGoogle Scholar
- 50.Phipps AI, Chlebowski RT, Prentice R, McTiernan A, Wactawski-Wende J, Kuller LH, Adams-Campbell LL, Lane D, Stefanick ML, Vitolins M, Kabat GC, Rohan TE, Li CI (2011) Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer. J Natl Cancer Inst 103(6):470–477CrossRefPubMedPubMedCentralGoogle Scholar
- 51.Ritte R, Tikk K, Lukanova A, Tjønneland A, Olsen A, Overvad K, Dossus L, Fournier A, Clavel-Chapelon F, Grote V, Boeing H, Aleksandrova K, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Berrino F, Mattiello A, Tumino R, Sacerdote C, Quirós JR, Buckland G, Molina-Montes E, Chirlaque MD, Ardanaz E, Amiano P, Bueno-de-Mesquita HB, van Gils CH, Peeters PHM, Wareham N, Khaw KT, Key TJ, Travis RC, Weiderpass E, Dumeaux V, Lund E, Sund M, Andersson A, Romieu I, Rinaldi S, Vineis P, Merritt MA, Riboli E, Kaaks R (2013) Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study. BMC Cancer 13(1):584CrossRefPubMedPubMedCentralGoogle Scholar
- 52.Work ME, John EM, Andrulis IL, Knight JA, Liao Y, Mulligan AM, Southey MC, Giles GG, Dite GS, Apicella C, Hibshoosh H, Hopper JL, Terry MB (2014) Reproductive risk factors and oestrogen/progesterone receptor-negative breast cancer in the Breast Cancer Family Registry. Br J Cancer 110(5):1367–1377CrossRefPubMedPubMedCentralGoogle Scholar
- 53.Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn H-J, Panel members (2011) Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22(8):1736–1747CrossRefPubMedPubMedCentralGoogle Scholar
- 54.Lancet (1996) Collaborative Group on Hormonal Factors in Breast Cancer. 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. 347: p. 1713–27Google Scholar
- 57.Janssen Pharmaceutical, Inc, 2015, Ortho Novum and Modicon (norethindrone and ethinyl estradiol) package insertGoogle Scholar
- 62.Ma H, Wang Y, Sullivan-Halley J, Weiss L, Marchbanks PA, Spirtas R, Ursin G, Burkman RT, Simon MS, Malone KE, Strom BL, McDonald JA, Press MF, Bernstein L (2010) Use of four biomarkers to evaluate the risk of breast cancer subtypes in the women’s contraceptive and reproductive experiences study. Cancer Res 70:575–587CrossRefPubMedPubMedCentralGoogle Scholar