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.
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