Ana Babic1,2, Naoko Sasamoto1, Bernard A Rosner3,4, Shelley S Tworoger5, Susan J Jordan6,7, Harvey A Risch8, Holly R Harris9,10, Mary Anne Rossing9,10, Jennifer A Doherty11, Renée T Fortner12, Jenny Chang-Claude12,13, Marc T Goodman14, Pamela J Thompson15, Kirsten B Moysich16, Roberta B Ness17, Susanne K Kjaer18,19, Allan Jensen18, Joellen M Schildkraut20, Linda J Titus21, Daniel W Cramer1, Elisa V Bandera22, Bo Qin22, Weiva Sieh23, Valerie McGuire24, Rebecca Sutphen25, Celeste L Pearce26, Anna H Wu27, Malcolm Pike28, Penelope M Webb6, Francesmary Modugno29, Kathryn L Terry1,30. 1. Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 3. Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 4. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. 5. Division of Population Sciences, Moffitt Cancer Center, Tampa, Florida. 6. Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 7. The University of Queensland School of Public Health, Brisbane, Queensland, Australia. 8. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. 9. Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. 10. Department of Epidemiology, School of Public Health, University of Washington, Seattle. 11. Department of Population Health Science, Huntsman Cancer Institute, University of Utah, Salt Lake City. 12. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 13. Cancer Epidemiology Group, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 14. Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California. 15. Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. 16. Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 17. School of Public Health, University of Texas Health Science Center at Houston, Houston. 18. Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. 19. Rigshospitalet, Department of Gynaecology, University of Copenhagen, Copenhagen, Denmark. 20. Department of Epidemiology, Rollins School of Public Health, Atlanta, Georgia. 21. Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire. 22. Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick. 23. Department of Population Health Science and Policy, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York. 24. Department of Epidemiology & Population Health, Stanford University School of Medicine, Stanford, California. 25. Epidemiology Center, College of Medicine, University of South Florida, Tampa. 26. Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor. 27. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles. 28. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. 29. Women's Cancer Research Center, Magee-Womens Research Institute, Hillman Cancer Center, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 30. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Abstract
Importance: Breastfeeding has been associated with a reduced risk of epithelial ovarian cancer in multiple studies, but others showed no association. Whether risk reduction extends beyond that provided by pregnancy alone or differs by histotype is unclear. Furthermore, the observed associations between duration and timing of breastfeeding with ovarian cancer risk have been inconsistent. Objective: To determine the association between breastfeeding (ie, ever/never, duration, timing) and ovarian cancer risk overall and by histotype. Design, Setting, and Participants: A pooled analysis of parous women with ovarian cancer and controls from 13 case-control studies participating in the Ovarian Cancer Association Consortium was performed. Odds ratios (ORs) and 95% CIs of the overall association were calculated using multivariable logistic regression and polytomous logistic regression for histotype-specific associations. All data were collected from individual sites from November 1989 to December 2009, and analysis took place from September 2017 to July 2019. Exposures: Data on breastfeeding history, including duration per child breastfed, age at first and last breastfeeding, and years since last breastfeeding were collected by questionnaire or interview and was harmonized across studies. Main Outcomes and Measures: Diagnosis of epithelial ovarian cancer. Results: A total of 9973 women with ovarian cancer (mean [SD] age, 57.4 [11.1] years) and 13 843 controls (mean [SD] age, 56.4 [11.7] years) were included. Breastfeeding was associated with a 24% lower risk of invasive ovarian cancer (odds ratio [OR], 0.76; 95% CI, 0.71-0.80). Independent of parity, ever having breastfed was associated with reduction in risk of all invasive ovarian cancers, particularly high-grade serous and endometrioid cancers. For a single breastfeeding episode, mean breastfeeding duration of 1 to 3 months was associated with 18% lower risk (OR, 0.82; 95% CI, 0.76-0.88), and breastfeeding for 12 or more months was associated with a 34% lower risk (OR, 0.66; 95% CI, 0.58-0.75). More recent breastfeeding was associated with a reduction in risk (OR, 0.56; 95% CI, 0.47-0.66 for <10 years) that persisted for decades (OR, 0.83; 95% CI, 0.77-0.90 for ≥30 years; P for trend = .02). Conclusions and Relevance: Breastfeeding is associated with a significant decrease in risk of ovarian cancer overall and for the high-grade serous subtype, the most lethal type of ovarian cancer. The findings suggest that breastfeeding is a potentially modifiable factor that may lower risk of ovarian cancer independent of pregnancy alone.
Importance: Breastfeeding has been associated with a reduced risk of epithelial ovarian cancer in multiple studies, but others showed no association. Whether risk reduction extends beyond that provided by pregnancy alone or differs by histotype is unclear. Furthermore, the observed associations between duration and timing of breastfeeding with ovarian cancer risk have been inconsistent. Objective: To determine the association between breastfeeding (ie, ever/never, duration, timing) and ovarian cancer risk overall and by histotype. Design, Setting, and Participants: A pooled analysis of parous women with ovarian cancer and controls from 13 case-control studies participating in the Ovarian Cancer Association Consortium was performed. Odds ratios (ORs) and 95% CIs of the overall association were calculated using multivariable logistic regression and polytomous logistic regression for histotype-specific associations. All data were collected from individual sites from November 1989 to December 2009, and analysis took place from September 2017 to July 2019. Exposures: Data on breastfeeding history, including duration per child breastfed, age at first and last breastfeeding, and years since last breastfeeding were collected by questionnaire or interview and was harmonized across studies. Main Outcomes and Measures: Diagnosis of epithelial ovarian cancer. Results: A total of 9973 women with ovarian cancer (mean [SD] age, 57.4 [11.1] years) and 13 843 controls (mean [SD] age, 56.4 [11.7] years) were included. Breastfeeding was associated with a 24% lower risk of invasive ovarian cancer (odds ratio [OR], 0.76; 95% CI, 0.71-0.80). Independent of parity, ever having breastfed was associated with reduction in risk of all invasive ovarian cancers, particularly high-grade serous and endometrioid cancers. For a single breastfeeding episode, mean breastfeeding duration of 1 to 3 months was associated with 18% lower risk (OR, 0.82; 95% CI, 0.76-0.88), and breastfeeding for 12 or more months was associated with a 34% lower risk (OR, 0.66; 95% CI, 0.58-0.75). More recent breastfeeding was associated with a reduction in risk (OR, 0.56; 95% CI, 0.47-0.66 for <10 years) that persisted for decades (OR, 0.83; 95% CI, 0.77-0.90 for ≥30 years; P for trend = .02). Conclusions and Relevance: Breastfeeding is associated with a significant decrease in risk of ovarian cancer overall and for the high-grade serous subtype, the most lethal type of ovarian cancer. The findings suggest that breastfeeding is a potentially modifiable factor that may lower risk of ovarian cancer independent of pregnancy alone.
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