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  • br Because of the large age range in

    2020-08-24


    Because of the large age range in our study population, we cannot eliminate the possible influence of cohort effects. We controlled for age in our models and our analyses restricting subjects to women 50
    + years of age produced findings similar to those of the overall popula-tion. In addition, including a term for decade of birth (as a marker for co-horts) and analyses including a term for subject birth year pre- or post-1950 (as a more gross marker for cohorts) did not impact effect estimates.
    As in all case-control studies, we cannot eliminate the possibility of recall bias. However, participants were not aware of the study hypothe-ses since questions regarding breastfeeding were collected as part of a more detailed interview regarding various aspects of reproductive health and behavior. In addition, trained interviewers used structured, standardized interview questions and prompts, including life event cal-endars, which provided graphical time frames to help improve respon-dents' long-term recall. Selection bias is also a concern. The population-
    based design and frequency-matching by three-digit telephone prefix, a marker of geographical location, increased the likelihood that controls were representative of the CVT12012 from which the cases arose. How-ever, we cannot exclude the possibility that controls who chose to par-ticipate in HOPE differed in important exposure or confounding factors from potential controls who did not, thereby over- or under-estimating the true association. The lack of information on lactational amenorrhea, exclusive breastfeeding, and effects of breastfeeding on maternal an-thropometry are also limitations. Our inability to control for total estro-gen exposure prior to diagnosis and cumulative months of pregnancy in our models are additional limitations. Finally, because more than 97% of controls and 94% of cases were white women from western PA, eastern
    OH, and southwestern NY, the generalizability of our findings to other races or ethnicities cannot be assumed.
    Approximately 82% of U.S. women give birth to at least one child [33]. The American Academy of Pediatrics (AAP) recommends exclusive breastfeeding for 6 months and continued breastfeeding for at least
    1 year [34]. The American College of Obstetricians and Gynecologists
    (ACOG) affirms this recommendation [35]. Despite these recommenda-tions, b20% of infants are exclusively breastfed for 6 months, b50% are breastfed for 6 months, and only 27% are still breastfeeding at 1 year [36]. Our findings suggest that improving compliance with AAP and ACOG recommendations could impact EOC risk in the vast majority of U.S. women.
    In conclusion, interventions to encourage and support women in breastfeeding may help reduce EOC risk. Breastfeeding any offspring for as little as 3 months is associated with a statistically significant pro-tective effect. Thus, encouraging women to breastfeed even if only dur-ing a maternity leave may provide benefit. Notably, spindle apparatus association persists for more than 30 years and is similar to the magnitude and du-ration of protection associated with oral contraceptive use and bearing children, the two well-established EOC protective factors. Studies exam-ining the biological bases for the observations presented in this and other work examining the EOC-breastfeeding link can potentially shed light on EOC etiology and open pathways to identifying new prevention modalities, which are critical in overcoming this highly fatal malignancy.
    Funding
    This work supported by National Cancer Institute (K07-CA80668, R01CA095023); the Department of Defense (DAMD17-02-1-0669); and the University of Pittsburgh School of Medicine Dean's Faculty Ad-vancement Fund.
    Conflict of interest
    The authors report no conflicts of interest.
    Author contributions
    Francesmary Modugno: Contributed to the conception and design of the study, analysis, and interpretation of data, drafted the article, and approved the final version submitted for publication.
    Sharon L. Goughnour: Contributed to the analysis and interpretation of data, revision of the article, and approved the final version submitted for publication.
    Danielle Wallack: Contributed to the analysis and interpretation of data, revision of the article, and approved the final version submitted for publication.
    Robert P. Edwards: Contributed to the collection of study data, revi-sion of the article, and approved the final version submitted for publication.
    Kunle Odunsi: Contributed to the collection of study data, revision of the article, and approved the final version submitted for publication.