br Conclusions Breastfeeding for as
Conclusions. Breastfeeding for as few as 3 months is associated with reduced EOC risk. Although this associa-tion decreases over time, it persists for more than 30 years. Longer cumulative duration, increasing number of breastfeeding episodes, and earlier age at first breastfeeding episode are each associated with increased benefit.
☆ An early version of this work was presented at the AACR Special Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment, Pittsburgh, PA. October 2017. Corresponding author at: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Hospital of UPMC, Suite 2130, 300 Halket Street, Pittsburgh, PA 15213, USA.
E-mail addresses: [email protected], [email protected] (F. Modugno), [email protected] (S.L. Goughnour), [email protected] (R.P. Edwards), [email protected] (K. Odunsi), [email protected] (J.L. Kelley), [email protected] (K. Moysich), [email protected] (R.B. Ness), [email protected] (M.M. Brooks).
Ovarian cancer is the most lethal gynecologic malignancy . In 2018, approximately 22,240 women in the United States will be diag-nosed with the disease and over 14,000 women will die from it . When diagnosed at an early stage, 5-year survival is more than 90% . Unfortunately, more than 70% of cases are diagnosed at a late stage, when 5-year survival is b30% . This high fatality rate, coupled with the lack of a screening test for early detection , makes it critical to identify modifiable risk factors to reduce disease burden .
Epithelial ovarian cancer (EOC), which accounts for 90% of ovarian cancers , is believed to arise from the ovary or fallopian tubes . Oral contraceptive (OC) use and bearing children have consistently been shown to reduce the risk of EOC. Each factor is associated with about a 30% decrease in risk, with greater protection conferred by in-creasing duration of OC use  and greater parity . The benefits of OCs persist for more than 30 years, although the Ruxolitinib in risk de-creases as time since last use increases . A similarly durable, but somewhat attenuated protective effect remains after the last live birth . OC use and child bearing are hypothesized to reduce risk via several ways, although the exact mechanisms remain unknown. Both factors suppress ovulation, thereby reducing repetitive trauma to ovarian sur-face or tubal epithelium that can result in aberrant repair and subse-quent malignant transformation [9,10]. Both factors also reduce gonadotropin levels, which result in lower estrogen levels. Estrogen can increase ovarian surface and tubal epithelial proliferation, poten-tially leading to malignant transformation [11,12]. Finally, pregnancy and OCs alter endogenous estrogen and progesterone levels, two hor-mones that have been implicated in EOC risk .
Breastfeeding also suppresses ovulation, reduces gonadotropin levels, and alters the hormonal milieu ; thus, it may reduce EOC risk. Most case-control studies report a protective association with ever breastfeeding [7,15,16]. Some also report an increasing reduction in risk associated with increasing cumulative duration [7,15,16]. In con-trast, the handful of cohort studies examining breastfeeding found a weak, statistically non-significant reduction in risk , except for the Nurses' Health Study, which reported a statistically significant protec-tive effect only after 18 cumulative months of breastfeeding .
Beyond the association with ever breastfeeding and breastfeeding duration, there has been little exploration of factors that may influence the breastfeeding-EOC association. Questions remain about the effects of age at breastfeeding, time since breastfeeding, and influence of birth order among offspring breastfed. We used data from a large, population-based case-control study to examine these questions.
2. Material and methods
Details of the Hormones and Ovarian cancer PrEdiction (HOPE) Study are described elsewhere . Cases were women diagnosed with incident, histologically-confirmed epithelial ovarian, peritoneal, or fallopian tube cancer from February 2003 to November 2008 in the contiguous regions of western Pennsylvania, eastern Ohio, and south-western New York. Eligible participants were at least 25 years old, resid-ing within the catchment region, and within 9 months of diagnosis at the time of interview. Women were identified through a network of hospital and physician practices using pathology records, physician practice records, and hospital cancer registries. Among 2878 potentially eligible cases, 1608 were excluded due to ineligibility (time since diag-nosis more than 9 months, residence outside catchment region, prior di-agnosis of ovarian cancer, inability to speak English, deceased). Of the 1270 remaining eligible cases, 902 (71%) consented to study participation.