br Results br Cases were more likely to be
Cases were more likely to be non-white and less educated, as well as to have an increased family history of breast or ovarian cancer (Table 1). They were less likely to have used OCs, borne children, or had a tubal ligation.
Longer total breastfeeding duration across all breastfeeding episodes was also associated with increased protection (OR = 0.75 and 0.62 for less than and greater than 1-year total duration, respectively; Table 3). An average duration of 3 months per breastfeeding episode was associ-ated with statistically significant risk BODIPY 505/515 (OR = 0.73, 95%CI = 0.58–0.93). Longer average duration per breastfeeding episode ap-peared more protective although the difference was not statistically sig-nificant (OR = 0.73 and OR = 0.67 for 1–3 and 4 or more months average per episode, respectively). Longer duration for both the first (OR = 0.75 and OR = 0.66 for 1–3 and 4 or more months, respectively) and last (OR = 0.75 and OR = 0.65) breastfeeding episodes was associ-ated with statistically significant reduced risk.
More recent breastfeeding was associated with a statistically signif-icant 44% reduction in EOC risk (OR = 0.56, 95%CI = 0.32–0.95 for time since last breastfeeding within the last 10 years, Table 4). Although the association with reduced risk decreased over time, the effect persisted for more than 30 years after the last breastfeeding episode (OR = 0.69, 95%CI = 0.53–0.88).
Results were similar when examining women over 50 (Supplemen-tal Tables S1a–S1c), when restricting cases to women with invasive dis-ease (Supplemental Tables S2a–S2c), and when restricting cases to high grade serous histotype (Supplemental Tables S3a–S3c).
In the HOPE Study, breastfeeding was associated with a 30% reduc-tion in EOC risk. While this association decreased over time, it persisted
Characteristics of HOPE Study participants, 2003–2008.
Oral contraceptive use
Duration of oral contraceptive use, years
Number of full births
Hormone replacement therapy use
Family history of breast or ovarian cancer
History of endometriosis
for more than 30 years. Breastfeeding for as little as three months was associated with statistically significant reduction in risk. Longer breastfeeding duration, greater number of breastfeeding episodes, and earlier age at first breastfeeding were each associated with increased protection.
Our results are consistent with the majority of studies that have shown an inverse association between ever breastfeeding and EOC
Association of breastfeeding patterns with epithelial ovarian cancer, the HOPE Study 2003–2008.
Odds ratio 95% confidence interval Adjusted odds ratioa 95% confidence interval
a Separate models and analyses for each factor. Each model adjusted for age, race, education, duration of oral contraceptive use, and number of pregnancies.
risk. A meta-analysis of 35 studies  reported a summary relative risk of 0.76, which is similar in magnitude to the point estimate (0.70) we report. Data examining the effect of duration are less consistent. Some studies have reported a decrease in risk with increasing total or average duration, whereas others report no trend with increasing duration or no additional benefit from breastfeeding beyond a certain number of months [17,20–23]. Despite reporting inter-study heterogeneity, a re-cent meta-analysis of 40 studies  found a statistically significant point estimate of 0.64 (95%CI 0.56–0.73) for total breastfeeding dura-tion of greater than one year, which is similar to the protective associa-tion we observed (OR = 0.62).
Only one previous study explored factors related to age and timing of breastfeeding, with no effects noted . This stands in contrast to our findings in which an earlier age at first breastfeeding episode was associated with a statistically significant reduction in EOC risk. That pro-tective association was evident but decreased with increasing age at first breastfeeding episode. We further found that while more recent breastfeeding was associated with greater protection, the reduced risk associated with breastfeeding persisted for more than 30 years.
A differential effect of age and recency of breastfeeding as well as a persistent effect of exposure is similar to what is observed with OC
use . Specifically, as we found for breastfeeding, earlier age at first OC use is associated with increased protection against EOC, with the magnitude of the protective effect decreasing with increasing age at first use . More recent OC use is also associated with greater protec-tion, and while the magnitude of that association decreases with time, it remains for more than 30 years after cessation . The impact of age and timing of childbearing on EOC risk is less clear. Recent full-term birth has been associated with a greater decrease in risk in most studies. In contrast to our findings of greater EOC protection associated with an earlier age at first breastfeeding, a later age at last birth may provide the greatest protection. In particular, age at last pregnancy has been found to be more critical to EOC risk reduction than number of pregnancies [8,25,26]. This observation is often attributed to the apoptotic effect of high progesterone levels in pregnancy potentially “clearing” premalig-nant ovarian epithelial cells .