Mandy Goldberg

Pubertal Timing and Incident Ovarian Cancer in the Sister Study Cohort

Abstract Background: Pubertal milestones such as menarche (first period) and thelarche (onset of breast development) are markers of hormonal changes that may be relevant to the hormonal etiology of ovarian cancer. Prior studies of the association between age at menarche and ovarian cancer risk have been inconsistent, whereas age at thelarche has not been examined in relation to ovarian cancer incidence. Methods: With data from 40,809 women in the Sister Study, we used multivariable-adjusted Cox proportional hazards regression to estimate HRs and 95% confidence intervals (CI) for associations of self-reported ages at thelarche and menarche with incident ovarian cancer, both overall and by histotype. Results: During a median follow-up of 13.3 years, 291 women reported a diagnosis of ovarian cancer. Ages at thelarche (HR = 0.94; 95% CI, 0.87–1.02 per 1-year older) and menarche (HR = 0.99; 95% CI, 0.91–1.07 per 1-year older) were not associated with ovarian cancer overall. Although imprecise, HRs suggested a possible inverse association of ages at thelarche (HR = 0.71; 95% CI, 0.48–1.04) and menarche (HR = 0.79; 95% CI, 0.59–1.04) with the incidence of clear-cell tumors. Conclusions: Ages at thelarche and menarche were not associated with ovarian cancer incidence overall. Impact: Though our results do not provide clear evidence of associations of pubertal timing with ovarian cancer incidence, possible associations of earlier thelarche and menarche with increased incidence of ovarian clear-cell carcinoma may warrant further investigation, especially considering secular trends toward earlier thelarche.

Pubertal timing and incident uterine cancer in the Sister Study cohort

Abstract Younger age at menarche is an established uterine cancer risk factor. Age at onset of breast development (thelarche), the earliest marker of pubertal “unopposed” estrogen exposure, may also be relevant to uterine cancer risk, particularly considering rapid declines in age at thelarche over time in parallel with increasing uterine cancer incidence rates. Using data from 34,152 participants with an intact uterus when they enrolled in the US Sister Study cohort (2003–2009; ages 35–74 years), we examined associations of self‐reported ages at thelarche and menarche with incident uterine cancer using multivariable‐adjusted Cox proportional hazards regression. We stratified by birth cohort, race, weight relative to peers in childhood, and body mass index (BMI) at enrollment to explore potential effect measure modification and tested for statistical heterogeneity across strata. During follow‐up (median = 13.3 years), 445 women reported an incident uterine cancer diagnosis. Ages at thelarche (hazard ratio [HR] per 1‐year older: 0.91, 95% confidence interval [CI]: 0.85–0.97) and menarche (HR per 1‐year older: 0.90, 95% CI: 0.84–0.96) were inversely associated with uterine cancer incidence. Associations were similar in non‐Hispanic Black and White women and did not vary by relative childhood weight or BMI in adulthood. Inverse associations of thelarche and menarche were limited to women born in 1950 or later ( p ‐het <.05). These findings suggest that younger ages at thelarche and menarche, markers of earlier and potentially prolonged exposure to estrogen in the absence of progesterone during puberty, may enhance susceptibility to uterine carcinogenesis.

Use of personal care product mixtures and incident hormone-sensitive cancers in the Sister Study: A U.S.-wide prospective cohort

Personal care products (PCPs), a source of endocrine-disrupting chemical exposure, may be associated with the risk of hormone-sensitive cancers. Few studies have investigated associations for PCP use with the incidence of hormone-sensitive cancers or considered the joint effect of multiple correlated PCPs. We examined associations between frequently used, or "everyday", PCPs and incident cancers of the breast, ovary, and uterus with a fucus on the joint effect of multiple product exposure. Sister Study participants (n=49 899) self-reported frequency of use in the year before enrollment (2003-2009) for 41 PCPs. Using five-level frequency categories based on questionnaire options, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the associations between multiple PCP use and incident breast, ovarian, and uterine cancer using quantile-based g-computation with Cox proportional hazards regression as the underlying model. Multiple PCP use was examined using groupings (beauty, hygiene, and skincare products) determined by both a priori knowledge and Spearman correlation coefficients for co-occurring product use. Associations between individual PCPs and the three cancers were also examined using Cox proportional hazards models coupling with Benjamini-Hochberg procedure for multiple comparisons. Over an average of 11.6 years, 4 226 breast, 277 ovarian, and 403 uterine cancer cases were identified. Positive associations were observed between the hygiene mixture and ovarian cancer (HR=1.35, 95%CI=1.00, 1.83) and the beauty mixture with postmenopausal breast cancer (HR=1.08, 95%CI=1.01, 1.16). Additionally, we observed an inverse association between the skincare mixture and breast cancer (HR=0.91, 95%CI=0.83, 0.99). No significant associations were observed for individual products after corrected for multiple comparison. Findings from this multi-product, joint-effect approach contribute to the growing body of evidence for associations between PCPs and breast cancer and provides novel information on ovarian and uterine cancer.