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Objective: To estimate whether the protective effect of premenopausal bilateral oophorectomy on breast cancer risk is mitigated by estrogen therapy use after surgery.Methods: In pooled data from four population-based case-control studies spanning 1992-2007, we examined estrogen use after total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) and subsequent breast cancer risk. We identified cases of postmenopausal invasive breast cancer in women (n=10,449) aged 50-79 years from three state tumor registries and age-matched control group participants without breast cancer (n=11,787) from driver's license and Medicare lists. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and estrogen use were queried during structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with multivariable logistic regression.Results: Breast cancer risk comparisons were made relative to women who experienced natural menopause and never used hormones. Overall, breast cancer risk increased 14% among women currently using estrogens after TAHBSO (OR 1.14, 95% CI 1.03-1.28), 32% for estrogen durations less than 10 years (OR 1.32, 95% CI 1.11-1.57), and 22% for estrogen initiation within 5 years of TAHBSO (OR 1.22, 95% CI 1.09-1.37). Among women who underwent early TAHBSO (younger than 40 years), 24-30% decreases in breast cancer risk were observed among both never (OR 0.70, 95% CI 0.55-0.88) and current (OR 0.76, 95% CI 0.61-0.96) estrogen users.Conclusion: Unopposed estrogen use does not negate the reduction in breast cancer risk associated with early (younger than 40 years) bilateral oophorectomy. However, initiating estrogen therapy after TAHBSO at ages 45 and older can increase breast cancer risk and should be considered carefully. [ABSTRACT FROM AUTHOR]

Objective: To assess the presence of sociodemographic and clinical disparities in fertility-sparing treatment and assisted reproductive technology (ART) use among patients with a history of cervical, endometrial, or ovarian cancer., Methods: We conducted a population-based cohort study of patients aged 18-45 years who were diagnosed with cervical cancer (stage IA, IB), endometrial cancer (grade 1, stage IA, IB), or ovarian cancer (stage IA, IC) between January 1, 2000, and December 31, 2015, using linked data from the CCR (California Cancer Registry), the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. The primary outcome was receipt of fertility-sparing treatment , defined as surgical or medical treatment to preserve the uterus and at least one ovary. The secondary outcome was fertility preservation , defined as ART use after cancer diagnosis. Multivariable logistic regression analysis was used to estimate odds ratios and 95% CIs for the association between fertility-sparing treatment and exposures of interest: age at diagnosis, race and ethnicity, health insurance, socioeconomic status, rurality, and parity., Results: We identified 7,736 patients who were diagnosed with cervical, endometrial, or ovarian cancer with eligible histology. There were 850 (18.8%) fertility-sparing procedures among 4,521 cases of cervical cancer, 108 (7.2%) among 1,504 cases of endometrial cancer, and 741 (43.3%) among 1,711 cases of ovarian cancer. Analyses demonstrated nonuniform patterns of sociodemographic disparities by cancer type for fertility-sparing treatment, and ART. Fertility-sparing treatment was more likely among young patients, overall, and of those in racial and ethnic minority groups among survivors of cervical and ovarian cancer. Use of ART was low (n=52) and was associated with a non-Hispanic White race and ethnicity designation, being of younger age (18-35 years), and having private insurance., Conclusion: This study demonstrates that clinical and sociodemographic disparities exist in the receipt of fertility-sparing treatment and ART use among patients with a history of cervical, endometrial, or ovarian cancer., Competing Interests: Financial Disclosure Caitlin C. Murphy reports receiving payment from Freenome. Jose Alejandro Rauh-Hain reports receiving payment from the Schlesinger Group and Guidepoint. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate obstetric and neonatal outcomes of the first live birth conceived 1 or more years after breast cancer diagnosis., Methods: We performed a population-based study to compare live births between women with a history of breast cancer (case group) and matched women with no cancer history (control group). Individuals in the case and control groups were identified using linked data from the California Cancer Registry and California Office of Statewide Health Planning and Development data sets. Individuals in the case group were diagnosed with stage I-III breast cancer at age 18-45 years between January 1, 2000, and December 31, 2012, and conceived 12 or more months after breast cancer diagnosis. Individuals in the control group were covariate-matched women without a history of breast cancer who delivered during 2000-2012. The primary outcome was preterm birth at less than 37 weeks of gestation. Secondary outcomes were preterm birth at less than 32 weeks of gestation, small for gestational age (SGA), cesarean delivery, severe maternal morbidity, and neonatal morbidity. Subgroup analyses were used to assess the effect of time from initial treatment to fertilization and receipt of additional adjuvant therapy before pregnancy on outcomes of interest., Results: Of 30,021 women aged 18-45 years diagnosed with stage I-III breast cancer during 2000-2012, 553 met the study inclusion criteria. Those with a history of breast cancer and matched women in the control group had similar odds of preterm birth at less than 37 weeks of gestation (odds ratio [OR], 1.29; 95% CI 0.95-1.74), preterm birth at less than 32 weeks of gestation (OR 0.77; 95% CI 0.34-1.79), delivering an SGA neonate (less than the 5th percentile: OR 0.60; 95% CI 0.35-1.03; less than the 10th percentile: OR 0.94; 95% CI 0.68-1.30), and experiencing severe maternal morbidity (OR 1.61; 95% CI 0.74-3.50). Patients with a history of breast cancer had higher odds of undergoing cesarean delivery (OR 1.25; 95% CI 1.03-1.53); however, their offspring did not have increased odds of neonatal morbidity compared with women in the control group (OR 1.15; 95% CI 0.81-1.62)., Conclusion: Breast cancer 1 or more years before fertilization was not strongly associated with obstetric and neonatal complications., Competing Interests: Financial Disclosure Mark A. Clapp received payment from Delfina Care for serving on the advisory board (no relation to content of submitted work) and was not included in the decision to publish this. Jose Alejandro Rauh-Hain received payment from the NIH, Guidepoint, and the Schlesinger Group. He also received payment once as a speaker for J&J. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: In a previous exploratory study, we reported lower concentrations of the ovarian reserve biomarker anti-Müllerian hormone (AMH) in adulthood with prenatal farm exposure. We now examine this association as well as childhood farm exposure using enrollment data from the Sister Study, a large US cohort of women., Methods: We collected prenatal and childhood farm exposure data by questionnaire and telephone interview. However, serum AMH data were available only for a nested subset: premenopausal women ages 35-54 subsequently diagnosed with breast cancer (n = 418 cases) and their matched controls (n = 866). To avoid potential bias from restricting analyses to only premenopausal controls, we leveraged the available cohort data. We used data from both premenopausal cases and controls as well as postmenopausal women ages 35-54 (n = 3,526) (all presumed to have undetectable AMH concentrations) and applied weights to produce a sample representative of the cohort ages 35-54 (n = 17,799). The high proportion of undetectable AMH concentrations (41%) was addressed using reverse-scale Cox regression. An adjusted hazard ratio (HR) <1.0 indicates that exposed individuals had lower AMH concentrations than unexposed individuals., Results: Prenatal exposure to maternal residence or work on a farm was associated with lower AMH concentrations (HR 0.66; 95% confidence intervals [CI] = 0.48 to 0.90). Associations between childhood farm residence exposures and AMH were null or weak, except childhood contact with pesticide-treated livestock or buildings (HR 0.69; 95% CI = 0.40 to 1.2)., Conclusions: Replication of the prenatal farm exposure and lower adult AMH association raises concern that aspects of prenatal farm exposure may result in reduced adult ovarian reserve., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Detrimental effects of oxidative stress are widely recognized, but induction of apoptosis and senescence may also have benefits for cancer prevention. Recent studies suggest oxidative stress may be associated with lower breast cancer risk before menopause., Methods: We conducted a nested case-control study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of 50,884 women. Premenopausal women ages 35-54 were eligible for selection. We matched controls 2:1 to cases on age and enrollment year and were breast cancer-free at the time of the corresponding case's diagnosis. Oxidative stress was measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M) concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with multivariable conditional logistic regression., Results: After multivariable adjustment for body mass index (BMI) and other potential confounders, the OR for breast cancer comparing the >90th (≥2.94 ng/mgCr) to <25th percentile (1.01 ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and 0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were associated with lower breast cancer risk among women who were also premenopausal (353 cases, OR: 0.59, CI: 0.34, 1.0) or <46 years (82 cases, OR: 0.15, CI: 0.06, 0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among women with BMI 18.5-24.9 kg/m (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30 kg/m (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9 kg/m (OR: 0.98, CI: 0.39, 2.5, 138 cases)., Conclusions: Together with other studies, our results support a possible inverse association between oxidative stress and premenopausal breast cancer risk.

Background: To date, epidemiologic studies have not strongly supported an association between pesticide exposure and breast cancer. However, few previous studies had the ability to assess specific time periods of exposure. Studies that relied on adult serum levels of metabolites of organochlorine pesticides may not accurately reflect exposure during developmental periods. Furthermore, exposure assessment often occurred after diagnosis and key tumor characteristics, such as hormone receptor status, have rarely been available to evaluate tumor subtype-specific associations. We examined the association between pesticide exposure during childhood and adolescence and breast cancer risk in the prospective Sister Study cohort (N = 50,884 women) to assess this relation by tumor subtype., Methods: During an average 5-year follow-up, 2,134 incident invasive and in situ breast cancer diagnoses were identified. Residential and farm exposure to pesticides were self-reported at study enrollment during standardized interviews. Multivariable hazard ratios and 95% confidence intervals for breast cancer risk were calculated with Cox proportional hazards regression., Results: HRs were near null for the association between childhood/adolescent pesticide exposure and breast cancer risk overall or among ER+/PR+ invasive tumors. However, among women who were ages 0-18 before the ban of dichlordiphenyltrichloroethane in the US, exposure to fogger trucks or planes was associated with a hazard ratio = 1.3 for premenopausal breast cancer (95% confidence interval: 0.92, 1.7)., Conclusion: These findings do not support an overall association between childhood and adolescent pesticide exposure and breast cancer risk. However, modest increases in breast cancer risk were associated with acute events in a subgroup of young women.

Background: Early life risk factors for breast cancer have been investigated in relation to hormonal, nutritional, infectious, and genetic hypotheses. Recent studies have also considered potential health effects associated with exposure to environmental contaminants in breastmilk., Methods: We analyzed data from a population-based case-control study of women living in Wisconsin. Cases (n = 2016) had an incident diagnosis of invasive breast cancer in 2002-2006 reported to the statewide tumor registry. Controls (n = 1960) of similar ages were randomly selected from driver's license lists. Risk-factor information was collected during structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multivariable logistic regression., Results: In multivariable models, maternal age and birth order were not associated with breast cancer risk in the full study population. The odds ratio for breast cancer risk associated with having been breast-fed in infancy was 0.83 (95% CI = 0.72-0.96). In analyses restricted to breast-fed women, maternal age associations with breast cancer were null (P = 0.2). Increasing maternal age was negatively associated with breast cancer risk among women who were not breast-fed; the odds ratio for breast cancer associated with each 5-year increase in maternal age was 0.90 (0.82-1.00). Higher birth order was inversely associated with breast cancer risk among breast-fed women (for women with 3 or more older siblings compared with first-born women, OR = 0.58 [CI = 0.39-0.86]) but not among nonbreast-fed women (1.13 [0.81-1.57])., Conclusion: These findings suggest that early life risk factor associations for breast cancer may differ according to breast-feeding status in infancy.

Background: Although the associations with cigarette smoking have been explored extensively for invasive breast cancer, the relation to in situ cancer has not previously been examined in depth., Methods: We analyzed data from a population-based case-control study of women living in Wisconsin, Massachusetts, and New Hampshire. Eligible cases of incident breast carcinoma in situ were reported to statewide registries in 1997-2001 (n = 1878); similarly aged controls (n = 8041) were randomly selected from population lists. Smoking history and other risk factor information were collected through structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated from logistic regression models adjusting for potential confounders., Results: In multivariate models, the OR for breast carcinoma in situ among current smokers was 0.8, compared with never-smokers (95% CI = 0.7-1.0). Risk estimates increased towards the null with greater time since smoking cessation. Odds ratios were also less than 1.0 among women who initiated smoking in adolescence (OR = 0.8) or after a full-term birth (OR = 0.7), relative to women who never smoked. The reduced odds ratios associated with current smoking were strongest among women with annual screening mammograms (OR = 0.7; 95% CI = 0.6-0.9). Odds ratios were not less than 1.0 among current smokers without a recent screening mammogram (1.3; 0.9-2.0)., Conclusions: Our findings suggest an inverse association between current smoking and risk of breast carcinoma in situ among women undergoing breast cancer screening.