Physical activity during adolescence and early adulthood and breast cancer risk before age 40 years.

BACKGROUND: Breast cancer (BC) incidence is increasing in women under age 40 years, underscoring the need for research on BC risk factors for younger women. METHODS: We used data from an international family cohort (n=26,348) to examine whether recreational physical activity (RPA) during adolescence and early adulthood are associated with BC risk before age 40. The cohort includes 2,502 women diagnosed with BC before age 40, including 2,408 diagnosed before study enrollment (68% within 5 years of enrollment). Women reported their average hours-per-week of moderate and strenuous RPA during adolescence (12-17 years) and early adulthood (25-34 years), which were converted to total age-adjusted metabolic equivalents-per-week and categorized into quartiles. We conducted attained age analyses until age 40 (follow-up time began at age 18) using Cox proportional hazards regression models adjusted for study center, race and ethnicity, and education. RESULTS: Being in the highest versus lowest quartile of RPA during adolescence and early adulthood were respectively associated with 12% [HR (95% CI): 0.88 (0.78, 0.98)] and 16% [HR (95% CI): 0.84 (0.74, 0.95) lower BC risks before age 40. Being in the highest quartile of RPA during both adolescence and early adulthood (Pearson correlation=0.52) versus neither timepoint was associated with a 22% lower risk [HR (95% CI): 0.78 (0.68, 0.89)]. CONCLUSIONS: Findings suggest that RPA during adolescence and early adulthood may lower BC risk before age 40. IMPACT: Policies promoting physical activity during adolescence and early adulthood may be important for reducing the growing burden of breast cancer in younger women.

Trends in the Care of Locally Advanced Pancreatic Cancer in the Modern Era of Chemotherapy.

INTRODUCTION: Current guidelines for treatment for locally advanced pancreatic cancer recommend chemotherapy ± radiation, or radiation alone when multimodal therapy is contraindicated. In a subset of patients, guideline-recommended treatment (GRT) achieves sufficient response to qualify for potentially curative resection. This study evaluated trends in treatment utilization and aimed to identify barriers to GRT. METHODS: Patients with clinical T4M0 disease in the National Cancer Database from 2010 to 2017 were included. Potential predictors were assessed by relative risk regression with Poisson distribution and compared by log-link function. RESULTS: In total, 28 056 patients met the criteria. Among 17 059 (67.67%) patients treated primarily with chemotherapy, 41.19% also had radiation and 8.89% went onto resection. Many received no cancer-directed treatment or failed to receive GRT. Another 710 patients had radiation (±surgery) without chemotherapy despite few contraindications to chemotherapy. Over time, patients were more likely to undergo resection after chemotherapy (aRR = 1.58; p < 0.0001) and less likely to have chemoradiation (aRR = 0.78; p < 0.0001) or go untreated (aRR = 0.90; p < 0.0001). Socioeconomic factors (race, education, income, and insurance status) affected the likelihood of receiving chemotherapy and surgery. Median overall survival (OS) was significantly improved for patients treated with chemotherapy and particularly in those patients who went on to receive RT or undergo surgical resection. OS was also longer for patients treated at high-volume academic centers. Patients insured by Medicaid, Medicare, or those without insurance had worse OS. CONCLUSIONS: Despite improvement over time, many patients go untreated. Clinical factors were influential, but the impact of vulnerable social standing suggests persistent inequity in access to care.

Pregnancy-Related Factors and Breast Cancer Risk for Women Across a Range of Familial Risk.

Importance: Few studies have investigated whether the associations between pregnancy-related factors and breast cancer (BC) risk differ by underlying BC susceptibility. Evidence regarding variation in BC risk is critical to understanding BC causes and for developing effective risk-based screening guidelines. Objective: To examine the association between pregnancy-related factors and BC risk, including modification by a of BC where scores are based on age and BC family history. Design, Setting, and Participants: This cohort study included participants from the prospective Family Study Cohort (ProF-SC), which includes the 6 sites of the Breast Cancer Family Registry (US, Canada, and Australia) and the Kathleen Cuningham Foundation Consortium (Australia). Analyses were performed in a cohort of women enrolled from 1992 to 2011 without any personal history of BC who were followed up through 2017 with a median (range) follow-up of 10 (1-23) years. Data were analyzed from March 1992 to March 2017. Exposures: Parity, number of full-term pregnancies (FTP), age at first FTP, years since last FTP, and breastfeeding. Main Outcomes and Measures: BC diagnoses were obtained through self-report or report by a first-degree relative and confirmed through pathology and data linkages. Cox proportional hazards regression models estimated hazard ratios (HR) and 95% CIs for each exposure, examining modification by PARS of BC. Differences were assessed by estrogen receptor (ER) subtype. Results: The study included 17 274 women (mean [SD] age, 46.7 [15.1] years; 791 African American or Black participants [4.6%], 1399 Hispanic or Latinx participants [8.2%], and 13 790 White participants [80.7%]) with 943 prospectively ascertained BC cases. Compared with nulliparous women, BC risk was higher after a recent pregnancy for those women with higher PARS (last FTP 0-5 years HR for interaction, 1.53; 95% CI, 1.13-2.07; P for interaction < .001). Associations between other exposures were limited to ER-negative disease. ER-negative BC was positively associated with increasing PARS and increasing years since last FTP (P for interaction < .001) with higher risk for recent pregnancy vs nulliparous women (last FTP 0-5 years HR for interaction, 1.54; 95% CI, 1.03-2.31). ER-negative BC was positively associated with increasing PARS and being aged 20 years or older vs less than 20 years at first FTP (P for interaction = .002) and inversely associated with multiparity vs nulliparity (P for interaction = .01). Conclusions and Relevance: In this cohort study of women with no prior BC diagnoses, associations between pregnancy-related factors and BC risk were modified by PARS, with greater associations observed for ER-negative BC.

Tumor detection by analysis of both symmetric- and hemi-methylation of plasma cell-free DNA.

Aberrant DNA methylation patterns have been used for cancer detection. However, DNA hemi-methylation, present at about 10% CpG dinucleotides, has been less well studied. Here we show that a majority of differentially hemi-methylated regions (DHMRs) in liver tumor DNA or plasma cells free (cf) DNA do not overlap with differentially methylated regions (DMRs) of the same samples, indicating that DHMRs could serve as independent biomarkers. Furthermore, we analyzed the cfDNA methylomes of 215 samples from individuals with liver or brain cancer and individuals without cancer (controls), and trained machine learning models using DMRs, DHMRs or both. The models incorporated with both DMRs and DHMRs show a superior performance compared to models trained with DMRs or DHMRs, with AUROC being 0.978, 0.990, and 0.983 in distinguishing control, liver and brain cancer, respectively, in a validation cohort. This study supports the potential of utilizing both DMRs and DHMRs for multi-cancer detection.

Postpartum Obesity Is Associated With Increases in Child Adiposity in Midchildhood in a Cohort of Black and Dominican Youth.

Background: Obesity disproportionately affects marginalized and low-income populations. Birth parent obesity from the prenatal period and childhood has been associated with child obesity. It is unknown whether prenatal or postnatal birth parent obesity has differential effects on subsequent changes in adiposity and metabolic health in children. Objectives: We evaluated how birth parent obesity 7 y after delivery was associated with child body composition changes and cardiometabolic health in midchildhood and further assessed the influence of the perinatal and postpartum period on associations. Methods: Black and Dominican pregnant individuals were enrolled, and dyads (n = 319) were followed up at child age 7 and 9 y. Measures included, height, weight, waist circumference (WC), and percent body fat (BF%). Multiple linear regression was used to relate postpartum weight status with child outcomes accounting for attrition, and a series of secondary analyses were conducted with additional adjustment for perinatal weight status, gestational weight gain (GWG), and/or long-term weight retention to evaluate how these factors influenced associations. Results: Almost one-quarter (23%) of birth parents and 24.1% children were classified with obesity at child age 7 y, while at 9 y, 30% of children had obesity. Birth parent obesity at child age 7 y was associated with greater changes, from ages 7 to 9 y, in child BMI z-score (ß: 0.13; 95% CI: 0.02, 0.24) and BF% (ß: 1.15; 95% CI: 0.22, 2.09) but not obesity at age 9 y. All observed associations crossed the null after additional adjustment for prenatal factors. Conclusions: Birth parent obesity at 7-y postpartum is associated with greater gains in child BMI z-score and BF% in midchildhood. These associations diminish after accounting for prenatal size, suggesting a lasting impact of the perinatal environment and that interventions supporting families from the prenatal period through childhood are needed.

Racial and ethnic disparities in robot-assisted radical prostatectomy: testing the physician-level segregated and differential treatment hypotheses.

BACKGROUND: Mechanisms underlying racial and ethnic disparities in robot-assisted radical prostatectomy (RARP) vs open radical prostatectomy (ORP) are unclear. We sought to test 2 physician-level hypotheses: 1) Segregated Treatment and 2) Differential Treatment. METHODS: This observational study used the New York State Cancer Registry linked to discharge records and included patients undergoing radical prostatectomy for localized prostate cancer from October 1, 2008 to December 31, 2018. For hypothesis 1, we examined the association between patient race and ethnicity and treating surgeon RARP use (high-use surgeons, low-use surgeons, and surgeons at non-RARP facilities). For hypothesis 2, we determined the association between patient race and ethnicity and receipt of RARP when matching on treating surgeon, age, year of procedure, and Gleason group. We explored the role of insurance in both analyses. RESULTS: This study included 18 926 patients (8.0% Hispanic, 16.9% non-Hispanic Black, 75.1% non-Hispanic White), with a mean age of 60.4 ± 7.1 years. Compared with non-Hispanic White patients, Hispanic and non-Hispanic Black patients had higher odds of being treated by low-RARP-use surgeons (odds ratio [OR] = 2.16, 95% confidence interval [CI] = 1.20 to 3.88; OR = 1.76, 95% CI = 1.06 to 2.94, respectively) and by surgeons at non-RARP facilities (OR = 4.19, 95% CI = 2.18 to 8.07; OR = 4.60, 95% CI = 2.58 to 8.23, respectively). In the matched cohorts, Hispanic and non-Hispanic Black patients were less likely to receive RARP than non-Hispanic White patients (OR = 0.78, 95% CI = 0.62 to 0.98; OR = 0.75, 95% CI = 0.57 to 1.00, respectively). These associations were partially attenuated after accounting for insurance. CONCLUSIONS: Racial and ethnic disparities in RARP use are related to patients being treated by different surgeons and treated differently by the same surgeons. Identifying and addressing multilevel barriers to equitable surgical treatment is needed to reduce disparities among prostate cancer patients.

Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies.

BACKGROUND: Evidence of an association between dietary fiber intake and risk of advanced and aggressive forms of prostate cancer (PC) and PC mortality is limited. OBJECTIVE: The aim of this study was to examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC. DESIGN: The study design was a pooled analysis of the primary data from 15 cohorts in 3 continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study. PARTICIPANTS/SETTING: There were 842 149 men followed for up to 9 to 22 years between 1985 and 2009 across studies. MAIN OUTCOME MEASURES: The primary outcome measures were advanced (stage T4, N1, or M1 or PC mortality), advanced restricted (excluded men with missing stage and those with localized PC who died of PC), and high-grade PC (Gleason score ≥8 or poorly differentiated/undifferentiated) and PC mortality. STATISTICAL ANALYSIS PERFORMED: Study-specific multivariable hazard ratios (MVHR) were calculated using Cox proportional hazards regression and pooled using random effects models. RESULTS: Intake of dietary fiber overall, from fruits, and from vegetables was not associated with risk of advanced (n = 4863), advanced restricted (n = 2978), or high-grade PC (n = 9673) or PC mortality (n = 3097). Dietary fiber intake from grains was inversely associated with advanced PC (comparing the highest vs lowest quintile, MVHR 0.84; 95% CI 0.76-0.93), advanced restricted PC (MVHR 0.85; 95% CI 0.74-0.97), and PC mortality (MVHR 0.78; 95% CI 0.68-0.89); statistically significant trends were noted for each of these associations (P ≤ .03), and a null association was observed for high-grade PC for the same comparison (MVHR 1.00; 95% CI 0.93-1.07). The comparable results were 1.06 (95% CI 1.01-1.10; P value, test for trend = .002) for localized PC (n = 35,199) and 1.05 (95% CI 0.99-1.11; P value, test for trend = .04) for low/intermediate grade PC (n = 34 366). CONCLUSIONS: Weak nonsignificant associations were observed between total dietary fiber intake and risk of advanced forms of PC, high-grade PC, and PC mortality. High dietary fiber intake from grains was associated with a modestly lower risk of advanced forms of PC and PC mortality.

Dietary nitrate intake and net nitrite-generating capacity of the oral microbiome interact to enhance cardiometabolic health: Results from the Oral Infections Glucose Intolerance and Insulin Resistance Study (ORIGINS).

Background: We investigated the association between dietary nitrate intake and early clinical cardiometabolic risk biomarkers, and explored whether the oral microbiome modifies the association between dietary nitrate intake and cardiometabolic biomarkers. Methods: Cross-sectional data from 668 (mean [SD] age 31 [9] years, 73% women) participants was analyzed. Dietary nitrate intakes and alternative healthy eating index (AHEI) scores were calculated from food frequency questionnaire responses and a validated US food database. Subgingival 16S rRNA microbial genes (Illumina, MiSeq) were sequenced, and PICRUSt2 estimated metagenomic content. The Microbiome Induced Nitric oxide Enrichment Score (MINES) was calculated as a microbial gene abundance ratio representing enhanced net capacity for NO generation. Cardiometabolic risk biomarkers included systolic and diastolic blood pressure, HbA1c, glucose, insulin, and insulin resistance (HOMA-IR), and were regressed on nitrate intake tertiles in adjusted multivariable linear models. Results: Mean nitrate intake was 190[171] mg/day. Higher nitrate intake was associated with lower insulin, and HOMA-IR but particularly among participants with low abundance of oral nitrite enriching bacteria. For example, among participants with a low MINES, mean insulin[95%CI] levels in high vs. low dietary nitrate consumers were 5.8[5.3,6.5] vs. 6.8[6.2,7.5] (p=0.004) while respective insulin levels were 6.0[5.4,6.6] vs. 5.9[5.3,6.5] (p=0.76) among partcipants with high MINES (interaction p=0.02). Conclusion: Higher dietary nitrate intake was only associated with lower insulin and insulin resistance among individuals with reduced capacity for oral microbe-induced nitrite enrichment. These findings have implications for future precision medicine-oriented approaches that might consider assessing the oral microbiome prior to enrollment into dietary interventions or making dietary recommendations.

Racial and Ethnic Disparities in the Use of Robot-Assisted Surgery and Minimally Invasive Surgery in Pelvic Cancer Treatment: A Systematic Review.

Surgical innovations for cancer treatment may penetrate differentially across racial and ethnic groups and contribute to disparities in health and health care quality. We summarized the current evidence of racial and ethnic disparities in robot-assisted surgery (RAS) and minimally invasive surgery (MIS) use in four major pelvic cancer treatments. We identified studies related to racial and ethnic disparities in RAS and/or MIS use in the treatment of prostate, endometrial, bladder, and rectal cancers during 2001 to 2022 from PubMed, EMBASE, and the Cochrane database. Twenty-eight studies were selected (prostate = 7, endometrial = 14, bladder = 1, rectal = 5, multiple cancers = 1) and all were retrospective. Thirteen and 23 studies examined racial and ethnic differences in individual patients' receipt of RAS and MIS, respectively. Black patients were less likely to receive RAS/MIS than White patients in most studies. Hispanic patients were less likely to receive RAS/MIS than White patients in just over half of the studies. Studies of Asian patients were few and reported mixed results. Three studies examined disparities on the center level and found that racial and ethnic minority prostate cancer patients were less likely to be treated at RAS-performing or high-technology facilities. More work is needed to improve understanding of the mechanisms underlying racial and ethnic disparities in RAS and MIS use and their impact on disparities in health outcomes.

Robot-Assisted Surgery and Racial and Ethnic Disparities in Post-Prostatectomy Outcomes Among Prostate Cancer Patients.

BACKGROUND: We sought to determine whether the differences in short-term outcomes between patients undergoing robot-assisted radical prostatectomy (RARP) and those treated with open radical prostatectomy (ORP) differ by race and ethnicity. METHODS: This observational study used New York State Cancer Registry data linked to discharge records and included patients undergoing radical prostatectomy for localized prostate cancer during 2008-2018. We used logistic regression to examine the association between race and ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic), surgical approach (RARP, ORP), and postoperative outcomes (major events, prolonged length of stay [pLOS], 30-day re-admission). We tested interaction between race and ethnicity and surgical approach on multiplicative and additive scales. RESULTS: The analytical cohort included 18,926 patients (NHW 14,215 [75.1%], NHB 3195 [16.9%], Hispanic 1516 [8.0%]). The average age was 60.4 years (standard deviation 7.1). NHB and Hispanic patients had lower utilization of RARP and higher risks of postoperative adverse events than NHW patients. NHW, NHB, and Hispanic patients all had reduced risks of adverse events when undergoing RARP versus ORP. The absolute reductions in the risks of major events and pLOS following RARP versus ORP were larger among NHB {relative excess risk due to interaction (RERI): major events -0.32 [95% confidence interval (CI) -0.71 to -0.03]; pLOS -0.63 [95% CI -0.98 to -0.35]) and Hispanic (RERI major events -0.27 [95% CI -0.77 to 0.09]; pLOS -0.93 [95% CI -1.46 to -0.51]) patients than among NHW patients. The interaction was absent on the multiplicative scale. CONCLUSIONS: RARP use has not penetrated and benefited all racial and ethnic groups equally. Increasing utilization of RARP among NHB and Hispanic patients may help reduce disparities in patient outcomes after radical prostatectomy.

The effects of glycemic index on prostate cancer progression in a xenograft mouse model.

BACKGROUND: Previously, we found low-carbohydrate diets slowed prostate cancer (PC) growth and increased survival vs. a Western diet in mice, by inhibiting the insulin/IGF-1 axis. Thus, we tested whether modifying carbohydrate quality to lower glycemic index (GI) without changing quantity results in similar benefits as with reduced quantity. METHODS: Male SCID mice injected with LAPC-4 cells were single-housed and randomized when their tumors reached 200 mm3 on average to a LoGI (48% carbohydrate kcal, from Hylon-VII) or HiGI Western diet (48% carbohydrate kcal, from sucrose). Body weight and tumor volume were measured weekly. Body composition was assessed 35 days after randomization. Blood glucose and serum insulin, IGF-1 and IGFBP3 were measured at study end when tumor volumes reached 800 mm3. We analyzed gene expression of mice tumors by RNA-sequencing and human tumors using the Prostate Cancer Transcriptome Atlas. RESULTS: There were no significant differences in tumor volume (P > 0.05), tumor proliferation (P = 0.29), and overall survival (P = 0.15) between groups. At 35 days after randomization, the LoGI group had 30% lower body fat (P = 0.007) despite similar body weight (P = 0.58). At sacrifice, LoGI mice had smaller livers (P < 0.001) and lower glucose (P = 0.15), insulin (P = 0.11), IGF-1 (P = 0.07) and IGF-1:IGFBP3 ratio (P = 0.05), and higher IGFBP3 (P = 0.09) vs. HiGI, although none of these metabolic differences reached statistical significance. We observed differential gene expression and pathway enrichment in mice tumors by diet. The most upregulated and downregulated gene in the LoGI group showed expression patterns more closely resembling expression in human benign prostate tissue vs. PC. CONCLUSIONS: In this single mouse xenograft model, consuming a low GI diet did not delay PC growth or survival vs. a high GI diet despite suggestions of decreased activation of the insulin/IGF-1 pathway. These data suggest that improving carbohydrate quality alone while consuming a high carbohydrate diet may not effectively slow PC growth.

A blood-based metabolomic signature predictive of risk for pancreatic cancer.

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the top 2.5th percentile have absolute 5-year risk estimates of >13%. The risk prediction model based on circulating microbial and non-microbial metabolites provides a potential tool to identify individuals at high risk of PaCa that would benefit from surveillance and/or from potential cancer interception strategies.

Risk factors for developing both primary breast and primary ovarian cancer: A systematic review.

OBJECTIVE: Women with breast cancer have an increased risk of primary ovarian cancer (BR→OV), and women with ovarian cancer have an increased risk of primary breast cancer (OV→BR). This systematic review summarizes risk factors for developing BR→OV and OV→BR. METHODS: We searched PubMed and Embase until June 2022. RESULTS: We identified 23 articles meeting our inclusion criteria. Studies observed a lower risk of BR→OV for Black versus White women, alcohol consumption, radiotherapy and hormone therapy, BRCA2 versus BRCA1, and ER/PR positive versus negative breast tumors, and a higher risk with family history of breast/ovarian cancer, triple negative versus luminal breast cancer, and higher grade breast tumors. There was an increased risk of OV→BR with family history of cancer. CONCLUSIONS: Tumor characteristics, and genetic and familial factors are associated with risk of BR→OV and OV→BR. These results could aid clinicians in decision-making for breast and ovarian cancer patients, including risk-reducing strategies.

Diet Quality and All-Cause Mortality in Women with Breast Cancer from the Breast Cancer Family Registry.

BACKGROUND: The impact of diet on breast cancer survival remains inconclusive. We assessed associations of all-cause mortality with adherence to the four diet quality indices: Healthy Eating Index-2015 (HEI-2015), Alternative Healthy Eating Index (AHEI), Alternative Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH). METHODS: Dietary intake data were evaluated for 6,157 North American women enrolled in the Breast Cancer Family Registry who had been diagnosed with invasive breast cancer from 1993 to 2011 and were followed through 2018. Pre-diagnosis (n = 4,557) or post-diagnosis (n = 1,600) dietary intake was estimated through a food frequency questionnaire. During a median follow-up time of 11.3 years, 1,265 deaths occurred. Cox proportional hazards models were used to estimate multivariable-adjusted HR and 95% confidence intervals (CI). RESULTS: Women in the highest versus lowest quartile of adherence to the HEI-2015, AHEI, aMED, and DASH indices had a lower risk of all-cause mortality. HR (95% CI) were 0.88 (0.74-1.04; Ptrend = 0.12) for HEI-2015; 0.82 (0.69-0.97; Ptrend = 0.02) for AHEI; 0.73 (0.59-0.92; Ptrend = 0.02) for aMED; and 0.78 (0.65-0.94; Ptrend = 0.006) for DASH. In subgroup analyses, the associations with higher adherence to the four indices were similar for pre- or post-diagnosis dietary intake and were confined to women with a body mass index <25 kg/m2 and women with hormone receptor positive tumors. CONCLUSIONS: Higher adherence to the HEI-2015, AHEI, aMED, and DASH indices was associated with lower mortality among women with breast cancer. IMPACT: Adherence to a healthy diet may improve survival of women with breast cancer.

Racial and ethnic differences in type II endometrial cancer mortality outcomes: The contribution of sociodemographic, clinicopathologic, and treatment factors.

OBJECTIVE: The burden of type II endometrial cancer (EC) is rising dramatically in the U.S. Although type II EC disproportionately affects Black women, the magnitude of racial/ethnic differences in type II EC mortality outcomes and factors underlying these differences remain understudied. We examined racial/ethnic differences in cancer-specific and overall mortality in women with type II EC and quantified the extent to which mortality differences are mediated by sociodemographic, clinicopathologic, and treatment factors. METHODS: 14,710 women ≥18 years with type II EC from 2007 to 2016 were identified from the Surveillance, Epidemiology, and End Results database. The association between race/ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic, and non-Hispanic Asian/Pacific Islander [NHAPI]) and cancer-specific and overall mortality was examined. Mediation analysis was used to identify factors underlying differences in mortality outcomes. RESULTS: NHB women had a higher risk of cancer-specific mortality than NHW women (hazard ratio [HR]: 1.22, 95% CI: 1.12-1.33), whereas NHAPI (HR: 0.88, 95% CI: 0.78-0.99) and Hispanic women (HR: 0.91, 95% CI: 0.81-1.01) had a lower risk of cancer-specific mortality than NHW women. Differences in clinicopathologic (stage, grade, histologic subtype), sociodemographic (insurance type, geographic region and location, neighborhood socioeconomic status), and treatment factors (treatment type, lymphadenectomy) explained 43.5%, 8.1%, and 7.3% of the difference in cancer-specific mortality between NHB and NHW women, respectively. Similar results were noted for overall mortality. CONCLUSIONS: Multidisciplinary and multilevel approaches that integrate and address social and biological factors are needed to reduce the disproportionate burden of type II EC mortality in NHB women.

Adherence to the 2020 American Cancer Society Guideline for Cancer Prevention and risk of breast cancer for women at increased familial and genetic risk in the Breast Cancer Family Registry: an evaluation of the weight, physical activity, and alcohol consumption recommendations.

PURPOSE: The American Cancer Society (ACS) published an updated Guideline for Cancer Prevention (ACS Guideline) in 2020. Research suggests that adherence to the 2012 ACS Guideline might lower breast cancer risk, but there is limited evidence that this applies to women at increased familial and genetic risk of breast cancer. METHODS: Using the Breast Cancer Family Registry (BCFR), a cohort enriched for increased familial and genetic risk of breast cancer, we examined adherence to three 2020 ACS Guideline recommendations (weight management (body mass index), physical activity, and alcohol consumption) with breast cancer risk in 9615 women. We used Cox proportional hazard regression modeling to calculate hazard ratios (HRs) and 95% confidence intervals (CI) overall and stratified by BRCA1 and BRCA2 pathogenic variant status, family history of breast cancer, menopausal status, and estrogen receptor-positive (ER +) breast cancer. RESULTS: We observed 618 incident invasive or in situ breast cancers over a median 12.9 years. Compared with being adherent to none (n = 55 cancers), being adherent to any ACS recommendation (n = 563 cancers) was associated with a 27% lower breast cancer risk (HR = 0.73, 95% CI: 0.55-0.97). This was evident for women with a first-degree family history of breast cancer (HR = 0.68, 95% CI: 0.50-0.93), women without BRCA1 or BRCA2 pathogenic variants (HR = 0.71, 95% CI: 0.53-0.95), postmenopausal women (HR = 0.63, 95% CI: 0.44-0.89), and for risk of ER+ breast cancer (HR = 0.63, 95% CI: 0.40-0.98). DISCUSSION: Adherence to the 2020 ACS Guideline recommendations for BMI, physical activity, and alcohol consumption could reduce breast cancer risk for postmenopausal women and women at increased familial risk.

Racial and ethnic differences in the adoption of opportunistic salpingectomy for ovarian cancer prevention in the United States.

BACKGROUND: Clinicians in the United States have rapidly adopted opportunistic salpingectomy for ovarian cancer prevention. However, little is known about racial and ethnic differences in opportunistic salpingectomy adoption. Surgical innovations in gynecology may be adopted differentially across racial and ethnic groups, exacerbating current disparities in quality of care. OBJECTIVE: This study aimed to evaluate racial and ethnic differences in opportunistic salpingectomy adoption across inpatient and outpatient settings and assess the effect of national guidelines supporting opportunistic salpingectomy use on these differences. STUDY DESIGN: A sample of 650,905 women aged 18 to 50 years undergoing hysterectomy with ovarian conservation or surgical sterilization from 2011 to 2018 was identified using the Premier Healthcare Database, an all-payer hospital administrative database, including more than 700 hospitals across the United States. The association between race and ethnicity and opportunistic salpingectomy use was examined using multivariable-adjusted mixed-effects log-binomial regression models accounting for hospital-level clustering. Models included race and ethnicity by year of surgery (2011-2013 [before guideline] and 2014-2018 [after guideline]) interaction term to test whether racial and ethnic differences in opportunistic salpingectomy adoption changed with the release of national guidelines supporting opportunistic salpingectomy use. RESULTS: From 2011 to 2018, 82,792 women underwent hysterectomy and opportunistic salpingectomy (non-Hispanic White, 60.3%; non-Hispanic Black, 18.8%; Hispanic, 12.2%; non-Hispanic other race, 8.7%) and 23,398 women underwent opportunistic salpingectomy for sterilization (non-Hispanic White, 64.7%; non-Hispanic Black, 10.8%; Hispanic, 16.7%; non-Hispanic other race, 7.8%). The proportion of hysterectomy procedures involving an opportunistic salpingectomy increased from 6.3% in 2011 to 59.7% in 2018 (9.5-fold increase), and the proportion of sterilization procedures involving an opportunistic salpingectomy increased from 0.7% in 2011 to 19.4% in 2018 (27.7-fold increase). In multivariable-adjusted models, non-Hispanic Black (risk ratio, 0.94; 95% confidence interval, 0.92-0.97), Hispanic (risk ratio, 0.98; 95% confidence interval, 0.95-1.00), and non-Hispanic other race women (risk ratio, 0.93; 95% confidence interval, 0.90-0.96) were less likely to undergo hysterectomy and opportunistic salpingectomy than non-Hispanic White women. A significant interaction between race and ethnicity and year of surgery was noted in non-Hispanic Black compared with non-Hispanic White women (P<.001), with a reduction in differences in hysterectomy and opportunistic salpingectomy use after national guideline release (risk ratio2011-2013, 0.80 [95% confidence interval, 0.73-0.88]; risk ratio2014-2018, 0.98 [95% confidence interval, 0.95-1.01]). Moreover, non-Hispanic Black women were less likely to undergo an opportunistic salpingectomy for sterilization than non-Hispanic White women (risk ratio, 0.91; 95% confidence interval, 0.88-0.95), with no difference by year of surgery (P=.62). Stratified analyses by hysterectomy route and age at surgery revealed similar results. CONCLUSION: Although opportunistic salpingectomy for ovarian cancer prevention has been rapidly adopted in the United States, our findings suggested that its adoption has not been equitable across racial and ethnic groups. Non-Hispanic Black, Hispanic, and non-Hispanic other race women were less likely to undergo opportunistic salpingectomy than non-Hispanic White women even after adjusting for sociodemographic, clinical, procedural, hospital, and provider characteristics. These differences persisted after the release of national guidelines supporting opportunistic salpingectomy use. Future research should focus on understanding the reasons for these differences to inform interventions that promote equity in opportunistic salpingectomy use.

Sustained Weight Loss, Weight Cycling, and Weight Gain During Adulthood and Pancreatic Cancer Incidence in the Women's Health Initiative.

Pancreatic cancer (PC) is the fourth leading cause of cancer mortality among women in the United States. Obesity is positively associated with PC risk. Current health recommendations focus on weight maintenance for healthy-weight individuals and weight loss for overweight/obese individuals; however, little research has assessed associations between PC risk and changes in weight throughout the life course. Using prospective cohort study data, we examined the relationship between baseline adulthood weight patterns self-reported between 1993 and 1998 and PC risk in 136,834 postmenopausal women with 873 incident PC cases through September 30, 2015, in the Women's Health Initiative. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models, adjusting for age, smoking habits, heavy alcohol consumption, and body mass index. Compared with women with stable weight, no significant associations were found between steady weight gain (HR = 1.01, 95% CI: 0.83, 1.22), sustained weight loss (HR = 1.26, 95% CI: 0.85, 1.87), or weight cycling patterns (HR = 1.08, 95% CI: 0.89, 1.30) and PC. Results were similar when the outcome definition was restricted to pancreatic adenocarcinoma cases. Overall, we did not find evidence to suggest that weight changes in adulthood significantly impact PC risk among postmenopausal women.

Cancer-Specific Mortality in Asian American Women Diagnosed with Gynecologic Cancer: A Nationwide Population-Based Analysis.

BACKGROUND: Cancer is the leading cause of death in Asian Americans (AA), the fastest-growing U.S. population group. Despite heterogeneity in socioeconomic status and health behaviors by ethnicity, few studies have assessed cancer outcomes across AA ethnic groups. We examined differences in gynecologic cancer mortality between AA ethnic groups and non-Hispanic Whites (NHW). METHODS: Using the Surveillance, Epidemiology, and End Results database, we identified ovarian (n = 69,113), uterine (n = 157,340), and cervical cancer cases (n = 41,460) diagnosed from 1991-2016. Competing risk regression was used to compare cancer-specific mortality for AAs by ethnicity, using NHW as the reference population. RESULTS: In adjusted analyses, AAs had a lower risk of ovarian [HR, 0.90; 95% confidence interval (CI), 0.86-0.94] and cervical cancer death (HR, 0.80; 95% CI, 0.75-0.87) than NHWs, with stronger associations among those ≥50 years at diagnosis [(HRovary, 0.87; 95% CI, 0.82-0.92); (HRcervix, 0.74; 95% CI, 0.67-0.81)]. No overall difference was noted for uterine cancer death (HR, 1.03; 95% CI, 0.97-1.10); however, AAs <50 years at diagnosis had a higher risk of uterine cancer death than NHWs (HR, 1.26; 95% CI, 1.08-1.46). Patterns of cancer mortality were heterogeneous, with Filipino and Chinese women at the highest risk of uterine cancer death and Indian/Pakistani women at the lowest risk of ovarian and cervical cancer death. CONCLUSIONS: There are significant differences in gynecologic cancer mortality between AAs and NHWs, with heterogeneity by AA ethnicity. IMPACT: Disaggregated analysis of AA is needed to better understand the burden of gynecologic cancer and identify high-risk groups for cancer prevention efforts.