Trends in chemotherapy use for early-stage breast cancer from 2006 to 2019.

BACKGROUND: Little is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington). FINDINGS: Among 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend < 0.001). Among 13,089 women receiving chemotherapy, neoadjuvant treatment increased (4.1-14.7%; p-trend < 0.001), as did receipt of anti-HER2 therapies (20.8-30.9%) (p-trend < 0.001). The average treatment duration increased (5.3 to 6.0 months; p-trend < 0.001), as did the number of infusion visits (10.8 to 12.5; p-trend < 0.001). For those receiving anti-HER2 therapies, treatment duration and average number of visits decreased; among those not receiving anti-HER2 therapies, number of visits increased, with no change in duration. CONCLUSIONS: While the prevalence of chemotherapy receipt has decreased over time, the use of neoadjuvant chemotherapy has increased, as has use of anti-HER2 therapies; duration and number of administration visits have also increased. Understanding these trends is useful to inform clinical and administrative planning.

Patient characteristics associated with delayed time to adjuvant chemotherapy among women treated for stage I-IIIA breast cancer.

For patients with breast cancer, delays in chemotherapy initiation have been adversely associated with recurrence and survival. We evaluated patient-level factors associated with delayed chemotherapy initiation, from both diagnosis and surgery, in a community-based cohort of women with early-stage breast cancer. For the Optimal Breast Cancer Chemotherapy Dosing study, we identified a cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at two U.S. integrated healthcare delivery systems between 2004 and 2019. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify patient factors associated with delays in chemotherapy initiation after diagnosis (≥90 days) and surgery (≥60 days). Among 10,968 women receiving adjuvant chemotherapy, 21.1% experienced delays in chemotherapy initiation after diagnosis and 21.3% after surgery. Older age, non-Hispanic Black and Hispanic race and ethnicity, and ER+ and/or PR+ disease were associated with increased likelihood of delays to chemotherapy initiation after diagnosis and surgery. People diagnosed in 2012-2019 (vs. 2005-2011), with a higher grade and larger tumor size were less likely to experience delays. Other factors were associated with a higher likelihood of delays specifically from diagnosis (earlier stage, mastectomy vs. breast-conserving surgery), or surgery (higher comorbidity, increased nodal number). Women diagnosed with breast cancer who were at highest risk of progression and recurrence were less likely to experience delays in chemotherapy initiation after diagnosis and surgery. Understanding reasons for chemotherapy delays beyond patient factors may be potentially important to reduce risk of breast cancer recurrence and progression.

Traditional Mexican dietary pattern and cancer risk among women of Mexican descent.

PURPOSE: To examine the association of a traditional Mexican diet score with risk of total, breast, and colorectal cancer among women of Mexican ethnic descent in the Women's Health Initiative (WHI). METHODS: Participants were WHI enrollees who self-identified as being of Mexican descent. Data from food frequency questionnaires self-administered at study baseline were used to calculate the MexD score, with higher scores indicating greater adherence to an a priori-defined traditional Mexican diet (high in dietary fiber, vegetables, and legumes). Incident cancers were self-reported by participants from 1993 to 2020 and adjudicated by trained physicians. We used multivariable-adjusted Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 2,343 Mexican descent women (median baseline age: 59 years), a total of 270 cancers (88 breast, 37 colorectal) occurred during a mean follow-up of 14.4 years. The highest tertile of MexD score was associated with a lower risk of all-cancer incidence (HR: 0.67; 95% CI 0.49-0.91; p-trend: 0.01) and colorectal cancer (HR: 0.38; 95% CI 0.14-0.998; p-trend < 0.05), with each unit increase in the MexD score associated with a 6% lower risk of all-cancer incidence (HR: 0.94; 95% CI 0.88-0.99). There was no statistically significant association with risk of breast cancer. CONCLUSION: Consumption of a traditional Mexican diet was associated with a significantly lower risk of all-cancer incidence and colorectal cancer. Confirmation of these findings in future studies is important, given the prevalence of colorectal cancer and a growing U.S. population of women of Mexican descent.

Association between dietary inflammatory potential and mortality after cancer diagnosis in the Women's Health Initiative.

BACKGROUND: Chronic inflammation is implicated in cancer prognosis and can be modulated by diet. We examined associations between post-diagnosis dietary inflammatory potential and mortality outcomes among post-menopausal women diagnosed with cancer in the Women's Health Initiative (WHI). METHODS: Energy-adjusted dietary inflammatory index scores (E-DII) were calculated from dietary and supplemental intake data collected on the first food frequency questionnaire following the diagnosis of primary invasive cancer for 3434 women in the WHI. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for risk of death from any cause, cancer, cardiovascular disease (CVD) and other causes by post-diagnosis quartiles of E-DII. Subgroup analyses by cancer stage and grade were performed. RESULTS: There were 1156 deaths after a median 13 years of follow-up from the date of a cancer diagnosis. In the multivariable-adjusted analyses, a more anti-inflammatory diet plus supplements after cancer diagnosis was associated with lower all-cause mortality, cancer mortality, CVD mortality and mortality from other causes with HRsQ1vs.Q4 ranging from 0.47 to 0.68 (all P-trends < 0.05). Associations were stronger for cancers diagnosed at more distant stages or moderately differentiated grades. CONCLUSION: A more anti-inflammatory diet plus supplements after a cancer diagnosis may improve survival for post-menopausal cancer survivors.

Evaluation of approaches to recruitment of racially and ethnically diverse breast cancer patients from an integrated health care setting for collection of observational social network data.

PURPOSE: We compared approaches to recruitment of diverse women with breast cancer in a study designed to collect complex social network data. METHODS: We recruited 440 women from the Kaiser Permanente Northern California population newly diagnosed with breast cancer, either in person at a clinic, by email, or by mailed letter. In clinic and mail recruitment, women completed a brief 3-page paper survey (epidemiologic data only), and women had the option to complete a separate, longer (30-40 min) personal social network survey online. In email recruitment, we administered epidemiologic and personal social network measures together in a single online survey. In email and mail recruitment, we limited the sample of non-Hispanic white (NHW) women to 30% of their total. We used descriptive analysis and multinomial logistic regression to examine odds of recruitment vs. mailed letter. RESULTS: Women responded to the social network surveys on average 3.7 months post-diagnosis. Mean age was 59.3 (median = 61.0). In-person clinic recruitment was superior with a 52.1% success rate of recruitment compared with 35.6% by mail or 17.3% by email (χ2 = 65.9, p < 0.001). Email recruitment produced the highest completion rate (82.1%) of personal network data compared with clinic (36.5%) or mail (28.7%), (χ2 = 114.6, p < 0.001). Despite intentional undersampling of NHW patients, response rates for Asian, Hispanic, and Black women by email were lower. However, we found no significant differences in recruitment rates by race and ethnicity for face-to-face clinic recruitment vs. by letter. Letter recruitment produced the highest overall response. CONCLUSION: Mailed letter was the best approach to representative recruitment of diverse women with breast cancer and collection of social network data, and further yielded the highest absolute response.

Racial differences in anthropometric measures as risk factors for triple-negative breast cancer.

PURPOSE: The incidence of triple-negative breast cancer (TNBC) is higher in Black women compared to White women which is not explained by racial differences in body mass index (BMI). As BMI has limitations as an anthropometric measure, we used different anthropometric measures to examine associations with TNBC by race. METHOD: Of 161,808 postmenopausal participants in Women's Health Initiative, eligible were a subsample of 121,744 White and Black postmenopausal women enrolled from 1993 to 1998, 50-79 years of age with anthropometric measures who were followed for breast cancer incidence until March 2019. At entry, BMI, waist circumference (WC), and waist-hip ratio (WHR) were measured using standardized methods. Breast cancers were verified by central medical record review. Associations between anthropometric measures and triple-negative breast cancer risk were examined using Cox proportional hazards regression models. RESULTS: After 17.6 years (median) follow-up, there were 87 Black women and 529 White women with incident triple-negative breast cancer. Overall, there were no significant associations between anthropometric measures and risk of triple-negative breast cancer. However, compared to White women with normal BMI, White women with obesity (BMI ≥ 30) (HR 0.76, 95% CI 0.60, 0.96) were significantly associated with a lower risk of triple-negative breast cancer. And larger waist circumference (HR per centimeter 0.99, 95% CI 0.99, 1.00) was significantly associated with a lower risk of triple-negative breast cancer among White women. CONCLUSION: Overall, among postmenopausal women, anthropometric measures were not associated with risk of TNBC. The association among White women with larger waist circumference and women with obesity with a lower risk of triple-negative breast cancer needs further confirmation.

Social Support, social ties, and cognitive function of women with breast cancer: findings from the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) Study.

PURPOSE: This study examined associations between self-reported cognitive functioning and social support as well as social ties among women with breast cancer. METHODS: The study included 3351 women from the Women's Health Initiative Life and Longevity After Cancer cohort who were diagnosed with breast cancer stages I-III. Social support was assessed using a modified Medical Outcomes Study (MOS) Social Support Survey, and marital status was obtained from the baseline questionnaire. We also assessed social ties (e.g., number of friends, relatives, living children) and cognitive function (Functional Assessment of Cancer Therapy-Cognitive Function [FACT-COG]) on the year-1-follow up questionnaire. Multivariable quantile regression was used to estimate the changes in median cognitive scores. Kruskal-Wallis tests were used to assess the association of cognitive function with social ties. RESULTS: The majority of participants were non-Hispanic White (93.3%), presently married (49%), with at least a 4-year college degree (53.2%), and had been diagnosed with localized breast cancer (79%). A 10-point higher social support score correlated to a 0.32 higher (better) median cognitive score (p < 0.001). Women who were presently married tended to have better cognition than women who were divorced/separated or widowed (p = 0.01). Significant associations were also present for having close relatives (p < 0.001) or friends (p < 0.001), with cognitive scores being higher in those with at least one close relative or friend compared to none. CONCLUSION: Women reporting higher social support and greater numbers of friends or relatives have higher cognitive functioning. Compared to divorced or separated women, married women were likely to have higher cognitive functioning. These findings suggest that social support assessments have the potential to help identify women at higher risk of cognitive decline.

Cardiometabolic risk factors, physical activity, and postmenopausal breast cancer mortality: results from the Women's Health Initiative.

BACKGROUND: Higher physical activity levels are associated with lower breast cancer-specific mortality. In addition, the metabolic syndrome is associated with higher breast cancer-specific mortality. Whether the physical activity association with breast cancer mortality is modified by number of metabolic syndrome components (cardiometabolic risk factors) in postmenopausal women with early-stage breast cancer remains unknown. METHODS: Cardiovascular risk factors included high waist circumference, hypertension, high cholesterol, and diabetes. Breast cancers were verified by medical record review. Mortality finding were enhanced by serial National Death Index queries. Cox proportional hazards regression models were used to estimate associations between baseline physical activity and subsequent breast cancer-specific and overall mortality following breast cancer diagnosis in Women's Health Initiative participants. These associations were examined after stratifying by cardiometabolic risk factor group. RESULTS: Among 161,308 Women's Health Initiative (WHI) participants, 8543 breast cancers occurred after 9.5 years (median) follow-up in women, additionally with information on cardiometabolic risk factors and physical activity at entry. In multi-variable analyses, as measured from cancer diagnosis, higher physical activity levels were associated with lower all-cause mortality risk (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.78-0.95, trend P < 0.001) but not with breast cancer-specific mortality (HR 0.85, 95% CI 0.70 to 1.04, trend P = 0.09). The physical activity and all-cause mortality association was not significantly modified by cardiometabolic risk factor number. CONCLUSIONS: Among women with early-stage breast cancer, although higher antecedent physical activity was associated with lower risk of all-cause mortality, the association did not differ by cardiometabolic risk factor number.

Metabolic syndrome risk components and mortality after triple-negative breast cancer diagnosis in postmenopausal women in the Women's Health Initiative.

BACKGROUND: Triple-negative breast cancer (TNBC) has a high recurrence risk and poor clinical outcomes. Associations between metabolic syndrome (MetS) risk components and mortality in postmenopausal women with TNBC were examined in the Women's Health Initiative. METHODS: Five hundred forty-four postmenopausal women were diagnosed with nonmetastatic TNBC. Baseline risk components included a high waist circumference (≥88 cm), high blood pressure, hypercholesterolemia, and diabetes. Groups were categorized by the number of MetS risk components: none, 1 or 2, or 3 or 4. Hazard ratios (HRs) and 95% confidence intervals (CIs) across groups were computed with multivariable adjusted Cox models. Outcomes included breast cancer-specific mortality and breast cancer overall mortality (breast cancer followed by death from any cause). Variables in the multivariable model included age at TNBC diagnosis; race/ethnicity; income; education; clinical/observational trial status; history of oral contraceptive, hormone, and/or statin use; cancer stage; and chemotherapy and/or radiation treatment status. RESULTS: Of the 544 participants with TNBC, 33% had no MetS risk components (n = 178), 59% had 1 or 2 risk components (n = 323), and 8% had 3 or 4 risk components (n = 43). After a median follow-up from diagnosis of 8.3 years, multivariable results showed that women with 3 or 4 risk components had a nonsignificantly higher risk of breast cancer mortality (HR, 2.05; 95% CI, 0.94-4.47 trend P = .114) and a significantly higher risk of overall mortality (HR, 2.13; 95% CI, 1.22-3.71; trend P = .006) versus women with 0 risk components. CONCLUSIONS: Postmenopausal women with TNBC and 3 or 4 MetS risk components have a nonsignificantly higher breast cancer mortality risk and a significantly higher overall mortality risk, likely because of negative influences of metabolic risk factors on several causes of death.

Individual- and neighborhood-level socioeconomic status and risk of aggressive breast cancer subtypes in a pooled cohort of women from Kaiser Permanente Northern California.

BACKGROUND: Low socioeconomic status (SES) has been associated with a higher risk of aggressive breast cancer (BC) subtypes, but few studies have examined the independent effects of both neighborhood-level socioeconomic status (nSES) and individual-level SES measures. METHODS: This study included 5547 women from the Pathways and Life After Cancer Epidemiology cohorts who were diagnosed with invasive BC. Generalized estimating equation models were used to examine associations of nSES (a composite score based on income, poverty, education, occupation, employment, rent, and house value) and individual-level SES (income and education) with BC subtypes: luminal B (LumB), Her2-enriched (Her2-e), and triple-negative breast cancer (TNBC) relative to luminal A (LumA). Models controlled for age, race, nativity, stage, days from diagnosis to survey, and study cohort and simultaneously for nSES and individual-level SES. RESULTS: In fully adjusted models, low nSES was significantly associated with the LumB (odds ratio for quartile 1 vs quartile 4 [ORQ1vQ4 ], 1.31; 95% confidence interval [CI], 1.11-1.54; P for trend = .005) and TNBC subtypes (ORQ1vQ4 , 1.32; 95% CI, 1.02-1.71; P for trend = .037) relative to LumA. Conversely, individual education was significantly associated with only the Her2-e subtype (odds ratio for high school degree or less vs postgraduate, 1.68; 95% CI, 1.03-2.75; P for trend = .030) relative to LumA. Individual income was not significantly associated with any BC subtype. CONCLUSIONS: nSES and individual-level SES are independently associated with different BC subtypes; specifically, low nSES and individual-level education are independent predictors of more aggressive BC subtypes relative to LumA.

Mediation analysis of racial disparities in triple-negative breast cancer incidence among postmenopausal women.

BACKGROUND: Triple-negative breast cancer (TNBC) is disproportionately higher in Black women relative to White women. The objective of this study was to examine to what extent the association between race/ethnicity and risk of TNBC is mediated by potentially modifiable factors. METHODS: A total of 128,623 Black and White women aged 50-79 years from the Women's Health Initiative were followed for a mean of 15.8 years. 643 incident TNBC cases (92 Black women and 551 White women) were confirmed by medical record review. Mediation analyses were conducted using an approach under a counterfactual framework. RESULTS: Black women had approximately twofold higher risk of TNBC compared with white women (HR = 1.93, 95% CI 1.52-2.45). We observed that 48% of the racial disparity was mediated by metabolic dysfunction defined by having 3 or more cardiometabolic risk factors including elevated waist circumference, having history of diabetes, high cholesterol and hypertension. The racial disparity was not significantly mediated by other factors studied, including socioeconomic, lifestyle or reproductive factors. CONCLUSION: Our study observed that approximately half of the racial disparity between postmenopausal Black and White women in TNBC incidence was driven by metabolic dysfunction.

Clustering of Social and Physical Pain Variables and Their Association With Mortality in Two Population-Based Cohorts.

OBJECTIVE: Social pain and physical pain are related bidirectionally, but how these variables cluster in the population is unknown. METHODS: This study included 2833 women from the Study of Women's Health Across the Nation (SWAN), a community-based cohort of middle-aged women, and 3972 women from the Pathways Study, a population-based cohort of women diagnosed with American Joint Committee on Cancer stages I-IV breast cancer diagnosed between 2005 and 2013. Women provided data on measures related to social pain (social network size, social support, loneliness, social well-being) and physical pain (sensitivity to pain, bodily pain) at study baseline. Analyzing each cohort separately, we used latent class analysis to evaluate social-physical pain clusters, logistic regression to evaluate predictors of categorization into clusters, and Cox proportional hazards models to evaluate associations of clusters with all-cause mortality. We also performed a meta-analysis to combine cohort mortality associations. RESULTS: Each cluster analysis produced a "low social-physical pain" cluster (SWAN, 48.6%; Pathways, 35.2%) characterized by low social and pain symptoms, a "high social-physical pain" cluster (SWAN, 17.9%; Pathways, 17.9%) characterized by high symptoms, and a "low social/high physical pain" cluster of women with high pain and compromised social functioning but otherwise low social symptoms (SWAN, 33.5%; Pathways, 46.9%). In meta-analysis, categorization into the high social-physical pain cluster was associated with elevated mortality (adjusted hazard ratio = 1.34, 95% confidence interval = 1.05-1.71, Q statistic = 0.782), compared with those in the low social-physical pain cluster. CONCLUSIONS: In two cohorts of women, latent class analysis produced similar sets of social-physical pain clusters, with the same proportion having both high social and pain symptoms; women in this cluster had elevated mortality.

Does the Hispanic Mortality Advantage Vary by Marital Status Among Postmenopausal Women in the Women's Health Initiative?

BACKGROUND: Literature assessing the effect of marital status on mortality has underrepresented, or altogether omitted Hispanics and the potential moderating effect of Hispanic ethnicity on these relationships. Given cultural and network dynamics, marital advantages in older Hispanic women may be greater than other groups given their family-focused, collectivist orientation. PURPOSE: The purpose of this study was to understand whether older Hispanic women exhibited a more pronounced marital advantage as compared with non-Hispanic Whites. METHODS: We used longitudinal data from the Women's Health Initiative (WHI) Observational Study and Clinical Trials (N = 161,808) collected initially from 1993 to 1998 and followed until 2018. Our sample excluded those respondents indicating "other" as their race-ethnicity and those missing marital status and race-ethnicity variables (N = 158,814). We used Cox-proportional hazards models to assess the association between race-ethnicity, marital status, and the interactive effect of race-ethnicity and marital status on survival. RESULTS: After controlling for socioeconomic status (SES) and health controls, we found a Hispanic survival advantage when compared with non-Hispanic Whites and all other racial-ethnic groups with the exception of Asian/Pacific Islander women (all significant HRs < 0.78, all ps ≤ 0.001). Hispanics had a higher rate of divorce when compared with non-Hispanic Whites. The interactive effect of race-ethnicity and marital status was not significant. CONCLUSIONS: U.S. Hispanic, postmenopausal women exhibit a mortality advantage over and above marital status despite their high rates of divorce. Implications and potential explanations are discussed. CLINICAL TRIAL REGISTRATION: NCT00000611.

"I Had to Make Them Feel at Ease": Narrative Accounts of How Women With Breast Cancer Navigate Social Support.

Social scientific studies of social support predominantly focus on the positive associations between social support and emotional well-being. The negative aspects of social support have received much less attention. We conducted semi-structured interviews of women with breast cancer (n = 47) to examine the emotional strain associated with social support and how recipients navigate it in ways that protect themselves and their relationships. Based on our analysis of narratives of women's lived experiences of breast cancer, we found that social support can be perceived negatively and associated with experiences of emotional strain. Interviewees engaged in strategies of avoidance, information control, and cognitive reframing to minimize emotional strain. We applied the concept of emotion work to understand the complexity of emotional strain in this context. The findings highlight the difficulties of social support from a recipient's perspective and emphasize the importance of perception and agency in navigating this experience.

A descriptive pilot study of structural and functional social network ties among women in the women's health initiative (WHI) study.

Few studies examine the network structure and function of older women's health discussion networks. We sought to assess the feasibility and acceptability of collecting social network data via telephone from 72 women from the Women's Health Initiative study and to describe structural and functional characteristics. Women were socially connected and had dense networks. Women were emotionally close to network members, but their networks were not used to facilitate communication with health-care providers. One-third of network members was not influential on health-related decision-making. Collecting social network data via telephone is feasible and an acceptable, though un-preferred, mode of data collection.

Prediagnosis social support, social integration, living status, and colorectal cancer mortality in postmenopausal women from the women's health initiative.

BACKGROUND: We evaluated associations between perceived social support, social integration, living alone, and colorectal cancer (CRC) outcomes in postmenopausal women. METHODS: The study included 1431 women from the Women's Health Initiative who were diagnosed from 1993 through 2017 with stage I through IV CRC and who responded to the Medical Outcomes Study Social Support survey before their CRC diagnosis. We used proportional hazards regression to evaluate associations of social support (tertiles) and types of support, assessed up to 6 years before diagnosis, with overall and CRC-specific mortality. We also assessed associations of social integration and living alone with outcomes also in a subset of 1141 women who had information available on social ties (marital/partner status, community and religious participation) and living situation. RESULTS: In multivariable analyses, women with low (hazard ratio [HR], 1.52; 95% CI, 1.23-1.88) and moderate (HR, 1.21; 95% CI, 0.98-1.50) perceived social support had significantly higher overall mortality than those with high support (P [continuous] < .001). Similarly, women with low (HR, 1.42; 95% CI, 1.07-1.88) and moderate (HR, 1.28; 95% CI, 0.96-1.70) perceived social support had higher CRC mortality than those with high social support (P [continuous] = .007). Emotional, informational, and tangible support and positive interaction were all significantly associated with outcomes, whereas affection was not. In main-effects analyses, the level of social integration was related to overall mortality (P for trend = .02), but not CRC mortality (P for trend = .25), and living alone was not associated with mortality outcomes. However, both the level of social integration and living alone were related to outcomes in patients with rectal cancer. CONCLUSIONS: Women with low perceived social support before diagnosis have higher overall and CRC-specific mortality.

The association of delay in curative intent treatment with survival among breast cancer patients: findings from the Women's Health Initiative.

PURPOSE: Delays in adjuvant breast cancer (BC) therapy have been shown to worsen outcomes. However, thus far studies have only evaluated delays to initial treatment, or a particular modality, such as chemotherapy, leaving uncertainty about the role of delay to subsequent therapy and the effects of cumulative delay, on outcomes. We investigated the associations of delays across treatment modalities with survival. METHODS: We included 3368 women with incident stage I-III BC in the Women's Health Initiative (WHI) enrolled in fee-for-service Medicare who underwent definitive surgery. This prospective analysis characterized treatment delays by linking WHI study records to Medicare claims. Delays were defined as > 8 weeks to surgery, chemotherapy, and radiation from diagnosis or prior treatment. We used Cox proportional hazards models to estimate BC-specific mortality (BCSM) and all-cause mortality (ACM) in relation to treatment delays. RESULTS: We found 21.8% of women experienced delay to at least one therapy modality. In adjusted analysis, delay to chemotherapy was associated with a higher risk of BCSM (HR = 1.71; 95% CI 1.07-2.75) and ACM (HR = 1.39; 95% CI 1.02-1.90); delay in radiation increased BCSM risk (HR = 1.49; 95% CI 1.00-2.21) but not ACM risk (HR = 1.19; 95% CI 0.99-1.42). Delays across multiple treatment modalities increased BCSM risk threefold (95% CI 1.51-6.12) and ACM risk 2.3-fold (95% CI 1.50-3.50). CONCLUSIONS: A delay to a single treatment modality and delay to a greater extent an accumulation of delays were associated with higher BCSM and ACM after BC. Timely care throughout the continuum of breast cancer treatment is important for optimal outcomes.

Post-cancer diagnosis dietary inflammatory potential is associated with survival among women diagnosed with colorectal cancer in the Women's Health Initiative.

PURPOSE: Dietary factors may influence colorectal cancer (CRC) survival through effects on inflammation. We examined the association between post-CRC diagnosis inflammatory potential of diet and all-cause and cancer-specific mortality in the Women's Health Initiative. METHODS: The study included 463 postmenopausal women who developed CRC during follow-up and completed a food frequency questionnaire (FFQ), on average 1.7 years after diagnosis. Women were followed from CRC diagnosis until death, censoring, or the end of follow-up in October 2014. Energy-adjusted dietary inflammatory index (E-DII)® scores were calculated from the FFQ and dietary supplement inventory. Cox proportional hazards models were fitted to estimate multivariable-adjusted HRs and 95% confidence intervals (CIs) for all-cause, total cancer, and CRC-specific mortality with the most pro-inflammatory E-DII scores (tertile 3) as referent. RESULTS: After a median 11.6 years of follow-up, 162 deaths occurred, including 77 from CRC. Lowest tertile (i.e., most anti-inflammatory) E-DII scores from diet plus supplements were associated with significantly lower all-cause mortality (HRT1vsT3 = 0.49; 95% CI 0.31-0.79) compared to the most pro-inflammatory E-DII tertile. Modest associations with total cancer mortality or CRC-specific mortality were observed, though 95% CIs included 1. CONCLUSIONS: Consuming a dietary pattern and supplements with more anti-inflammatory potential after CRC diagnosis may improve overall survival among postmenopausal women.

Lifestyle and Psychosocial Patterns and Diabetes Incidence Among Women with and Without Obesity: a Prospective Latent Class Analysis.

We conducted latent class analyses to identify women with homogeneous combinations of lifestyle and behavioral variables and tested whether latent classes were prospectively associated with diabetes incidence for women with or without baseline obesity. A total of 64,710 postmenopausal women aged 50-79 years without prevalent diabetes at baseline (years 1993-1998) were followed until 2018 with a mean follow-up of 14.6 years (sd = 6.4). Lifestyle variables included smoking, diet quality, physical activity, and sleep quality. Psychosocial variables included social support, depression, and optimism. Multivariable Cox proportional hazards regression models tested associations between latent classes and diabetes incidence controlling for age, race/ethnicity, and education. During follow-up, 8076 (12.4%) women developed diabetes. For women without baseline obesity, five latent classes were identified. Compared with a lower risk referent, diabetes incidence was higher in classes characterized by high probability of multiple lifestyle and psychosocial risks (HR = 1.45; 95% CI 1.28, 1.64), poor diet and exercise (HR = 1.23; 95% CI 1.13, 1.33), and psychosocial risks alone (HR = 1.20; 95% CI 1.12, 1.29). For women with baseline obesity, four latent classes were identified. Compared with a lower risk referent, diabetes incidence was higher for women with obesity in classes characterized by high probability of multiple lifestyle and psychosocial risks (HR = 1.48; 95% CI 1.32, 1.66), poor diet and exercise (HR = 1.32; 95% CI 1.19, 1.47), and intermediate probabilities of multiple risks (HR = 1.17; 95% CI 1.05, 1.30). Diabetes prevention efforts that focus on diet and exercise may benefit from attention to how lifestyle behaviors interact with psychosocial variables to increase diabetes risks, and conversely, how psychological or social resources may be leveraged with lifestyle changes to reduce the risk for women with and without obesity.

Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium.

OBJECTIVE: Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk. DESIGN: This nested case-control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy. RESULTS: Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORsquartile 4 vs 1=2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker-cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity-oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk. CONCLUSION: This prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.