Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Low physical function Post-Cancer diagnosis is associated with higher mortality risk in postmenopausal women.

BACKGROUND: Postmenopausal women with cancer experience an accelerated physical dysfunction beyond that expected through aging alone due to cancer and its treatments. The aim of this study is to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality. METHODS: This prospective cohort study included 8,068 postmenopausal women enrolled in the Women's Health Initiative (WHI) who were diagnosed with cancer and had physical function assessed within 1-year of cancer diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the RAND 36-Item Health Survey. Cause of death was determined by medical record review with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022. RESULTS: Over a median follow-up of 7.7 years from cancer diagnosis 3,316 (41.1%) women died. Our results showed that for every 10% decline in the physical function score after cancer diagnosis, all-cause mortality and cancer-specific mortality were significantly reduced by 12% (HR, 0.88; 95% CI, 0.87 to 0.89) and (HR, 0.88; 95%CI, 0.86 to 0.91), respectively. Further categorical analyses showed a significant dose-response relationship between post-diagnosis physical function categories and mortality outcomes (trend test P < .001), where the median survival time for women in the lowest physical function quartile was 9.1 (8.6, 10.6) years compared to 18.4 (15.8, 22.0) years for women in the highest physical function quartile. CONCLUSION: Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.

SGLT2 Inhibitor Use and Risk of Breast Cancer Among Adult Women with Type 2 Diabetes.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic agents, with the potential to inhibit breast cancer development. However, the association between SGLT2 inhibitors and risk of breast cancer in human studies is unclear. OBJECTIVE: The aim of our study is to use a large national claims database to assess the association between SGLT2 inhibitor use and risk of breast cancer. METHODS: We considered a study population of 158,483 adult women with type 2 diabetes who newly initiated SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP4) inhibitors using Optum's deidentified Clinformatics Data Mart Database between 1 January 2013 and 31 March 2022. The association between SGLT2 inhibitor use and risk of breast cancer was examined using Cox proportional hazard models stratified by age in the overall sample and in a subsample based on propensity score and medication initiation time matching. The effect of medication use duration was explored. RESULTS: With an average follow-up of 2.2 years, 2154 breast cancer cases were identified. There was no significant association between SGLT2 inhibitor use and the risk of breast cancer in overall sample (HR = 0.96; 95% CI 0.87, 1.06), in women younger than 51 years old (HR = 0.88; 95% CI 0.59, 1.32), or in women aged 51 years or older (HR = 0.95; 95% CI 0.86, 1.04). The results remained nonsignificant using matching, medication use duration, and sensitivity analyses. CONCLUSION: Our findings suggest SGLT2 inhibitors use was not associated with breast cancer risk compared with DPP4 inhibitors use. Studies with longer follow-up and better adjustments are needed to confirm the finding.

Allostatic load and risk of invasive breast cancer among postmenopausal women in the U.S.

OBJECTIVE: Allostatic load can reflect the body's response to chronic stress. However, little is known about the association between allostatic load and risk of breast cancer in postmenopausal women. This study used a large prospective cohort in the United States to examine the relationship between allostatic load and invasive breast cancer risk, and to evaluate the relationship by racial and ethnic identity and breast cancer subtypes. METHODS: Among 161,808 postmenopausal participants in Women's Health Initiative, eligible were a subsample of 27,393 postmenopausal women aged 50-79 years old, who enrolled from 1993 to 1998, had serum test biomarkers, and were followed for breast cancer incidence through February 2022. Allostatic load at enrollment was computed based on eight biomarkers from lab serum tests and a questionnaire about participants' prescription drug use. The associations between allostatic scores and risk of breast cancer (overall and by subtypes) were assessed using Cox proportional hazards models. The race and ethnic differences were examined. RESULTS: Over a median follow-up time of 17.24 years, 1722 invasive breast cancer cases were identified. High allostatic load was associated with an increased risk of breast cancer (HR = 1.36, 95%CI: 1.20, 1.54 for third tertile vs first tertile, Ptrend < 0.0001). Similar trends were found in White women and non-Hispanic women. Higher allostatic load was associated with hormone receptor-positive and HER2/Neu-negative breast cancer (HR = 1.54, 95%CI: 1.30, 1.80 for third tertile vs first tertile, Ptrend < 0.0001). CONCLUSION: In this study, we found that higher allostatic load was significantly associated with an increased risk of breast cancer in postmenopausal women.

Hysterectomy, oophorectomy and risk of non-Hodgkin's lymphoma.

Hysterectomy is associated with an increased risk for adverse health outcomes. However, its connection to the risk of non-Hodgkin's lymphoma (NHL) remains unclear. The aims of our study were to investigate the associations between hysterectomy, oophorectomy and risk of NHL and its major subtypes (eg, diffuse large B-cell lymphoma [DLBCL]), and whether these associations were modified by exogenous hormone use. Postmenopausal women (n = 141,621) aged 50-79 years at enrollment (1993-1998) from the Women's Health Initiative were followed for an average of 17.2 years. Hysterectomy and oophorectomy were self-reported at baseline. Incident NHL cases were confirmed by central review of medical records and pathology reports. During the follow-up period, a total of 1719 women were diagnosed with NHL. Hysterectomy, regardless of oophorectomy status, was associated with an increased risk of NHL (hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.05-1.44). Oophorectomy was not independently associated with NHL risk after adjusting for hysterectomy. When stratified by hormone use, the association between hysterectomy and NHL risk was confined to women who had never used hormone therapy (HR = 1.35, 95% CI: 1.06-1.71), especially for DLBCL subtype (P for interaction = .01), and to those who had undergone hysterectomy before the age of 55. Our large prospective study showed that hysterectomy was a risk factor of NHL. Findings varied by hormone use. Future studies incorporating detailed information on the types and indications of hysterectomy may deepen our understanding of the mechanisms underlying DLBCL development and its potential interactions with hormone use.

Changes in physical function in older women with endometrial cancer with or without adjuvant therapy.

OBJECTIVE: To evaluate changes in physical function (PF) for older women with endometrial cancer (EC) + / - adjuvant therapy in the Women's Health Initiative Life and Longevity after Cancer cohort. MATERIALS AND METHODS: This study examined women ≥ 70 years of age with EC with available treatment records. Change in PF was measured using the RAND-36 and compared between groups using Wilcoxon rank-sum tests. Multivariable median regression was used to compare the changes in scores while adjusting for confounding variables. RESULTS: Included in the study were 287 women, 150 (52.3%) women who did not receive adjuvant therapy and 137 (47.7%) who received adjuvant therapy. When comparing PF scores, there was a statistically significant difference in the median percent change in functional decline, with a greater decline in those who received adjuvant therapy (- 5.9% [- 23.5 to 0%]) compared to those who did not (0 [- 18.8 to + 6.7%]), p = 0.02). Results were not statistically significant after multivariable adjustment, but women who underwent chemotherapy had a greater percent change (median ∆ - 13.8% [- 35.5 to 0%]) compared to those who received radiation alone (median ∆ - 5.9% [- 31.3 to 0%]) or chemotherapy and radiation (median ∆ - 6.5% [- 25.8 to + 5.7%]. CONCLUSIONS: Older women with EC who received adjuvant therapy experienced greater change in PF than those who did not receive adjuvant therapy, particularly women who received chemotherapy. These results were not statistically significant on multivariate analysis. IMPLICATIONS FOR CANCER SURVIVORS: EC survivors may experience changes in PF because of chemotherapy and/or radiation therapy. Additional supportive care may need to be provided to older women to mitigate functional decline.

Bilateral Oophorectomy and Colorectal Cancer Incidence and Mortality in the Women's Health Initiative.

BACKGROUND: The few cohort studies examining oophorectomy and colorectal cancer risk provide mixed results. Therefore, we examined this issue in Women's Health Initiative Observational Study participants. METHODS: A total of 71,312 postmenopausal women were followed for 22.1 years (median). At enrollment, 55,643 (78%) had intact ovaries and 15,669 (22%) had undergone a bilateral oophorectomy. Colorectal cancers were verified by central medical record review with mortality findings enhanced by National Death Index queries. RESULTS: With 1,421 incident colorectal cancers, 450 colorectal cancer-specific mortalities, after controlling for covariates, bilateral oophorectomy was not associated with colorectal cancer incidence or colorectal cancer mortality. CONCLUSIONS: No significant associations between oophorectomy and colorectal cancer incidence and mortality were seen in a large cohort study with long follow-up. IMPACT: As the oophorectomy and colorectal cancer question remains open, further studies of high quality, even with null findings, should be encouraged.

Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival.

BACKGROUND: Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated. METHODS: Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR). RESULTS: Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15-2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46-1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51-0.84, and HR, 1.33; 95% CI, 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25-1.90), 0.72 (95% CI, 0.59-0.88), and 0.70 (95% CI, 0.56-0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23-0.66; Pinteraction = 0.0002). CONCLUSIONS: High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival. IMPACT: Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.

New-Onset Diabetes after an Obesity-Related Cancer Diagnosis and Survival Outcomes in the Women's Health Initiative.

BACKGROUND: Individuals diagnosed with an obesity-related cancer (ORC survivors) are at an elevated risk of incident diabetes compared with cancer-free individuals, but whether this confers survival disadvantage is unknown. METHODS: We assessed the rate of incident diabetes in ORC survivors and evaluated the association of incident diabetes with all-cause and cancer-specific mortality among females with ORC in the Women's Health Initiative cohort (N = 14,651). Cox proportional hazards regression models stratified by exposure-risk periods (0-1, >1-3, >3-5, >5-7, and >7-10 years) from ORC diagnosis and time-varying exposure (diabetes) analyses were performed. RESULTS: Among the ORC survivors, a total of 1.3% developed diabetes within ≤1 year of follow-up and 2.5%, 2.3%, 2.3%, and 3.6% at 1-3, 3-5, 5-7, and 7-10 years of follow-up, respectively, after an ORC diagnosis. The median survival for those diagnosed with diabetes within 1-year of cancer diagnosis and those with no diabetes diagnosis in that time frame was 8.8 [95% confidence interval (CI), 7.0-14.5) years and 16.6 (95% CI, 16.1-17.0) years, respectively. New-onset compared with no diabetes as a time-varying exposure was associated with higher risk of all-cause (HR, 1.27; 95% CI, 1.16-1.40) and cancer-specific (HR, 1.17; 95% CI, 0.99-1.38) mortality. When stratified by exposure-risk periods, incident diabetes in ≤1 year of follow-up was associated with higher all-cause (HR, 1.76; 95% CI, 1.40-2.20) and cancer-specific (HR0-1, 1.82; 95% CI, 1.28-2.57) mortality, compared with no diabetes diagnosis. CONCLUSIONS: Incident diabetes was associated with worse cancer-specific and all-cause survival, particularly in the year after cancer diagnosis. IMPACT: These findings draw attention to the importance of diabetes prevention efforts among cancer survivors to improve survival outcomes.

Optimal objective measurement of physical function and its predictive capacity for mortality among community-dwelling older women.

AIM: Objective measurements of physcial function, including gait speed, handgrip strength, and the chair stand test, have been shown to have predictive capacity for negative health-related outcomes. The aim of this study was to examine campariatively which of these common assessments may be optimal in terms of their predictive capacity for mortality. METHODS: A total of 9834 community-dwelling older women aged 65-89 years from the Study of Osteoporotic Fractures (SOF) were followed for 20 years. Gait speed, handgrip strength, and the chair stand test were measured every 2-4 years on up to 9 visits. All deaths were adjudicated. RESULTS: All three measurements of physical function were significantly associated with overall, cardiovascular disease and other mortality. Gait speed had the greatest magnitude of hazard ratios (HRs) for all outcomes of interest. A one-unit standard deviation increase in gait speed was associated with a 33% (HR = 0.67, 95% confidence interval [95% CI]: 0.64-0.70) lower risk for overall mortality, a 31% (HR = 0.69, 95% CI: 0.64-0.73) lower risk for cardiovascular disease mortality, a 15% (HR = 0.85, 95% CI: 0.78-0.92) lower risk for cancer mortality and a 42% (HR = 0.58, 95% CI: 0.55-0.62) lower risk for other mortality. Further examination of gait speed identified two cut-points (0.9 and 0.7 m/s) that were strongly indicative of increased mortality risk. CONCLUSION: Our large prospective study indicates that gait speed possesses a better prediction of mortality among older women compared with handgrip strength or the chair stand test. Using cut-points of 0.9 and 0.7 m/s can help identify older women at higher mortality risk, who may benefit from physical function improvement interventions. Geriatr Gerontol Int 2023; 23: 715-721.

Birth weight, adult body size, and risk of colorectal cancer.

BACKGROUND: Evidence suggests that birth weight may be associated with colorectal cancer (CRC) risk later in life. Whether the association is mediated by adult body size remains unexamined. METHOD: Cox proportional hazards models (Hazard Ratio (HR) and 95 % Confidence Intervals (CI)) were used to evaluate the association between self-reported birth weight (<6 lbs, 6-<8 lbs, ≥8 lbs) and CRC risk among 70,397 postmenopausal women from the Women's Health Initiative. Further, we assessed whether this association was mediated by adult body size using multiple mediation analyses. RESULTS: Compared with birth weights of 6-< 8 lbs, birth weight ≥ 8 lbs was associated with higher CRC risk in postmenopausal women (HR = 1.31, 95 % CI 1.16-1.48). This association was significantly mediated by adult height (proportion mediated =11.4 %), weight (11.2 %), waist circumference (10.9 %), and body mass index at baseline (4.0 %). The joint effect of adult height and weight explained 21.6 % of this positive association. CONCLUSION: Our data support the hypothesis that the intrauterine environment and fetal development may be related to the risk of developing CRC later in life. While adult body size partially explains this association, further investigation is required to identify other factors that mediate the link between birth weight and CRC.

A Longitudinal Study of Sleep Habits and Leukemia Incidence Among Postmenopausal Women.

We sought to assess the relationship between sleep duration, sleep disturbance, and leukemia incidence among postmenopausal women. This study included 130,343 postmenopausal women aged 50-79 years who were enrolled in the Women's Health Initiative (WHI) during 1993-1998. Information on self-reported typical sleep duration and sleep disturbance was obtained by questionnaire at baseline, and sleep disturbance level was defined according to the Women's Health Initiative Insomnia Rating Scale (WHIIRS). WHIIRS scores of 0-4, 5-8, and 9-20 comprised 37.0%, 32.6%, and 30.4% of all women, respectively. After an average of 16.4 years (2,135,109 cumulative person-years) of follow-up, 930 of the participants were identified as having incident leukemia. Compared with women with the lowest level of sleep disturbance (WHIIRS score 0-4), women with higher sleep disturbance levels (WHIIRS scores of 5-8 and 9-20) had 22% (95% confidence interval (CI): 1.04, 1.43) and 18% (95% CI: 1.00, 1.40) excess risks of leukemia, respectively, after multivariable adjustment. A significant dose-response trend was found for the association between sleep disturbance and leukemia risk (P for trend = 0.048). In addition, women with the highest level of sleep disturbance had a higher risk of myeloid leukemia (for WHIIRS score 9-20 vs. WHIIRS score 0-4, hazard ratio = 1.39, CI: 1.05, 1.83). Higher sleep disturbance level was associated with increased risk of leukemia, especially for myeloid leukemia among postmenopausal women.

Body size over the adult life course and the risk of colorectal cancer among postmenopausal women.

OBJECTIVE: To assess the associations among several anthropometric measures, as well as BMI trajectories and colorectal cancer (CRC) risk in older women. DESIGN: Prospective cohort study. SETTING: Forty clinical centres in the USA. PARTICIPANTS: Totally, 79 034 postmenopausal women in the Women's Health Initiative Observational Study. RESULTS: During an average of 15·8 years of follow-up, 1514 CRC cases were ascertained. Five BMI trajectories over 18-50 years of age were identified using growth mixture model. Compared with women who had a normal BMI at age 18, women with obesity at age 18 had a higher risk of CRC (HR 1·58, 95 % CI 1·02, 2·44). Compared with women who kept relatively low normal body size during adulthood, women who progressed from normal to obesity (HR 1·29, 95 % CI 1·09, 1·53) and women who progressed from overweight to obesity (HR 1·37, 95 % CI 1·13, 1·68) had higher CRC risks. A weight gain > 15 kg from age 18 to 50 (HR 1·20, 95 % CI 1·04, 1·40) and baseline waist circumference > 88 cm (HR 1·33, 95 % CI 1·19, 1·49) were associated with higher CRC risks, compared with stable weight and waist circumference ≤ 88 cm, respectively. CONCLUSION: Women who have a normal weight in early adult life and gain substantial weight later, as well as those who are persistently heavy over adulthood, demonstrated a higher risk of developing CRC. Our study highlights the importance of maintaining a healthy body weight over the life course for reducing the risk of developing CRC in women.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and non-small cell lung cancer survival.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs with demonstrated renal and cardiovascular disease benefit. This study evaluates the role of SGLT2 inhibitors on the survival of non-small cell lung cancer (NSCLC) patients. METHODS: We used National Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. Twenty four thousand nine hundred fifteen NSCLC patients newly diagnosed between 2014 and 2017 with pre-exiting diabetes and aged 66 years or older were included and followed to the end of 2019. Information on SGLT2 inhibitors use was extracted from the Medicare Part D file. RESULTS: SGLT2 inhibitor use was associated with significantly reduced mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.60-0.77) with stronger association for longer duration of use (HR = 0.54, 85% CI = 0.44-0.68). Further, we found that SGLT2 inhibitor use was associated with a significant reduced risk of mortality regardless of patients' demographic, tumour characteristics and cancer treatments. CONCLUSION: Our large SEER-Medicare linked data study indicates that SGLT2 inhibitors use was associated with improved overall survival of NSCLC patients with pre-existing diabetes. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.

Long-term Trajectories of Physical Function Decline in Women With and Without Cancer.

Importance: Patients with cancer experience acute declines in physical function, hypothesized to reflect accelerated aging driven by cancer-related symptoms and effects of cancer therapies. No study has examined long-term trajectories of physical function by cancer site, stage, or treatment compared with cancer-free controls. Objective: Examine trajectories of physical function a decade before and after cancer diagnosis among older survivors and cancer-free controls. Design, Setting, and Participants: This prospective cohort study enrolled patients from 1993 to 1998 and followed up until December 2020. The Women's Health Initiative, a diverse cohort of postmenopausal women, included 9203 incident cancers (5989 breast, 1352 colorectal, 960 endometrial, and 902 lung) matched to up to 5 controls (n = 45 358) on age/year of enrollment and study arm. Exposures: Cancer diagnosis (site, stage, and treatment) via Medicare and medical records. Main Outcomes and Measures: Trajectories of self-reported physical function (RAND Short Form 36 [RAND-36] scale; range: 0-100, higher scores indicate superior physical function) estimated from linear mixed effects models with slope changes at diagnosis and 1-year after diagnosis. Results: This study included 9203 women with cancer and 45 358 matched controls. For the women with cancer, the mean (SD) age at diagnosis was 73.0 (7.6) years. Prediagnosis, physical function declines of survivors with local cancers were similar to controls; after diagnosis, survivors experienced accelerated declines relative to controls, whose scores declined 1 to 2 points per year. Short-term declines in the year following diagnosis were most severe in women with regional disease (eg, -5.3 [95% CI, -6.4 to -4.3] points per year in regional vs -2.8 [95% CI, -3.4 to -2.3] for local breast cancer) or who received systemic therapy (eg, for local endometrial cancer, -7.9 [95% CI, -12.2 to -3.6] points per year with any chemotherapy; -3.1 [95% CI, -6.0 to -0.3] with radiation therapy alone; and -2.6 [95% CI, -4.2 to -1.0] with neither, respectively). While rates of physical function decline slowed in the later postdiagnosis period (eg, women with regional colorectal cancer declined -4.3 [95% CI, -5.9 to -2.6] points per year in the year following diagnosis vs -1.4 [95% CI, -1.7 to -1.0] points per year in the decade thereafter), survivors had estimated physical function significantly below that of age-matched controls 5 years after diagnosis. Conclusions and Relevance: In this prospective cohort study, survivors of cancer experienced accelerated declines in physical function after diagnosis, and physical function remained below that of age-matched controls even years later. Patients with cancer may benefit from supportive interventions to preserve physical functioning.

Diabetes, metformin use and risk of non-Hodgkin's lymphoma in postmenopausal women: A prospective cohort analysis in the Women's Health Initiative.

Epidemiologic evidence is limited about associations between T2DM, metformin, and the risk of non-Hodgkin's lymphoma (NHL). We aimed to examine associations between T2DM, metformin, and the risk of NHL in the Women's Health Initiative (WHI) Study. Information on T2DM status (diabetes status/types of antidiabetic drug use/diabetes duration) from study enrollment and during follow-up were assessed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate associations of T2DM status with risks of overall NHL and its three major subtypes [diffuse large B-cell lymphoma (DLBCL, n = 476), follicular lymphoma (FL, n = 301) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, n = 136)] based on multivariable-adjusted Cox proportional hazards models. During a median follow-up of 18.86 years (range, 0.01-25.13; SD ± 6.55), a total of 1637 women developed NHL among 147 885 postmenopausal women. Women with T2DM and with self-reported oral medication use had 38% and 55% higher risk of DLBCL, respectively [multivariable-adjusted model HR = 1.38, 95% CI (1.06-1.81) and HR = 1.55, 95% CI (1.16-2.06)] compared to the reference group (nondiabetics/untreated diabetes). Risks of NHL and DLBCL [multivariable-adjusted model: HR = 1.28, 95% CI (1.06-1.54) and HR = 1.56, 95% CI (1.13-2.14), respectively] were significantly higher in associations with relatively short duration (≤7 years) of diabetes, compared to reference group. Additionally, an increased risk of DLBCL [HR = 1.76, 95% CI (1.13-2.75)] was found in metformin users compared to the reference group. Postmenopausal women who had T2DM, who were oral antidiabetic drug users, especially metformin, and who had a shorter diabetes duration may have higher risks of DLBCL. Further well-designed research is needed to confirm our findings.

Long-term changes of cognitive impairment among older breast cancer survivors.

PURPOSE: Cancer-related cognitive impairment is common during cancer treatment; however, it is unclear whether the impairment persists over time. Our study aimed to examine long-term cognitive impairment among older breast cancer survivors. METHODS: Participants included 2420 community-dwelling women aged 65 years or older at enrollment (1986-1988) (404 breast cancer cases and 1:5 matched cancer-free controls) from the Study of Osteoporotic Fractures. Participants were followed for 20 years with measured cognitive function repeated up to 6 times. Cognitive impairment was defined by the Modified Mini-Mental State Examination and Trail Making Test B. Generalized linear models were used to model risk of cognitive impairment in relation to breast cancer status and time from breast cancer diagnosis. RESULTS: Compared with controls, cognitive impairment in women with breast cancer significantly accelerated after cancer diagnosis. We also observed a more pronounced cognitive impairment after cancer diagnosis for women diagnosed with breast cancer at age ≥ 80 years or at advanced stage for both measures. CONCLUSION: Our study with more than 20 years of follow-up data found that breast cancer survivors had accelerated cognitive impairment after cancer diagnosis, especially among women diagnosed at older age or at advanced stage, relative to women without cancer. IMPLICATIONS FOR CANCER SURVIVORS: Breast cancer survivors may be encouraged to engage in both physical activity and cognitive training.

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.

Sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation and hepatocellular carcinoma prognosis.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs. Emerging findings from laboratory studies indicate that SGLT2 inhibitors can improve liver function and suppress the proliferation of hepatocellular carcinoma (HCC) cells. The aim of this study was to test the hypothesis that initiation of SGLT2 inhibitors improves HCC prognosis in a human population. METHODS: We used National Surveillance, Epidemiology and End Results (SEER)-Medicare linked data in the United States to evaluate the role of SGLT2 inhibitor initiation on the survival of HCC patients. 3,185 HCC patients newly diagnosed between 2014 and 2017 aged 66 years or older with pre-existing type 2 diabetes were included and followed to the end of 2019. Information on SGLT2 inhibitor initiation was extracted from the Medicare Part D file. RESULTS: SGLT2 inhibitor initiation was associated with significantly lower mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.54-0.86) with stronger association for longer duration of use (HR = 0.60, 95% CI = 0.41-0.88). Further, we found that SGLT2 inhibitor initiation was associated with a lower risk mortality risk ranging from 14% to 60% regardless of patient demographic variables, tumor characteristics, and cancer treatments. CONCLUSION: Our large SEER-Medicare linked data study indicates that SGLT2 inhibitor initiation was associated with improved overall survival of HCC patients with pre-existing type 2 diabetes compared with no SGLT2 inhibitor use. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.

Dietary selenium intake and thyroid cancer risk in postmenopausal women.

OBJECTIVE: It has been suggested that higher selenium intake and consumption of supplements protect against several cancers. To our knowledge, epidemiologic evidence is rare and inconsistent on the association of selenium level and the risk for thyroid cancer. Therefore, the aim of this study was to examine the association between selenium intake and thyroid cancer risk in postmenopausal women using the Women's Health Initiative (WHI) database. METHODS: The WHI recruited 161 808 postmenopausal women 50 to 79 y of age between September 1, 1993 and December 31, 1998. The present study included 147 348 women 63.15 y of age (SD = 7.21) at baseline. The main exposure was baseline total selenium intake including dietary selenium measured by food frequency questionnaire (FFQ) and supplemental selenium. The outcome was thyroid cancer, which was adjudicated by trained physicians. Cox proportional hazard models were used to analyze the association. RESULTS: During a mean follow-up of 16.4 y until September 30, 2020, 442 thyroid cancer cases were identified. There was no significant association between total selenium intake and thyroid cancer risk after adjusting for multiple covariates (highest versus lowest quartile: hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.60-1.29). Association between total selenium intake and the risk for papillary thyroid cancer was also not significant (highest versus lowest quartile: HR, 1.02; 95% CI, 0.66-1.52). CONCLUSIONS: The present data did not support that either total or dietary selenium intake was associated with the risk for thyroid cancer or the papillary subtype in postmenopausal women ages 50 to 79 y in the United States.