Search

Purpose: To examine whether overall survival (OS) differs for male and female patients with advanced soft-tissue sarcoma (STS)., Experimental Design: The study included patients from Kaiser Permanente Northern California and Stanford Cancer Center with grade 2 and 3 locally advanced or metastatic STS whose tumor underwent next-generation sequencing. We used Cox regression modeling to examine association of sex and OS adjusting for other important factors., Results: Among 388 eligible patients, 174 had leiomyosarcoma (LMS), 136 had undifferentiated pleomorphic sarcoma (UPS), and 78 had liposarcoma. OS for male versus female patients appeared to be slightly better among the full cohort [HR = 0.89; 95% confidence interval (CI), 0.66-1.20]; this association appeared to be stronger among the subsets of patients with LMS (HR = 0.76; 95% CI, 0.39-1.49) or liposarcoma (HR = 0.74; 95% CI, 0.32-1.70). Better OS for male versus female patients was also observed among all molecular subgroups except mutRB1 and mutATRX, especially among patients whose tumor retained wtTP53 (HR = 0.73; 95% CI, 0.44-1.18), wtCDKN2A (HR = 0.85; 95% CI, 0.59-1.23), wtRB1 (HR = 0.73; 95% CI, 0.51-1.04), and among patients whose tumor had mutPTEN (HR = 0.37; 95% CI, 0.09-1.62). OS also appeared to be better for males in the MSK-IMPACT and TCGA datasets., Conclusions: A fairly consistent pattern of apparent better OS for males across histologic and molecular subgroups of STS was observed. If confirmed, our results could have implications for clinical practice for prognostic stratification and possibly treatment tailoring as well as for future clinical trials design., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively. Alcohol and tobacco use have been associated with increased breast cancer risk. However, their effects on mammographic density (MD) phenotypes are poorly understood., Methods: We examined associations of alcohol and tobacco use with PD, DA, and NDA in a population-based cohort of 23,456 women screened using full-field digital mammography machines manufactured by Hologic or General Electric. MD was measured using Cumulus. Machine-specific effects were estimated using linear regression, and combined using random effects meta-analysis., Results: Alcohol use was positively associated with PD ( P trend = 0.01), unassociated with DA ( P trend = 0.23), and inversely associated with NDA ( P trend = 0.02) adjusting for age, body mass index, reproductive factors, physical activity, and family history of breast cancer. In contrast, tobacco use was inversely associated with PD ( P trend = 0.0008), unassociated with DA ( P trend = 0.93), and positively associated with NDA ( P trend <0.0001). These trends were stronger in normal and overweight women than in obese women., Conclusions: These findings suggest that associations of alcohol and tobacco use with PD result more from their associations with NDA than DA., Impact: PD and NDA may mediate the association of alcohol drinking, but not tobacco smoking, with increased breast cancer risk. Further studies are needed to elucidate the modifiable lifestyle factors that influence breast tissue composition, and the important role of the fatty tissues on breast health., (©2020 American Association for Cancer Research.)

Background: Several epidemiologic studies have reported strong inverse associations between metformin use and risk of colorectal cancer, although time-related biases, such as immortal time bias, may in part explain these findings. We reexamined this association using methods to minimize these biases. Methods: A cohort study was conducted among 47,351 members of Kaiser Permanente Northern California with diabetes and no history of cancer or metformin use. Follow-up for incident colorectal cancer occurred from January 1, 1997, until June 30, 2012. Cox regression was used to calculate HRs and 95% confidence intervals (CIs) for colorectal cancer risk associated with metformin use (ever use, total duration, recency of use, and cumulative dose). Results: No association was observed between ever use of metformin and colorectal cancer risk (HR, 0.90; 95% CI, 0.76-1.07) and there was no consistent pattern of decreasing risk with increasing total duration, dose, or recency of use. However, long-term use (≥5.0 years) appeared to be associated with reduced risk of colorectal cancer in the full population (HR, 0.78; 95% CI, 0.60-1.02), among current users (HR, 0.78; 95% CI, 0.59-1.04), and in men (HR, 0.65; 95% CI, 0.45-0.94) but not in women. Higher cumulative doses of metformin were associated with reduced risk. In initial users of sulfonylureas, switching to or adding metformin was also associated with decreased colorectal cancer risk. Conclusions: Our findings showed an inverse association between long-term use of metformin and colorectal cancer risk. Findings, especially the risk reduction among men, need to be confirmed in large, well-conducted studies. Impact: If our findings are confirmed, metformin may have a role in the chemoprevention of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(5); 525-30. ©2018 AACR See related commentary by Jackson and García-Albéniz, p. 520 ., (©2018 American Association for Cancer Research.)

Cancer is the second leading cause of death among American Indians and Alaskan Natives (AIAN), although cancer survival information in this population is limited, particularly among urban AIAN. In this retrospective cohort study, we compared all-cause and prostate, breast, lung, and colorectal cancer-specific mortality among AIAN ( n = 582) and non-Hispanic white (NHW; n = 82,696) enrollees of Kaiser Permanente Northern California (KPNC) diagnosed with primary invasive breast, prostate, lung, or colorectal cancer from 1997 to 2015. Tumor registry and other electronic health records provided information on sociodemographic, comorbidity, tumor, clinical, and treatment characteristics. Cox regression models were used to estimate adjusted survival curves and hazard ratios (HR) with 95% confidence intervals (CI). AIAN had a significantly higher comorbidity burden compared with NHW ( P < 0.05). When adjusting for patient, disease characteristics, and Charlson comorbidity scores, all-cause mortality and cancer-specific mortality were significantly higher for AIAN than NHW patients with breast cancer (HR, 1.47; 95% CI, 1.13-1.92) or with prostate cancer (HR, 1.87; 95% CI, 1.14-3.06) but not for AIAN patients with lung and colorectal cancer. Despite approximately equal access to preventive services and cancer care in this setting, we found higher mortality for AIAN than NHW with some cancers, and a greater proportion of AIAN cancer patients with multiple comorbid conditions. This study provides severely needed information on the cancer experience of the 71% of AIANs who live in urban areas and access cancer care outside of the Indian Health Services, from which the vast majority of AIAN cancer information comes. Cancer Res; 77(23); 6770-6. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: High mammographic density is strongly associated with increased breast cancer risk. Some, but not all, risk factors for breast cancer are also associated with higher mammographic density. Methods: The study cohort ( N = 24,840) was drawn from the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California and included non-Hispanic white females ages 40 to 74 years with a full-field digital mammogram (FFDM). Percent density (PD) and dense area (DA) were measured by a radiological technologist using Cumulus. The association of age at menarche and late adolescent body mass index (BMI) with PD and DA were modeled using linear regression adjusted for confounders. Results: Age at menarche and late adolescent BMI were negatively correlated. Age at menarche was positively associated with PD ( P value for trend <0.0001) and DA ( P value for trend <0.0001) in fully adjusted models. Compared with the reference category of ages 12 to 13 years at menarche, menarche at age >16 years was associated with an increase in PD of 1.47% (95% CI, 0.69-2.25) and an increase in DA of 1.59 cm 2 (95% CI, 0.48-2.70). Late adolescent BMI was inversely associated with PD ( P < 0.0001) and DA ( P < 0.0001) in fully adjusted models. Conclusions: Age at menarche and late adolescent BMI are both associated with Cumulus measures of mammographic density on processed FFDM images. Impact: Age at menarche and late adolescent BMI may act through different pathways. The long-term effects of age at menarche on cancer risk may be mediated through factors besides mammographic density. Cancer Epidemiol Biomarkers Prev; 26(9); 1450-8. ©2017 AACR ., (©2017 American Association for Cancer Research.)