BRCA testing and outcomes in women with breast cancer.

MAIN PURPOSE: Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer. RESEARCH QUESTION: The research question is "Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?" METHODS: In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status. RESULTS: Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000-2004 to 13.3% in 2010-2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients. CONCLUSIONS: The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.

Prevalence of germline BRCA mutations in HER2-negative metastatic breast cancer: global results from the real-world, observational BREAKOUT study.

BACKGROUND: The global observational BREAKOUT study investigated germline BRCA mutation (gBRCAm) prevalence in a population of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). METHODS: Eligible patients had initiated first-line cytotoxic chemotherapy for HER2-negative MBC within 90 days prior to enrollment. Hormone receptor (HR)-positive patients had experienced disease progression on or after prior endocrine therapy, or endocrine therapy was considered unsuitable. gBRCAm status was determined using baseline blood samples or prior germline test results. For patients with a negative gBRCAm test, archival tissue was tested for somatic BRCAm and homologous recombination repair mutations (HRRm). Details of first-line cytotoxic chemotherapy were also collected. RESULTS: Between March 2017 and April 2018, 384 patients from 14 countries were screened and consented to study enrollment; 341 patients were included in the full analysis set (median [range] age at enrollment: 56 [25-89] years; 256 (75.3%) postmenopausal). Overall, 33 patients (9.7%) had a gBRCAm (16 [4.7%] in gBRCA1 only, 12 [3.5%] in gBRCA2 only, and 5 [1.5%] in both gBRCA1 and gBRCA2). gBRCAm prevalence was similar in HR-positive and HR-negative patients. gBRCAm prevalence was 9.0% in European patients and 10.6% in Asian patients and was higher in patients aged ≤ 50 years at initial breast cancer (BC) diagnosis (12.9%) than patients aged > 50 years (5.4%). In patients with any risk factor for having a gBRCAm (family history of BC and/or ovarian cancer, aged ≤ 50 years at initial BC diagnosis, or triple-negative BC), prevalence was 10.4%, versus 5.8% in patients without these risk factors. HRRm prevalence was 14.1% (n = 9/64) in patients with germline BRCA wildtype. CONCLUSIONS: Patient demographic and disease characteristics supported the association of a gBRCAm with younger age at initial BC diagnosis and family history of BC and/or ovarian cancer. gBRCAm prevalence in this cohort, not selected on the basis of risk factors for gBRCAm, was slightly higher than previous results suggested. gBRCAm prevalence among patients without a traditional risk factor for harboring a gBRCAm (5.8%) supports current guideline recommendations of routine gBRCAm testing in HER2-negative MBC, as these patients may benefit from poly(ADP-ribose) polymerase (PARP) inhibitor therapy. TRIAL REGISTRATION: NCT03078036 .

Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small-Cell Lung Cancer: The Phase II BALTIC Study.

PURPOSE: The phase II, multiarm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations for platinum-refractory/resistant extensive-stage small-cell lung cancer (ES-SCLC). EXPERIMENTAL DESIGN: Patients with ES-SCLC with progressive disease during or within 90 days of completing first-line platinum-based chemotherapy received one of three regimens: durvalumab plus tremelimumab followed by durvalumab monotherapy (arm A), adavosertib plus carboplatin (arm B), or ceralasertib plus olaparib (arm C). The primary endpoint was objective response rate (ORR). Prespecified exploratory biomarker analyses were conducted in arms A and C. RESULTS: In arm A (n=41), arm B (n=10), and arm C (n=21), confirmed ORR was 7.3%, 0%, and 4.8%, respectively. Safety profiles in all arms were consistent with those of the individual drugs. In arm A, patients with PD-L1 expression (tumor cells [TC] or immune cells [IC]) ≥1% appeared to have a greater likelihood of achieving disease control with durvalumab plus tremelimumab than those with PD-L1 (TC and IC) <1%, and lower baseline circulating tumor DNA (ctDNA) and reduction in on-treatment ctDNA level were both associated with longer overall survival (OS). Among patients treated with ceralasertib plus olaparib in arm C, specific immune response-relevant circulating chemokines and cytokines were identified as early biomarkers of survival and pharmacodynamic biomarkers. CONCLUSIONS: In BALTIC, all combination regimens demonstrated tolerable safety profiles, but antitumor activity was limited in refractory/resistant ES-SCLC. Among patients treated with durvalumab plus tremelimumab, an association of on-treatment reduction in ctDNA with longer OS suggests the potential use of ctDNA as a surrogate of treatment response, warranting further investigation.

Biomarker expression and survival in patients with non-small cell lung cancer receiving adjuvant chemotherapy in Denmark.

INTRODUCTION: Programmed cell death ligand-1 (PD-L1) expression may help identify patients with non-small cell lung cancer (NSCLC) who would benefit from immunotherapy. We assessed PD-L1 expression, and epidermal growth factor receptor (EGFR) and V-Ki-Ras2 Kirsten rat sarcoma (KRAS) mutations in NSCLC patients receiving adjuvant chemotherapy. METHODS: Data for stage IB/II/IIIA NSCLC patients (diagnosed: 2001-2012) were retrieved from Danish population-based registries. Tumor tissue samples were tested for PD-L1 expression using VENTANA PD-L1 (SP263) Assay in tumor cells (TC) at ≥25% cutoff and immune cells (IC) at ≥1% and ≥25% cutoffs. KRAS and EGFR mutations were tested using PCR-based assays. Follow-up began 120 days after diagnosis until death/emigration/January 1, 2015, whichever came first. Using Cox proportional hazard regression, hazard ratios (HRs) were computed for overall survival (OS) for each biomarker, adjusting for age, sex, histology, comorbidities, and tissue specimen age. RESULTS: Among 391 patients identified, 40.4% had stage IIIA disease, 49.9% stage II, and 8.7% stage IB. PD-L1-TC was observed in 38% of patients, EGFR mutations in 4%, and KRAS mutations in 29%. KRAS mutations were more frequent among patients with PD-L1 TC≥25% versus TC<25% (37% versus 24%). OS was not associated with PD-L1 TC≥25% versus TC<25% (stage II: adjusted HR = 1.15 [95% confidence interval: 0.66-2.01]; stage IIIA: 0.72 [0.44-1.19]). No significant association was observed with OS and PD-L1-IC ≥1% and ≥25%. EGFR and KRAS mutations were not associated with a prognostic impact. CONCLUSION: A prognostic impact for NSCLC patients receiving adjuvant chemotherapy was not associated with PD-L1 expression, or with EGFR and KRAS mutations.

Prevalence of mutations in BRCA and homologous recombination repair genes and real-world standard of care of Asian patients with HER2-negative metastatic breast cancer starting first-line systemic cytotoxic chemotherapy: subgroup analysis of the global BREAKOUT study.

BACKGROUND: The multinational BREAKOUT study (NCT03078036) sought to determine the prevalence of germline BRCA1/2 (gBRCA1/2) and somatic BRCA1/2 (sBRCA1/2) mutations and mutations in other homologous recombination repair (HRR) genes in women with HER2-negative metastatic breast cancer (MBC) starting first-line chemotherapy. METHODS: Genetic testing for gBRCA, sBRCA, and HRR gene mutations was performed in patients who started first-line chemotherapy for MBC in the last 90 days (341 patients across 14 countries) who were not selected based on risk factors for gBRCA mutations. We report data from the Asian cohort, which included patients in Japan (7 sites), South Korea (10 sites), and Taiwan (8 sites). RESULTS: Of 116 patients screened, 104 patients were enrolled in the Asian cohort. The median age was 53.0 (range 25-87) years. gBRCA1/2, gBRCA1, and gBRCA2 mutations were detected in 10.6% (11/104), 5.8% (6/104), and 4.8% (5/104) of patients, respectively; none had mutations in both gBRCA1 and gBRCA2. gBRCA1/2 mutations were detected in 10.0% (6/60) and 11.6% (5/43) of patients with hormone receptor-positive and triple-negative MBC, respectively. HRR gene mutations were tested in 48 patients without gBRCA mutations, and 5 (10.4%) had at least one HRR mutation in sBRCA, ATM, PALB2, and CHEK2. CONCLUSION: We report for the first time the prevalence of gBRCA and HRR mutations in an Asian cohort of patients with HER2-negative MBC. Our results suggest that BRCA mutation testing is valuable to determine appropriate treatment options for patients with hormone receptor-positive or triple-negative MBC. STUDY REGISTRATION: NCT03078036.

Impact of Brain Metastases on Treatment Patterns and Outcomes With First-Line Durvalumab Plus Platinum-Etoposide in Extensive-Stage SCLC (CASPIAN): A Brief Report.

Introduction: In the phase 3 study involving the use of durvalumab with or without tremelimumab in combination with platinum-based chemotherapy in untreated extensive-stage SCLC (CASPIAN study), first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone (p = 0.0047). We report exploratory subgroup analyses of treatment patterns and outcomes according to the presence of baseline brain or central nervous system metastases. Methods: Patients (WHO performance status 0 or 1), including those with asymptomatic or treated-and-stable brain metastases, were randomized to four cycles of durvalumab plus EP followed by maintenance durvalumab until progression or up to six cycles of EP and optional prophylactic cranial irradiation. Prespecified analyses of OS and progression-free survival (PFS) in subgroups with or without brain metastases used unstratified-Cox proportional hazards models. The data cutoff was on January 27, 2020. Results: At baseline, 28 out of 268 patients (10.4%) in the durvalumab plus EP arm and 27 out of 269 patients (10.0%) in the EP arm had known brain metastases, of whom 3 of 28 (10.7%) and 4 of 27 (14.8%) had previous brain radiotherapy, respectively. Durvalumab plus EP (versus EP alone) prolonged OS (hazard ratio, 95% confidence interval) in patients with (0.79, 0.44-1.41) or without (0.76, 0.62-0.92) brain metastases, with similar PFS results (0.73, 0.42-1.29 and 0.80, 0.66-0.97, respectively). Among patients without brain metastases, similar proportions in each arm developed new brain lesions as part of their first progression (8.8% and 9.5%), although 8.3% in the EP arm received prophylactic cranial irradiation. Similar proportions in each arm received subsequent brain radiotherapy (20.5% and 21.2%), although more common in patients with than without baseline brain metastases (45.5% and 18.0%). Conclusions: The OS and PFS benefit with first-line durvalumab plus EP were maintained irrespective of the presence of brain metastases, further supporting its standard-of-care use.

A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status.

INTRODUCTION: Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer. METHODS: Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. RESULTS: Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group. CONCLUSION: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.

PD-L1 expression, EGFR and KRAS mutations and survival among stage III unresected non-small cell lung cancer patients: a Danish cohort study.

Programmed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001-2012 and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating immune cells (ICs) by immunohistochemistry ([Formula: see text] 1% threshold for PD-L1+). We genotyped KRAS and EGFR. Follow-up extended from 120 days post-diagnosis to death, emigration, or 31/12/2014. We computed median survival using Kaplan-Meier methods, and hazard ratios (HRs) using Cox regression associating the biomarkers with death, adjusting for confounders. Among 305 patients, 48% had adenocarcinoma; 38% squamous cell carcinoma. Forty-nine percent had PD-L1+ tumors-51% stage IIIA and 26% KRASm. Few (2%) patients had EGFRm. Median survival in months was 14.7 (95% CI = 11.8-17.9) and 13.4 (95% CI = 9.5-16.3) in PD-L1+ and PD-L1- tumors, respectively. KRASm was not associated with death (HR = 1.06, 95% CI = 0.74-1.51 versus wildtype). PD-L1+ tumors yielded a HR = 0.83 (95% CI = 0.63-1.10); PD-L1+ ICs a HR = 0.51 (95% CI = 0.39-0.68). Tumor expression of PD-L1 did not influence survival. PD-L1+ ICs may confer survival benefit in stage III unresected NSCLC patients.

Programmed cell death ligand-1 expression and survival in a cohort of patients with non-small cell lung cancer receiving first-line through third-line therapy in Denmark.

BACKGROUND: PD-L1 expression on tumor cells (TCs) or immune cells (ICs) may be used as a prognostic marker for survival in patients with NSCLC. We characterized PD-L1 expression on TCs or ICs in a patient cohort with NSCLC to determine associations between PD-L1 expression and overall survival (OS), according to EGFR and KRAS mutation status. METHODS: Danish patients aged >18 years diagnosed with NSCLC before 2014 on first- (N = 491), second- (N = 368), or third-line (N = 498) therapy were included. Data were extracted from population-based medical registries. Tumor samples from pathology archives were tested for biomarkers. High PD-L1 expression was defined as expression on ≥25 % of TCs or ICs based on first diagnostic biopsy or surgical resection. KRAS and EGFR mutation status were tested using PCR-based assays. Cox regression analysis was used to compute adjusted HRs and associated 95 % CIs. RESULTS: PD-L1 TC and IC ≥ 25 % were observed in 24.3 %-31.0 % and 11.7-14.7 % of patients, respectively. EGFR and KRAS mutations were detected in 4.7 %-8.8 % and 26.5 %-30.7 % of patients, respectively. PD-L1 TC ≥ 25 % was not associated with survival advantage in first- (HR = 0.96, 95 % CI: 0.75-1.22), second- (1.08, 0.81-1.42), or third-line (0.94, 0.74-1.20) therapy. PD-L1 IC ≥ 25 % was associated with survival advantage in second-line (HR = 0.56, 95 % CI: 0.36-0.86) and third-line (0.69, 0.49-0.97) but not first-line (1.00, 0.70-1.41) therapy. CONCLUSION: No association was observed between PD-L1 TC ≥ 25 % and OS in any therapy line. PD-L1 IC ≥ 25 % may confer survival benefit among some patients who reach second-line therapy.

A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer.

PURPOSE: To characterize programmed cell death ligand-1 (PD-L1) expression in relation to survival and gene mutation status in patients with advanced NSCLC. The study also explored the influence of tumor mutational burden (TMB) on PD-L1 expression and patient characteristics. PATIENTS AND METHODS: Adult patients with histologically or cytologically documented Stage IIIB/Stage IV/recurrent/progressive NSCLC, Eastern Cooperative Oncology Group performance status 0 to 3, and >2 lines of prior systemic treatment regimens were included in this retrospective analysis. Patients were treated from 1997 to 2015 at H. Lee Moffitt Cancer Center and Research Institute, Tampa, or at 7 community centers across the United States. PD-L1 expression level was determined using the VENTANA PD-L1 (SP263) Assay. EGFR and KRAS mutation status and ALK rearrangements were determined by targeted DNA sequencing; these were obtained from clinical records where targeted DNA sequencing was not performed. TMB was calculated as the total number of somatic mutations per sample. RESULTS: From a total of 136 patients included in the study, 23.5% had tumors with high PD-L1 expression (≥25%). There were no significant differences in patient characteristics, overall survival (OS), and progression-free survival (PFS) between patients with high PD-L1 expression (median OS: 39.5 months; median PFS: 15.8 months) vs low PD-L1 expression (<25%; median OS: 38.1 months; median PFS: 18.6 months). PD-L1 expression level correlated (P=0.05) with TMB and was consistent with The Cancer Genome Atlas data. CONCLUSION: In this retrospective analysis, survival outcomes of patients with advanced NSCLC were comparable by PD-L1 expression level. EGFR and KRAS mutation status were not found to be significantly associated with PD-L1 expression level, while TMB was weakly associated with PD-L1 expression level. Overall, PD-L1 expression level was not observed to be an independent prognostic biomarker in this cohort of patients with advanced NSCLC treated with chemotherapy.

The effect of vitamins C and E on biomarkers of oxidative stress depends on baseline level.

Oxidative stress is elevated in obesity, and may be a major mechanism for obesity-related diseases. Nonsmokers (n=396) were randomized to 1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for 2 months. Treatment effect was examined in multiple regression analyses using an intention-to-treat approach. Vitamin C (P=0.001) and vitamin E (P=0.043) reduced plasma F2-isoprostanes. In the overall sample, changes from baseline were +6.8, -10.6, and -3.9% for placebo, vitamin C, and vitamin E groups, respectively. However, a significant interaction with baseline F2-isoprostane was found. When baseline F2-isoprostane was >50 microg/mL, vitamin C reduced F2-isoprostane by 22% (P=0.01). Vitamin E reduced it by 9.8% (P=0.46). Below that cut point, neither treatment produced further reductions. F2-isoprostane>50 microg/mL was strongly associated with obesity, and was present in 42% of the sample. Change in malondialdehyde concentration was minimal. These findings suggest a role for vitamin C in reducing lipid peroxidation. Future research on effects of vitamins C or E on plasma F2-isoprostane should limit participants to those with baseline levels >50 mug/mL. Further studies are needed to establish whether treatment with vitamins C or E in persons with concentrations above that cut point could slow the development of cardiovascular disease.

Usage patterns, health, and nutritional status of long-term multiple dietary supplement users: a cross-sectional study.

BACKGROUND: Dietary supplement use in the United States is prevalent and represents an important source of nutrition. However, little is known about individuals who routinely consume multiple dietary supplements. This study describes the dietary supplement usage patterns, health, and nutritional status of long-term multiple dietary supplement users, and where possible makes comparisons to non-users and multivitamin/mineral supplement users. METHODS: Using a cross-sectional study design, information was obtained by online questionnaires and physical examination (fasting blood, blood pressure, body weight) from a convenience sample of long-term users of multiple dietary supplements manufactured by Shaklee Corporation (Multiple Supp users, n = 278). Data for non-users (No Supp users, n = 602) and multivitamin/mineral supplement users (Single Supp users, n = 176) were obtained from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and NHANES III 1988-1994. Logistic regression methods were used to estimate odds ratios with 95% confidence intervals. RESULTS: Dietary supplements consumed on a daily basis by more than 50% of Multiple Supp users included a multivitamin/mineral, B-complex, vitamin C, carotenoids, vitamin E, calcium with vitamin D, omega-3 fatty acids, flavonoids, lecithin, alfalfa, coenzyme Q10 with resveratrol, glucosamine, and a herbal immune supplement. The majority of women also consumed gamma linolenic acid and a probiotic supplement, whereas men also consumed zinc, garlic, saw palmetto, and a soy protein supplement. Serum nutrient concentrations generally increased with increasing dietary supplement use. After adjustment for age, gender, income, education and body mass index, greater degree of supplement use was associated with more favorable concentrations of serum homocysteine, C-reactive protein, high-density lipoprotein cholesterol, and triglycerides, as well as lower risk of prevalent elevated blood pressure and diabetes. CONCLUSION: This group of long-term multiple dietary supplement users consumed a broad array of vitamin/mineral, herbal, and condition-specific dietary supplements on a daily basis. They were more likely to have optimal concentrations of chronic disease-related biomarkers, and less likely to have suboptimal blood nutrient concentrations, elevated blood pressure, and diabetes compared to non-users and multivitamin/mineral users. These findings should be confirmed by studying the dietary supplement usage patterns, health, and nutritional status of other groups of heavy users of dietary supplements.

Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

Residential history, family characteristics and non-Hodgkin lymphoma, a population-based case-control study in the San Francisco Bay Area.

A population-based, case-control study (N = 1,593 cases, N = 2,515 controls) was conducted in the San Francisco Bay Area, California, to determine risk factors for non-Hodgkin lymphoma (NHL). This report examines residential characteristics, number of siblings, childhood infections, and allergic rhinitis to evaluate the association between NHL and the hygiene hypothesis. Adjusted unconditional logistic regression analyses included HIV-negative participants (N = 1,304 cases, N = 2,402 controls) ages 21 to 74 years, who completed in-person interviews. At childhood ages, odds ratios (OR) for NHL decreased with increasing number of household rooms (age 8 years, P(trend) = 0.08; age 15 years, P(trend) < 0.0001) and increased with more crowded living conditions (quartiles of no. people/no. rooms; age 8 years, P(trend) < 0.0001; age 15 years, P(trend) = 0.0004), whereas at older ages a greater number of people in the household and greater number of household rooms were positively associated with NHL. ORs increased with increasing number of siblings (P(trend) = 0.0003) and increasing birth order (P(trend) = 0.01). Participants with five or more younger siblings had a 50% increased OR for NHL. ORs for NHL decreased with an increasing number of different infections during childhood (age 8 years, P(trend) < 0.0001; age 15 years, P(trend) = 0.0003) and with history of allergic rhinitis (P < 0.0001). Our results are somewhat consistent with the hygiene hypothesis that less crowding and better sanitation results in fewer infections early in life and an increased incidence of immune-related conditions later in life. The role of the complex relationship between residential history, family characteristics, childhood infections, and immune function in the development of NHL warrants further investigation in pooled analyses.

Mesothelioma in the United States: a Surveillance, Epidemiology, and End Results (SEER)-Medicare investigation of treatment patterns and overall survival.

INTRODUCTION: Mesothelioma is a rare malignancy typically associated with exposure to asbestos and poor survival. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and overall survival (OS) utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results-Medicare database. MATERIALS AND METHODS: Patients in this study were diagnosed with malignant mesothelioma of the pleura or peritoneum between January 1, 2005 and December 31, 2009 with follow-up for survival through December 31, 2010. We examined both patient and tumor characteristics at time of diagnosis and subsequent treatment patterns (surgery, radiation, and chemotherapy). Among patients treated with chemotherapy, we determined chemotherapy regimen and OS by line of therapy. RESULTS: Of the 1,625 patients considered eligible for this investigation, the median age at diagnosis was 78 years. Nearly a third of patients (30%) had surgery as part of their treatment and 45% were given chemotherapy. The median OS was 8 months (range 1-69 months). Among chemotherapy patients, the most commonly (67%) prescribed regimen for first-line therapy was cisplatin or carboplatin (Ca/Ci) combined with pemetrexed (Pe). Among those prescribed Ca/Ci + Pe as first-line therapy, retreatment with Ca/Ci + Pe (28%) or treatment with gemcitabine (30%) were the most common second-line therapies. Median OS for those receiving first-line chemotherapy was 7 months, and among those receiving second-line therapy median OS was extended an additional 5 months. CONCLUSION: Irrespective of surgical resection, mesothelioma patients receiving some form of chemotherapy survived longer than patients who did not, with an additional survival benefit among those patients receiving multimodal treatment.

The work and home activities questionnaire: energy expenditure estimates and association with percent body fat.

BACKGROUND: Understanding and increasing physical activity requires assessment of occupational, home, leisure and sedentary activities. METHODS: A physical activity questionnaire was developed using data from a large representative U.S. sample; includes occupational, leisure and home-based domains; and produces estimates of energy expenditure, percent body fat, minutes in various domains, and meeting recommendations. It was tested in 396 persons, mean age 44 years. Estimates were evaluated in relation to percent body fat measured by dual-energy x-ray absorptiometry. RESULTS: Median energy expenditure was 2365 kcal (women) and 2960 kcal (men). Women spent 35.1 minutes/day in moderate household activities, 13.0 minutes in moderate leisure and 4.0 minutes in vigorous activities. Men spent 18.0, 22.5 and 15.6 minutes/day in those activities, respectively. Men and women spent 276.4 and 257.0 minutes/day in sedentary activities. Respondents who met recommendations through vigorous activities had significantly lower percent body fat than those who did not, while meeting recommendations only through moderate activities was not associated with percent body fat. Predicted and observed percent body fat correlated at r = .73 and r = .82 for men and women respectively, P < .0001. CONCLUSIONS: This questionnaire may be useful for understanding health effects of different components of activity, and for interventions to increase activity levels.

Vitamin C treatment reduces elevated C-reactive protein.

Plasma C-reactive protein (CRP) is an inflammatory biomarker that predicts cardiovascular disease. Lowering elevated CRP with statins has reduced the incidence of cardiovascular disease. We investigated whether vitamin C or E could reduce CRP. Healthy nonsmokers (N=396) were randomized to three groups, 1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for 2 months. Median baseline CRP was low, 0.85 mg/L. No treatment effect was seen when all participants were included. However, a significant interaction was found, indicating that treatment effect depends on baseline CRP concentration. Among participants with CRP indicative of elevated cardiovascular risk (> or =1.0 mg/L), vitamin C reduced the median CRP by 25.3% vs placebo (p=0.02) (median reduction in the vitamin C group, 0.25 mg/L, 16.7%). These effects are similar to those of statins. The vitamin E effect was not significant. In summary, treatment with vitamin C but not vitamin E significantly reduced CRP among individuals with CRP > or =1.0 mg/L. Among the obese, 75% had CRP > or =1.0 mg/L. Research is needed to determine whether reducing this inflammatory biomarker with vitamin C could reduce diseases associated with obesity. But research on clinical benefits of antioxidants should limit participants to persons with elevations in the target biomarkers.

Dietary patterns and risk of ovarian cancer in the California Teachers Study cohort.

Previous studies have examined the association between individual foods or nutrients, but not overall diet, and ovarian cancer risk. To account for the clustering of foods in the diet, we investigated the association between dietary patterns and risk of ovarian cancer in the prospective California Teachers Study cohort. Of 97,292 eligible women who completed the baseline dietary assessment in 1995-1996, 311 women developed epithelial ovarian cancer on or before December 31, 2004. Based on principal components analysis, 5 major dietary patterns were identified and termed plant-based, high-protein/high-fat, high-carbohydrate, ethnic, and salad-and-wine. Multivariable Cox proportional hazards regression analysis was used to estimate associations between these dietary patterns and risk of incident ovarian cancer. Most of the dietary patterns were not significantly associated with ovarian cancer risk. However, women who followed a plant-based diet had higher risk; comparing those in the top quintile of plant-based food intake with those in the lowest quintile, the relative risk of ovarian cancer was 1.65 (95% confidence interval = 1.07-2.54; P(trend) = 0.03). Associations with the 5 dietary patterns did not vary by known ovarian cancer risk factors or other behavioral or sociodemographic characteristics. Overall, our results show no convincing associations between dietary patterns and ovarian cancer risk.

Dietary patterns, Mediterranean diet, and endometrial cancer risk.

This study examines the association between dietary patterns and endometrial cancer risk. A case-control study of endometrial cancer was conducted from 1996 to 1999 in the San Francisco Bay Area in white, African-American, and Latina women age 35-79. Dietary patterns were defined using a principal components analysis; scoring dietary intake based on correspondence to a Mediterranean-style diet; and by jointly categorizing intake of fruits/vegetables and dietary fat. Four dietary patterns were identified and labeled "plant-based," "western," "ethnic," and "phytoestrogen-rich." None of these dietary patterns nor adherence to a Mediterranean diet (to the extent consumed by this population) was associated with endometrial cancer risk. However, among non-users of supplements, greater consumption of the "western" dietary pattern was associated with a 60% increase in risk (95% CI: 0.95-2.7 per unit change; P-interaction = 0.10). A diet characterized by high fat consumption increased risk, regardless of fruit and vegetable consumption (OR = 1.4, 95% CI: 0.97-2.1 for high fat, low fruit/vegetable intake and OR = 1.4, 95% CI: 0.95-2.1 for high fat, high fruit/vegetable intake compared to low fat, high fruit/vegetable intake). Thus, while like others we found that dietary fat increases endometrial cancer risk, the evaluation of dietary patterns did not provide any additional information regarding risk.