Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010

PURPOSE: Two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, have been shown in randomized clinical trials to reduce the risk of developing primary invasive breast cancer (IBC) in high-risk women. In 1998, the U.S. Food and Drug Administration (FDA) used these studies as a basis for approving tamoxifen for primary breast chemoprevention in both premenopausal and postmenopausal women at high risk. In 2007, the FDA approved raloxifene for primary breast cancer chemoprevention for postmenopausal women. METHODS: Data from the year 2010 National Health Interview Survey (NHIS) were analyzed to estimate the prevalence of tamoxifen and raloxifene use for chemoprevention of primary breast cancers among U.S. women. RESULTS: Prevalence of use of chemopreventive agents for primary tumors was 20,598 (95% CI, 518–114,864) for U.S. women aged 35 to 79 for tamoxifen. Prevalence was 96,890 (95% CI, 41,277–192,391) for U.S. women aged 50 to79 for raloxifene. CONCLUSION: Use of tamoxifen and raloxifene for prevention of primary breast cancers continues to be low. In 2010, women reporting medication use for breast cancer chemoprevention were primarily using the more recently FDA-approved drug raloxifene. Multiple possible explanations for the low use exist, including lack of awareness and/or concern about side effects among primary care physicians and patients

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Cumulative Exposure to E-Cigarette Coupons and Changes in E-Cigarette Use Among U.S. Adults

INTRODUCTION: Coupons are an effective, frequently used tobacco marketing strategy. This study examined prospective associations between cumulative exposure to e-cigarette coupons and changes in e-cigarette use among U.S. adults. METHODS: Data were from a representative U.S. adult cohort (n=19,824) in the Population Assessment of Tobacco and Health Study (waves [W] 2, 3, 4, and 5), collected from October 2014 to November 2019. Analysis was conducted in 2022. Four logistic regression models examined associations of a number of waves for which participants received e-cigarette coupons during W2-W4 with changes in e-cigarette use: W2 never use to W5 current use (initiation); W2 current nondaily use to W5 daily use (progression); W2 current use to W5 former use (cessation), and W2 former use to W5 current use (return-to-use). RESULTS: Overall, 66.1% of U.S. adults never used e-cigarettes, 10.6% currently used e-cigarettes, and 23.4% formerly used e-cigarettes at W2. The average number of waves for which participants received e-cigarette coupons during W2-W4 was 0.13: 0.10 among W2 individuals who never used e-cigarettes, 0.30 among individuals who currently used e-cigarettes on a nondaily basis, 0.50 among individuals who currently used e-cigarettes, and 0.17 among individuals who formerly used e-cigarettes. Receiving coupons at increased waves was associated with (1) greater odds of initiation (AOR=1.58, 95% CI=1.26-1.97); (2) lower odds of cessation (AOR=0.78, 95% CI=0.67-0.91); and (3) increased odds of return-to-use (AOR=1.39, 95% CI=1.14-1.69). Findings did not differ by W2 cigarette smoking status. CONCLUSIONS: E-cigarette coupons may encourage and sustain e-cigarette use. Policies restricting e-cigarette coupons may curb e-cigarette use

E-cigarette initiation predicts subsequent academic performance among youth: Results from the PATH Study

Research shows cigarette smoking is associated with lower academic performance among youth. This study examines how initiating e-cigarette use is associated with subsequent academic performance. Data from Waves 2–4 youth and parent surveys of the Population Assessment of Tobacco and Health (PATH) Study were analyzed. Youth (12–15 years old) who reported never using any tobacco products at Wave 2 were included in the analysis (n = 4960). Initiation of e-cigarettes and cigarettes was assessed at Wave 3. Weighted multivariable linear regression models were tested to assess the association between e-cigarette and cigarette initiation at Wave 3 and academic performance at Wave 4, controlling for covariates at Wave 2. At Wave 3, 4.3% and 1.9% of youth initiated e-cigarette and cigarette use, respectively. Youth who initiated e-cigarette use at Wave 3 had lower academic performance at Wave 4, compared to those who did not initiate e-cigarette use (adjusted regression coefficient [ARC] -0.22, 95% confidence interval [CI] -0.43, −0.02). Initiating cigarettes was also associated with lower academic performance (ARC -0.51, 95% CI -0.84, −0.18). Results indicate that e-cigarette use initiation is associated with lower subsequent academic performance, independent from the association between cigarette use initiation and lower academic performance among U.S. youth. Future research needs to examine whether preventing youth e-cigarette and cigarette use can lead to improvement in academic performance

Awareness of Alcohol and Cancer Risk and the California Proposition 65 Warning Sign Updates: A Natural Experiment

In 1986, California enacted Proposition 65 (P65), requiring businesses to display warning signs informing consumers that specific chemicals and alcohol exposure increase the risk of cancer and reproductive harm. In 2018, the P65 alcohol warning signs were updated to include an informational P65 website link, and the update was associated with media coverage and increased enforcement of warning requirements. This study examines knowledge of the association between alcohol use and cancer risk in California compared to the rest of the US before and after the 2018 P65 update. We analyzed state-level data on alcohol and cancer knowledge from the Health Information National Trends Survey from 2017 (n = 3285), 2019 (n = 5438), and 2020 (n = 3865). We performed multinomial logistic regressions to examine knowledge levels by survey year and location (California vs. all other states) and reported the predicted marginals of knowledge by survey year and location. The adjusted prevalence of respondents who reported an association between alcohol and cancer risk was higher in California (41.6%) than the remaining states (34.1%) (p = 0.04). However, knowledge levels decreased significantly over survey years, and there was no evidence for an effect of the P65 update on knowledge in California compared to other states based on the testing of an interaction between state and year (p = 0.32). The 1986 warning signs may have had an enduring effect on awareness, though the update, so far, has not. Further efforts are needed to determine how to increase alcohol and cancer knowledge to address the burden of alcohol-attributable cancers

Differences in Fruit and Vegetable Intake among Hispanic Subgroups in California: Results from the 2005 California Health Interview Survey

Objective: To compare total fruit and vegetable intake in cup equivalents and its individual components among Hispanic subgroups in California. Methods: Data are from the adult portion of the 2005 California Health Interview Survey. Hispanic/Latino subjects (n=7,954) were grouped into six subcategories (Mexican, Central American, Caribbean, Spanish American, South American, and \u3e1 group). Total fruit and vegetable intake in cup equivalents was estimated from frequency responses about seven food categories. Both t test and χ2 test were used to assess differences in sociodemographic characteristics across Hispanic subgroups. Multivariate linear regressions using SUDAAN software (Survey Data Analysis, version 9.0.1, 2005, Research Triangle Institute, Research Triangle Park, NC) were conducted to obtain means of total fruit and vegetable intake in cup equivalents and its components by Hispanic subgroups controlling for confounders. Results: Hispanic subgroups did not differ in their intake of total fruit and vegetable intake in cup equivalents (mean 3.4 c and 2.9 c for men and women, respectively). Small but significant differences (P\u3c0.01) were found across Hispanic subgroups in individual fruit and vegetable components (green salad [women only], cooked dried beans and nonfried white potatoes) after adjusting for potential sociodemographic and acculturation confounders. Conclusions: Fruit and vegetable intake by Hispanic respondents did not meet the national recommendation, although their reported intake is higher compared to other race/ethnicity groups. The public health message remains the same: Increase fruit and vegetable intake. Examination of intake for subgroups of Hispanics may enhance the utility of dietary information for surveillance, program and message design, and intervention and evaluation. © 2009 American Dietetic Association

Phase II Trial of a DNA Vaccine Encoding Prostatic Acid Phosphatase (pTVG-HP [MVI-816]) in Patients With Progressive, Nonmetastatic, Castration-Sensitive Prostate Cancer.

PurposeWe previously reported the safety and immunologic effects of a DNA vaccine (pTVG-HP [MVI-816]) encoding prostatic acid phosphatase (PAP) in patients with recurrent, nonmetastatic prostate cancer. The current trial evaluated the effects of this vaccine on metastatic progression.Patients and methodsNinety-nine patients with castration-sensitive prostate cancer and prostate-specific antigen (PSA) doubling time (DT) of less than 12 months were randomly assigned to treatment with either pTVG-HP co-administered intradermally with 200 μg granulocyte-macrophage colony-stimulating factor (GM-CSF) adjuvant or 200 μg GM-CSF alone six times at 14-day intervals and then quarterly for 2 years. The primary end point was 2-year metastasis-free survival (MFS). Secondary and exploratory end points were median MFS, changes in PSA DT, immunologic effects, and changes in quantitative 18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) imaging.ResultsTwo-year MFS was not different between study arms (41.8% vaccine v 42.3%; P = .97). Changes in PSA DT and median MFS were not different between study arms (18.9 v 18.3 months; hazard ratio [HR], 1.6; P = .13). Preplanned subset analysis identified longer MFS in vaccine-treated patients with rapid (&lt; 3 months) pretreatment PSA DT (12.0 v 6.1 months; n = 21; HR, 4.4; P = .03). PAP-specific T cells were detected in both cohorts, including multifunctional PAP-specific T-helper 1-biased T cells. Changes in total activity (total standardized uptake value) on 18F-NaF PET/CT from months 3 to 6 increased 50% in patients treated with GM-CSF alone and decreased 23% in patients treated with pTVG-HP (n = 31; P = .07).ConclusionpTVG-HP treatment did not demonstrate an overall increase in 2-year MFS in patients with castration-sensitive prostate cancer, with the possible exception of a subgroup with rapidly progressive disease. Prespecified 18F-NaF PET/CT imaging conducted in a subset of patients suggests that vaccination had detectable effects on micrometastatic bone disease. Additional trials using pTVG-HP in combination with PD-1 blockade are under way