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In node-positive breast cancer, adjuvant doxorubicin plus cyclophosphamide followed by docetaxel was associated with significantly better disease-free survival than the three drugs together or doxorubicin–docetaxel. Premenopausal women who became amenorrheic as a consequence of treatment had significantly improved overall and disease-free survival, regardless of their treatment or the hormone-receptor status of their tumor. In node-positive breast cancer, adjuvant doxorubicin plus cyclophosphamide followed by docetaxel was associated with significantly better disease-free survival than the three drugs together or doxorubicin–docetaxel. Premenopausal women who became amenorrheic as a consequence of treatment had significantly improved overall and disease-free survival. Chemotherapy regimens that combine anthracyclines and taxanes with other agents such as cyclophosphamide result in improved disease-free and overall survival among women with operable lymph-node–positive breast cancer. 1 , 2 The contribution of cyclophosphamide to these regimens has not been defined. Initial evaluations of taxanes in the adjuvant setting used a sequential approach of administration after completion of the anthracycline-based regimen. Phase 3 trials in advanced breast cancer have shown superiority with a doxorubicin–docetaxel combination as compared with doxorubicin–cyclophosphamide and with doxorubicin, cyclophosphamide, and docetaxel (ACT, also known as the TAC regimen), and as compared with fluorouracil, doxorubicin, and cyclophosphamide. 3 , 4 These . . .

Background With the increasing changes in tobacco use patterns, “current use” definition and the survey used may have important implications for monitoring population use trends. Methods Using three US surveys (2014/15 TUS-CPS, NHIS and PATH), we compared the adult (age 18+) prevalence of four product groups (cigarettes, other combustibles, smokeless tobacco, and e-cigarettes) based on three past 30-day frequency of use thresholds: 1+, 10+, and 25+ days. We also examined mutually exclusive single, dual, and polytobacco users as a percentage of total users for each product group. Results Regardless of threshold or product, the prevalence was higher in PATH followed by NHIS and TUS-CPS, in some cases by large percentages. The differences in cigarette and smokeless tobacco use prevalence in going from the 1+ to 10+ days and to the 25+ days threshold were minimal. Applying different frequency thresholds had the largest impact on other combustibles prevalence, with a 60% reduction with the 10+ days threshold and a 80% reduction with the 25+ days threshold, compared to the 1+ days threshold, followed by e-cigarettes with 40 and 60% reductions, respectively. The proportion of dual and polytobacco users decreased considerably when using the 10+ vs. the 1+ days threshold and polytobacco use was almost non-existent with the 25+ days threshold. Conclusion The estimated prevalence of each tobacco product use depends largely on the survey and frequency of use threshold adopted. The choice of survey and frequency threshold merits serious consideration when monitoring patterns of tobacco use.

The NSABP B-30 trial addresses whether amenorrhea after adjuvant chemotherapy increases survival. Preliminary to the trial outcome analysis, we examined the incidence of amenorrhea and its relationship to symptoms and quality of life (QOL) in the standard-care arm of this adjuvant breast cancer trial. Premenopausal women treated on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm were included. Questionnaires assessing menstrual history, QOL, and symptoms were administered at baseline, day 1 of cycle 4 (or 9 weeks from start of chemotherapy for those who stopped chemotherapy early), and at 6, 12, and 24 months. Seven hundred and eight patients were evaluable for the analysis, with median potential follow-up of 57.5 months. Of these, 321 patients also participated in the QOL substudy. Of the 708 patients, 83% reported >=1 episode of amenorrhea for >=6 months. The estimated rate of resumption of menses at 24 months was 45.3% for women <40 years, 10.9% for women 40-50, and 3.2% for women >50 years. Those treated with tamoxifen were more likely to become amenorrheic (p = 0.003). Menstrual status was not significantly associated with QOL or symptoms. Prolonged amenorrhea is associated with a regimen that contains doxorubicin, cyclophosphamide, and docetaxel, and is age dependent and impacted by tamoxifen use. Vasomotor symptoms are common in this patient population but are not associated with menstrual status. These results can be used to inform premenopausal women about the risk and time course of amenorrhea associated with this common adjuvant therapy regimen, along with the effects on symptoms and QOL.

Previous research has demonstrated that loss-framed messages are more effective than gain-framed messages in motivating detection behaviors such as screening. The present study examined whether affective context moderates the degree to which message frame is associated with behavioral intentions to engage in colorectal cancer screening. In particular, we buttressed a framing manipulation with an “affective booster” to increase anticipated and anticipatory emotions associated with the framed messages. Consistent with previous research, we found that loss-framed messages are more effective in increasing intentions to screen. However, we found that among individuals who received gain-framed messages (but not loss-framed messages), the affective booster increased message persuasiveness. This effect on intentions was partially mediated by self-efficacy for engaging in screening. This study indicates that in the presence of emotional boosters, loss-framed messages may lose their advantage over gain-framed messages in motivating detection behaviors, and that self-efficacy may partially explain these effects.

IntroductionEven prior to 2018, electronic nicotine delivery systems (ENDS) began to dramatically change the landscape of tobacco products and product use patterns in the USA.MethodsUsing a Markov multistate transition model accounting for complex survey design, transition rates between never, non-current, cigarette, ENDS and dual use states were estimated for 23 253 adult participants in waves 1–4 (approximately 2013–2017) of the Population Assessment of Tobacco and Health study. We made short-term transition projections and estimated HRs for age, sex, race/ethnicity, education and income.ResultsCigarette use was persistent among adults, with 89.7% (95% CI 89.1% to 90.3%) of exclusive cigarette users and 86.1% (95% CI 84.4% to 87.9%) of dual users remaining cigarette users (either exclusive or dual) after one wave. In contrast, ENDS use was less persistent, with 72.1% (95% CI 69.6% to 74.6%) of exclusive ENDS users and 50.5% (95% CI 47.8% to 53.3%) of dual users remaining ENDS users (with or without cigarettes) after one wave. Exclusive ENDS users were more likely to start cigarette use after one wave than either never users (HR 25.2; 95% CI 20.9 to 30.5) or non-current users (HR 5.0; 95% CI 4.3 to 5.8). Dual users of ENDS and cigarettes were more likely to stop using cigarettes than exclusive cigarette users (HR 1.9; 95% CI 1.6 to 2.3). Transition rates varied among sociodemographic groups.ConclusionsMultistate transition models are an effective tool for uncovering and characterising longitudinal patterns and determinants of tobacco use from complex survey data. ENDS use among US adults was less persistent than cigarette use prior to 2018.

IntroductionIt is unknown how recent changes in the tobacco product marketplace have impacted transitions in cigarette and electronic nicotine delivery system (ENDS) use.MethodsA multistate transition model was applied to 24 242 adults and 12 067 youth in waves 2–4 (2015–2017) and 28 061 adults and 12 538 youth in waves 4 and 5 (2017–2019) of the Population Assessment of Tobacco and Health Study. Transition rates for initiation, cessation and product transitions were estimated in multivariable models, accounting for gender, age group, race/ethnicity and daily versus non-daily product use.ResultsChanges in ENDS initiation/relapse rates depended on age, including among adults. Among youth who had never established tobacco use, the 1-year probability of ENDS initiation increased after 2017 from 1.6% (95% CI 1.4% to 1.8%) to 3.8% (95% CI 3.4% to 4.2%). Persistence of ENDS-only use (ie, 1-year probability of continuing to use ENDS only) increased for youth from 40.7% (95% CI 34.4% to 46.9%) to 65.7% (95% CI 60.5% to 71.1%) and for adults from 57.8% (95% CI 54.4% to 61.3%) to 78.2% (95% CI 76.0% to 80.4%). Persistence of dual use similarly increased for youth from 48.3% (95% CI 37.4% to 59.2%) to 60.9% (95% CI 43.0% to 78.8%) and for adults from 40.1% (95% CI 37.0% to 43.2%) to 63.8% (95% CI 59.6% to 67.6%). Youth and young adults who used both products became more likely to transition to ENDS-only use, but middle-aged and older adults did not.ConclusionsENDS-only and dual use became more persistent. Middle-aged and older adults who used both products became less likely to transition to cigarette-only use but not more likely to discontinue cigarettes. Youth and young adults became more likely to transition to ENDS-only use.

Neutrophil elastase speeds up the progression of lung cancer by degrading insulin receptor substrate-1 and thereby phosphatidylinositol 3-kinase. This is the first description of a secreted proteinase gaining access to the inside of a cell to alter intracellular signaling ( pages 161–163 ). Lung cancer is the leading cause of cancer death worldwide 1 . Recent data suggest that tumor-associated inflammatory cells may modify lung tumor growth and invasiveness 2 , 3 . To determine the role of neutrophil elastase (encoded by Elane ) on tumor progression, we used the loxP -Stop- loxP K-ras G12D (LSL–K-ras) model of mouse lung adenocarcinoma 4 to generate LSL–K-ras- Elane −/− mice. Tumor burden was markedly reduced in LSL–K-ras- Elane −/− mice at all time points after induction of mutant K-ras expression. Kaplan-Meier survival analysis showed that whereas all LSL–K-ras- Elane +/+ mice died, none of the mice lacking neutrophil elastase died. Neutrophil elastase directly induced tumor cell proliferation in both human and mouse lung adenocarcinomas by gaining access to an endosomal compartment within tumor cells, where it degraded insulin receptor substrate-1 (IRS-1). Immunoprecipitation studies showed that, as neutrophil elastase degraded IRS-1, there was increased interaction between phosphatidylinositol 3-kinase (PI3K) and the potent mitogen platelet-derived growth factor receptor (PDGFR), thereby skewing the PI3K axis toward tumor cell proliferation. The inverse relationship identified between neutrophil elastase and IRS-1 in LSL–K-ras mice was also identified in human lung adenocarcinomas, thus translating these findings to human disease. This study identifies IRS-1 as a key regulator of PI3K within malignant cells. Additionally, to our knowledge, this is the first description of a secreted proteinase gaining access to the inside of a cell and altering intracellular signaling.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its related disease (COVID-19) constitute the greatest global public health crisis in more than a century. As of October 2023, there have been more than 771 million confirmed cases of COVID-19, resulting in more than 6.9 million deaths, despite the 13.5 billion vaccine doses administered worldwide.1 In the United States alone, confirmed cases of COVID-19 have exceeded 103 million and caused more than 1.1 million deaths.2 The health impact of the pandemic has been most disproportionate in underserved racial and ethnic minority communities. For example, at the start of the pandemic, COVID-19-related hospitalization rates were nearly four times higher in Hispanic/Latino and non-Hispanic Black/African American communities and death rates were three times higher in American Indian/Alaska Native communities compared with the nonHispanic White population.3-8 These disparities are the result of multiple factors, including long-standing challenges in health care access as well as structural racism.9Although highly efficacious vaccines and therapeutics and community mitigation strategies are among the resources needed to control the pandemic, communities that have been hardest hit also have a high prevalence ofvaccine hesitancy-largely a result of widespread misinformation and mistrust of science, fueled in part by past research misdeeds. The National Institutes of Health (NIH) established the Community Engagement Alliance (CEAL) to address the challenges seen in the most burdened communities through community engagement and communityengaged research, with the goal of building trust in science and promoting inclusive participation in all aspects of NIH-led scientific responses to the pandemic.10 This response includes participation in clinical trials of therapeutics, vaccines, and other preventive interventions as well as the development of strategies to promote vaccination uptake and sustained adoption of community mitigation practices.11 We address the adverse impact of misinformation and mistrust on COVID-19 disparities and the CEAL research teams' approaches, in strong alliance with community partners, to promote inclusive participation and uptake of effective treatments, vaccines, and community mitigation efforts against COVID-19.

PurposeLung cancer is the leading cause of cancer death, but the advent of lung cancer screening using low-dose computed tomography offers a tremendous opportunity to improve lung cancer outcomes. Unfortunately, implementation of lung cancer screening has been hampered by substantial barriers and remains suboptimal. Specifically, the commentary emphasizes the intersectionality of smoking history and several important sociodemographic characteristics and identities that should inform lung cancer screening outreach and engagement efforts, including socioeconomic considerations (e.g., health insurance status), racial and ethnic identity, LGBTQ + identity, mental health history, military experience/veteran status, and geographic residence in addressing specific community risk factors and future interventions in efforts to make strides toward equitable lung cancer screening.MethodsMembers of the Equitable Implementation of Lung Cancer Screening Interest Group with the Cancer Prevention and Control Network (CPCRN) provide a critical commentary based on existing literature regarding smoking trends in the US and lung cancer screening uptake to propose opportunities to enhance implementation and support equitable distribution of the benefits of lung cancer screening.ConclusionThe present commentary utilizes information about historical trends in tobacco use to highlight opportunities for targeted outreach efforts to engage communities at high risk with information about the lung cancer screening opportunity. Future efforts toward equitable implementation of lung cancer screening should focus on multi-level implementation strategies that engage and work in concert with community partners to co-create approaches that leverage strengths and reduce barriers within specific communities to achieve the potential of lung cancer screening.

IntroductionThe use of cigarettes and electronic nicotine delivery system (ENDS) has likely changed since 2019 with the rise of pods and disposables, the lung injuries outbreak, flavour bans, Tobacco 21 and the COVID-19 pandemic.MethodsUsing the Population Assessment of Tobacco and Health Study, we applied a multistate transition model to 28 061 adults in waves 4–5 (2017–2019) and 24 584 adults in waves 5–6 (2019–2021), estimating transition rates for initiation, cessation and switching products for each period overall and by age group.ResultsCigarette initiation among adults who never used either product decreased from 2017–2019 to 2019–2021, but ENDS initiation did not significantly change. The persistence of ENDS-only use remained high (75%–80% after 1 year). Cigarette-only use transitions remained similar (88% remaining, 7% to non-current use and 5% to dual or ENDS-only use). In contrast, dual use to ENDS-only transitions increased from 9.5% (95% CI 7.3% to 11.7%) to 20.0% (95% CI 17.4% to 22.6%) per year, decreasing the persistence of dual use. The dual to cigarette-only use transition remained at about 25%. These changes were qualitatively similar across adult age groups, though adults ages 18–24 years exhibited the highest probability of switching from cigarette-only use to dual use and from dual use to ENDS-only use.ConclusionsThe persistence of ENDS use among adults remained high in 2019–2021, but a larger fraction of dual users transitioned to ENDS-only use compared with 2017–2019. Because the fraction of cigarette-only users switching to dual use remained low, especially among older adults, the public health implications of this change are minimal.