Retailers' Compliance with Federal Age of Cigarette Sales Policies -- Pitt County, North Carolina, January-March 2022.

BACKGROUND: Tobacco use remains a leading cause of preventable morbidity and premature mortality. In December 2019, the federal age of sale for tobacco products increased from 18 to 21 years of age. This study aimed to evaluate the implementation of federal tobacco 21 policies in Pitt County, North Carolina (NC), by conducting multiple purchase attempts for cigarettes. METHOD: Stores in Pitt County that sold cigarettes were randomly sampled and visited by up to six different underage (18-20) buyers who attempted to buy cigarettes from January-March 2022. Buyers made a total of 217 cigarette purchase attempts from 49 Pitt County retailers. Analyses were conducted using SPSS Complex Samples (v.28/Macintosh) and estimate retailer prevalence of requesting identification (ID) and selling to underage buyers across multiple purchase attempts. RESULTS: On average, retailers failed to request ID in 15.4% of purchase attempts (95% CI: 9.4%-21.3%) and sold to an underage buyer 34.2% of the time (95% CI: 27.0-41.4%). Additionally, 75.5% (95% CI: 63.4%-84.6%) of retailers sold to an underage buyer at least once. LIMITATIONS: This study is limited to a single county in NC and to underage buyers aged 18 to 20. CONCLUSION: There is widespread non-compliance with federal age of sale policies for tobacco products in Pitt County, NC. State enforcement is warranted, and NC's youth access law should be amended to match the federal age of sale. Changes to the law should allow research involving underage purchases.

Neighbourhood inequities in the availability of retailers selling tobacco products: a systematic review.

OBJECTIVE: To examine inequities in tobacco retailer availability by neighbourhood-level socioeconomic, racial/ethnic and same-sex couple composition. DATA SOURCES: We conducted a 10 November 2022 search of PubMed, PsycINFO, Global Health, LILACS, Embase, ABI/Inform, CINAHL, Business Source Complete, Web of Science and Scopus. STUDY SELECTION: We included records from Organisation for Economic Co-operation and Development member countries that tested associations of area-level measures of tobacco retailer availability and neighbourhood-level sociodemographic characteristics. Two coders reviewed the full text of eligible records (n=58), including 41 records and 205 effect sizes for synthesis. DATA EXTRACTION: We used dual independent screening of titles, abstracts and full texts. One author abstracted and a second author confirmed the study design, location, unit of analysis, sample size, retailer data source, availability measure, statistical approach, sociodemographic characteristic and unadjusted effect sizes. DATA SYNTHESIS: Of the 124 effect sizes related to socioeconomic inequities (60.5% of all effect sizes), 101 (81.5%) indicated evidence of inequities. Of 205 effect sizes, 69 (33.7%) tested associations between retailer availability and neighbourhood composition of racially and ethnically minoritised people, and 57/69 (82.6%) documented inequities. Tobacco availability was greater in neighbourhoods with more Black, Hispanic/Latine and Asian residents (82.8%, 90.3% and 40.0% of effect sizes, respectively). Two effect sizes found greater availability with more same-sex households. CONCLUSIONS: There are stark inequities in tobacco retailer availability. Moving beyond documenting inequities to partnering with communities to design, implement, and evaluate interventions that reduce and eliminate inequities in retail availability is needed to promote an equitable retail environment. PROSPERO REGISTRATION NUMBER: CRD42019124984.

In-silico identification of deleterious non-synonymous SNPs of TBX1 gene: Functional and structural impact towards 22q11.2DS.

The TBX1 gene plays a critical role in the development of 22q11.2 deletion syndrome (22q11.2DS), a complex genetic disorder associated with various phenotypic manifestations. In this study, we performed in-silico analysis to identify potentially deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the TBX1 gene and evaluate their functional and structural impact on 22q11.2DS. A comprehensive analysis pipeline involving multiple computational tools was employed to predict the pathogenicity of nsSNPs. This study assessed protein stability and explored potential alterations in protein-protein interactions. The results revealed the rs751339103(C>A), rs780800634(G>A), rs1936727304(T>C), rs1223320618(G>A), rs1248532217(T>C), rs1294927055 (C>T), rs1331240435 (A>G, rs1601289406 (A>C), rs1936726164 (G>A), and rs911796187(G>A) with a high-risk potential for affecting protein function and stability. These nsSNPs were further analyzed for their impact on post-translational modifications and structural characteristics, indicating their potential disruption of molecular pathways associated with TBX1 and its interacting partners. These findings provide a foundation for further experimental studies and elucidation of potential therapeutic targets and personalized treatment approaches for individuals affected by 22q11.2DS.

Divergent Cellular Expression Patterns of PD-L1 and PD-L2 Proteins in Breast Cancer.

PD-L1 immunohistochemistry (IHC) has become an established method for predicting cancer response to targeted anti-PD1 immunotherapies, including breast cancer (BC). The alternative PD-1 ligand, PD-L2, remains understudied but may be a complementary predictive marker. Prospective analysis of 32 breast cancers revealed divergent expression patterns of PD-L1 and PD-L2. PD-L1-positivity was higher in immune cells than in cancer cells (median = 5.0% vs. 0.0%; p = 0.001), whereas PD-L2-positivity was higher in cancer cells than immune cells (median = 30% vs. 5.0%; p = 0.001). Percent positivity of PD-L1 and PD-L2 were not correlated, neither in cancer cells nor immune cells. Based on a cut-point of ≥1% positivity, ER+ tumors (n = 23) were frequently PD-L2-positive (73.9%), whereas only 40.9% were PD-L1-positive. These data suggest differential control of cellular PD-L1 and PD-L2 expression in BC and a potential role for PD-L2 IHC as a complementary marker to PD-L1 to improve selection of aggressive ER+ BC that may benefit from anti-PD-1 therapy.

Comparison of Tobacco Product Prices at Fort Liberty Army Installation and Surrounding Community Areas, 2021.

INTRODUCTION: High rates of tobacco use persist in the U.S. military, with 18.4% of service members smoking cigarettes in 2018. The Department of Defense's (DoD) 2017 policy required that tobacco retailers on military installations set tobacco product prices equal to the most common community price, including tax, but there is limited evidence confirming whether local retailers are adhering to this policy. We examined tobacco product pricing in tobacco retailers on- and off-post at the largest U.S. Army installation, Fort Liberty, and Cumberland County, North Carolina. METHODS: Between June-August 2021, we collected data on tobacco product availability, price, and promotions from retailers on Fort Liberty (n=14) and a random sample of off-post retailers within 10-miles of installation gates (n=52). We calculated the mode, mean, and median price of each product, plus the difference in these prices at on- and off-post retailers. We used Welch's t-test to test differences in mean prices between on- vs. off-post retailers. RESULTS: The mode, mean, and median prices of cigarette packs and cartons were lower on-post than off-post (e.g., $0.51-$0.55 cheaper for Marlboro cigarette packs on-post). However, the mode, mean, and median prices of smokeless tobacco products and little cigars were higher on-post than off-post (e.g., $0.82-$0.89 more costly for Swisher Sweets 2-packs on-post). CONCLUSION: Results highlight the need for continued enforcement to ensure compliance with the 2017 DoD policy. Comprehensive policy action to reduce tobacco price disparities on- and off-post is critical to reducing high rates of tobacco use among service members. IMPLICATIONS: Despite the implementation of the 2017 DoD pricing policy, some tobacco products remain cheaper at tobacco retailers on-post compared to off-post retailers. Our results highlight the need for greater routine surveillance to increase implementation of the policy-particularly for cigarettes-to reduce high rates of tobacco use among service members.

Neighborhood Inequities in Tobacco Product Descriptors, Washington, DC, 2018-2019.

BACKGROUND: The tobacco industry uses product descriptors to communicate reduced harm and increase appeal. This cross-sectional study assessed store-level racial, ethnic, and socioeconomic inequities in the distribution of retail tobacco product descriptors in a convenience sample of retailers in Washington, DC. METHODS: Young adults (n = 146) who did not currently use tobacco reported real-time store visits over 14 days. Trained data collectors took high-resolution photographs of all tobacco (including e-cigarette) marketing in each store (n = 96) participants visited. We coded text descriptors on tobacco product advertisements and displays into descriptor categories (eg, fruit, sweet, concept). We fit multilevel models to examine relationships between store neighborhood census tract-level racial, ethnic, and socioeconomic characteristics and tobacco product descriptors in stores. As a supplementary analysis, we used geospatial methods to model predicted patterns of descriptors at the census tract level. RESULTS: Stores located in census tracts with the highest versus lowest percentage of Black residents had a greater count of fruit, sweet or dessert, alcohol, and concept descriptors (p < .05), similar to findings from the geospatial approach. Adjusted models also indicated some inequities in stores in census tracts with higher percentages of Hispanic or Latino residents for fruit, alcohol, and concept descriptors; however, tract-level models showed opposite results for concept flavors. CONCLUSIONS: In this convenience sample, fruit, alcohol, sweet/dessert, and concept FTP descriptors were prevalent in stores in neighborhoods with more Black residents demonstrated through two analytic approaches. Surveillance using representative samples of tobacco retailers could improve the ability to track the extent of this inequity. IMPLICATIONS: We document inequities in the amount of fruit, sweet or dessert, alcohol, and concept flavor descriptors in stores across neighborhoods in Washington, DC. Federal, state, and local regulatory action is needed to reduce inequities in flavored tobacco product availability and marketing, including for concept flavors.

Risk Factors for Skin Flap and Nipple-Areolar Necrosis in Patients Undergoing Nipple-Sparing Mastectomy With Deep Inferior Epigastric Perforator Flap Reconstruction.

INTRODUCTION: Nipple-sparing mastectomy (NSM) with deep inferior epigastric perforator (DIEP) flap reconstruction is a surgical option for select patients with or at risk of breast cancer. However, post-operative skin flap and nipple-areolar complex (NAC) necrosis remain common complications. This study aimed to identify factors associated with necrosis in patients undergoing NSM with DIEP reconstruction. METHODS: A retrospective cohort study was performed from 2015 to 2023. 74 variables were analyzed in patients undergoing NSM with DIEP. Patients were stratified into 3 groups based on post-operative skin/NAC necrosis: none, partial thickness, and full thickness. Comparative and descriptive statistics were performed via t-tests, ANOVA, and chi-squared tests. RESULTS: 34 women with 31 breast cancers met inclusion. 44% experienced necrosis: 15% partial thickness and 29% full thickness. The majority were white (85.3%) with mean age of 50 years (SD = 9.11). In patients with immediate DIEP reconstruction, hypoperfused areas identified by SPY angiography increased risk of necrosis (P = .012). Approximately 50% of both partial thickness and full thickness necrosis patients had concerns on SPY angiography. Former smokers in the full thickness necrosis group had more pack years than those without necrosis (9 vs .65 pack years, P = .035). CONCLUSION: In patients receiving NSM with DIEP flap reconstruction, those with hypoperfusion on SPY angiography and longer smoking history had higher necrosis rates. This supports the continued used of SPY angiography and the role of pre-operative counseling in former smokers with increased pack years on their risk of necrosis and the role of preventative measures in the perioperative setting.

Geographical differences in the financial impacts of different forms of tobacco licence fees on small retailers in Scotland.

OBJECTIVE: Retailer licencing fees are a promising avenue to regulate tobacco availability. However, they face strong opposition from retailers and the tobacco industry, who argue significant financial impacts. This study compares the impacts of different forms of tobacco licence schemes on retailers' profits in Scotland. METHODS: We calculated gross profits from tobacco sales in 179 convenience stores across Scotland using 1 099 697 electronic point-of-sale records from 16 weeks between 2019 and 2022. We estimated different fees using universal, volumetric and separate urban/rural schemes. We identified the point at which 50% of retailers would no longer make a gross profit on tobacco sales for each scheme and modelled the financial impact of 10 incremental fee levels. The financial impact was assessed based on changes in retailers' tobacco gross profits. Differences by neighbourhood deprivation and urban/rural status were examined. RESULTS: The gross profit from tobacco per convenience store averaged £15 859/year. Profits were 2.29 times higher in urban (vs rural) areas and 1.59 times higher in high-deprivation (vs low-deprivation) areas, attributable to higher sales volumes. Tobacco gross profit decreased proportionally with increasing fee levels. Universal and urban/rural fees had greater gross profit reductions in rural and/or less deprived areas, where profits were lower, compared with volumetric fees. CONCLUSION: The introduction of tobacco licence fees offers a potential opportunity for reducing the availability of tobacco retailers. The likely impact of a tobacco licence fee is sensitive to the type of licence scheme implemented, the level at which fees are set and the retailers' location in relation to neighbourhood deprivation and rurality.

Does Neoadjuvant Chemotherapy in Clinical T1-T2 N0 Triple-Negative Breast Cancer Increase the Extent of Axillary Surgery?

BACKGROUND: Current management strategies for early-stage triple-negative breast cancer (TNBC) include upfront surgery to determine pathologic stage to guide chemotherapy recommendations, or neoadjuvant chemotherapy (NAC) to de-escalate surgery, elucidate tumor response, and determine the role of adjuvant chemotherapy. However, patients who receive NAC with residual pathological nodal (pN) involvement require axillary lymph node dissection (ALND) as they are Z11/AMAROS ineligible. We aimed to evaluate the impact of NAC compared with upfront surgery on pN status and ALND rates in cT1-2N0 TNBC. METHODS: The National Cancer Database (NCDB) was queried for women with operable cT1-2N0 TNBC from 2014 to 2019. Demographic, clinicopathologic, and treatment data were collected. Multivariable linear regression analysis was performed to assess the odds of pN+ disease and undergoing ALND. RESULTS: Overall, 55,624 women were included: 26.9% (n = 14,942) underwent NAC and 73.1% (n = 40,682) underwent upfront surgery. The NAC cohort was younger (mean age 52.9 vs. 61.3 years; p < 0.001) with more cT2 tumors (71.6% vs. 31.0%; p < 0.001), and had lower ALND rates (4.3% vs. 5.5%; p < 0.001). The upfront surgery cohort was more likely to have one to three pathologically positive nodes (12.1% vs. 6.5%; odds ratio [OR] 2.37, 95% confidence interval (CI) 2.17-2.58; p < 0.001) but there was no difference in the likelihood of ALND (OR 1.1, 95% CI 0.99-1.24; p = 0.08). CONCLUSION: Patients who underwent upfront surgery were more likely to be pN+; however, ALND rates were similar between the two cohorts. Thus, the use of NAC does not result in a higher odds of ALND and the decision for NAC should be individualized and based on modern guidelines and systemic therapy benefits.

Spatial Clustering of Tobacco Retailers Near US Public Schools.

INTRODUCTION: Previous studies have found that tobacco retailers cluster near schools. However, all retail outlets may be located near each other and near schools due to existing infrastructure and zoning policies. We assessed whether tobacco retailers cluster near schools in the United States more than expected when accounting for existing retail locations. AIMS AND METHODS: We identified 322 056 probable tobacco retailers, 95 110 public schools, and more than 3.8 million businesses comparable to tobacco retailers in land use and business type. We created 500 simulated tobacco retailer datasets by randomly selecting from the larger list of businesses. For each simulated dataset, we calculated the distance from schools to the nearest tobacco retailer (proximity) and the count of tobacco retailers within 800 m of schools (density). Observed proximity and density values were compared to 95% coverage intervals from the 500 simulations. We stratified analyses by urbanicity, percentage of students in the free and reduced-priced lunch program (FRLP), and percentage of Hispanic/Latino, non-Hispanic Black, and non-Hispanic white students. RESULTS: Tobacco retailers were closer to schools in rural areas, cities, and towns and more dense around schools in rural areas, cities, and suburbs compared to random locations in potential retail space. Schools with more students receiving FRLP had higher density than expected while schools with fewer students receiving FRLP had lower density than expected. Within rural areas, clustering did not vary across sociodemographic groups. Within non-rural areas, there were inequities in clustering by racial, ethnic, and socioeconomic school composition. CONCLUSIONS: Tobacco retailers cluster near schools after accounting for existing business patterns. There are inequities in clustering by sociodemographic school composition. IMPLICATIONS: This study provides compelling evidence that tobacco retailers cluster near US public schools and that there are racial, ethnic, and socioeconomic inequities in clustering, even when accounting for overall retail location patterns. Given that public schools tend to reflect neighborhood demographics, policies to limit tobacco retailers near schools may reduce both school-based and neighborhood-based inequities.

National trends in neoadjuvant chemotherapy utilization in patients with early-stage node-negative triple-negative breast cancer: the impact of the CREATE-X trial.

PURPOSE: Neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) allows for assessment of tumor pathological response and has survival implications. In 2017, the CREATE-X trial demonstrated survival benefit with adjuvant capecitabine in patients TNBC and residual disease after NAC. We aimed to assess national rates of NAC for cT1-2N0M0 TNBC before and after CREATE-X and examine factors associated with receiving NAC vs adjuvant chemotherapy (AC). METHODS: A retrospective cohort study of women with cT1-2N0M0 TNBC diagnosed from 2014 to 2019 in the National Cancer Database (NCDB) was performed. Variables were analyzed via ANOVA, Chi-squared, Fisher Exact tests, and a multivariate linear regression model was created. RESULTS: 55,633 women were included: 26.9% received NAC, 52.4% AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71 years, p < 0.01). NAC utilization significantly increased over time: 19.5% in 2014-15 (n = 3,465 of 17,777), 27.1% in 2016-17 (n = 5,140 of 18,985), and 33.6% in 2018-19 (n = 6,337 of 18,871, p < 0.001). On multivariate analysis, increased NAC was associated with younger age (< 50), non-Hispanic white race/ethnicity, lack of comorbidities, cT2 tumors, care at an academic or integrated-network cancer program, and diagnosis post-2017 (p < 0.05 for all). Patients with government-provided insurance were less likely to receive NAC (p < 0.01). Women who traveled > 60 miles for treatment were more likely to receive NAC (p < 0.01). CONCLUSION: From 2014 to 2019, NAC utilization increased for patients with cT1-2N0M0 TNBC. Racial, socioeconomic, and access disparities were observed in who received NAC vs AC and warrants interventions to ensure equitable care.

Impact and Equity of New York City's Tobacco Retail Reduction Initiative.

INTRODUCTION: High levels of tobacco retailer density in communities is associated with a range of tobacco use behaviors and is a key structural driver of tobacco-related disparities. This study evaluates the impacts of New York City's (NYC) novel policy intervention to cap tobacco retail licenses on tobacco retailer density levels and neighborhood inequities in tobacco access. METHODS: Using geocoded tobacco retail licensing data from 2010 to 2022, Bayesian conditional autoregressive Poisson panel models estimated the association between policy implementation in 2018 and retailer density per 1,000 population, controlling for neighborhood-level sociodemographic factors. Data were analyzed in 2023. RESULTS: The number of tobacco retail licenses decreased from 9,304 in 2010 to 5,107 in 2022, with the rate of decline significantly accelerating post-policy (-14·2% versus -34·2%). Policy effects were stronger in districts with lower income and greater proportions of non-Hispanic Black residents. CONCLUSIONS: NYC's policy substantially reduced tobacco retailer density and appeared to close longstanding patterns of inequity in tobacco access, serving as a rare example of a tobacco control policy that may effectively reduce tobacco-related disparities. This emergent approach to restructure tobacco retail in communities may reach populations that have not benefitted from traditional tobacco control policies and should be considered by other localities.

"If You Just Tell Me You're 18, I'll Still Sell to You": A Qualitative Study of Underage Tobacco Product Purchasing Experiences in a Tobacco 21 Compliance Study.

BACKGROUND: Tens of thousands of underage tobacco buy attempts are conducted each year for research, compliance, and public health surveillance. However, little research has qualitatively examined the perceptions and experiences of underage buyers participating in these programs. We sought to understand underage buyers' experiences and gather recommendations for protocol improvements. METHODS: We conducted semi-structured interviews in the fall of 2022 to assess experiences with underage tobacco product purchasing. Participants (N = 19, 58% male, 42% White) were research assistants aged 18-20 in New Jersey, New York, or North Carolina. Interviews examined purchasing experiences in relation to store characteristics, clerk interactions, and buyer identities. We used deductive and inductive thematic coding to explore key themes related to buyer experiences. RESULTS: We identified four themes: (1) non-chain stores lacked consistency in verifying age; (2) female data collectors experienced uncomfortable situations more frequently than male data collectors; (3) not identifying with the store's typical demographics impacted purchase attempts; and (4) participants suggested improvements for inspections and research during training. DISCUSSION: Retailer education, widespread adoption of ID scanners, and enforcement could increase standardization of ID requests and verification. Male and female buyers can be trained on what they might expect based on their gender, as well as how to maneuver through unwanted situations. Consideration of shared identity is important for future waves of data collection and research. Efforts to improve training include more extensive mock purchase training with supervisors well-versed in this area. IMPLICATIONS: Electronic ID verification and promoting compliance at non-chain retailers could impact access to tobacco products for underage buyers. Training for underage buyers in research and compliance assessments should focus on ways to enhance data collectors' confidence when making a purchase attempt, which may improve the validity of the rate of sales to individuals under 21.

Identifying disparities in suicidal thoughts and behaviors among US adolescents during the COVID-19 pandemic.

BACKGROUND: Suicidal thoughts and behaviors (STBs) became more common among racial and ethnic minorities and sexual and gender minorities (SGM) during the COVID-19 pandemic relative to White and non-SGM adolescents. This study examines associations between pandemic-related stressors and STBs among a nationally representative sample of adolescents to identify vulnerable subpopulations. METHODS: We analyzed data from 6769 high school students using the 2021 Adolescent Behaviors and Experiences Survey. Pandemic-related stressors were assessed via seven items related to negative experiences (e.g., parent job loss; food insecurity) during the COVID-19 pandemic. Logistic regression analyses estimated the association between pandemic-related stressors and four outcomes: (1) sadness/hopelessness; (2) suicidal ideation; (3) suicide planning; and (4) recent suicide attempt (i.e., past 12 months). Interactions were modeled by sex, race/ethnicity, and sexual identity. RESULTS: A greater number of pandemic-related stressors was associated with higher odds for sadness and hopelessness (aOR: 1.55; 95% CI:1.44-1.67), suicidal ideation (aOR: 1.48; 95% CI:1.39-1.57), suicide planning (aOR:1.47; 95% CI: 1.36-1.59), and recent suicide attempt (aOR: 1.64; 95% CI:1.42-1.88). Pandemic-related stressors were also more strongly associated with some types of STBs in males (relative to females) and SGM females (relative to heterosexual females). CONCLUSION: Study findings indicate that pandemic-related stressors are associated with STBs within the US adolescent population, particularly among male and SGM female adolescents. Researchers are encouraged to use this knowledge to ensure nationwide suicide prevention efforts adequately address inequities in suicide risk.

A thematic content analysis of 2010-2015 state tobacco control legislation in the United States: Bill rationales and priority populations.

Objective: Tobacco use causes numerous types of cancers, heart diseases, and chronic illnesses, and is responsible for nearly 1 in every 5 deaths in the United States (U.S.) annually. This study assessed whether tobacco control laws introduced in state legislatures between 2010 and 2015 provided a rationale for the proposed bill and/or specified priority population groups, and we then examined emerging themes in the text that did so. Methods: Using LexisNexis® State Net®, we identified tobacco control bills introduced in all states and coded their bill rationales and population category. We then conducted qualitative thematic analysis on a sample of bills with rationales or specified populations. Results: Of the 2815 tobacco control bills introduced in state legislatures in the analysis period, 422 (15.0%) included a bill rationale, and 1309 (46.5%) specified at least one priority population. Four overarching themes emerged: 1) Addressing tobacco-related health harms and financial costs incurred to society; 2) Protecting the public from tobacco-related harms as a government responsibility; 3) Providing services to priority populations; 4) Exempting or preempting some population groups and localities. Conclusions: Rationalizing tobacco control legislation by focusing on both health and cost implications was a key feature of tobacco policy bill text we analyzed; given the history of this approach, it is likely to remain so in the future. Our study may serve as a benchmark for tracking current and future tobacco control legislation to examine whether there is a growth in prioritizing populations experiencing unjust burdens of tobacco use and related disease.

Frequent upregulation of HER2 protein in hormone-receptor-positive HER2-negative breast cancer after short-term neoadjuvant endocrine therapy.

BACKGROUND: Endocrine resistant metastatic disease develops in ~ 20-25% of hormone-receptor-positive (HR+) breast cancer (BC) patients despite endocrine therapy (ET) use. Upregulation of HER family receptor tyrosine kinases (RTKs) represent escape mechanisms in response to ET in some HR+ tumors. Short-term neoadjuvant ET (NET) offers the opportunity to identify early endocrine escape mechanisms initiated in individual tumors. METHODS: This was a single arm, interventional phase II clinical trial evaluating 4 weeks (± 1 week) of NET in patients with early-stage HR+/HER2-negative (HER2-) BC. The primary objective was to assess NET-induced changes in HER1-4 proteins by immunohistochemistry (IHC) score. Protein upregulation was defined as an increase of ≥ 1 in IHC score following NET. RESULTS: Thirty-seven patients with cT1-T3, cN0, HR+/HER2- BC were enrolled. In 35 patients with evaluable tumor HER protein after NET, HER2 was upregulated in 48.6% (17/35; p = 0.025), with HER2-positive status (IHC 3+ or FISH-amplified) detected in three patients at surgery, who were recommended adjuvant trastuzumab-based therapy. Downregulation of HER3 and/or HER4 protein was detected in 54.2% of tumors, whereas HER1 protein remained low and unchanged in all cases. While no significant volumetric reduction was detected radiographically after short-term NET, significant reduction in tumor proliferation rates were observed. No significant associations were identified between any clinicopathologic covariates and changes in HER1-4 protein expression on multivariable analysis. CONCLUSION: Short-term NET frequently and preferentially upregulates HER2 over other HER family RTKs in early-stage HR+/HER2- BC and may be a promising strategy to identify tumors that utilize HER2 as an early endocrine escape pathway. CLINICAL TRIAL REGISTRY: Trial registration number: NCT03219476.

National Trends in "Going Flat" After Mastectomy.

INTRODUCTION: The "Going Flat" movement became widely publicized in 2016 and provides information and support to women who choose to forego post-mastectomy breast reconstruction (PMBR). The objectives of this study were to evaluate temporal trends in PMBR to ascertain the potential impact of this movement and assess which factors are associated with going flat. METHODS: A retrospective cohort analysis was performed using the NCDB of women with non-metastatic breast cancer who underwent mastectomy between 2004 and 2019. Trends in going flat after mastectomy were examined and stratified by age (< 50, 50-69, ≥ 70). A multivariate logistic regression model was used to identify factors associated with going flat. RESULTS: 650,983 patients met the inclusion criteria: 244,201 (37.5%) underwent PMBR and 406,782 (62.5%) went flat. Among women < 70, rates of going flat steadily decreased from 2004 to 2015 and then stabilized after 2015, coinciding with the rise of the "Going Flat" movement. In multivariate analysis, non-White race, older age, increasing comorbidities, government provided insurance, treatment at a community program, radiotherapy, and adjuvant chemotherapy were associated with a higher likelihood of going flat (p < 0.001). CONCLUSION: In the first 2 years after the "Going Flat" movement, the number of women going flat after mastectomy has stabilized in women < 70 for the first time in over a decade. These trends suggest that the social and cultural impact of this movement may have contributed to the stabilization of PMBR rates.