Faculty Bibliography

PURPOSE/OBJECTIVE:EA1181 (ClinicalTrials.gov identifier: NCT04266249) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point-3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)-will be reported when data mature. METHODS:Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS:A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER-]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER- and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER- tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION/CONCLUSIONS:Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER- and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

BACKGROUND:People with multiple sclerosis (pwMS) treated with anti-CD20 monoclonal antibodies have an elevated infection risk, yet long-term comparative data with oral fumarates are limited. OBJECTIVE:To compare infection incidence, healthcare resource utilization, and relapse outcomes among pwMS receiving fumarate or anti-CD20 therapy for ⩾2 years. METHODS:This retrospective propensity-matched (1:2) analysis used US Komodo Health claims (1 January 2016-31 May 2022) for pwMS aged 18-64 years with ⩾2 years of continuous follow-up. Outcomes were assessed using Poisson generalized linear models. RESULTS: = 0.021). CONCLUSIONS:Fumarate therapy was associated with a lower infection risk versus anti-CD20s. The infection rate in the fumarates group remained relatively stable over time, but it progressively increased in the anti-CD20 group, with the most prominent differences observed at year 4 and beyond.

Nuisance property ordinances are municipal laws that penalize property owners or renters for alleged criminal activity or repeated disturbances, including emergency calls. As these laws have expanded, concerns have grown that they may disproportionately impact marginalized populations, including people who use drugs, by targeting drug-related activities and exacerbating chronic housing instability. This study examines the demographic and municipal-level characteristics associated with the presence of drug-related nuisance property ordinances (DNPOs) across major U.S. municipalities. Municipal codes were systemically analyzed for DNPOs across 482 municipalities in the U.S. DNPOs were classified as ordinances that list specific activities related to drugs, drug paraphernalia, or illegal activity as a nuisance. A chi-square test was used to compare proportions of demographic and socioeconomic characteristics between municipalities with and without DNPOs. 202 of 482 municipalities had DNPOs (41.9%). 73 of 202 municipalities, 36.1% of DNPOs, authorized eviction as a legal method of abatement. DNPOs were more likely to be found in municipalities with higher proportion of Black, non-Hispanic populations, lower median household income, higher poverty rates, higher unemployment rates, higher population density, higher proportions of renters, and moderate to higher rates of overdose (p < 0.05). DNPOs are prevalent across U.S. municipalities and frequently include eviction as a permitted or required abatement strategy. Our findings show that DNPOs are more likely to be present in socioeconomically disadvantaged communities. These findings underscore the need to further evaluate the health and equity consequences of nuisance property ordinances for people who use drugs.

IMPORTANCE/UNASSIGNED:Many patients are diagnosed with atypical lesions or lobular carcinoma in situ (LCIS); however, evidence- and consensus-based guidelines for the management of many of these lesions are limited. OBSERVATIONS/UNASSIGNED:The American Society of Breast Surgeons, in collaboration with the Society of Breast Imaging and College of American Pathology, assembled a steering group to create guidelines for the management of atypical lesions and LCIS, inclusive of flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), classic LCIS (C-LCIS), and the variant LCIS forms pleomorphic LCIS (P-LCIS) and florid LCIS (F-LCIS). The natural history of ADH, ALH, and C-LCIS suggests that these lesions are associated with an elevated future breast cancer risk; therefore, patients diagnosed with these lesions should be recommended to undergo comprehensive risk assessment and counseling about breast cancer risk-reducing strategies. The magnitude of future breast cancer risk associated with P-LCIS and F-LCIS remains uncertain, yet if these lesions are determined to be hormone receptor positive, risk-reducing medications should be considered. There is no evidence that FEA is associated with an elevated future breast cancer risk. A second pathology review confirmation is recommended for ADH, should be considered for FEA, and is not necessary for ALH or LCIS. Currently available evidence supports the need to diagnostically excise most ADH, P-LCIS, and F-LCIS cases identified on core biopsy, although some ADH cases fulfilling strict criteria and multidisciplinary consensus can be observed. P-LCIS and F-LCIS require a negative margin, but ADH does not. ALH and C-LCIS can be safely observed if the core biopsy diagnosis is concordant with imaging features (ie, radiographic-pathologic concordance is established). Provided radiologic-pathologic concordance is confirmed, diagnostic excision is generally not indicated after a diagnosis of FEA alone. CONCLUSIONS AND RELEVANCE/UNASSIGNED:These guidelines provide evidence-informed, consensus-based recommendations for the management of atypical lesions of the breast, including ADH, ALH, FEA, C-LCIS, P-LCIS, and F-LCIS. Practicing clinicians who treat patients with atypical breast lesions or LCIS should consider integrating these guidelines into clinical management.

APG157DS is a multi-component investigational drug which is currently the subject of multiple cancer trials. It has shown promising efficacy in patients with head and neck cancer. We report its immuno-modulatory effect in a syngeneic mouse model of glioblastoma (GBM). Long-term treatment with APG157DS led to durable tumor remission in 50% of mice, while all vehicle-treated mice reached humane endpoints within 42 days. Mechanistically, the drug induced selective repolarization of tumor-associated macrophages (TAMs) from an immunosuppressive Arg1^high/iNOS^low phenotype to a tumoricidal Arg1^low/iNOS^high state, accompanied by increased intratumoral recruitment of activated (NKp46+) natural killer cells and CD8+ cytotoxic T-cells. APG157DS also suppressed vascular endothelial growth factor (VEGF) and Hypoxia-inducible factor 1-alpha (HIF-1α) expression in tumors, further impairing tumor growth. Notably, APG157DS did not elicit off-target macrophage activation in peripheral tissues such as the spleen, highlighting its selective immune targeting. These findings provide a mechanistic rationale for further clinical development of APG157DS in GBM and potentially other immune-evasive cancers.

BACKGROUND:While payers and health systems are increasingly interested in addressing health-related social needs (HRSNs) to reduce health care use and align with value-based care incentives and regulatory requirements, limited evidence enables actionable strategies to manage and address social needs across population groups. OBJECTIVES/OBJECTIVE:To understand the relationship between HRSNs and health care access and use for adults with Medicare, Medicaid, and private health insurance coverage. RESEARCH DESIGN/METHODS:Survey data from adult participants from the All of Us Research Program (2017-2023; n=126,490) and logistic regression were used to examine the association between food insecurity and housing instability and having a usual source of care, seeing a health care provider, and forgoing care due to cost-stratified by payer type. RESULTS:The prevalence of HRSNs varied substantially by insurance: food insecurity affected 49.20% of Medicaid beneficiaries 18-64 years of age, 11.89% of privately insured adults 18-64 years of age, and 5.20% of Medicare beneficiaries 65 years of age and older; housing instability affected 54.61%, 25.18%, and 14.99%, respectively. Food insecurity was associated with lower odds of having a usual source of care for Medicaid and privately insured adults, lower odds of use for privately insured adults, and higher odds of forgone care for all 3 payer types. Housing instability was associated with lower odds of having a usual source of care for all 3 papers and with higher odds of forgone care for all groups. CONCLUSIONS:HRSNs like food insecurity and housing instability vary substantially by payer type and influence health care access and utilization in different ways. This can inform the design of payer-specific health management strategies that incorporate HRSNs.

BackgroundCervical cancer is a preventable disease, and reaching populations who are under-screened and/or at highest risk is essential to the goal of disease elimination. Hispanic women in the US have a disproportionately higher incidence rate than non-Hispanic women.ObjectivePost hoc analysis of the SELF-CERV study of the unique experience and preferences among Hispanic compared to non-Hispanic participants with the goal of facilitating and improving screening and follow-up in more vulnerable populations.MethodsWomen 25 to 65 years who were enrolled performed self-collection (SC) of vaginal samples for high-risk human papillomavirus (hrHPV) testing using a unique device in a simulated at-home environment. For method comparison, a clinician-collected (CC) sample was obtained. Participants also completed usability and screening preference surveys.ResultsA total of 609 participants were consented and 603 used the SC device. Of the 603 SC users, 115 (19.1%) identified themselves as Hispanic/Latinx. Compared to non-Hispanic women, Hispanic women, had significantly lower annual income (p < .001), a lower percentage of private insurance with more uninsured (p < .001) and lower levels of education (p < .001). There was no significant difference between Hispanic and non-Hispanic women in understanding the purpose of cervical cancer screening. No difference was noted in delaying screening, although English Not Primary speaking Hispanic women were somewhat more likely to delay (p = 0.22). Financial barriers were observed to be more of an impediment to Hispanic women compared to non-Hispanic women (p = 0.016). Negative experiences with in-clinic speculum exams were similar; however, Hispanic women (78%) expressed a significantly higher endorsement of SC than non-Hispanic women (62%), (p = 0.001). Both populations reported that they would be more likely to stay up to date with cervical cancer screening with the at-home SC device, but non-Hispanic women to a significantly lesser degree (p = 0.002). In terms of assessing utility of telemedicine in screening, both populations reported similar engagement in healthcare activities, willingness to try new technology and current use of smartphones. Hispanic and non-Hispanic women were both nearly equally divided as to their preference for in-clinic visits vs telehealth.ConclusionsFacilitating screening uptake is especially critical for Hispanic women, who bear a disproportionate burden of cervical cancer diagnoses and mortality while facing more obstacles to screening than non-Hispanic women. A clinically validated and accessible at-home SC alternative holds potential for meaningful impact and improved health outcomes within this community.