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Background: Inflammatory breast cancer (IBC) is associated with a poor prognosis. While many stage III IBC patients (pts) experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to permit subsequent surgical therapy, the prognostic significance of requiring additional NAC to enable resectability is unknown. We sought to describe the pathologic complete response (pCR) rates, breast cancer-free survival (BCFS) and overall survival (OS) among pts requiring 1 vs >1 lines of NAC prior to surgery. Methods: Upon IRB approval, pts with stage III IBC from 2 academic institutions (Dana-Farber Cancer Institute and MD Anderson Cancer Center) who received 1L or 2-3 lines (2-3L) of NAC prior to surgery were identified. Standard NAC regimens containing different drugs, such as AC-T or TCHP, were considered as 1L. Pts with locoregional progression or metastatic disease prior to surgery were excluded. Hormone receptor (HR), HER2 status, grade, and pCR, defined as no residual invasive cancer in the breast and the axilla, were evaluated. BCFS, defined as time from surgery to locoregional and/or distant recurrence, and OS, defined as time from surgery to death, were evaluated by the Kaplan-Meier method. Multivariable Cox models stratified by institution and containing the covariates pCR and tumor subtype were utilized to estimate the HR of 2-3L vs. 1L of therapy. Results: 808 eligible pts diagnosed between 1997 and 2020 were identified. 733 (91%) had 1L and 75 (9%) had 2-3L of NAC, and the median age was 50 years. 295 (37%) had HER2+, 282 (35%) HR+HER2-, 211 (26%) had HR-HER2- disease and for 20 (2%) pts, the receptor status was unknown. The median time from diagnosis to surgery was 6 months. Grade III disease, triple-negative and HER2-positive disease were more prevalent in pts receiving 2-3L of therapy (table). pCR was achieved in 178 (24%) pts receiving 1L of NAC, and in 14 (19%) pts receiving 2-3L of NAC. At 68 months of median follow-up, 417 (52%) pts experienced a recurrence with 376 in the 1L group and 41 in the 2-3L group. The 5-year BCFS was shorter for the 2-3L group compared to the 1L group (33% v 46%, HR=1.37; 95% CI:0.99-1.91). However, in 192 pts with a pCR, BCFS was similar, regardless of the number of NAC lines. There were 38 recurrences among 178 1L pts, and 3 recurrences among 14 2-3L pts, resulting in BCFS of 76% and 83% in 1L and 2-3L pts, respectively. Overall, there were 308 deaths, 276 deaths among 1L pts and 32 among 2-3L pts. The 5-yr OS estimate in 1L versus 2-3L pts was 60% versus 53% (HR=1.32, 95% CI: 0.91-1.93). Conclusion: Among pts with stage III IBC, pCR was observed among 24% who had 1L and 19% of pts who required 2-3L of NAC. BCFS and OS were comparable among pts with pCR after 1L and 2-3L. Our results suggest the need to continue to optimize current treatment strategies in IBC to improve pCR rates across all disease subtypes regardless of the number of lines of NAC required. Citation Format: Faina Nakhlis, Samuel Niman, Naoto T. Ueno, Elizabeth Troll, Sean Ryan, Eren Yeh, Laura Warren, Jennifer Bellon, Beth Harrison, Toshiaki Iwase, H. T. Carisa Le-Petross, Sadia Saleem, Mediget Teshome, Gary J. Whitman, Wendy Woodward, Beth Overmoyer, Sara Tolaney, Meredith Regan, Filipa Lynce, Rachel M. Layman. Long-term Outcomes After 1 or 2-3 Lines of Neoadjuvant Therapy in Stage III Inflammatory Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-14.

Background: The introduction of immune checkpoint inhibitors (ICI) to standard neoadjuvant chemotherapy regimens has been shown to significantly improve outcomes in patients with triple negative breast cancer and is being investigated for high-risk hormone receptor-positive (HR+)/human epidermal growth factor-2 negative (HER2-) breast cancer. Preclinical evidence suggests radiation therapy (RT) can stimulate intra-tumoral T cell infiltration and enhance the expression and immune detection of tumor-specific neoantigens. This phase II pilot randomized study (NCT04443348) aims to evaluate the safety and efficacy of two different doses of preoperative primary tumor RT boost when combined with neoadjuvant pembrolizumab, then followed by standard neoadjuvant chemotherapy. Dual co-primary endpoints include determining the pathologic complete response (pCR) rate in the non-irradiated and pathologically confirmed metastatic axillary lymph node(s) in each treatment arm and quantifying tumor-infiltrating T lymphocytes in on-treatment (C1D14) tumor biopsies. We hypothesize that high-dose RT will increase the proportion of tumors with high T cell infiltration (i.e., top quartile) from 25% to 55%. Secondary endpoints include measuring residual cancer burden, evaluating tolerability of the regimen, and assessing quality of life. Exploratory endpoints include evaluation of treatment-associated changes in the tumor immune microenvironment, circulating immune cell analyses, and circulating tumor DNA kinetics. Methods: The study plans to enroll 128 participants with either triple negative (n=80) or high-risk HR=/HER2- (n=48) breast cancer who will be randomized to receive no, low (9 Gy), or high (24 Gy) dose of preoperative RT boost, after which 24 participants of either breast cancer subtype will be enrolled to an exploratory high dose proton therapy boost cohort. The eligibility criteria include patients who have biopsy-proven, axillary lymph node-positive breast cancer that is either triple negative (defined as ER< 10%, PR< 10%, and HER2-negative) or high-risk HR+/HER2- (grade III or having a high-risk genomic assay score). Study treatment is given in 6-week cycles, with 400 mg Pembrolizumab given on day 1 of each cycle. For those participants randomized to receive a preoperative RT boost, treatment is delivered in 3 fractions (3 × 3 Gy or 3 × 8 Gy) over consecutive business days, where one of the fractions is given on the same day as C1D1 Pembrolizumab. Standard neoadjuvant chemotherapy begins on C1D15 with paclitaxel (plus carboplatin for triple negative) administered weekly for 12 weeks, and then starting on C3D15, dose-dense doxorubicin/cyclophosphamide is administered every 2 weeks for 8 weeks. Following neoadjuvant treatment, participants will receive standard breast surgery (including removal of the pathologically confirmed metastatic lymph node) followed by adjuvant pembrolizumab, radiation therapy, and standard-of-care systemic therapy as clinically indicated. Tissue samples from the primary tumor and biopsy-proven lymph node are taken at baseline, C1D14, and at the time of surgery. There are eleven blood collection timepoints throughout the neoadjuvant and adjuvant settings. Participants will be followed for 2 years after surgery to assess safety and durability of responses. Results: This study has accrued 12 participants to date, including 10 with triple negative breast cancer and 2 with high-risk HR+/HER2- breast cancer. Formal results for this study are forthcoming, as the trial is actively accruing at 6 institutions, with plans to open at 3 more within the year. For persons with a specific interest in this trial, please contact Joseph Connolly, Multi-Center Coordinator, at jconnolly28@mgh.harvard.edu. Citation Format: Joseph J. Connolly, Laura M. Spring, Alphonse G. Taghian, Michele Gadd, Laura Warren, Ana C. Garrido-Castro, Tari King, Elizabeth A. Mittendorf, Jose P. Leone, Dana L. Casey, Lisa Carey, Tiffany A. Traina, Yara Abdou, Atif Khan, George Plitas, Jean Wright, Cesar Augusto Santa-Maria, Lisa Jacobs, Rachel Blitzblau, E Shelley Hwang, Carey Anders, Ian Krop, Antonio C. Wolff, Alastair M. Thompson, Elyssa Denault, Gaorav Gupta, Alice Ho. TBCRC-053: P-RAD: A Randomized Study of Preoperative Chemotherapy, Pembrolizumab and No, Low or High Dose RADiation in Node-Positive, HER2-Negative Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-15-01.

Background: Breast conserving surgery (BCS) is typically followed by adjuvant radiotherapy (RT) based on several landmark trials demonstrating improvements in disease control and survival. Since completion of these historical trials, the advent of molecular subtyping has revealed that breast cancer is not a single disease entity, but rather a class of cancers with differential risk profiles. We evaluated whether RT could be safely omitted following BCS for patients with the most favorable subtype as defined by the Prosigna PAM50 assay. Methods: We conducted a multicenter prospective single-arm cohort study with IRB approval and an FDA investigational device exemption (IDE). Eligible patients were women 50 to 75 years of age (inclusive) who had undergone BCS revealing tumors ≤2cm in size, that were estrogen or progesterone receptor positive (HR+), HER2 negative, grade 1-2, node negative (N0), with negative excision margins (no ink on tumor). Intent to take endocrine therapy was required. Upon registration, tumors were submitted for central Prosigna testing and those with Risk of Recurrence (ROR) score ≤40 were deemed eligible for the investigational omission of RT. The primary endpoint was the 5-year locoregional recurrence rate (LRR). Anticipating a total of 345 RT-omitting patients to enroll over 3.5 years, the study was designed with 90% power to exclude a 5-year LRR of 5% using a one-sample exponential test with one-sided type I error of 0.025. Results: From 2016 to 2020, 671 patients were registered from 13 centers, inclusive of affiliated regional network sites. Of these, 382 patients had a ROR Score ≤40 and opted to forego RT, comprising the main intention-to-treat (ITT) study population. Median age was 65 years (range 50 to 75), and median tumor size was 0.9 cm (range 0.1 to 2.0 cm). At a median follow-up of 26.9 months, 12 events were observed: 4 patients had ipsilateral in-breast recurrences, 7 had contralateral breast cancers, and 1 developed an unrelated melanoma. There were no regional-nodal or distant recurrences. The 2-year cumulative rate of LRR was 0.3% (95% CI: 0 – 1.0%). Of the 4 ipsilateral breast recurrences, 2 were in the same quadrant as the original primary tumor. Conclusion: In this preliminary report of the PRECISION trial, patients 50-75 years of age undergoing BCS and endocrine therapy for pT1N0 HR+ HER2-negative breast cancer with ROR score ≤40 had exceedingly low rates of LRR in the absence of adjuvant RT at a median follow-up of 26.9 months. Additional follow-up is required to determine whether these favorable results are durable. Citation Format: Lior Z. Braunstein, Julia Wong, Deborah A. Dillon, Yu-Hui Chen, Paul Catalano, Oren Cahlon, Mahmoud B. El-Tamer, Rachel Jimenez, Atif Khan, Carmen Perez, Rinaa Punglia, Ron Shiloh, Laura Warren, David Wazer, Jean Wright, Elizabeth Buckley, Tari King, Simon Powell, Eric Winer, Jennifer Bellon. Preliminary report of the PRECISION Trial (Profiling Early Breast Cancer for Radiotherapy Omission): A Phase II Study of Breast-Conserving Surgery Without Adjuvant Radiotherapy for Favorable-Risk Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-12-02.

While it is widely accepted that affective states precede facial expressions, the facial feedback hypothesis (FFH) proposes the inverse. The FFH postulates that facial muscle region activity (e.g., smiling or frowning) directly influences the experience of emotion. The purpose of the present study was to evaluate the validity of the FFH - specifically whether smiling independently enhances positive mood.

The Greater Toronto Area (GTA) is home to 39% of Canada's population living with HIV. To identify gaps in access and engagement in care and treatment, we assessed the care cascade of women living with HIV (WLWH) in the GTA versus the rest of Ontario and Canada (in this case: Quebec and British Columbia).We analyzed 2013-2015 self-reported baseline data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study for six care cascade stages: linked to care, retained in care, initiated antiretroviral therapy (ART), currently on ART, ART adherence (≥90%), and undetectable (50 copies/mL). Multivariable logistic regression was used to reveal associations with being undetectable.Comparing the GTA to the rest of Ontario and Canada, respectively: 96%, 98%, 100% were linked to care; 92%, 94%, 98% retained in care; 72%, 89%, 96% initiated ART; 67%, 81%, 90% were currently using ART; 53%, 66%, 77% were adherent; 59%, 69%, 81% were undetectable. Factors associated with viral suppression in the multivariable model included: living outside of the GTA (Ontario: aOR = 1.72, 95% CI: 1.09-2.72; Canada: aOR = 2.42, 95% CI: 1.62-3.62), non-Canadian citizenship (landed immigrant/permanent resident: aOR = 3.23, 95% CI: 1.66-6.26; refugee/protected person/other status: aOR = 4.77, 95% CI: 1.96-11.64), completed high school (aOR = 1.77, 95% CI: 1.15-2.73), stable housing (aOR = 2.13, 95% CI: 1.33-3.39), income of ≥$20,000 (aOR = 1.52, 95% CI: 1.00-2.31), HIV diagnosis6 years (6-14 years: aOR = 1.75, 95% CI: 1.16-2.63;14 years: aOR = 1.87, 95% CI: 1.19-2.96), and higher resilience (aOR = 1.02, 95% CI: 1.00-1.04).WLWH living in the GTA had lower rates of viral suppression compared to the rest of Ontario and Canada even after adjustment of age, ethnicity, and HIV diagnosis duration. High-impact programming for WLWH in the GTA to improve HIV outcomes are greatly needed.

This chapter traces the eruption of the Black community in response to police brutality, noting July 24, 1964 as one of the era's very first “race riots” that occurred in Rochester. It discusses how a response to police brutality ended as an indictment of the economic conditions in Rochester's ghettoes. It also argues that the three-day rebellion, which ended with the calling up of the National Guard, became a watershed moment in the city of Rochester. The chapter describes the impressive degree of precision that those men and women, youth and senior citizens demonstrated in the rebellion when they attacked the police and private property with vengeance, but exempted community institutions and stores with a reputation for fairness. It investigates the 1964 uprising that seared Black Rochester into the nation's conscience, noting the uprising as the beginning of a series of Black rebellions that rocked the nation's urban centers in the 1960s.

This chapter charts the emergence of a sizable Black population in New York city, starting with the Black renaissance that happened in the fields and orchards surrounding the city, an agricultural belt responsible for growing a significant portion of the nation's food supply. It talks about local white agricultural workers that abandoned the fields for better-paying factory jobs in Rochester, Buffalo, and Syracuse, which created a labor shortage in the fields. It also mentions how farmers turned to places like Sanford, Florida, and to the “East Coast Migrant Stream” to employ Black agricultural migrants. The chapter recounts how the agricultural migrants eventually left the stream and opted instead to put down roots in the North, with Rochester becoming a popular destination. It discusses how the new influx of Black migrants created a demographic shift, the likes of which Rochester had never seen before.

This chapter talks about a group of white ministers who aided Black Rochesterians in their struggle to create a police review board and expanded their commitment to the struggle for racial justice. It details how the white ministers acted through the local council of churches and joined forces with Rochester's Black ministers to found and fund an organizational structure capable of building a Black movement. It also traces the abortive engagement with the Southern Christian Leadership Conference and Chicago's Saul Alinsky and his Industrial Areas Foundation. The chapter refers to FIGHT, Action for a Better Community (ABC), and the Urban League as the three groups that were competing for the hearts and minds of Black Rochester within a year of the uprising. It argues that in order for FIGHT to attract and retain the loyalty of the masses, it adopted an “oppositional identity.”

This chapter shows how the militant organization FIGHT targeted the Eastman Kodak Company by pressing the film conglomerate to hire and train the hard-core unemployed in 1966. It recounts how FIGHT's crusade jumped to the national scene in 1967, making major waves in the business world. It also elaborates how the corporate leaders of KODAK simply handled FIGHT when it came calling, with Kodak representatives explaining their own programs and suggested that FIGHT get in line. The chapter details how FIGHT continued to pressure Kodak locally by engaging the media and even drawing national Black Power leader Stokely Carmichael to join its efforts. It argues that FIGHT's campaign against Kodak significantly rewrote the rules of corporate responsibility in the era of Black Power.

This chapter documents several brutal clashes between African Americans and the police, which engendered a loose coalition of Black organizations and a number of sympathetic white ministers. It recounts the Rochester cases that garnered significant attention, while police clashes occurred throughout most cities in the postwar era. It also mentions a case where the US Justice Department interceded and another case where the famed Nation of Islam leader Malcolm X joined the protest efforts. The chapter argues that police brutality became a salient issue for a broad cross section of the Black community, which included ministers who cultivated and promoted a unified response. It talks about the local National Association for the Advancement of Colored People (NAACP) that worked closely with Malcolm X and local Nation of Islam leaders to organize a unity rally, chastising the Rochester branch for consorting with reputed Black separatists.

On July 24, 1964, chaos erupted in Rochester, New York. This book examines the unrest — rebellion by the city's Black community, rampant police brutality — that would radically change the trajectory of the Civil Rights movement. After overcoming a violent response by State Police, the fight for justice, in an upstate town rooted in black power movements, was reborn. That resurgence owed much to years of organizing and resistance in the community. This book examines Rochester's long Civil Rights history and, drawing extensively on oral accounts of the northern, urban community, offers rich and detailed stories of the area's protest tradition. The book paints a compelling picture of the foundations for the movement. Now, especially, this story of struggle for justice and resistance to inequality resonates. The book leads us to consider the social, political, and economic environment more than fifty years ago and how that founding generation of activists left its mark on present-day Rochester.

BackgroundNatural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.MethodsIn a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PCR-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after one versus two vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing.Results13,109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses) and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and two vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95%CI ConclusionNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.SummaryNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provided ≥ 85% protection against symptomatic and asymptomatic SARS-CoV-2 infection in healthcare workers, including against the B.1.1.7 variant. Single dose vaccination reduced symptomatic infection by 67%.

Background Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. Methods In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, United Kingdom, we investigated the protection from symptomatic and asymptomatic polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after 1 versus 2 vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing. Results In total, 13 109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses), and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and 2 vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95% confidence interval {CI} Conclusions Natural infection resulting in detectable anti-spike antibodies and 2 vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.

Introduction The hippocampus uniquely supports the acquisition and retention of spatial information, and sleep supports the consolidation of hippocampal-dependent memories. However, support for the role of sleep in spatial memory and navigation is mixed. We developed and tested a novel Minecraft Memory and Navigation (MMN) task in adults which showed that sleep uniquely supports the memory for spatial locations, but navigation improved regardless of delay condition (Simon et al., submitted). Here, we tested participants during the developmental transition from childhood to adolescence, a time known for structural and functional hippocampal maturation. Methods Thirty-one youth (Mage = 10.6, SD = 1.56, 9-13 years, grouped: child, early adolescent, adolescent) were administered the MNN task. Training included two free-explorations trials to learn 12 unique object-locations associations in an open-field Minecraft environment. At test, participants were cued to place objects from randomly teleported locations. They were tested twice, immediately and 12-hours later, after a period of sleep or wake. Conditions and environments were counterbalanced in a within-subject design. Each step-by-step movement was recorded for navigation analyses including path length, orientation angle, and search behaviors. Results We found a significant benefit of sleep, compared to wake, on the spatial location accuracy when accounting for age group (F(1,27) = 6.153, p = .02), such that similar to young adults, youth’s metric accuracy of spatial locations improved. We found no change in navigation performances from Test 1 to Test 2 in either condition. Between the start and target locations, youth initiated and maintained similar trajectory angles with similar total path lengths (p’s > .068). Spatial location memory did not correlate with any navigation metrics (p’s > .361). Navigation metrics correlated among themselves, which withstood correction (p’s < .005). Conclusion Youth demonstrated similar sleep-dependent benefits for the metric accuracy of the spatial locations. In contrast to adults, youth’s navigation performance did not improve over delay, regardless condition. Our findings are in line with sleep’s promotion of hippocampal-dependent information, with retention of the spatial locations. Our data are consistent with the hypothesis that sleep does not facilitate navigation, and points to potential developmental maturation required to support navigation behaviors. Support (If Any)