Hopkins, Judith O.

Importance The NRG Oncology research organization and NSABP B-35 randomized clinical trial prospectively collected margin width data on postmenopausal women with hormone receptor (HR)–positive ductal carcinoma in situ (DCIS) who underwent lumpectomy, whole-breast irradiation (WBI), and randomly assigned adjuvant anastrozole or tamoxifen therapy. This permitted analysis of outcomes per margin width. Objective To analyze the effect of margin width on ipsilateral breast tumor recurrence (IBTR). Design, Setting, and Participants NSABP B-35 was a phase 3, double-blind, randomized clinical trial in which patients were randomized to either 5 years of tamoxifen or anastrozole. Postmenopausal women with HR-positive DCIS and tumor-free margins were eligible. Enrollment was from January 6, 2003, to June 15, 2006, in academic and community hospital members of the NSABP. Study data were analyzed from July 2024 to April 2025. Interventions There were no specific interventions based on lumpectomy margin width. Main Outcomes and Measures Lumpectomy margin width data were prospectively collected within 3 months of randomization. A pathology form classified margins as positive (ink on tumor), close (<1 mm), or negative (≥1 mm). For the negative margin subgroup, closest margin width was stated separately. Thus, an ancillary analysis using 1-mm and 2-mm margin width partitions was performed. Results A total of 3104 postmenopausal women (mean [SD] age, 61 [7.8] years) were enrolled in NSABP B-35. In an ancillary analysis, 2707 patients were included in the 1-mm margin width partition group, and 2546 patients were included in the 2-mm margin width partition group. IBTR was the most common first event, occurring in 90 of 2707 patients (3.3%): 24 of 502 patients (4.8%) with a margin width less than 1 mm and 66 of 2205 patients (3.0%) with a margin width greater than or equal to 1 mm. Ten-year unadjusted cumulative incidence of IBTR events was 5.6% vs 4.0% for margins less than 1 mm vs margins greater than or equal to 1 mm ( P = .04). Using 2 mm as the discriminant threshold for margin width, 39 of 879 patients (4.4%) with margins less than 2 mm and 49 of 1667 patients (2.9%) with margins greater than or equal to 2 mm experienced an IBTR first. Ten-year unadjusted cumulative incidence of IBTR events with margins less than or equal to 2 mm was 5.3% vs 3.8% for those with margins greater than 2 mm ( P = .05). In models adjusting for other patient and tumor factors, margin width was not a significant predictor of IBTR risk (2-mm threshold hazard ratio, 1.33; 95% CI, 0.86-2.06). Conclusions and Relevance Results of this ancillary analysis of the NSABP B-35 trial show that absolute differences in IBTR rates using margin width groupings of less than 1 mm or greater than or equal to 1 mm and margin width groupings of less than 2 mm or greater than or equal to 2 mm in postmenopausal women with HR-positive DCIS receiving lumpectomy, WBI, and adjuvant endocrine therapy were small. Omission of reexcision lumpectomies based on margin widths of less than 1 mm or less than 2 mm can be reconsidered in appropriate patients. Trial Registration ClinicalTrials.gov Identifier: NCT00053898

12010 Background: BWEL (Alliance A011401; NCT02750826) is a Phase III trial that randomizes patients (pts) with stage II-III breast cancer and body mass index (BMI) ≥27 kg/m 2 1:1 to a 24-month (mo) lifestyle-based WLI + health education (HE) or HE alone. Here we report prespecified secondary outcomes of the impact of the WLI on patient-reported QOL and symptoms. Methods: The first 540 BWEL pts (randomized between 9/2016 and 7/2017) were included in this substudy that collected PROMIS 29 Profile 2.0 and Global Health scores at enrollment, 6 and 24 mos. Adjusting for baseline scores, mean physical function (predefined substudy primary outcome), global physical and mental health, fatigue and other scores were compared at 6 and 24 mos using analysis of covariance (ANCOVA). P-values <0.05 were considered significant. Positive differences in positive attributes (e.g., physical function) and negative differences in negative attributes (e.g., anxiety) represented better outcomes in the WLI arm. Results: At baseline, median BMI was 32.9 kg/m 2 (26.5 – 69.1), median age was 53 (25 - 78) years; 83.9% of pts were non-Hispanic White, 10.7% were Black and 5.9% were Hispanic. At 6 mos, the WLI (vs HE) arm had significantly better physical function (ANCOVA-based mean difference between arms 1.9 [95% CI 0.8, 3.0]; p<0.001), global physical health (2.0 [95% CI 0.9, 3.0]; p<0.001), global mental health (1.30 [95% CI 0.2, 2.4], p=0.03), social roles and activities (2.3 [95% CI 1.1, 3.6]; p<0.001), and fatigue (-1.7 [95% CI -3.1, -0.4], p=0.01) (Table). Improvements were generally maintained at 24 mos. Similar findings were seen in analyses using longitudinal mixed modeling. Conclusions: The BWEL WLI demonstrated QOL benefits for patients with breast cancer, resulting in significantly better physical function, global physical and mental health, and symptoms. Future analyses will evaluate which populations experienced the most benefit, as well as the relationships among QOL, symptoms, and weight loss. Support: U10CA180821, U10CA180882, UG1CA189823; U10CA180820; U10CA180868; U10CA180863, CCS 707213; U10CA180888; UG1CA189858; https://acknowledgments.alliancefound.org. Clinical trial information: NCT02750826 . Analysis of covariance-adjusted least squares means values at 6-mos adjusted for baseline scores. QOL/Symptom Attributes HE WLI Between arm difference (95% CI)* P value Physical Function 47.1 49.0 1.9 (0.8, 3.0) <0.001 Global Physical Health 46.2 48.1 2.0 (0.9, 3.0) <0.001 Global Mental Health 48.6 49.9 1.3 (0.2, 2.4) 0.03 Social Roles and Activities 52.7 55.0 2.3 (1.1, 3.6) <0.001 Anxiety 50.2 50.0 -0.2 (-1.6, 1.2) 0.77 Depression 47.5 47.5 -0.0 (11.2, 1.2) 0.96 Fatigue 50.6 48.9 -1.7 (-3.1, -0.4) 0.01 Sleep Disturbance 51.0 51.1 0.1 (-0.6, 0.8) 0.80 Pain Interference 51.3 50.3 -1.0 (-2.4, 0.4) 0.15 *Positive differences in positive attributes and negative differences in negative attributes favor WLI arm.

Importance Obesity is associated with a higher risk of recurrence, mortality, comorbidities, treatment-related adverse effects, and poor quality of life in patients with breast cancer. Scalable interventions are needed to promote weight loss in this population. Objective To evaluate the impact of a remotely delivered weight loss intervention (WLI) on weight change at 1 year in patients with breast cancer and obesity and to explore factors associated with weight change. Design, Setting, and Participants The Breast Cancer Weight Loss trial is a phase 3, randomized clinical trial evaluating the impact of a telephone-based WLI on invasive disease–free survival and other outcomes in women with obesity and early breast cancer at 637 sites across the US and Canada. Participants were enrolled to the study between August 2016 and February 2021. Participants included women with stage II to III, ERBB2 -negative breast cancer and a body mass index (BMI) of 27 or higher. Interventions Participants were randomized to a 2-year, telephone-based WLI plus health education or health education alone control group. Main Outcome and Measures The primary end point for this prespecified secondary analysis was weight change at 1 year. Weight was measured at baseline and 1 year, and changes in weight were compared between groups. Weight change was evaluated with a linear mixed-effects model including treatment group, weight over time, a time-by-group interaction, menopausal status, race and ethnicity, and hormone receptor status. Results A total of 3180 women with breast cancer and BMI of 27 and higher were included in the study; 1591 were randomized to the WLI and 1589 to the control group. At baseline, the mean (SD) age of participants was 53.4 (10.6), and the mean (SD) BMI was 34.4 (5.6). The racial and ethnic breakdown included 406 (12.8%) Black, 231 (7.3%) Hispanic or Latino, 2906 (91.4%) non-Hispanic, and 2555 (80.3%) White participants. WLI participants lost a mean of 4.3 kg (95% CI 3.9-4.6 kg), or 4.7% (95% CI, 4.3%-5.0%) of baseline body weight at 1 year vs control participants, who gained 0.9 kg (95% CI, 0.5-1.3 kg), or 1.0% (95% CI 0.1%-1.4%) of baseline body weight ( P &amp;lt; .001). Participants randomized to WLI experienced significant weight loss (vs control group participants) across demographic and tumor factors. WLI effect differed significantly by menopausal status, with postmenopausal participants having greater weight loss than premenopausal participants, and by race and ethnicity, with Black and Hispanic participants having less weight loss compared to other races and ethnicities. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, a telephone-based WLI induced significant weight loss in patients with breast cancer with overweight and obesity across demographic and treatment factors. Further follow-up of the Breast Cancer Weight Loss trial will evaluate whether the WLI improves disease outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT02750826

1586 Background: Black and Hispanic breast cancer (BC) survivors have a higher prevalence of obesity and experience less success with weight loss interventions (WLI) than White BC survivors. The BWEL trial (Alliance A011401; NCT02750826) is a phase III randomized trial evaluating the impact of a 2-year telephone-based WLI on invasive disease-free survival in participants (pts) with stage II-III HER2-negative BC and a BMI ≥ 27 kg/m 2 . At 12-months, the WLI induced significant weight loss across demographic factors, including race and ethnicity. However, Black and Hispanic pts lost less weight and completed fewer calls than White pts. Here, we evaluate intervention adherence, engagement and tool utilization in BWEL pts by race and ethnicity. Methods: BWEL randomized pts to a WLI plus health education (HE) or HE alone. WLI pts received semi-structured telephone-based health coaching, delivered in English or Spanish, and received an activity monitor and wireless scale. Pts self-reported race and ethnicity. Mean values for call duration, call density (time to complete the initial 12-week intensive intervention phase), intervention attrition, and frequency of Fitbit use and weight tracking over 12-months were compared by race and ethnicity, comparing least squares means with Tukey-Kramer adjustment for multiple comparisons with adjusted p-values. Results: Of 3181 pts randomized to the study between 08/2016 and 02/2021, 1591 pts were allocated to the WLI arm. 80.5% of pts were White, 12.8% Black, and 7.1% Hispanic. Average BMI was 34.5 (±5.7) kg/m2. Compared to White pts, Black pts had fewer days of Fitbit usage (113.6 vs. 159.8, p<0.0001) and weight tracking (77.9 vs. 135.6 days, p< 0.0001). Hispanic pts had fewer days of Fitbit usage (108.8 vs. 154.9, p= 0.001) and weight tracking (87 vs. 129.5 days, p=0.0002) compared to non-Hispanic pts. There were no differences in attrition rate, average call duration, or call density by race or ethnicity. Conclusions: In a phase III WLI trial, engagement with tools designed to support weight loss was significantly lower in Black and Hispanic pts. Future work is needed to explore ways to enhance engagement and improve weight loss outcomes for racial and ethnic minority pts. Support: U10CA180821, U10CA180882, UG1CA189823; https://acknowledgments.alliancefound.org . Clinical trial information: NCT02750826 . Measure of engagement Race Ethnicity WhiteN=1281 BlackN=204 p-value Non-HispanicN=1459 HispanicN=113 p-value Withdrew from intervention n (%) 58 (4.5%) 13 (6.4%) 0.56 70 (4.8%) 6 (5.3%) 0.51 Call Duration (min)Mean (SD) 34.5 (7.6) 34.6 (9.1) 0.99 34.6 (7.8) 33.3 (7.9) 0.25 Call density(weeks)Mean (SD) 14.2 (7.2) 14.2 (8.8) 0.99 14.2 (7.3) 14.2 (9.7) 0.99 Days of Fitbit UseMean (SD) 159.8 (132.2) 113.6 (124.7) < 0.0001 154.9 (131.8) 108.8 (125.7) 0.001 Days of weight trackingMean (SD) 135.6 (109.5) 77.9 (87.5) < 0.0001 129.5 (108.8) 87 (96.5) 0.0002

561 Background: Obesity and other lifestyle factors are associated with breast cancer (BC) risk and outcomes. These relationships appear to vary in pre- vs postmenopausal women. Here we explore associations between pathological features, diet quality and physical activity (PA) in patients (pts) with BC enrolled in the BWEL (Alliance for Clinical Trials in Oncology A011401) trial, stratifying for menopausal status. Methods: BWEL is a phase III trial evaluating the impact of a weight loss intervention on disease outcomes in 3180 pts with stage II-III HER2– BC and body mass index ≥27 kg/m 2 . The first 542 BWEL pts underwent assessment of PA (7-Day PA Recall) and diet (24-hour Diet Recall) at enrollment. Healthy Eating Index 2020 (HEI) score (0-100, higher value = healthier diet) and minutes/week (min/wk) of moderate/vigorous PA (MVPA) were calculated. Estrogen receptor (ER) and progesterone receptor (PR) expression level (%) were abstracted from pathology reports. Analyses of links between HEI score, MVPA min/wk, % ER/PR, stratified by menopausal status, were conducted using t-tests; differential associations by menopausal status used linear regression models with interaction term. Results: In 523 pts with available pathology data, 76.5% had ER/PR+ BC, 56.2% were postmenopausal. Median HEI score was 50.1 (range 18.1-96.4), median MVPA min/wk was 0 (range 0-630), median time from diagnosis to enrollment was 10.0 months (range 2.4-13.1). In postmenopausal pts, higher diet quality was linked to increased % ER and PR (HEI above vs below median, mean % ER 78.0 vs 66.1, p=0.012; mean % PR 57.7 vs 43.1, p=0.004). The relationship between HEI score and % ER/PR differed significantly by menopausal status (interaction term of menopausal status and % ER: p=0.006; and % PR: p=0.012); there were no significant associations between HEI scores and % ER/PR in premenopausal pts. There were no significant associations between PA and % ER/PR. Conclusions: Healthier diet was associated with higher % ER and PR in postmenopausal pts with BC, but no relationship was seen in premenopausal pts. These data suggest that lifestyle factors may influence BC pathologic features related to outcomes in older women. Support: U10CA180821, U10CA180882, UG1CA189823, U24CA196171, https://acknowledgments.alliancefound.org . Clinical trial information: NCT02750826 . % ER mean (SD) p value % PR mean (SD) p value Post-Menopausal HEI* score≤50.1 [n=134]>50.1 [n=156] 66.1 (43.3)78.0 (36.8) 0.012 43.1 (41.8)57.7 (41.0) 0.004 MVPA † min/wk0 [n=147]≥1 [n=147] 74.5 (39.3)70.3 (41.2) 0.37 50.0 (41.8)53.0 (42.0) 0.41 Pre-Menopausal HEI* score≤50.1 [n=124]>50.1 [n=103] 70.5 (38.5)65.5 (43.0) 0.15 53.5 (41.1)49.1 (43.0) 0.43 MVPA † min/wk0 [n=112]≥1 [n=113] 66.3 (41.0)66.3 (41.2) 0.99 49.5 (41.4)52.6 (42.7) 0.59 *Healthy Eating Index. † Moderate/Vigorous Physical Activity.

PURPOSE This study determined whether an electronic version of the geriatric assessment is feasible in a multi-institutional, diverse setting. METHODs Ten sites within the Alliance for Clinical Trials in Oncology participated. Patients who had active cancer or a history of cancer and were 65 years of age or older were eligible. The geriatric assessment was completed with an electronic data capture system that had been loaded onto iPads. Feasibility was defined a priori as completion in at least 70% of patients either with or without help. To enhance racial diversity, the original sample size was later changed and augmented by 50% with the intention of increasing enrollment of older minority patients. RESULTS A total of one hundred fifty-four patients were registered with a median age of 72 years (range, 65-91 years). Forty-three (28%) identified themselves as African American or Black. One hundred forty-one patients (92%) completed the electronic geriatric assessment. Feasibility was observed across all subgroups, regardless of race, education, performance status, comorbidities, and cognition; 124 patients (81%) completed the geriatric assessment without help. Reasons for not completing the geriatric assessment are as follows: clinic visit did not occur (n = 6), no iPad connection to the Internet (n = 3), patient declined (n = 2), prolonged hospitalization (n = 1), and patient died (n = 1). Reasons for needing help, as reported by study personnel, were as follows: the patient preferred that research personnel ask the questions (n = 9), vision problem (n = 3), lack of comfort with the iPad (n = 2), questions were not clear (n = 1), less proficient in English (n = 1), and challenge in pressing the green button to go to the next question (n = 1). CONCLUSION The electronic geriatric assessment is feasible in a multi-institutional setting that includes a notable proportion of African American or Black patients.

Abstract Although recent scientific advances have improved our understanding of basic biological mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN), few interventions are available to prevent or treat CIPN. Although some biological targets from preclinical studies show promise in nonhuman animal models, few targets have been translated to successful clinical trials. To address this problem, the National Cancer Institute’s Symptom Management and Health-Related Quality of Life Steering Committee convened a meeting of experts in the CIPN and oncology symptom management fields to participate in a Clinical Trials Planning Meeting (CTPM). Investigators presented data from preclinical and translational studies for possible CIPN interventions; these were evaluated for readiness of randomized clinical trial testing by experts, and recommendations were provided. Breakout sessions were convened to discuss and develop future studies. The CTPM experts concluded that there is compelling evidence to move forward with selected pharmacological and nonpharmacological clinical trials for the prevention and treatment of CIPN. Several key feasibility issues need to be addressed, however. These include identification of optimal outcome measures to define the CIPN phenotype, establishment of parameters that guide the evaluation of clinically meaningful effects, and adoption of approaches for inclusion of translational and biomarker and/or genetic measures. The results of the CTPM provide support for conducting clinical trials that include both pharmacological and nonpharmacological approaches, alone or in combination, with biomarkers, genetics, or other measures designed to inform underlying CIPN mechanisms. Several working groups were formed to design rigorous CIPN clinical trials, the results of which are ongoing.

LBA500 Background: The primary endpoint of NSABP B-35, a phase III trial comparing 1 mg/day anastrozole to 20 mg/day tamoxifen, each given for 5 years, was breast cancer-free interval (BCFI), defined as the time from randomization to any breast cancer (BC) event including local, regional, or distant recurrence or contralateral disease, invasive or DCIS. Methods: Postmenopausal women with ER-receptor or PgR-receptor positive (by IHC analysis) DCIS and no invasive BC who had undergone a lumpectomy with clear resection margins were randomly assigned to receive either 20 mg/day tam or 1 mg/day A (blinded) for 5 years. Stratification was by age (<60 v ≥60). Results: From 1/6/2003 to 6/15/2006, 3,104 pts were entered and randomized (1552 in groups tam and A each). As of 2/28/15, follow-up information was available on 3,083 pts for OS and on 3,077 pts for all other disease-free endpoints, with mean time of follow-up of 8.6 years. There were 198 BCFI events, 114 in the tam group and 84 in the A group (HR, 0.73; p=0.03). 10-year point estimates for BCFI were 89.2% for tam and 93.5% for A. A significant time-by-treatment interaction (p=0.02) indicated that the effect was not evident until later in the study. There was a significant interaction between treatment and age group (p=0.04); benefit of A is only in women <60 years old. As to secondary endpoints, there were 495 DFS events, 260 in the tam group and 235 in the A group (HR, 0.89; p=0.21). 10-year point estimates for DFS were 77.9% for tam and 82.7% for A. There were 186 deaths, 88 in the tam group and 98 in the A group (HR, 1.11; p=0.48). 10-year point estimates for OS were 92.1% for tam, 92.5% for A. There were 8 deaths due to breast cancer in the tam group and 5 in the A group. There were 63 cases of invasive breast cancer in the tam group and 39 in the A group (HR, 0.61; p=0.02). There was a non-significant trend for a reduction in breast second primary cancers with A (HR, 0.68; p=0.07). Conclusions: Anastrozole provided a significant improvement compared to tamoxifen for BCFI, which was seen later in the study, primarily in women <60 years. Support: CA12027, 37377, 69651, 69974; 180868, 180822, 189867 196067, 114732; AstraZeneca Pharmaceuticals LP. Clinical trial information: NCT00053898.

AbstractBackgroundStudies point to a direct association between social support and better cancer outcomes. This study examined whether baseline social support is associated with better survival and fewer chemotherapy‐related adverse events in older, early‐stage breast cancer patients.MethodsThis study is a pre‐planned secondary analysis of CALGB 49907/Alliance A171301, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in breast cancer patients 65 years of age or older. A subset reported on the extent of their social support with questionnaires that were completed 6 times over 2 years.ResultsThe median age of this 331‐patient cohort was 72 years (range: 65, 90); 179 (55%) were married, and 210 (65%) lived with someone. One hundred forty‐five patients (46%) described a social network of 0–10 people; 110 (35%) of 11–25; and 58 (19%) of 26 or more. The Medical Outcomes Study (MOS) social support survey revealed that the median scores (range) for emotional/informational, tangible, positive social interaction, and affectionate social support were 94 (3, 100), 94 (0, 100), 96 (0, 100), and 100 (8, 100), respectively. Social support scores appeared stable over 2 years and higher (more support) than in other cancer settings. No statistically significant associations were observed between social support and survival and adverse events in multivariate analyses. However, married patients had smaller tumors, and those with arthritis reported less social support.ConclusionAlthough social support did not predict survival and adverse events, the exploratory but plausible inverse associations with larger tumors and arthritis suggest that social support merits further study. Copyright © 2015 John Wiley & Sons, Ltd.