McCall, Linda

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.

Abstract Background: Patients with HER2+ early breast cancer (EBC) and invasive residual disease (RD) after neoadjuvant therapy (NAT) have a higher risk of relapse than patients who have a pathologic complete response (pCR). Escalation of therapy in patients with RD using post-neoadjuvant T-DM1 has become the new standard of care, leading to improved invasive disease-free survival (iDFS), but patients with estrogen receptor (ER)-negative or nodal RD have suboptimal outcomes, and central nervous system recurrences are a challenge. More effective treatment strategies are urgently needed. Alliance A011801 (CompassHER2 RD) is an escalation trial for patients with high-risk HER2+ RD after neoadjuvant systemic therapy, evaluating the addition of the HER2 selective tyrosine kinase inhibitor (TKI) tucatinib to post-neoadjuvant T-DM1. Methods: Eligibility and Intervention: Patients with high-risk HER2+ RD (i.e., ER-, node-positive, or both) after a predefined course of neoadjuvant HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 + placebo, vs. T-DM1 and tucatinib with adjuvant RT +/- ET. Eligibility criteria include completion of ≥ 6 cycles of NAT, including ≥ 9 weeks of paclitaxel and trastuzumab +/- pertuzumab. All chemotherapy (CT) must be completed preoperatively unless participating in EA1181 (~15-30% will be participants in the CompassHER2 pCR de-escalation companion trial [NCT04266249]; these patients must receive postoperative CT to complete ≥ 6 cycles prior to enrollment on A011801). Patients who received prior HER2-targeted TKIs or antibody-drug conjugates are ineligible. Objectives: The primary objective is to determine if iDFS is improved with addition of tucatinib to T-DM1 in patients with HER2+ EBC with RD after neoadjuvant systemic therapy; secondary endpoints include overall survival, breast cancer free survival, distant recurrence-free survival, brain metastases-free survival and disease-free survival. Correlative objectives include the association of i) tumor infiltrating lymphocyte (TILs) levels in the primary tumor and RD with iDFS, ii) TILs with tucatinib benefit, iii) iDFS and circulating tumor cells (CTC) at serial timepoints and iv) the magnitude of benefit of tucatinib (iDFS) in patients with/without detectable pretreatment CTCs. Quality of life and pharmacokinetic endpoints are also being evaluated. Statistics: A011801 is a prospective, double-blind, randomized, phase III superiority trial; stratified by i) receipt of postoperative CT (Y/N), ii) hormone receptor-status (+/-), and iii) pathologic lymph node status (+/-). The study targets an absolute difference of 5% in iDFS (control vs. experimental arm 82% & 87%, HR = 0.7), with a two-sided alpha of 0.05 and power of 80%. The sample size is 981; target accrual = 1031 patients; activation and estimated completion dates are 01/6/21 and ~ 01/2028. Accrual as of 7/10/2023: 438 patients. Support: U10CA180821, U10CA180882; Seagen Inc; https://acknowledgments.alliancefound.org. ClinicalTrials.gov Identifier: NCT04457596 Citation Format: Ciara O'Sullivan, Karla Ballman, Linda McCall, Tyler Zemla, Anna Weiss, Melissa Mitchell, Victoria Blinder, Nadine Tung, William Irvin, Myounghee Lee, Sailaja Kamaraju, Matthew Goetz, W. Fraser Symmans, Virginia Borges, Ian Krop, Ann Partridge, Lisa Carey. A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-18-11.

PURPOSE Breast-conserving therapy (BCT) is the preferred treatment for unifocal breast cancer (BC). The oncologic safety of BCT for multiple ipsilateral breast cancer (MIBC) has not been demonstrated in a prospective study. ACOSOG Z11102 (Alliance) is a phase II, single-arm, prospective trial designed to evaluate oncologic outcomes in patients undergoing BCT for MIBC. PATIENTS AND METHODS Women age 40 years and older with two to three foci of biopsy-proven cN0-1 BC were eligible. Patients underwent lumpectomies with negative margins followed by whole breast radiation with boost to all lumpectomy beds. The primary end point was cumulative incidence of local recurrence (LR) at 5 years with an a priori rate of clinical acceptability of <8%. RESULTS Among 270 women enrolled between November 2012 and August 2016, there were 204 eligible patients who underwent protocol-directed BCT. The median age was 61 years (range, 40-87 years). At a median follow-up of 66.4 months (range, 1.3-90.6 months), six patients developed LR for an estimated 5-year cumulative incidence of LR of 3.1% (95% CI, 1.3 to 6.4). Patient age, number of sites of preoperative biopsy–proven BC, estrogen receptor status and human epidermal growth factor receptor 2 status, and pathologic T and N categories were not associated with LR risk. Exploratory analysis showed that the 5-year LR rate in patients without preoperative magnetic resonance imaging (MRI; n = 15) was 22.6% compared with 1.7% in patients with a preoperative MRI (n = 189; P = .002). CONCLUSION The Z11102 clinical trial demonstrates that breast-conserving surgery with adjuvant radiation that includes lumpectomy site boosts yields an acceptably low 5-year LR rate for MIBC. This evidence supports BCT as a reasonable surgical option for women with two to three ipsilateral foci, particularly among patients with disease evaluated with preoperative breast MRI.

Abstract Background Breast conserving therapy (BCT) is accepted as a preferred option for unifocal breast cancer. However, the oncologic safety of BCT for multiple ipsilateral breast cancer (MIBC), has not been demonstrated in a prospective study. The ACOSOG (Alliance) Z11102 phase II single arm prospective trial was designed to evaluate outcomes with BCT for MIBC. Methods Women age 40+ with 2 or 3 foci of biopsy proven breast cancer (BC) (each site &lt; 5cm in size with at least 1 site invasive) separated by &gt;2-3 cm of normal breast tissue and disease limited to two quadrants of the breast with cN0 or cN1 disease were eligible. All patients had pre-operative mammogram and breast MRI was initially required and subsequently made optional. Neoadjuvant therapy was not allowed. Patients were treated with lumpectomy resected to negative margins followed by whole breast radiation with boost to all lumpectomy beds. The primary endpoint of Z11102 is the cumulative incidence of local recurrence (LR, defined as histologic evidence of ductal carcinoma in situ or invasive BC in the ipsilateral breast or chest wall) at 5 years (treating death and distant and nodal/regional recurrence as competing risks) to assess whether the rate is greater than 8%. Data were frozen 5/25/2022. Results From 11/2012-8/2016, 270 women were enrolled. Of these, 33 were ineligible, 14 converted to mastectomy, 11 were unable to meet protocol-specific radiation endpoints, 1 had no definable tumor, 1 had 4 sites of cancer and 16 withdrew before completing surgery and radiation, leaving 194 patients [median age 61 (range 40-87)] eligible who completed breast conserving surgery and radiation therapy. With median follow-up of alive patients of 66.6 months (range: 4.1, 90.6), 6 patients have developed LR (5 ipsilateral breast and 1 chest wall), corresponding to an estimated cumulative incidence of local recurrence of 3.2% (95% CI: 1.3, 6.4) at 5 years. No patients have developed regional recurrence, 5 patients developed distant recurrence, 0 patients developed local and distant recurrence, 5 patients developed contralateral BC, 3 new non-BC primaries and 8 patients have died (1 related to BC). The rate of local recurrence in patients without a breast pre-op MRI (n=14) was 22.6% at 5 years compared to 1.7% among the 180 patients with a preop MRI (p=0.002). Patient age, number of sites of preoperative biopsy proven BC, HER2 status, pathologic T and N category were not statistically significantly associated with risk of LR. Conclusion The Z11102 clinical trial demonstrates that for women with MIBC breast conserving surgery with adjuvant radiation with lumpectomy site boosts has an acceptably low LR rate (3.2% at 5 years), making this a reasonable consideration for women with 2-3 ipsilateral foci. The LR rate was significantly higher in the small cohort of patients without preoperative breast MRI. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. ClinicalTrials.gov Identifier: NCT01556243 Table 1: Factors associated with LR after BCT for MIBC Citation Format: Judy C. Boughey, Kari M. Rosenkranz, Karla V. Ballman, Linda McCall, Bruce G. Haffty, Laurie W. Cuttino, Charlotte D. Kubicky, H. T. Carisa Le-Petross, Kimberly Van Zee, Armando E. Giuliano, Olwen M. Hahn, Kelly K. Hunt, Lisa Carey, Ann Partridge. Impact of Breast Conservation Therapy on Local Recurrence in Patients with Multiple Ipsilateral Breast Cancer – Results from ACOSOG Z11102 (Alliance) [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 GS4-01.

TPS595 Background: Patients (pts) with HER2+ early breast cancer (EBC) and invasive residual disease (RD) after neoadjuvant therapy (NAT) have a higher risk of relapse than pts with a pathologic complete response (pCR). Post neoadjuvant T-DM1 has improved invasive disease-free survival (iDFS), but pts with estrogen receptor (ER)-negative or nodal RD have suboptimal outcomes and recurrences in the central nervous system are a problem. More effective treatment strategies are needed. The CompassHER2 trials, EA1181 and A011801, leverage pCR to tailor post neoadjuvant therapy in HER2+ EBC. EA1181 is a NAT de-escalation trial of a taxane, trastuzumab and pertuzumab (THP) in clinical stage II-III HER2+ EBC; pts with a pCR complete HP +/- adjuvant radiation (RT) +/- endocrine therapy (ET). A011801 is an escalation trial for pts with high risk HER2+ RD after NAT, examining addition of the HER2 selective tyrosine kinase inhibitor (TKI) tucatinib to adjuvant T-DM1. Methods: Eligibility and Intervention: Pts. with high-risk HER2+ RD (e.g. ER-,node-positive, or both) after a predefined course of neoadjuvant HER2-directed treatment are randomized 1:1 to adjuvant T-DM1+ placebo (pb), vs. T-DM1 and tucatinib with adjuvant RT +/- ET. Eligibility criteria include completion of ≥ 6 cycles of NAT, including ≥ 9 weeks of T and H +/- P. All chemotherapy (CT) must be completed preoperatively unless participating in EA1181 (̃15-30% enrollees); these pts must receive postoperative CT to complete ≥ 6 cycles prior to enrollment on A011801. Pts who received prior HER2-targeted TKIs or antibody-drug conjugates are ineligible. Objectives: The primary objective is to determine if iDFS is higher with addition of T-DM1 to tucatinib in pts with HER2+ EBC with RD after NAT; secondary endpoints include overall survival, breast cancer free survival, distant recurrence-free survival, brain metastases-free survival and disease-free survival. Correlative objectives include the association of i) tumor infiltrating lymphocyte (TILs) levels in the primary tumor and RD with iDFS, ii) TILs with tucatinib benefit, iii) iDFS and circulating tumor cells (CTC) at serial timepoints and iv) the magnitude of benefit of tucatinib (iDFS) in pts with/without detectable pretreatment CTCs. Quality of life and pharmacokinetic endpoints will also be evaluated. Statistics: A011801 is a prospective, double-blind, randomized, phase III superiority trial; stratified by i) receipt of postoperative CT (Y/N), ii) hormone receptor-status (+/-),and iii) pathologic lymph node status (+/-). The study targets an absolute difference of 5% in iDFS (control vs. experimental arm 82% & 87%, HR = 0.7), with a two-sided alpha of 0.05 and power of 80%. The sample size is 981; target accrual = 1031 pts; activation and completion dates are 01/6/21 and ̃ 01/2028. Support: U10CA180821, U10CA180882; Seagen Inc; ClinicalTrials.gov Identifier: NCT04457596 Clinical trial information: NCT04457596.

526 Background: Z1041 randomized women with HER2+ operable breast cancer to: FEC → P+T (Arm 1) or P+T → FEC+T (Arm 2). Treatment administered as 5-FU 500 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 day 1 of a 21-day cycle x 4; paclitaxel 80 mg/m2weekly x 12 and T 4 mg/kg once then 2 mg/kg weekly x 11. T was to continue q3 weeks post-op for 40 weeks. A secondary aim was to examine the cardiotoxicity (CE). Methods: Ejection fraction (EF) was measured at baseline (BL), between regimens (wk 12), prior to surgery (wk 24) and PRN. Eligibility: BL EF ≥ 55%. CEs included decline in EF of > 15%, or >10% points to a value < LLN. Reversibility was adjudicated by blinded investigators as reversible (R: recovery of EF to ≤ 5% below BL), partially reversible (PR: recovery of > 10% points from nadir, but ≤ 5% points below BL), indeterminate (IN: no additional EF data), or irreversible (IRR:follow-up EF studies showed no improvement). Results: Of the 280 patients (Arm 1: 138) who began treatment, 15 pts (Arm 1: 10; Arm 2: 5) did not receive T. The number of weeks of T was 13 (range: 1-18) in Arm 1 and 24 (range: 1-31) in Arm 2. Changes in EF and severe treatment related cardiac toxicities prior to surgery (sx) are tabled below. There were 271 pts (Arm 1: 131) who had post-BL EFs. Prior to sx, there were 11 CE (8.3%) in Arm 1 and 13 CE (9.2%) in Arm 2. CEs were R in 12 pts (Arm 1: 5; Arm 2: 7); PR in 6 pts (Arm 1: 4; Arm 2: 2); IN in 4 pts (Arm 1: 2; Arm 2: 3) and IRR in 1 Arm 2 pt. Conclusions: The number of CE events in arms 1 and 2 showed no significant difference; greater scatter was observed in arm 2 patients. While concern for late cardiac events makes ongoing cardiac surveillance prudent due to A, concomitant use of A and T appear to not be associated with increased cardiac risk. Clinical trial information: NCT00513292. [Table: see text]