Radiation oncology residents report varying confidence with on-treatment setup challenges (J Cancer Educ Off J Am Assoc Cancer Educ 36(2):278–283 (2021)). Radiation therapy technologist (RTT) training is variable across institutions (Tech Innov Patient Support Radiat Oncol 24:59–62 (2022)). This study assesses the impact of an interprofessional educational course on RTT and radiation oncology resident knowledge and comfort with managing radiation therapy (RT) treatment challenges. An interprofessional course on managing RT treatment challenges was offered to radiation oncology residents, RTTs, and other team members. Each site-specific session was given by an expert radiation oncology attending with in-person and virtual attendees. Anonymous pre- and post-tests were collected via QR code. Pretests assessed demographics, knowledge (2 multiple choice questions), and comfort (Likert-type Scale, 1–5) with the material. Post-tests also assessed utility and potential implementation. Statistical tests compared pre- vs. post-tests. Nine one-hour sessions were conducted over one year. Respondents were mostly radiation oncology residents/attendings (47.5

BACKGROUND:Early-stage, hormone receptor positive (HR+) breast cancer has excellent outcomes with lumpectomy, radiotherapy, and endocrine therapy (ET), prompting interest in treatment de-escalation. Advances in stereotactic ablative radiotherapy (SABR) raise the possibility of definitive local therapy without surgery in select patients. We conducted a prospective, phase II trial (NCT02945579) evaluating SABR with ET as a non-operative strategy. MATERIALS AND METHODS:Patients aged ≥ 40 years with cT1N0M0, unicentric, HR+, HER2-negative breast cancer received 3 months of ET followed by SABR in 5 fractions. Vacuum-assisted image-guided core biopsy of the tumor bed was performed 6-12 months after SABR. Patients with pathologic complete response (pCR) omitted surgery. Co-primary endpoints were pCR and 3-year progression-free survival (PFS) rates. Patient-reported outcomes were collected as a secondary endpoint. A Bayesian framework evaluated futility using posterior probabilities to assess a clinically meaningful pCR rate. RESULTS:Twenty patients were enrolled (median age 70.5 years). Nineteen underwent biopsy after SABR. pCR was observed in 10/19 patients (53%, 95% CI 30-73%), and 7 (37%) had near complete response. Among the 12 patients managed without surgery, median follow-up was 44.9 months. Three-year PFS was 92% (95% CI 54-99%), with one non-breast cancer-related death and no breast cancer recurrences. Longitudinal patient-reported outcomes of decisional regret and breast-specific outcomes remained stable. CONCLUSION:Definitive SABR combined with ET achieved substantial pCR rates and encouraging tumor control. These findings support further evaluation of radiotherapy-based definitive treatment and potential surgery omission in carefully selected patients with favorable, HR + breast cancer.

Background/Purpose Optimal surgical management of occult breast cancer (OBC) with N2/N3 nodal disease remains uncertain, but current National Comprehensive Cancer Network guidelines recommend mastectomy. We aimed to evaluate whether oncologic outcomes differ by local therapy.Patients and Methods We conducted an observational cohort study of patients with cT0N1-3M0 OBC treated at our institution between 2010 and 2025. We also analyzed data from patients registered in the National Cancer Database (NCDB) from 2006 to 2022. All patients included underwent neoadjuvant systemic therapy. Overall survival (OS) was estimated using Kaplan-Meier methods.Results Among 85 patients treated at our institution, 42 (49.4%) had cN1 disease, 15 (17.6%) had cN2 disease, and 28 (32.9%) had cN3 disease. A total of 14 (16.5%) underwent mastectomy. Over a median follow-up of 3.6 years [IQR: 1.8, 7.9], no in-breast or chest wall recurrences occurred. The 5-year OS and disease-free survival (DFS) were similar among patients undergoing whole-breast radiation versus mastectomy, regardless of nodal status. The NCDB analysis included 632 patients, of whom 558 (88.3%) underwent mastectomy and 74 (11.7%) had radiation without breast surgery. For patients with cN2/N3 disease, 5-year OS was 96.3% (95% CI: 77.7-99.9%) with whole-breast radiation versus 84.3% (95% CI: 78.3-89.0%) with mastectomy.Conclusions There is not strong evidence for improved local control or survival with mastectomy in patients with OBC, even among those with advanced nodal disease. This lack of evidentiary support should be discussed in shared decision-making when mastectomy is presented as the default recommendation for all patients with OBC and N2/N3 disease.

Fam-trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that targets human epidermal growth factor receptor 2 (HER2) and delivers a topoisomerase inhibitor payload. T-DXd has been effectively used to treat metastatic breast cancer but causes pneumonitis in 10–15

Objective(s): To define pathologic response rates to endocrine therapy and ablative radiotherapy, with omission of breast surgery, for early-stage, hormone receptor (HR)+ breast cancer in a prospective, phase II trial (NCT02945579). Methods: Twenty eligible patients with HR+, HER2-, clinical stage I, unicentric, non-lobular breast cancers with no lymphovascular space invasion, Oncotype ≤25 and age ≥50 were accrued to an IRB approved-protocol. Enrolled patients received three months of endocrine therapy followed by restaging ultrasound and ablative radiotherapy, 37.5Gy/5 fractions every other day. MR LINAC was used when feasible. After radiotherapy, patients continued on endocrine therapy and underwent percutaneous vacuum-assisted, image-guided core biopsy (VAIGCB) of the tumor 6-12 months following radiation, with a minimum of 12 9G cores. Near complete response (nCR) was defined as Miller-Payne 4 and pCR as 5. Patients with a pathologic complete response (pCR) were followed every 6 months with imaging; those without a pCR were recommended for standard-of-care surgery. Miller-Payne score was evaluated on core biopsy and surgical specimens. Co-primary endpoints are pCR on VAIGCB and tumor control at 3 years. We report here the former co-primary endpoint of pCR along with the 95% credible interval (CI). Results: 19 of 20 (95%) of patients underwent VAIGCB; 1 declined and elected continued observation. Of the 19 biopsies, 10 (52.6%) demonstrated pCR (Miller-Payne 5), 7 (36.8%) nCR (Miller-Payne 4) and 2 (10.5%) Miller-Payne 3. Of patients who had a VAIGCB 6 months after radiotherapy, 5/11 (45.4%, 95% CI 18.9%-71.5%) had pCR; of those with VAIGCB 12 months after RT, 5/8 (62.5%, 95% CI 27.4%-86.6%) had pCR. 7/9 patients with residual disease (Miller-Payne <5) underwent surgery, one of whom had pCR in the surgical specimen, consistent with complete removal at VAIGCB. There were no postoperative complications. Two patients with nCR declined surgery: one underwent cryoablation and one continued endocrine therapy and underwent repeat biopsy 4 months later with pCR. In total, 17/19 pts who underwent VAIGCB (89.5%) had pCR or nCR. The 1 patient who declined VAIGCB has no residual disease on imaging 2 years after RT. Median follow-up time for all patients who did not have surgery is 26 (range 18 to 38 mo months), with none (0/12) experiencing progression or recurrence. Conclusion: This is the first study to demonstrate a high rate of VAIGCB pCR and nCR following endocrine therapy and ablative radiotherapy for early stage, HR+, HER2- breast cancers. This may be an appealing approach for patients with breast cancer interested in non-surgical approaches to definitively treat their tumors and highlights the efficacy for non-surgical candidates. Citation Format: Simona Shaitelman, Savitri Krishnamurthy, Gaiane M. Rauch, Yu Shen, PhD, Yan H. Lin, Benjamin D. Smith, Melissa P. Mitchell, Karen E. Hoffman, Chelain R. Goodman, Vicente Valero, Helen M. Johnson, Wendy A. Woodward, Henry Kuerer. Eliminating breast surgery for invasive, hormone-positive breast cancers with an exceptional response to endocrine therapy and ablative radiotherapy: a single-arm, phase 2 trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS6-04.

Neoadjuvant systemic therapy (NST) has been associated with pathologic complete response (pCR) in up to 60% of breast cancers (BCs). The findings of this trial question the necessity of surgery. To report preplanned 5-year efficacy outcomes evaluating radiotherapy alone without breast surgery in patients selected with image-guided vacuum assisted biopsy (VAB). This single-arm, prospective, phase 2 nonrandomized clinical trial was conducted at 7 US medical centers and included women 40 years or older with cT1-2N0-1M0 ERBB2-positive (formerly HER2-positive) or triple-negative invasive BC who showed residual breast lesions after NST of less than 2 cm on imaging. Enrollment was from March 6, 2017, to November 9, 2021. Data analysis was from October to December 2024. Image-guided VAB of the tumor bed (9G with a minimum of 12 cores) was performed after standard NST. Patients with clinically node-negative disease at diagnosis and no residual cancer in the breast on post-NST VAB underwent whole-breast radiotherapy with a boost without breast or axillary surgery. Patients with initial documented nodal disease and a breast pCR on VAB underwent targeted axillary dissection, while those with residual cancer when undergoing VAB had standard breast and axillary surgery. Patients were monitored with physical examinations and mammography every 6 months. The primary outcome was ipsilateral breast tumor recurrence. Fifty patients (median [IQR] age, 62 [55-77] years) were enrolled and underwent post-NST VAB. Twenty-nine (58%) and 21 (42%) patients had ERBB2-positive and triple-negative invasive BC, respectively. Breast pCR on VAB was identified in 31 patients (62%; 95% CI, 47.2%-75.34%), and axillary pCR was identified among all 8 patients with initial nodal metastases and breast pCR on VAB who underwent targeted axillary dissection. At a median follow-up of 55.4 (IQR, 44.0-63.5) months, the ipsilateral breast tumor recurrence rate was 0%, and disease-free and overall survival rates were 100% for patients without breast surgery. The results of this nonrandomized clinical trial that reported preplanned 5-year outcomes suggest that omission of breast surgery in select patients after NST may be feasible, with no recurrences seen. More confirmatory studies are necessary before this new approach alters surgical practice. ClinicalTrials.gov Identifier: NCT02945579

Background: Regional nodal irradiation (RNI) improves breast cancer survival but is associated with treatment-related toxicity. Volumetric Modulated Arc Therapy (VMAT)/Intensity Modulated Radiation Therapy (IMRT) treatment technique has been shown in other disease sites to improve dose homogeneity while reducing side effects compared to 3-Dimensional Conformal Radiation Therapy (3D-CRT). To evaluate the association of radiotherapy (RT) treatment technique with acute toxicity for patients receiving RNI, we performed a secondary analysis of the Shortening Adjuvant Photon Irradiation to Reduce Edema (SAPHIRe) trial, a Phase III trial evaluating conventional (CFx) vs. hypofractionation (HFx). We hypothesized that VMAT technique would be associated with reduced acute toxicity compared to 3D-CRT. Methods: Patients with clinical or pathologic T0-3 N0-2a/3a invasive breast cancer dispositioned to receive comprehensive RNI were randomized to CFx vs. HFx (50Gy/25Fx or 40.05Gy/15Fx). Nodal target volumes included the axilla, infraclavicular and supraclavicular nodal basins, and internal mammary chain. Acute RT-related toxicity was graded utilizing the NCI CTCAE v4.0 scale at the end of RT. Associations between treatment technique with clinicopathologic and treatment variables, dosimetric data, and toxicity endpoints were determined using the Fisher’s Exact, Mann-Whitney U, and Kruskal-Wallis tests. Univariate analysis and multivariable binomial logistic regression were performed to calculate adjusted odds ratios (OR) for factors associated with Grade 2+ toxicity at the end of RT. Results: A total of 645 patients with available RT variables and end of RT toxicity assessments were enrolled from 2017-2024 (median follow-up, 20 months [IQR, 7-35]). Patients treated with VMAT technique were balanced across randomization arm (CFx vs HFx) as well as clinicopathologic and treatment variables but had significantly higher body mass index (BMI) (30 [25-34] vs. 28 [24-33], p=0.004) and were more likely to undergo plastic surgery reconstruction (40% vs. 21%, p<0.001). Patients treated with VMAT technique experienced significantly reduced Grade 2+ toxicity at the end of RT treatment compared to 3D-CRT (38% vs. 51%, p=0.002), including Grade 2+ dermatitis (32% vs. 47%, p<0.001), Grade 1+ fatigue (50% vs. 60%, P=0.03), Grade 1+ pruritus (40% vs. 49%, p=0.02), and Grade 1+ breast edema (0.4% vs. 3.9%, p=0.02). VMAT technique was associated with significantly reduced volume of the body receiving ≥105% (V105%) of the prescription dose (72cc vs. 351cc), V107% (2cc vs. 186cc), and V110% (0cc vs. 77cc; all p<0.001), as well as the maximum percentage dose (Dmax) to the nodes (106% vs 120%, p<0.001). 3D-CRT technique was associated with significantly increased dose to the ipsilateral lung (V20Gy [CFx]/V16Gy [HFx]>35% = 12% vs. 1%, p<0.001) as well as mean heart dose (MHD>4Gy [CFx]/3.2Gy [HFx] = 6% vs. 1%, p=0.007). V105% to the body and Dmax to the nodes were significantly associated with increased rates of acute dermatitis (p=0.004 and p=0.01, respectively) and breast edema (p=0.02 and p=0.005, respectively) while V107% was associated with significantly increased fatigue (p=0.02). On multivariable analysis, increased BMI (OR [95% CI]=1.04 [1.00-1.07], p=0.03) was significantly associated with increased rates of Grade 2+ toxicity at the end of RT while hypofractionation (OR=0.28 [0.19-0.42], p<0.001), VMAT treatment technique (OR=0.38 [0.21-0.68], p=0.001), and absence of boost (OR=0.38 [0.15-0.87], p=0.03) were associated with significantly decreased rates of Grade 2+ toxicity at the End of RT. Conclusion: In this secondary analysis of a prospective randomized clinical trial, patients treated with RNI utilizing VMAT technique compared with 3D-CRT experienced significantly decreased rates of acute treatment-related toxicity, including any Grade 2+ toxicity, in the setting of improved dose homogeneity. Citation Format: Chelain Goodman, Melissa P. Mitchell, Saleh Ramezani, Simona F. Shaitelman, Rensi F. Zacharia, Isidora Y. Arzu, Elizabeth Bloom, Clifton D. Fuller, Melissa M. Joyner, Lauren L. Mayo, George H. Perkins, Jay Reddy, Puneet Singh, Michael C. Stauder, Eric A. Strom, Valerie K. Reed, Pamela J. Schlembach, Wendy A. Woodward, Benjamin D. Smith, Karen E. Hoffman. Association of VMAT versus 3D-CRT Radiotherapy Treatment Technique with Acute Toxicity of Regional Nodal Irradiation: A Secondary Analysis of the SAPHIRe Phase III Randomized Clinical Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS6-02.

The aim of this study was to evaluate trends in the total mastectomy (TM) rates in patients with early stage breast cancer (BC) undergoing surgery first at a single institution and compare overall (OS), distant metastasis-free (DMFS), local-regional recurrence (LRR), and BC-specific (BCSS) survival between lumpectomy followed by radiation (breast-conserving therapy (BCT)) and TM. A total of 8967 women with clinical stage T1–2, N0–1, M0 BC who underwent upfront surgery from 1 January 2000 to 31 December 2014 were included. TM rates were evaluated. Inverse probability weighting (IPW) based on propensity scores was used to remove confounding in the survival models in the whole cohort and subset analyses (different stage combined with different hormone receptor status). TM rates increased from 39.7 to 59.9

Importance:Neoadjuvant systemic therapy (NST) has been associated with pathologic complete response (pCR) in up to 60% of breast cancers (BCs). The findings of this trial question the necessity of surgery. Objective:To report preplanned 5-year efficacy outcomes evaluating radiotherapy alone without breast surgery in patients selected with image-guided vacuum assisted biopsy (VAB). Design, Setting, and Participants:This single-arm, prospective, phase 2 nonrandomized clinical trial was conducted at 7 US medical centers and included women 40 years or older with cT1-2N0-1M0 ERBB2-positive (formerly HER2-positive) or triple-negative invasive BC who showed residual breast lesions after NST of less than 2 cm on imaging. Enrollment was from March 6, 2017, to November 9, 2021. Data analysis was from October to December 2024. Intervention:Image-guided VAB of the tumor bed (9G with a minimum of 12 cores) was performed after standard NST. Patients with clinically node-negative disease at diagnosis and no residual cancer in the breast on post-NST VAB underwent whole-breast radiotherapy with a boost without breast or axillary surgery. Patients with initial documented nodal disease and a breast pCR on VAB underwent targeted axillary dissection, while those with residual cancer when undergoing VAB had standard breast and axillary surgery. Patients were monitored with physical examinations and mammography every 6 months. Main Outcome Measures:The primary outcome was ipsilateral breast tumor recurrence. Results:Fifty patients (median [IQR] age, 62 [55-77] years) were enrolled and underwent post-NST VAB. Twenty-nine (58%) and 21 (42%) patients had ERBB2-positive and triple-negative invasive BC, respectively. Breast pCR on VAB was identified in 31 patients (62%; 95% CI, 47.2%-75.34%), and axillary pCR was identified among all 8 patients with initial nodal metastases and breast pCR on VAB who underwent targeted axillary dissection. At a median follow-up of 55.4 (IQR, 44.0-63.5) months, the ipsilateral breast tumor recurrence rate was 0%, and disease-free and overall survival rates were 100% for patients without breast surgery. Conclusions and Relevance:The results of this nonrandomized clinical trial that reported preplanned 5-year outcomes suggest that omission of breast surgery in select patients after NST may be feasible, with no recurrences seen. More confirmatory studies are necessary before this new approach alters surgical practice. Trial Registration:ClinicalTrials.gov Identifier: NCT02945579.

Background:Magnetic resonance imaging-conditional tissue expanders (MRI-CTEs) were developed to address imaging artifacts and challenges in radiation planning associated with traditional tissue expanders (TTEs). This study compared the clinical outcomes and impact of radiation protocols of MRI-CTEs and TTEs in postmastectomy breast reconstruction.Methods:A retrospective review was conducted of immediate breast reconstruction performed with MRI-CTEs or TTEs between 2021 and 2024. Outcomes, such as seroma, infection, malposition, and expander loss, were analyzed.Results:A total of 867 tissue expanders were evaluated in 559 patients. The MRI-CTE cohort consisted of 103 patients (161 devices), and the TTE cohort included 456 patients (706 devices). Demographic characteristics, surgical details, and outcomes did not differ significantly, including seroma (P = 0.091), malposition (P = 0.827), and mastectomy skin flap necrosis (P = 0.251). Three cases (1.9%) in the MRI-CTE cohort required MRI evaluation but did not require explantation. The MRI-CTE group had a lower need for artifact management during radiation therapy and reduced imaging artifact size from 4 cm to 1 cm in diameter. This allowed for a reduction in planning target volume margins from 20 mm to 5 mm, which improved delineation accuracy by 75% and decreased irradiation of healthy tissue by up to 60%.Conclusions:MRI-CTEs may contribute to improved clinical outcomes, with fewer surgical interventions and enhanced precision in radiation treatment planning. MRI-CTEs demonstrated surgical outcomes similar to those for TTEs, but offered improved accuracy in radiation dose calculations. Reduced manual interventions for artifact adjustment decrease the potential for human error, enhancing the overall precision of radiation treatment delivery.CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, III.

BACKGROUND:Selective omission of sentinel lymph node biopsy (SLNB) in patients with early breast cancer limits surgical morbidity. Adoption of this strategy relies on multidisciplinary consensus. Understanding how SLNB omission influences guideline-based adjuvant treatment decisions, and the proportion of patients impacted, can help guide decision-making. PATIENTS AND METHODS:Data from the National Cancer Database (2018-2020) was used to estimate the proportions of patients with cT1N0 hormone receptor-positive breast cancer for whom adjuvant chemotherapy, CDK4/6 inhibitor therapy, and regional nodal irradiation decisions would be impacted by the absence of lymph node pathology if national treatment guidelines were followed. Because OncotypeDX score is essential to adjuvant decision-making when SLNB is omitted, inverse probability weighting was used to estimate the proportions of interest had all individuals undergone OncotypeDX testing. RESULTS:There were 119,312 included patients, with an average age of 63 years, 96,454 (80.8%) having invasive ductal histology, and 52,222 (43.8%) having cT1c tumors. The number of patients with SLNB positivity was 13,211 (11.1%). Among postmenopausal women, 7.9% (95% CI, 7.7-8.1) would have had at least one adjuvant decision impacted by the absence of lymph node pathology. For premenopausal women, the affected proportion was 13.7% (95% CI, 13.0-14.7). When ribociclib decision-making was not considered, these estimates were 2.5% for postmenopausal women and 12.6% for premenopausal women. CONCLUSIONS:SLNB omission has a small - but not negligible - influence on adjuvant decision making in postmenopausal women, whereas a larger proportion of premenopausal women would be impacted. The reported estimates may inform multidisciplinary decision-making related to SLNB omission.

TPS1120 Background: Breast radiotherapy (RT) is the standard of care for patients with early-stage breast cancer (BC) who undergo breast-conserving surgery (BCS). However, the magnitude of benefit of RT is less clear in BCS patients with low-risk disease who receive effective systemic therapy. Among patients with early-stage HER2-positive (HER2+) BC, 10-year locoregional recurrence has been reported as low as 1.5% following BCS, adjuvant chemotherapy and HER2-targeted therapy, and RT. Given these exceedingly favorable outcomes, with the addition of HER2-directed therapy, we seek to evaluate the feasibility of omitting RT among patients with early-stage HER2+ BC following BCS and appropriate systemic therapy. Methods: This is a phase III randomized trial for patients ≥18 years with early-stage, node-negative, HER2+ (IHC/FISH) BC treated with BCS with negative margins and sentinel lymph node biopsy or axillary dissection. Patients undergoing primary surgery must have pathologic T1-2 (≤3 cm) N0 disease, whereas patients receiving neoadjuvant therapy must have clinical T1-2 (with radiographically T≤5 cm) N0 disease and exhibit a pathologic complete response (ypT0N0) at surgery (residual DCIS [ypTis] spanning ≤1 cm is permitted, and surgical margins are negative for DCIS). All patients must receive cytotoxic chemotherapy and HER2-targeted therapy, either in the adjuvant or neoadjuvant setting. Stratification is by age (<60; ≥60), tumor size (≤1 cm; >1 cm), estrogen-receptor status (positive; negative), and systemic therapy sequencing (adjuvant v neoadjuvant). Patients will be randomized to standard breast RT in addition to continuation of trastuzumab to complete one year of treatment (Arm 1), or trastuzumab alone (Arm 2). Endocrine therapy will be recommended for patients with hormone-receptor-positive tumors. The primary endpoint is the recurrence-free interval (RFI). Secondary endpoints include time to ipsilateral breast recurrence, locoregional recurrence, disease-free survival, and overall survival, in addition to the 7-year ipsilateral breast recurrence rate among those not receiving RT. A health-related quality of life sub-study will assess differences in patient-reported breast pain and worry. We estimate a 7-year RFI of 97.5% with RT and allow for a clinically acceptable decrement of 3.63% without RT (7-year RFI of 93.87%; HR 2.5) to establish omission of RT as non-inferior. NRG-BR008 aims to enroll 1,300 patients over 7.25 years, yielding 80% power to detect the non-inferiority of RT omission with a one-sided α=0.05. We expect to observe the required 38 RFI events within 4.5 years of additional follow-up. The NRG-BR008/HERO trial opened to accrual in March 2023. Accrual is 64/1,300 as of 1/23/24. NCT #: NCT05705401. Support: U10 CA180868, -180822, UG1 CA189867, U24 CA196067. Clinical trial information: NCT05705401 .

Background: MRI-conditional tissue expanders (MRI-CTEs) were developed to address imaging artifacts and challenges in radiation planning associated with traditional tissue expanders (TTEs). This study aims to compare the clinical outcomes and radiation protocol impacts of MRI-CTEs versus TTEs in postmastectomy breast reconstruction. Methods: A retrospective review was conducted on immediate breast reconstruction with MRI-CTEs or TTEs between 2021 and 2024. Outcomes such as seroma, infection, malposition, and expander loss were analyzed. Results: A total of 867 tissue expanders were evaluated in 559 patients. The MRI-CTE cohort consisted of 103 patients (161 devices), and the TTE cohort included 456 patients (706 devices). Demographics, surgical details, and outcomes did not differ significantly including seroma (P=0.091), malposition (P=0.827), and mastectomy skin flap necrosis (P=0.251). Three cases (1.9%) in the MRI-CTE cohort required MRI evaluation but did not require explantation. The MRI-CTE group had a lower need for artifact management during radiation therapy and reduced imaging artifact size from 4 cm to 1 cm in diameter, allowing for a reduction in planning target volume margins from 20 mm to 5 mm, improving delineation accuracy by 75% and decreased irradiation of healthy tissue by up to 60%. Conclusions: MRI-CTEs may contribute to improved clinical outcomes with fewer surgical interventions and enhanced precision in radiation treatment planning. MRI-CTEs demonstrated similar surgical outcomes to TTEs but offered improved accuracy in radiation dose calculations. Reduced manual interventions for artifact adjustment decrease the potential for human error, enhancing the overall precision of radiation treatment delivery.

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. 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); these patients 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 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 pts; activation and estimated completion dates are 01/6/21 and ∼ 01/2028. Accrual as of 7/1/2024: 741 patients. Support: U10CA180821, U10CA180882; Pfizer Inc; ClinicalTrials.gov Identifier: NCT04457596 Citation Format: Ciara O'Sullivan, Karla V. Ballman, Linda M. McCall, Tyler J. Zemla, Anna C. Weiss, Melissa P. Mitchell, Victoria S. Blinder, Nadine M. Tung, William J. Irvin, Sailaja Kamaraju, Matthew P. Goetz, William F. Symmans, Virginia F. Borges, Ian E. Krop, Ann H. Partridge, Lisa A. Carey. A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-10-19.

Background: Breast radiotherapy (RT) is the standard of care for patients with early-stage breast cancer (BC) who undergo breast-conserving surgery (BCS). However, the magnitude of benefit of RT is less clear in BCS patients with low-risk disease who receive effective systemic therapy. Among patients with early-stage HER2-positive (HER2+) BC, 10-year locoregional recurrence has been reported as low as 1.5% following BCS, adjuvant chemotherapy and HER2-targeted therapy, and RT. Given these exceedingly favorable outcomes, with the addition of HER2-directed therapy, we seek to evaluate the feasibility of omitting RT among patients with early-stage HER2+ BC following BCS and appropriate systemic therapy. Methods: This is a phase III randomized trial for patients ≥40 years with early-stage, node-negative, HER2+ (IHC/FISH) BC treated with BCS with negative margins and sentinel lymph node biopsy or axillary dissection. Patients undergoing primary surgery must have pathologic T1 (≤2 cm) N0 disease, whereas patients receiving neoadjuvant therapy must have clinical T1-2 (with radiographically T≤3.0 cm) N0 disease and exhibit a pathologic complete response (ypT0N0) at surgery. All patients must receive cytotoxic chemotherapy and HER2-targeted therapy, either in the adjuvant or neoadjuvant setting. Stratification is by age (<60; ≥60), tumor size (≤1 cm; >1 cm), estrogen-receptor status (positive; negative), and systemic therapy sequencing (adjuvant v neoadjuvant). Patients will be randomized to standard breast RT in addition to continuation of trastuzumab to complete one year of treatment (Arm 1), or trastuzumab alone (Arm 2). Endocrine therapy will be recommended for patients with hormone-receptor positive tumors. The primary endpoint is the recurrence-free interval (RFI). Secondary endpoints include time to ipsilateral breast recurrence, locoregional recurrence, disease-free survival, and overall survival, in addition to the 7-year ipsilateral breast recurrence rate among those not receiving RT. A health-related quality of life sub-study will assess differences in patient-reported breast pain and worry. We estimate a 7-year RFI of 97.5% with RT and allow for a clinically acceptable decrement of 3.63% without RT (7-year RFI of 93.87%; HR 2.5) to establish omission of RT as non-inferior. NRG-BR008 aims to enroll 1,300 patients over 4.5 years, yielding 80% power to detect the non-inferiority of RT omission with a one-sided α=0.05. We expect to observe the required 38 RFI events within 6 years of additional follow-up.The NRG-BR008/HERO trial opened to accrual in March 2023. Accrual is 32/1,300 as of July 9, 2024. NCT #: NCT05705401. Support: U10CA180868, -180822, UG1CA189867, U24CA196067. Citation Format: Melissa P. Mitchell, Lior Z. Braunstein, Hanna Bandos, William M. Sikov, Atif J. Khan, Peter Y. Chen, Patricia A. Ganz, Reshma Jagsi, Julia R. White, Reena S. Cecchini, Hyejoo Kang, Shannon L. Puhalla, Kelly L. Bolton, Eileen P. Connolly, Erica M. Stringer-Reasor, Kimberly R. Gergelis, Thomas B. Julian, Eleftherios P. Mamounas, Norman Wolmark. NRG-BR008: A phase III randomized trial of radiotherapy optimization for low-risk HER2-positive breast cancer (HERO) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-12-19.