Candidates For Breast-conserving Surgery Research Articles

Abstract PO2-07-04: Applying the Alliance Trial Guidelines in Multi-focal Breast Disease Using an Artificial Intelligence Computational Platform: Economic Analysis and Cosmetic Sensitivity

Abstract Background: Traditionally, multi-focal breast cancer results in mastectomy. The Alliance Trial offers a paradigm shift in surgical options available for multi-focal breast cancer patients in the context of adjuvant chemotherapy. In the trial, patients with multi-focal disease (< 3 tumors) who underwent breast conservation surgery (BCS) were found to have similar outcomes to patients undergoing mastectomy. BCS for large volume tumors ( >30%) has been cited as having a high potential for cosmetic defect, and hence represents a typical upper limit for potential tissue removal in BCS. Here, we evaluated a patient cohort to better understand the economic impact of the Alliance trial and further categorize patients that would most benefit without suffering cosmetic impact. We employed a novel computational technology to quantify the ratio of tumor size to breast tissue volume. Methods: Using a publicly available, single site cohort (n=243, DUMC) of breast cancer patients that underwent mastectomy, we segmented the tumors using our TumorSight Viz software platform. This platform uses artificial intelligence to segment the tumor and surrounding tissues and allows for a volumetric and morphologic assessment in 3D space. We then applied relevant inclusion/exclusion criteria from the Alliance Trial to the cohort (Saha et al, 2018). In trial eligible patients, we used TumorSight Viz to create a convex hull (CH) around the multi-focal disease using dilations of 1 cm and 2 cm. The volume of the CH, corresponding to proposed surgical extirpation, and the overall breast volume (BV) were then computationally assessed in 3D. The ratio of CH to BV (CH:BV) was calculated and a cutoff of 30% (high potential for cosmetic deformity) was applied. A cost analysis was then carried out. We determined the aggregate per annum savings that could potentially be realized by transforming a subset of mastectomies to BCS by tabulating total costs of mastectomy+reconstruction vs. BCS+WBI (whole-breast irradiation), as well as adjusted for relative rates of adjuvant therapy (~80%) across the nationwide patient population. Results: We found that 19.3% of adjuvant mastectomy patients were eligible for BCS based on Alliance Trial criteria. Of those, 68% had tumor CH:BV < 30% when using a 1 cm dilation around the tumor. When using a 2 cm dilation, 56% had tumor CH:BV < 30%. Together, these results indicate that of all adjuvant mastectomy patients, an estimated 10.8-13.1% are eligible for BCS based on volumetric measures of cosmetically acceptable breast tissue removal. Our economic analysis of BCS vs. mastectomy revealed an estimated $28,500 cost savings for patients with private insurance, suggesting that both decreased costs and improved quality-of-life (QOL) can be mutually aligned. By assessing the nationwide number of patients receiving adjuvant therapy for breast cancer, alongside the percentage potentially eligible for BCS using the above cosmetic defect analysis, we estimate that BCS conversion from mastectomy offers to provide a net savings of $300-350 million annually. Conclusion: The Alliance Trial guidelines unveiled the potential option of BCS in ~20% of patients with multi-focal disease in our cohort, demonstrating considerable cost-savings. Computational tools can further differentiate individuals who may not be best candidates for BCS in this setting, ensuring high QOL and informed decision-making. Citation Format: John Pfeiffer, Matthew Biancalana, Dorys Lopez-Ramos, Bradley Feiger, Anuja Antony. Applying the Alliance Trial Guidelines in Multi-focal Breast Disease Using an Artificial Intelligence Computational Platform: Economic Analysis and Cosmetic Sensitivity [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 PO2-07-04.

Abstract PO4-22-05: Changes in Treatment Recommendation for Patients with Ductal Carcinoma In Situ Using a 7-Gene Predictive Biosignature: Analysis of the PREDICT Australia Study

Abstract Background: The role of adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) for women with ductal carcinoma in situ (DCIS) remains controversial. Although there is Level 1 evidence supporting the use of RT to reduce the risk of local recurrence, prognostic and predictive tools are needed to better stratify the individual risks and benefits of RT. The 7-gene predictive DCIS biosignature provides a validated score (DS) for women receiving BCS that assesses 10-year risk of DCIS recurrence and development of invasive breast cancer with and without adjuvant RT. We established a registry to evaluate the decision impact of the 7-gene predictive biosignature on DCIS treatment recommendations in an Australian setting. Methods: The PREDICT study is a prospective, multi-institutional registry for patients who received DCISionRT testing as part of their routine care. The registry includes females 26 and older who are diagnosed with DCIS and are candidates for BCS and eligible for RT. Treating physicians completed treatment recommendation forms before and after receiving test reports to capture surgical, radiation and hormonal treatment (HT) recommendations and patient preferences. Results: This planned interim analysis was performed in 483 patients with complete data treated at 43 clinical sites in Australia. The median age of patients was 61 years, 19% were 50 or younger, nuclear grade was high in 51%, and tumor size was 2.5 cm or greater in 15%. Overall, RT recommendation (yes/no) was changed for 41% of women and HT recommendation was changed for 9% after testing with a net reduction in recommended RT of 14% (66% pre-assay to 52% post-assay p< 0.001). Of patients recommended to receive RT pre-test, 42% were recommended to not receive RT post-test and of the patients recommended to not receive RT pre-test, 40% were recommended to receive RT post-test. The post-test RT recommendation rate increased with increasing DS score (< 2, 2-4, >4), with 9% of patients recommended RT for DS< 2, 62% for DS 2-4, and 100% for DS 4-10. The use of the test resulted in different RT recommendations than with clinicopathology alone, where RT recommendations were changed for 49%, 37%, and 34% for women of age< 50 yrs, with Grade 3 DCIS, or with DCIS > 2.5 cm, respectively. Collectively, this suggests that physicians had a high confidence in the test results when making their final treatment recommendations with the test results. Conclusions: This analysis demonstrates that the use of the 7-gene predictive biosignature resulted in significant changes in recommendations to add or omit RT in this study of 483 women. The integration of DCISionRT into the clinical decision-making processes has a substantial impact on recommendations to personalize care and prevent over- or under-treatment. Table 1: Impact of DCISionRT on Adjuvant Radiation Recommendations by Clinicopathologic Features Citation Format: Yvonne Zissiadis, Bruce Mann, David Speakman, Christobel Saunders, Marcus Dreosti, Christopher Pyke, Daniel De Viana, Melissa Bochner, James French, Sally Baron-Hay, Karuna Mittal, Steven Shivers, Troy Bremer. Changes in Treatment Recommendation for Patients with Ductal Carcinoma In Situ Using a 7-Gene Predictive Biosignature: Analysis of the PREDICT Australia Study [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 PO4-22-05.

Impact on Radiation Therapy Recommendation and Treatment Modality for Patients with Ductal Carcinoma In Situ Using the 7Gene Biosignature: Analysis of the PREDICT Study

Breast conserving surgery (BCS) followed by adjuvant radiotherapy (RT) has been a mainstay in the treatment of DCIS based on multiple randomized trials demonstrating a local recurrence benefit with RT. However, these studies have failed to identify subsets of patients who did or did not benefit from adjuvant RT after BCS, raising concerns regarding both over and undertreatment. Thus, better prognostic and predictive tools are needed to appropriately risk stratify patients and understand their benefit of RT. The 7-gene predictive DCIS biosignature provides a validated score (DS) for women undergoing BCS that assesses their 10-year risk of in-breast and invasive recurrence with and without adjuvant RT. This trail was designed to evaluate the decision impact of the 7-gene predictive biosignature score on DCIS treatment recommendations. The PREDICT study is a prospective, multi-institutional trial for patients who received DCISionRT testing as part of their routine care. The registry includes females 26 and older who are diagnosed with DCIS, are candidates for BCS, and eligible for RT. Treating physicians completed treatment recommendation forms before and after receiving test reports to capture surgical, radiation and hormonal treatment (HT) recommendations and patient preferences. Analysis was performed in 2,012 patients treated at 63 clinical sites. Median age was 62 years old with 32% grade 3 and 10% size 2.5 cm or greater. Post-test, RT recommendation changed for 38% of patients (p<0.001), with a net reduction of 20% in patients recommended to receive RT(p<0.001). The DCISionRT test results had the greatest impact (OR 26.2, 95% CI 19.1-36.4, when analyzed categorically using DS>3 cut-off; 2.3 per DS, 95% CI 2.1-2.6, when evaluated continuously) on post-test RT recommendation in multivariable analysis when compared to all other factors including patient preference, patient clinical and tumor pathological factors, patient race/ethnicity, treatment facility, physician specialty. The post-test RT recommendation rate increased with increasing DS (0-2, 2-4, 4-10) on a categorical basis, with odds ratios of 6.8 DS (2-4 vs 0-2), and 35.0 for DS (4-10 vs 0-2). After DCISionRT test result, patient preference was the second most important factor in post-testing RT recommendation. There was also a significant change in the modality of RT recommended to 34% of those patients recommended RT pre-test and post-test by radiation oncologists (n = 937), with intensified RT modality for higher DS (p<0.001) and de-escalation for lower DS (p<0.001). This analysis of over 2,000 patients demonstrates significant changes in recommendations to add or omit RT based on the 7-gene predictive. The integration of DCISionRT into clinical decision processes has substantial impact on recommendations aimed at optimal management to prevent over- or under-treatment.

Abstract P4-02-02: Changes in treatment recommendation for patients with Ductal Carcinoma In Situ using a 7-gene predictive biosignature: Analysis of the PREDICT Study

Abstract Background: The role of adjuvant radiotherapy (RT) following breast conserving surgery (BCS) for women with ductal carcinoma in situ (DCIS) remains controversial. Although there is Level 1 evidence supporting the use of RT in reducing the risk of local recurrence, prognostic and predictive tools are needed to better stratify individual risks and benefits of RT. The DCISionRT® Test (PreludeDx, Laguna Hills, CA) is a 7-gene predictive biosignature that uses tumor biology in conjunction with clinicopathologic factors. The test provides a validated score (DS) for women receiving BCS that assesses 10-year risk of DCIS recurrence and development of invasive breast cancer with and without adjuvant RT. We established a registry to evaluate the decision impact of the 7-gene predictive biosignature on DCIS treatment recommendations. Methods: The PREDICT study is a prospective, multi-institutional registry for patients who received DCISionRT testing as part of their routine care. The registry includes females 26 and older who are diagnosed with DCIS and are candidates for BCS and eligible for RT or systemic therapy. Treating physicians completed treatment recommendation forms before and after receiving test reports to capture surgical, radiation and hormonal treatment (HT) recommendations and patient preferences. The primary endpoint is to identify the proportion of patients where testing led to a change in RT recommendation. Additional analyses include changes in recommendations in patient subgroups based on clinicopathologic factors or clinician specialty. Results: Analysis was performed in 2,308 patients treated at 63 clinical sites. The median age of patients was 62 years, 18% were 50 or younger, nuclear grade was high in 33%, and tumor size was 2.5 cm or greater in 11%. Test results were DS Low Risk (DS ≤ 3) for 63% of women and 37% were DS Elevated Risk (DS &amp;gt; 3). Overall, RT recommendation (yes/no) was changed for 38% of women after the 7-gene biosignature testing and HT recommendation was changed for 11%. There was a net decrease in RT recommendation from 71% pre-assay to 53% post-assay (p&amp;lt; 0.001), where RT recommendations decreased 53% in DS Low Risk patients but increased 25% in DS Elevated Risk patients. Surgeons were more likely to change their RT recommendation (47%) than radiation oncologists (35%). When test results indicated DS Elevated Risk, both surgeons (79%) and radiation oncologists (88%) were likely to recommended RT, but when the results were DS Low risk, surgeons were more likely than radiation oncologists to recommend omitting RT (82% vs. 60%, respectively). Compared to traditional clinicopathologic features, the factor most strongly associated with RT recommendation was the biosignature result with other factors of importance being patient preference, tumor size and grade. Conclusions: This analysis demonstrates significant changes in recommendations to add or omit RT based on the 7-gene predictive biosignature in 2,308 patients. The integration of DCISionRT into clinical decision processes has substantial impact on recommendations aimed at optimal management to prevent over- or under-treatment. Table 1. Impact of the 7-gene predictive biosignature on adjuvant radiation recommended by clinicopathologic features. Citation Format: Pat Whitworth, Steven C. Shivers, Chirag Shah, Rakesh Patel, Karuna Mittal, Troy Bremer, Charles Cox. Changes in treatment recommendation for patients with Ductal Carcinoma In Situ using a 7-gene predictive biosignature: Analysis of the PREDICT Study [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 P4-02-02.

Abstract OT3-11-03: The PREDICT Registry Australia: A prospective registry to evaluate the clinical utility of a 7-gene predictive biosignature on treatment decisions in patients with ductal carcinoma in situ

Abstract Background: For women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS), the benefit of adjuvant radiation therapy (RT) remains controversial. Since there is level 1 evidence supporting the role of RT in reducing the risk of local recurrence, current guidelines generally recommend RT for all women having BCS even though the absolute benefit is variable. In response to the need for prognostic and predictive tools to better assess risk and RT benefit, a 7-gene predictive biosignature (DCISionRT, PreludeDx, Laguna Hills, CA) was developed. The test provides a validated score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology, as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool has on treatment decisions. Prospective Clinical Trial Design: This is a multicenter, prospective, observational registry for women diagnosed with DCIS in Australia. After DCIS diagnosis, sites will send the most representative tissue block or sections mounted on charged slides to the PreludeDx lab for biosignature testing. Treating physicians will complete a treatment recommendation survey before and after receiving the biosignature test results. Test results, treatment recommendations, patient preferences and clinicopathologic features will be stored in a de-identified registry for participating institutions from a variety of geographic regions across Australia. Women will then be followed for up to 10 years with completion of a follow-up form. The study has been approved by the North Shore Local Health District Human Research Ethics Committee, St Leonards, NSW, Australia. Universal Trial Number (UTN): U1111-1266-0439; ANZCTR: ACTRN12621000695808; ClinicalTrials.gov: NCT04916808. Eligibility Criteria: The study includes females age 26 or older who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. Specific Aims: The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status, patient preference and biosignature status. Statistical Methods: Changes in pre- and post-DCISionRT treatment recommendations will be analyzed using McNemar’s test (alpha level = 0.05). Multivariate logistic regression will be used to determine odds ratios of clinicopathologic factors leading to pre- and post-test treatment recommendations. Pre-test covariates include patient age, tumor size, palpability, margin status, hormone receptor status, nuclear grade, tumor necrosis, family history of breast cancer, race, ethnicity and patient preference, as well as physician specialty (surgeons vs. radiation oncologists) and post-test covariates will also include the DCISionRT Decision Score (DS). Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. Statistical analyses will be carried out using R (https://www.r-project.org) or SAS. An early interim analysis based on the first 200 enrolled patients is currently underway. Present and Planned Accrual: We are planning to enroll up to 1,500 women from up to 100 sites across Australia. A similar registry has recently completed enrollment of 2,500 women from 68 sites in the US. Citation Format: Yvonne Zissiadis, G Bruce Mann, David Speakman, Christobel Saunders, Christopher Pyke, Daniel De Viana, Melissa Bochner, James R. French, Marcus Dreosti, Sally Baron-Hay, Alexandra Feetham, Kim Kirkham, Shane Ryan, Karuna Mittal, Steven C. Shivers, Troy Bremer. The PREDICT Registry Australia: A prospective registry to evaluate the clinical utility of a 7-gene predictive biosignature on treatment decisions in patients with ductal carcinoma in situ [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 OT3-11-03.

Diffusion-Weighted Magnetic Resonance Imaging for Preoperative Evaluation of Patients With Breast Cancer: Protocol of a Prospective, Multicenter, Observational Cohort Study.

Detection of multifocal, multicentric, and contralateral breast cancers in patients affects surgical management. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can identify additional foci that were initially undetected by conventional imaging. However, its use is limited owing to low specificity and high false-positive rate. Multiparametric MRI (DCE-MRI + diffusion-weighted [DW] MRI) can increase the specificity. We aimed to describe the protocols of our prospective, multicenter, observational cohort studies designed to compare the diagnostic performance of DCE-MRI and multiparametric MRI for the diagnosis of multifocal, multicentric cancer and contralateral breast cancer in patients with newly diagnosed breast cancer. Two studies comparing the performance of DCE-MRI and multiparametric MRI for the diagnosis of multifocal, multicentric cancer (NCT04656639) and contralateral breast cancer (NCT05307757) will be conducted. For trial NCT04656639, 580 females with invasive breast cancer candidates for breast conservation surgery whose DCE-MRI showed additional suspicious lesions (breast imaging reporting and data system [BI-RADS] category ≥ 4) on DCE-MRI in the ipsilateral breast will be enrolled. For trial NCT05307757, 1098 females with invasive breast cancer whose DCE-MRI showed contralateral lesions (BI-RADS category ≥ 3 or higher on DCE-MRI) will be enrolled. Participants will undergo 3.0-T DCE-MRI and DW-MRI. The diagnostic performance of DCE-MRI and multiparametric MRI will be compared. The receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and characteristics of the detected cancers will be analyzed. The primary outcome is the difference in the receiver operating characteristic curve between DCE-MRI and multiparametric MRI interpretation. Enrollment completion is expected in 2024, and study results are expected to be presented in 2026. This prospective, multicenter study will compare the performance of DCE-MRI versus multiparametric MRI for the preoperative evaluation of multifocal, multicentric, and contralateral breast cancer and is currently in the patient enrollment phase. ClinicalTrials.gov Identifier: NCT04656639, NCT05307757. Registered on April 1 2022.

The PREDICT Registry Australia: A Prospective Registry to Evaluate the Clinical Utility of a Biomarker Assay on Treatment Decisions in Patients with DCIS Following Breast Conserving Surgery

<h3>Purpose/Objective(s)</h3> The benefit of adjuvant radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Although level-I evidence supports the role of RT in reducing the risk of local recurrence, the absolute benefit of RT is variable and so it is important to develop better prognostic and predictive tools. The assay under evaluation is a biologic signature that provides a validated decision score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool has on treatment decisions. The hypothesis is that the biomarker assay is associated with changes in treatment recommendations for surgical, hormonal and/or radiation therapy. <h3>Materials/Methods</h3> This is a multi-center, prospective, observational study for women diagnosed with DCIS of the breast. After diagnosis, sites will send the most representative tissue block or sections for testing. Treating physicians complete a treatment recommendation survey before and after receiving test results. Test results, treatment recommendations, patient preferences and clinicopathologic features will be stored in a de-identified registry for participating institutions from a variety of geographic regions across Australia. Women will be followed for up to 10 years with completion of a follow-up form. The study includes females age 26 or older who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including clinicopathologic factors and patient preference. Changes in pre- and post-test treatment recommendations will be analyzed using McNemar's test (alpha level = 0.05). Multivariate logistic regression will be used to determine odds ratios of clinicopathologic factors leading to pre- and post-test treatment recommendations. Pre-test covariates include patient age, tumor size, palpability, margin status, hormone receptor status, nuclear grade, tumor necrosis, family history, race, ethnicity and patient preference, as well as physician specialty and post-test covariates will also include the DS. Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. We are planning to enroll up to 1,500 women from up to 100 sites across Australia. A similar registry in the US has enrolled 2,500 women from 67 sites. <h3>Results</h3> TBD <h3>Conclusion</h3> TBD

A nomogram to identify appropriate candidates for breast-conserving surgery among young women with breast cancer: A large cohort study.

There is a gradual increase of female breast cancer under 35 years old, who was characterized as poor prognosis. Whether young patients could obtain greater survival benefits from breast-conserving surgery (BCS) than mastectomy remains controversial. Breast cancer patients (≤35 years old) were selected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into BCS and mastectomy group. Propensity score matching (PSM) was used to eliminate the distributional imbalance of variables among two groups. The influence of BCS on overall survival (OS) and breast cancer-specific survival (BCSS) was evaluated by Cox regression. Logistic regression was used to identify factors related to the benefit of BCS and to construct a nomogram. The nomogram was validated by the First Affiliated Hospital of Xi'an Jiaotong University cohort. Totally, 15,317 cases in the SEER database and 149 cases of external validation cohort were included. BCS was an independent protective factor for OS (P = 0.028) and BCSS (P = 0.042). A nomogram was established, and the AUC values both in the internal and external validation set were 0.780. The applicability of the model was verified in the PSM cohort and indicated that the survival advantage in the BCS-Benefit group was higher than that in the BCS-Nonbenefit and mastectomy group (P <0.001). For young breast cancer patients, BCS may bring better OS and BCSS than mastectomy, but not all benefit from it. We constructed a model for young patients (≤35 years old) that could identify appropriate candidates who benefit from BCS.

Abstract OT1-09-02: The PREDICT Registry: A prospective registry to evaluate the effect of a predictive assay on treatment decisions in patients with DCIS following breast conserving therapy

Abstract Background. The benefits of adjuvant radiation therapy (RT) in patients with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Although there is level-I evidence supporting the role of RT in reducing the risk of local recurrence, the absolute benefit is variable. Current guidelines generally recommend RT for all patients having BCS, but it is important to develop prognostic and predictive tools to better assess risk and understand the impact such a tool would have on treatment decisions. The DCISionRT Test(PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score for assessing 10-year risk of recurrence and RT benefit using individual tumor biology as assessed by clinical and pathologic biomarkers. Methods. This is a prospective cohort study for patients diagnosed with DCIS of the breast. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinico-pathologic features are stored in a de-identified registry for participating institutions from a variety of geographic regions across the US. The study will also collect 5- and 10-year recurrence and survival data. The study includes females over age 25 who are candidates for BCS and eligible for RT and/or systemic treatment with sufficient tissue to generate test results. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status and other clinico-pathologic factors. Changes in treatment recommendations will be assessed using McNemar's test with an alpha level of 0.05. Differences in recurrence-free and overall survival will be evaluated by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. A planned early interim analysis based on the first 200 patients has been recently completed and reported. Results. As of July 9, 2021, 1,986 patients have been accrued from 64 institutions. Ten additional institutions are currently in the process of joining the study. We are planning to enroll up to 2,500 patients from up to 100 institutions. Citation Format: Steven C Shivers, Pat W Whitworth, Rakesh Patel, Troy Bremer, Charles E Cox. The PREDICT Registry: A prospective registry to evaluate the effect of a predictive assay on treatment decisions in patients with DCIS following breast conserving therapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-09-02.

Abstract OT1-11-01: The PREDICT registry Australia: A prospective registry study to evaluate the clinical utility of the DCISionRT test on treatment decisions in patients with DCIS following breast conserving surgery

Abstract Background: The benefit of adjuvant radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Since there is level-I evidence supporting the role of RT in reducing the risk of local recurrence, current guidelines generally recommend adjuvant RT for all women having BCS. However, the absolute benefit of RT is variable in women with DCIS and so it is important to develop prognostic and predictive tools to better assess risk and RT benefit. The DCISionRT Test (PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology, as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool would have on treatment decisions. Prospective Clinical Trial Design: This is a multicenter, prospective, non-interventional (observational) cohort study for women diagnosed with DCIS of the breast. After diagnosis of DCIS, sites will send the most representative tissue block or sections mounted on charged slides to PreludeDx for DCISionRT testing. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinicopathologic features will be stored in a de-identified registry for participating institutions from a variety of geographic regions across Australia. Women will then be followed for up to 10 years with completion of a follow-up form. The study has been approved by the North Shore Local Health District Human Research Ethics Committee, St Leonards, NSW, Australia. Universal Trial Number (UTN): U1111-1266-0439; ANZCTR: ACTRN12621000695808; ClinicalTrials.gov: NCT04916808. Eligibility Criteria: The study includes females age 26 or older who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. Specific Aims: The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status and patient preference. Statistical Methods: Changes in pre- and post-DCISionRT treatment recommendations will be analyzed using McNemar's test (alpha level = 0.05). Multivariate logistic regression will be used to determine odds ratios of clinicopathologic factors leading to pre- and post-test treatment recommendations. Pre-test covariates include patient age, tumor size, palpability, margin status, hormone receptor status, nuclear grade, tumor necrosis, family history of breast cancer, race, ethnicity and patient preference, as well as physician specialty (surgeons vs. radiation oncologists) and post-test covariates will also include the DCISionRT Decision Score (DS). Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. Statistical analyses will be carried out using R (https://www.r-project.org) or SAS. An early interim analysis based on the first 200 enrolled patients is planned. Present and Planned Accrual: We are planning to enroll up to 1,500 women from up to 100 sites across Australia. A similar registry in the US has enrolled 1,985 women from 64 sites towards a goal of 2,500. Citation Format: Yvonne Zissiadis, G Bruce Mann, Steven C Shivers, Troy Bremer. The PREDICT registry Australia: A prospective registry study to evaluate the clinical utility of the DCISionRT test on treatment decisions in patients with DCIS following breast conserving surgery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-11-01.

Abstract P2-08-12: Interim analysis of the PREDICT Registry: Changes in treatment recommendation for a biologic signature predictive of radiation therapy (RT) benefit in patients with DCIS

Abstract Background: The role of adjuvant RT following breast conserving surgery (BCS) for women with ductal carcinoma in situ (DCIS) remains controversial. Although there is level I evidence supporting the role of RT in reducing the risk of local recurrence, prognostic and predictive tools are needed to better stratify individual risks and benefits of RT. The DCISionRT® Test (PreludeDx, Laguna Hills, CA) is a biosignature that uses individual tumor biology in conjunction with clinical and pathologic risk factors. The test provides a validated score (DS) for women receiving BCS that assesses 10-year risk of DCIS recurrence and development of invasive breast cancer with and without adjuvant RT. We established a registry to evaluate the decision impact of DCISionRT on DCIS treatment recommendations. Methods: The PREDICT study is a prospective, multi-institutional registry for patients who received DCISionRT testing as part of their routine care. The registry includes females 26 and older who are diagnosed with DCIS and are candidates for BCS and eligible for RT or systemic therapy. Treating physicians completed treatment recommendation forms before and after receiving test reports to capture surgical, radiation and hormonal treatment (HT) recommendations and patient preferences. The primary endpoint is to identify the proportion of patients where testing led to a change in RT recommendation. Additional analyses include changes in recommendations in patient subgroups based on clinicopathologic factors or type of treating physician. Results: Analysis was performed in 969 patients treated at 55 sites who had definitive BCS and subsequent DCISionRT testing. The median age of patients was 62 years, 19% were 50 or younger, nuclear grade was high in 31% and tumor size was 2.5 cm or greater for 11%. Test results were DS Low risk (DS ≤ 3) for 63% of women and 37% were DS Elevated risk (DS &amp;gt; 3). Overall, RT recommendation (yes/no) was changed for 40% of women after DCISionRT testing and HT recommendation was changed for 11%. There was a net decrease in RT recommendation from 69% pre-assay to 50% post-assay (p&amp;lt;0.001). RT recommendation decreased by 42% in DS Low risk patients, but increased 22% in DS Elevated risk patients. Among physicians, surgeons were more likely to change their RT recommendation (49%) than radiation oncologists (38%). When test results indicated DS Elevated risk, both surgeons (82%) and radiation oncologists (91%) were likely to recommended RT, but when the results were low risk, surgeons were more likely than radiation oncologists to recommend omitting RT (83% vs. 68%, respectively). Conclusions: This interim analysis demonstrates a significant percent change in recommendations to add or omit RT based on DCISionRT results in 969 patients. Compared to traditional clinicopathologic features, the factor most strongly associated with RT recommendation was the DCISionRT result with other factors of importance being patient preference, tumor size and grade. The integration of DCISionRT into clinical decision processes has substantial impact on recommendations aimed at optimal management to prevent over- or under-treatment. TABLE 1. Impact of DCISionRT on adjuvant radiation recommended by clinicopathologic features.RT recommendedPre- to post-test change in RT recommendedTotal change in RT recommendedClinical factorNPre-test(%)Post-test(%)Net change (%)Yes to no (%)No to yes (%)Overall change (%)95% CIp-ValueAge, years&amp;lt; 501648148-3243133730-45%&amp;lt;0.001≥ 508056651-1642374137-44%&amp;lt;0.001Grade1 or 26656144-1650354440-47%&amp;lt;0.00133048764-2332333227-37%&amp;lt;0.001Tumor size≤ 2.5 cm8596648-1845354238-45%&amp;lt;0.001&amp;gt; 2.5 cm1109269-2327222619-35%&amp;lt;0.001RTOG 9804 criteria‘Good risk’5005541-1452344440-49%&amp;lt;0.001Not ‘good risk’4598460-2436353632-40%&amp;lt;0.001 Citation Format: Steven C Shivers, Pat W Whitworth, Rakesh Patel, Troy Bremer, Charles E Cox. Interim analysis of the PREDICT Registry: Changes in treatment recommendation for a biologic signature predictive of radiation therapy (RT) benefit in patients with DCIS [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-12.

Abstract OT1-04-02: The NAUTILUS trial (No Axillary sUrgical Treatment In clinically Lymph node negative patients after UltraSonography): A prospective multicenter randomized phase III trial (NCT04303715)

Abstract Background. Sentinel lymph node biopsy (SLNB) is currently the standard axillary staging procedure for clinically node-negative breast cancer. According to the ACOSOG Z0011 trial, axillary lymph node dissection (ALND) is now often omitted for clinically node-negative cT1-2 breast cancer patients undergoing breast-conserving surgery even if 1 or 2 metastatic lymph nodes (LN) are identified. It was shown that radiotherapy contributes to regional control of the axilla non-inferior to ALND even in the presence of metastatic LNs. Furthermore, LN metastasis has a limited role in planning adjuvant systemic therapy for hormone receptor-negative breast cancers, and also for hormone receptor-positive, HER2-negative breast cancer with increased use of genomic assays. SLNB is not without complications and omitting axillary staging operation could improve quality of life. Trial Design. In this multicenter, phase III randomized controlled trial including 9 study sites in South Korea, we plan to 1:1 randomize 1734 patients to either omit SLNB (Arm 1) or receive SLNB (Arm 2). Additional ALND can be performed according to the discretion of the surgeon according to the SLNB results. All patients must receive whole-breast irradiation ± tumor bed boost. The recommended upper margin of the radiation field is within 2cm of the humeral head. ClinicalTrials.gov identifier: NCT04303715. Eligibility. Inclusion criteria: women ≥19 years; cT1-2N0M0 unilateral invasive breast carcinoma; all molecular subtypes; clinically and radiologically tumor size ≤ 5cm; clinically- and ultrasonogram-negative axillary lymph nodes, or no tumor on core needle biopsy or fine needle aspiration cytology in case of suspicious lymph nodes; candidate for breast-conserving surgery with no restriction to radiotherapy and adequate systemic therapy. Exclusion criteria: history of any malignancy within 5 years (exception: thyroid cancer and well-treated skin cancer except melanoma); bilateral breast cancer; neoadjuvant chemotherapy; candidate for total mastectomy; male breast cancer. Specific Aims. Primary objective is to test the hypothesis that omitting SLNB for breast cancer is non-inferior to axillary staging operation in terms of 5-year disease-free survival. Secondary objectives are to compare overall survival, distant metastasis-free survival, locoregional recurrence, quality of life assessment, and DFS and axillary recurrence according to molecular subtypes. Statistical Methods. With an expected 5-year DFS of 86% for Arm 2, Arm 1(SLNB omission) will be assessed with a non-inferiority limit of 5% and hazard ratio of 1.4, power 80%, and significance level of 5%, where 224 events are required. The calculated sample size is 780 per study arm, resulting in a total of 1,734 patients assuming a 10% drop-out rate. Present Accrual and Target Accrual. The first patient was randomized on September 15, 2020. As of July 9, 2021, 480 patients have been randomized. Target accrual of 1734 patients is expected to be complete by April 2023, with the primary endpoint analysis expected in 2028. Citation Format: Han-Byoel Lee, Ji Gwang Jung, Jung Min Chang, Ji Hyun Chang, Woo Kyung Moon, Kyung Hwan Shin, Il Yong Chung, Seok Jin Nam, Eun-Kyu Kim, Seeyoun Lee, Seho Park, Woo Sung Lim, Yongsik Jung, Wonshik Han. The NAUTILUS trial (No Axillary sUrgical Treatment In clinically Lymph node negative patients after UltraSonography): A prospective multicenter randomized phase III trial (NCT04303715) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-04-02.

Is Axillary Assessment of Ductal Carcinoma In Situ of the Breast Necessary in All Cases?

Staging of the axilla in women with ductal carcinoma in situ (DCIS) is a point of controversy. We aimed to assess whether there is a group of patients in whom axillary assessment can be avoided and whether the likelihood of underdiagnosis of infiltrating carcinoma is sufficient to justify this evaluation. This was a multicenter, prospective, observational study of patients who were operated on between 2008 and 2018 in three Spanish hospitals, with a diagnosis by radiological or excisional biopsy of DCIS and clinically and radiologically negative axilla. A total of 530 patients with a preoperative diagnosis of DCIS were studied. An axillary assessment was performed in 77% of the patients. In 397 patients, selective sentinel lymph node biopsy was performed. Axillary involvement was found in 7.2% of all patients, which dropped to 2.15% if we only included DCIS diagnosed after a definitive anatomical pathology analysis. Underdiagnosis was correlated with the type of biopsy performed: the risk was 1.34 times as high if the biopsy was performed with a core needle. The risk of lymph node metastasis was higher when there was lymphovascular invasion and when mastectomy was performed. We propose an axilla management algorithm in patients with a preoperative diagnosis of DCIS. The patients who would benefit from sentinel lymph node biopsy would be those who are not candidates for breast-conserving surgery, those with a BIRADS 5 lesion biopsied by core-needle biopsy, and those whose definitive diagnosis is lymphovascular invasion.

Laser ablation of multifocal breast carcinoma: Assessing viability for patients not accepting surgery.

e12584 Background: Breast carcinoma is a major public health problem in India and world. It is the leading cause of cancer in women in India. The overall 5 year survival rate in western countries is over 90%. In India it drops to 40 to 60%. The various factors responsible for this include presenting late due to unacceptability of many women for mutilation of their breasts. Breasts being a very important feminine cosmetic benchmark. Methods: Laser ablation of Breast tumours is now a USFDA and CE approved procedure. The aim of this observational study was to observe completion of tumour ablation by intralesional laser ablation. Laser Ablation was performed as a single procedure in 10 women over a 7 year period. All women who consented to the procedure were in stage late stage 2 and 3 with multifocal and/or multilocational disease. As such they were not candidates for Breast Conservation surgery. Pre laser PET scans confirmed the absence of Metastatic disease outside breast and Axilla. Results: All Post Menopausal patients showed a complete necrosis of the tumour and axillary lymph nodes on a follow up of 2 to 7 years. The findings were confirmed on serial PET scans after 6 months and 2 years. Pre menopausal women showed recurrence in non laserised areas and were given follow up Laser Ablation procedure. Conclusions: Laser Ablation is a viable procedure for patients unwilling for mastectomy in stage 3 Breast cancer. The skill sets required for the procedure are new and surgeons will have to be trained for the procedure.

Abstract OT-08-01: The PREDICT registry: A prospective registry to evaluate the effect of a predictive assay on treatment decisions in patients with DCIS following breast conserving therapy

Abstract Background. The benefits of adjuvant radiation therapy (RT) in patients with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Although there is level-I evidence supporting the role of RT in reducing the risk of local recurrence, the absolute benefit is variable. Current guidelines generally recommend RT for all patients having BCS, but it is important to develop prognostic and predictive tools to better assess risk and understand the impact such a tool would have on treatment decisions. The DCISionRT Test (PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score for assessing 10-year risk of recurrence and RT benefit using individual tumor biology as assessed by clinical and pathologic biomarkers.Methods. This is a prospective cohort study for patients diagnosed with DCIS of the breast. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinico-pathologic features are stored in a de-identified registry for participating institutions from a variety of geographic regions across the US. The study will also collect 5- and 10-year recurrence and survival data. The study includes females over age 25 who are candidates for BCS and eligible for RT and/or systemic treatment with sufficient tissue to generate test results. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status and other clinico-pathologic factors. Changes in treatment recommendations will be assessed using McNemar's test with an alpha level of 0.05. Differences in recurrence-free and overall survival will be evaluated by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. A planned early interim analysis based on the first 200 patients has been recently completed and reported. Results. As of July 6, 2020, 1,000 patients have been accrued from 49 institutions. Twenty additional institutions are currently in the process of joining the study. We are planning to enroll up to 2,500 patients from up to 100 institutions. Citation Format: Steve C Shivers, Pat W Whitworth, Rakesh Patel, Troy Bremer, Charles E Cox. The PREDICT registry: A prospective registry to evaluate the effect of a predictive assay on treatment decisions in patients with DCIS following breast conserving therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-08-01.

Abstract PS12-03: Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment in luminal breast cancer: Survival results of the UNICANCER-NeoPAL study

Abstract Background Palbociclib is a CDK4/6 inhibitor with demonstrated survival benefits in combination with endocrine therapy in advanced luminal breast cancer (LBC). Its potential role in early breast cancer is currently explored. The NeoPAL trial compared letrozole-palbociclib (LETPAL) combination to standard chemotherapy (CT) as neoadjuvant treatment in patients with high-risk LBC. Both LETPAL and CT were associated with poor pathological response, and equivalent clinical responses, while LETPAL let to encouraging biomarker responses in Prosigna®-defined high-risk LBC. We now evaluate the survival outcomes of both groups. Patients and Methods NeoPAL (UCBG10/4, NCT02400567) is a randomized, parallel, non-comparative phase II study. Postmenopausal women with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II-III breast cancer, not candidate for breast-conserving surgery, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks (LETPAL), or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) x3 21-day courses followed by docetaxel 100 mg/m2 x3 21-day courses (CT). Secondary endpoints included progression-free survival (PFS) and invasive-disease free survival (iDFS), all measured from the date of randomization. Exploratory objectives aimed at evaluating the impact of PEPI score and residual cancer burden (RCB) on survival outcomes in both arms. Results 53 pts were randomized in each arm (both with 11% Luminal A N+ and 89% Luminal B). 23 of the 53 pts in the LETPAL arm received postoperative adjuvant chemotherapy. Median follow-up is 40.4 months [0-56.6]. 11 progressions have been observed (10 metastatic events, 1 regional progression), of which 3 were in the LETPAL and 8 in the control arm. Two additional iDFS events were observed in the LETPAL arm (secondary malignancies). PFS (HR = 1.01; 95%CI [0.36; 2.90], p=0.98) and iDFS (HR= 0.83; 95%CI [0.31; 2.23], p=0.71) did not differ between both arms. 40 months PFS rate is 86.7% (78.0-96.4) and 87.2% (78.1-97.4) in LETPAL and CT arms respectively. PEPI (PEPI II/II vs I: HR 0.80, 95%CI 0.18-3.67) and RCB scores (RCB II/III vs 0/I: HR 1.36; 95%CI 0.17-10.6) did not appear as independent predictors of PFS or iDFS. Conclusions Despite its small size, NeoPAL suggests that a neoadjuvant LETPAL strategy, together with selected postoperative administration of chemotherapy, may spare chemotherapy in some pts with luminal breast cancer while allowing very good long-term outcomes. Citation Format: Suzette Delaloge, Sylvain Dureau, Véronique D'Hondt, Isabelle Desmoulins, Pierre-Etienne Heudel, François Duhoux, Christelle Levy, Florence Lerebours, Marie Ange Mouret-Reynier, Florence Dalenc, Jean-Sébastien Frenel, Christelle Jouannaud, Laurence Venat-Bouvet, Suzanne Nguyen, Cécile Callens, David Gentien, Jerome Lemonnier, Anne Vincent-Salomon, Hélène Manduzio, Paul-Henri Cottu. Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment in luminal breast cancer: Survival results of the UNICANCER-NeoPAL study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-03.

Trends in Contralateral Prophylactic Mastectomy Utilization for Small Unilateral Breast Cancer

BackgroundFor average-risk women with unilateral breast cancer, contralateral prophylactic mastectomy (CPM) offers no survival benefit and contributes to increased costs and patient harm. Despite recommendations from professional societies against CPM, utilization of this service is increasing, partly due to patients’ desire for breast symmetry when undergoing mastectomy. Most women with small tumors are candidates for breast-conserving surgery (BCS) and could avoid CPM. We describe CPM utilization in women with small, unilateral tumors, and identify determinants of possible overuse. MethodsUsing the National Cancer Database, we identified women with unilateral, T1 breast cancer. We evaluated utilization of BCS, unilateral mastectomy, and CPM and assessed patient, tumor, and facility factors associated with CPM. ResultsOf 765,487 women with small, unilateral breast cancer, 69% underwent BCS and 31% chose mastectomy. Of 176,673 women ≥70 y, 75% underwent BCS and 25% chose mastectomy. CPM rates in both cohorts have increased since 2006. Decreased adjuvant radiotherapy in older women was associated with increased BCS rates. Patient factors (younger age, white race, private insurance, and breast reconstruction), tumor factors (lobular histology, higher grade, and human epidermal growth factor receptor 2 positive/estrogen receptor negative status), and facility factors (type and geographic location) were associated with increased CPM rates compared with unilateral mastectomy in multivariable models. ConclusionsMost women with small unilateral breast cancer are candidates for BCS, yet one-third elects to undergo a mastectomy, of which a rising percentage opts for CPM. Tailoring deimplementation strategies to factors influencing treatment may help reduce CPM utilization and associated financial toxicity, pain, and disability.

A Retrospective Analysis of the Relationship Between the Result of BRCA1/2 Genetic Testing and Surgical Method Selection in Japan

BackgroundWe studied the extent of BRCA1/2 genetic testing to help select the surgical approach for patients with breast cancer in Japan remains unclear. Patients and MethodsThe study subjects were female patients with primary unilateral invasive breast cancer considered as candidates for breast-conserving surgery who underwent preoperative BRCA1/2 genetic testing. A retrospective analysis was performed on the results of BRCA1/2 genetic testing and surgical method selection using national registration data from the Japanese Hereditary Breast and Ovarian Cancer Syndrome Consortium. ResultsOur study included 318 female patients. Among these patients, 23.7% of patients with BRCA1/2 mutations and 61.8% of patients without these variants underwent breast-conserving surgery (P < .01). Among the patients with BRCA1/2 mutations, those who chose breast-conserving surgery tended not to undergo risk-reducing salpingo-oophorectomy (P < .05). Among the patients with BRCA1/2 mutations who underwent mastectomy for the affected side, 31.8% received contralateral risk-reducing mastectomy. Patients diagnosed with breast cancer under the age of 50 years were more likely to have contralateral risk-reducing mastectomy than patients over the age 50 years (P < .05). ConclusionsPatients with BRCA1/2 mutations tend to choose mastectomy. However, it is speculated that the final surgical method selection is made in consideration of not only the test results but also with careful consideration of the patient, taking into account other factors including individual values for risk-reducing surgeries and the age of breast cancer onset.

Oncoplastic Repair in Breast Conservation: Comprehensive Evaluation of Techniques and Oncologic Outcomes of 937 Patients

BackgroundBreast-conserving surgery, especially with oncoplastic breast surgery (OBS), is becoming the standard of care in the surgical management of breast cancer. We investigated the applied technique of OBS and oncologic outcomes in a large series of patients. Patients and MethodsThis study was conducted between January 2008 and June 2018 in two centers in Iran. Patients underwent OBS. Early and late postoperative complications, oncologic outcomes, and follow-up data were documented. ResultsNine hundred thirty-seven patients with a mean ± standard deviation age of 48.1 ± 11.3 underwent OBS. Most of the patients were diagnosed with early-stage disease, of which the most common pathology was invasive ductal carcinoma (83.3%). Lateral oncoplasty was the most commonly used OBS technique (324 cases, 34.6%). The most common complication was seroma formation. Reduction-type OBS technique had the highest rate of complications (13.1%). Thirty-four patients (5.4%) experienced local recurrence, with a median recurrence time of 26.4 months. Nine patients (1.3%) died from cancer recurrence. ConclusionOBS is a safe procedure with minor complications and good oncologic outcomes. These techniques can be applied to most patients who are candidates for breast-conserving surgery.

ALTERNATE: Neoadjuvant endocrine treatment (NET) approaches for clinical stage II or III estrogen receptor-positive HER2-negative breast cancer (ER+ HER2- BC) in postmenopausal (PM) women: Alliance A011106.

504 Background: For PM patients (pts) with locally advanced ER+ HER2- BC, NET improves breast conservation surgery (BCS) rates, and modified preoperative endocrine prognostic index (mPEPI) 0, defined as pT1-2 pN0 Ki67&lt; 2.7%, or pathologic complete response (pCR: no invasive disease in breast or lymph node) is associated with low risk of recurrence without adjuvant chemotherapy (CT). The ALTERNATE trial was initiated to assess if the endocrine-sensitive disease rate (ESDR: number of mPEPI 0 pts/number of eligible pts initiating NET) with fulvestrant (F) or F+anastrozole (A) is improved relative to A alone (reported here) and if the 5-year (yr) recurrence-free survival (RFS) rate for pts with mPEPI 0 on A alone without CT is ≥ 95% (awaits further follow-up). Methods: PM pts with clinical stage II/III ER+ HER2- BC were randomized 1:1:1 to 1 mg A po daily, 500 mg F IM every 4 week (wk)s after loading dose, or A+F for 6 months. Ki67 was tested centrally on biopsies acquired prior to NET, wk 4, wk 12 and at surgery. Pts with Ki67 &gt;10% at wk 4 or 12 were recommended to go off protocol-directed ET and switch to CT. Pts with mPEPI 0 at surgery were recommended to continue assigned ET for 1.5 yrs followed by A for a total of 5 yrs ET (and not to receive CT). The primary endpoint of the neoadjuvant phase was ESDR. ESDR of each F arm was compared to that of the A alone arm. With 425 pts per arm, a one-tailed alpha = 0.025 chi-square test of two independent proportions has 84% power to detect an increase of ≥10% in ESDR for F or F+A compared to the A arm, assuming ESDR ≤30% in A. Results: 1362 pts (A 452; F 454; A+F 456) were enrolled Feb 2014 to Nov 2018. 63 pts were excluded (did not start NET). Of the remaining 1299 pts (A 434; F 431, A+F 434), 42% were cN1-3 and 73% were considered candidates for BCS. ESDR was 18.6% (95%CI: 15.1-22.7%) with A, 22.7% (95%CI: 18.9-27.0%) with F, and 20.5% (95%CI: 16.8-24.6%) with A+F. No significant difference in ESDR was found between A and F (p=0.15) or A and A+F (p=0.55). Among the 825 pts with wk 4 Ki67 &lt; 10% who completed NET and surgery, ESDR and the BCS rate were 27.7% and 70.3% with A; 29.6% and 68.1% with F, and 26.8% and 69.9% with A+F, respectively. Conclusion: Neither F nor F+A significantly improved ESDR compared to A alone in PM pts with locally advanced ER+ HER2- BC. RFS data are awaited. Support: U10CA180821, U10CA180882, U24CA196171, https://acknowledgments.alliancefound.org ; NCI BIQSFP, BCRF, Genentech, AstraZeneca. Clinical trial information: NCT01953588 .