Radiation therapy in clinically node positive HER2 positive breast cancer after primary systemic therapy and breast conserving surgery: pooled analysis of TRYPHAENA and NeoSphere trials

Abstract Background The benefit of regional nodal irradiation (RNI) following modern primary systemic therapy (PST) in HER2-positive breast cancer (HER2 + BC) remains under investigation. The current study evaluates RNI practice patterns and outcomes based on the pathological response to PST in clin...

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Main Authors: Mohamad El-Jammal, Omran Saifi, Jose Bazan, Youssef H. Zeidan
Format: Article
Language:English
Published: BMC 2025-06-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-14289-4
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author Mohamad El-Jammal
Omran Saifi
Jose Bazan
Youssef H. Zeidan
author_facet Mohamad El-Jammal
Omran Saifi
Jose Bazan
Youssef H. Zeidan
author_sort Mohamad El-Jammal
collection DOAJ
description Abstract Background The benefit of regional nodal irradiation (RNI) following modern primary systemic therapy (PST) in HER2-positive breast cancer (HER2 + BC) remains under investigation. The current study evaluates RNI practice patterns and outcomes based on the pathological response to PST in clinically node-positive (cN+) HER2 + BC. Methods TRYPHAENA and NeoSphere are two randomized phase II trials that investigated PST for HER2 + BC. The current study is a pooled analysis of both trials, focusing on cN + patients treated with HER2-targeted PST followed by breast-conserving surgery. The primary goal is to describe patterns of RNI practicein this population and its impact on breast cancer recurrence-free survival (BCRFS) and loco-regional recurrence-free survival (LRRFS). Results Our analysis included a total of 90 patients with cN + disease. Complete nodal pathological response was achieved in 53 patients (58.9%). Patients with ypN0 had a 5-year LRRFS of 95.83% whereas patients with ypN + had 5-year LRRFS of 87.43% (p = 0.105). RNI was used in 16 ypN0 (48.5%) patients and 17 ypN+ (51.5%) patients. Patients treated with RNI had 5-year LRRFS of 93.4% as compared to 92.5% in the no RNI group (p = 0.868). Distant metastasis was detected in 5 patients (5%) with the most common sites being: liver, lung, bone, and CNS. Locoregional recurrence was significantly associated with distant failure (p = 0.002). Conclusions cN + HER2 + BC patients who achieve ypN0 after PST have excellent locoregional control. In contrast, patients with ypN + tend to have lower locoregional control. The utility of RNI in HER2 + BC warrants further investigation.
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spelling doaj-art-bcf6be1bb43641c5a6b36e8dee7044332025-08-20T02:30:42ZengBMCBMC Cancer1471-24072025-06-0125111110.1186/s12885-025-14289-4Radiation therapy in clinically node positive HER2 positive breast cancer after primary systemic therapy and breast conserving surgery: pooled analysis of TRYPHAENA and NeoSphere trialsMohamad El-Jammal0Omran Saifi1Jose Bazan2Youssef H. Zeidan3Faculty of Medicine, American University of BeirutDepartment of Radiation Oncology, Mayo ClinicDepartment of Radiation Oncology, City of Hope Comprehensive Cancer CenterDepartment of Radiation Oncology, Florida International University, Lynn Cancer Institute, Baptist Health South FloridaAbstract Background The benefit of regional nodal irradiation (RNI) following modern primary systemic therapy (PST) in HER2-positive breast cancer (HER2 + BC) remains under investigation. The current study evaluates RNI practice patterns and outcomes based on the pathological response to PST in clinically node-positive (cN+) HER2 + BC. Methods TRYPHAENA and NeoSphere are two randomized phase II trials that investigated PST for HER2 + BC. The current study is a pooled analysis of both trials, focusing on cN + patients treated with HER2-targeted PST followed by breast-conserving surgery. The primary goal is to describe patterns of RNI practicein this population and its impact on breast cancer recurrence-free survival (BCRFS) and loco-regional recurrence-free survival (LRRFS). Results Our analysis included a total of 90 patients with cN + disease. Complete nodal pathological response was achieved in 53 patients (58.9%). Patients with ypN0 had a 5-year LRRFS of 95.83% whereas patients with ypN + had 5-year LRRFS of 87.43% (p = 0.105). RNI was used in 16 ypN0 (48.5%) patients and 17 ypN+ (51.5%) patients. Patients treated with RNI had 5-year LRRFS of 93.4% as compared to 92.5% in the no RNI group (p = 0.868). Distant metastasis was detected in 5 patients (5%) with the most common sites being: liver, lung, bone, and CNS. Locoregional recurrence was significantly associated with distant failure (p = 0.002). Conclusions cN + HER2 + BC patients who achieve ypN0 after PST have excellent locoregional control. In contrast, patients with ypN + tend to have lower locoregional control. The utility of RNI in HER2 + BC warrants further investigation.https://doi.org/10.1186/s12885-025-14289-4Radiation therapyHER2-positivePrimary systemic therapy (PST)Breast conservationPathological complete response (pCR)Locoregional recurrence (LRR)
spellingShingle Mohamad El-Jammal
Omran Saifi
Jose Bazan
Youssef H. Zeidan
Radiation therapy in clinically node positive HER2 positive breast cancer after primary systemic therapy and breast conserving surgery: pooled analysis of TRYPHAENA and NeoSphere trials
BMC Cancer
Radiation therapy
HER2-positive
Primary systemic therapy (PST)
Breast conservation
Pathological complete response (pCR)
Locoregional recurrence (LRR)
title Radiation therapy in clinically node positive HER2 positive breast cancer after primary systemic therapy and breast conserving surgery: pooled analysis of TRYPHAENA and NeoSphere trials
title_full Radiation therapy in clinically node positive HER2 positive breast cancer after primary systemic therapy and breast conserving surgery: pooled analysis of TRYPHAENA and NeoSphere trials
title_fullStr Radiation therapy in clinically node positive HER2 positive breast cancer after primary systemic therapy and breast conserving surgery: pooled analysis of TRYPHAENA and NeoSphere trials
title_full_unstemmed Radiation therapy in clinically node positive HER2 positive breast cancer after primary systemic therapy and breast conserving surgery: pooled analysis of TRYPHAENA and NeoSphere trials
title_short Radiation therapy in clinically node positive HER2 positive breast cancer after primary systemic therapy and breast conserving surgery: pooled analysis of TRYPHAENA and NeoSphere trials
title_sort radiation therapy in clinically node positive her2 positive breast cancer after primary systemic therapy and breast conserving surgery pooled analysis of tryphaena and neosphere trials
topic Radiation therapy
HER2-positive
Primary systemic therapy (PST)
Breast conservation
Pathological complete response (pCR)
Locoregional recurrence (LRR)
url https://doi.org/10.1186/s12885-025-14289-4
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