Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy

<i>Background and Objectives</i>: The clinical value of HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) scores of 1+ or 2+/ISH-negative without HER2 amplification, remains unclear in the neoadjuvant setting. This study aimed to determine whether HER2-low and HER2-zero...

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Main Authors: Rumeysa Colak, Caner Kapar, Ezgi Degerli, Seher Yildiz Tacar, Aysegul Akdogan Gemici, Nursadan Gergerlioglu, Serdar Altinay, Mesut Yilmaz
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/7/1168
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author Rumeysa Colak
Caner Kapar
Ezgi Degerli
Seher Yildiz Tacar
Aysegul Akdogan Gemici
Nursadan Gergerlioglu
Serdar Altinay
Mesut Yilmaz
author_facet Rumeysa Colak
Caner Kapar
Ezgi Degerli
Seher Yildiz Tacar
Aysegul Akdogan Gemici
Nursadan Gergerlioglu
Serdar Altinay
Mesut Yilmaz
author_sort Rumeysa Colak
collection DOAJ
description <i>Background and Objectives</i>: The clinical value of HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) scores of 1+ or 2+/ISH-negative without HER2 amplification, remains unclear in the neoadjuvant setting. This study aimed to determine whether HER2-low and HER2-zero tumors differ in pathological complete response (pCR) rates and disease-free survival (DFS) among early-stage breast cancer patients undergoing neoadjuvant chemotherapy (NAC). <i>Materials and Methods</i>: We retrospectively analyzed 134 early BC patients treated with NAC between 2017 and 2023. Patients were categorized as HER2-zero (IHC 0) or HER2-low (IHC 1+ or 2+/ISH–). The primary endpoint was total pCR (tpCR); secondary endpoints included breast (bpCR), nodal (npCR), and radiologic complete response (rCR), alongside DFS analysis stratified by hormone receptor (HR) status. <i>Results</i>: Of the cohort, 91 patients (67.9%) were HER2-zero and 43 (32.1%) were HER2-low. There was no statistically significant difference in tpCR (26.4% vs. 27.9%, <i>p</i> = 0.852), bpCR (28.6% vs. 30.2%, <i>p</i> = 0.843), npCR (37.4% vs. 32.6%, <i>p</i> = 0.588), and rCR (23.1% vs. 30.2%, <i>p</i> = 0.374) between HER2-zero and HER2-low groups. DFS did not significantly differ between HER2-zero and HER2-low groups overall (<i>p</i> = 0.714), nor within HR-positive (<i>p</i> = 0.540) or TNBC (<i>p</i> = 0.523) subgroups. <i>Conclusions</i>: HER2-low tumors demonstrated similar pathological responses and survival outcomes compared to HER2-zero tumors. While a HER2-low status does not appear to define a distinct biological subtype in early BC, it remains a relevant classification for emerging HER2-targeted therapies, needing further investigation in prospective studies.
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spelling doaj-art-48af0af062d647dba279c54f045225d22025-08-20T03:35:38ZengMDPI AGMedicina1010-660X1648-91442025-06-01617116810.3390/medicina61071168Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant ChemotherapyRumeysa Colak0Caner Kapar1Ezgi Degerli2Seher Yildiz Tacar3Aysegul Akdogan Gemici4Nursadan Gergerlioglu5Serdar Altinay6Mesut Yilmaz7Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul 34147, TurkeyDepartment of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul 34147, TurkeyDepartment of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul 34147, TurkeyDepartment of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul 34147, TurkeyDepartment of Radiology, Istanbul Medipol Mega University Hospital, Istanbul 34214, TurkeyDepartment of Pathology, Faculty of Medicine, Arel University, Istanbul 34010, TurkeyDepartment of Pathology, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul 34371, TurkeyDepartment of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul 34147, Turkey<i>Background and Objectives</i>: The clinical value of HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) scores of 1+ or 2+/ISH-negative without HER2 amplification, remains unclear in the neoadjuvant setting. This study aimed to determine whether HER2-low and HER2-zero tumors differ in pathological complete response (pCR) rates and disease-free survival (DFS) among early-stage breast cancer patients undergoing neoadjuvant chemotherapy (NAC). <i>Materials and Methods</i>: We retrospectively analyzed 134 early BC patients treated with NAC between 2017 and 2023. Patients were categorized as HER2-zero (IHC 0) or HER2-low (IHC 1+ or 2+/ISH–). The primary endpoint was total pCR (tpCR); secondary endpoints included breast (bpCR), nodal (npCR), and radiologic complete response (rCR), alongside DFS analysis stratified by hormone receptor (HR) status. <i>Results</i>: Of the cohort, 91 patients (67.9%) were HER2-zero and 43 (32.1%) were HER2-low. There was no statistically significant difference in tpCR (26.4% vs. 27.9%, <i>p</i> = 0.852), bpCR (28.6% vs. 30.2%, <i>p</i> = 0.843), npCR (37.4% vs. 32.6%, <i>p</i> = 0.588), and rCR (23.1% vs. 30.2%, <i>p</i> = 0.374) between HER2-zero and HER2-low groups. DFS did not significantly differ between HER2-zero and HER2-low groups overall (<i>p</i> = 0.714), nor within HR-positive (<i>p</i> = 0.540) or TNBC (<i>p</i> = 0.523) subgroups. <i>Conclusions</i>: HER2-low tumors demonstrated similar pathological responses and survival outcomes compared to HER2-zero tumors. While a HER2-low status does not appear to define a distinct biological subtype in early BC, it remains a relevant classification for emerging HER2-targeted therapies, needing further investigation in prospective studies.https://www.mdpi.com/1648-9144/61/7/1168HER2-lowbreast cancerneoadjuvant chemotherapypathologic complete responsedisease-free survivalhormone receptor status
spellingShingle Rumeysa Colak
Caner Kapar
Ezgi Degerli
Seher Yildiz Tacar
Aysegul Akdogan Gemici
Nursadan Gergerlioglu
Serdar Altinay
Mesut Yilmaz
Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy
Medicina
HER2-low
breast cancer
neoadjuvant chemotherapy
pathologic complete response
disease-free survival
hormone receptor status
title Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy
title_full Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy
title_fullStr Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy
title_full_unstemmed Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy
title_short Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy
title_sort pathologic response and survival outcomes on her2 low vs her2 zero in breast cancer receiving neoadjuvant chemotherapy
topic HER2-low
breast cancer
neoadjuvant chemotherapy
pathologic complete response
disease-free survival
hormone receptor status
url https://www.mdpi.com/1648-9144/61/7/1168
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