HER2-Low Expression Predicts Improved Pathologic Response but not Disease-Free Survival in HR-Positive/HER2-Negative Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Yıl 2025, Cilt: 51 Sayı: 3, 569 - 575, 08.12.2025

Ahmet Bilgehan Şahin , Cagla Karaoglu , Mursel Sali , Buket Erkan Ozmarasali , Ender Eren Özçelik , Yagmur Karaman , Gul Akın , Hulya Odabası Bukun , Ali Aktas , Mine Özşen , Birol Ocak , Adem Deligönül , Erdem Çubukçu , Türkkan Evrensel

Öz

This retrospective single-center study aims to evaluate the predictive and prognostic significance of HER2-low (IHC 1+/2+ ISH–) compared with HER2-0 status in hormone receptor (HR)-positive / HER2-negative breast cancer patients treated with neoadjuvant chemotherapy (NACT). A cohort of 404 HR-positive / HER2-negative breast cancer patients treated with NACT between January 2008 and December 2019 at Bursa Uludag University was analyzed. Clinicopathologic variables, pathologic complete response (pCR), and long-term survival were assessed. Logistic regression identified independent predictors of pCR, and Cox proportional hazards modelling was used for disease-free survival (DFS). Of 404 patients, 117 (29.0%) were HER2-low and 287 (71.0%) were HER2-0. The pCR rate was significantly higher in the HER2-low group than in the HER2-0 group (9.4% vs 4.2%; p = 0.040). Multivariable logistic regression analysis revealed that HER2-low status (OR=2.88; 95% CI, 1.17–7.12; p=0.022) and a higher Ki-67 index (OR =1.03 per 1% increase; 95% CI, 1.01–1.05; p=0.003) were independent predictors of pathological complete response (pCR). The median follow-up time was 110.2 months (range, 10.5–248.9 months). The 5- and 10-year DFS rates were 85.1% and 73.7%, respectively; OS rates were 86.4% and 75.3%. In multivariable Cox regression, only pathological stage remained an independent predictor of DFS (HR=2.02; 95% CI 1.55–2.61; p<0.001), while HER2 status was not significant (HR=0.97; 95% CI 0.66–1.43; p=0.861). In conclusion, HER2-low status was associated with improved pCR but not with long-term survival. Pathologic stage remained the strongest determinant of DFS, and HER2-low appears to represent a biologic continuum within HER2-negative disease rather than a distinct prognostic subtype.

Anahtar Kelimeler

HER2-low breast cancer , hormone receptor-positive breast cancer , neoadjuvant chemotherapy , pathologic complete response , disease-free survival.

Etik Beyan

This investigation adhered to the ethical principles of the Declaration of Helsinki and received authorization from the Bursa Uludag University Institutional Review Board (Approval ID: 2020-6/31).

Destekleyen Kurum

The authors declare that this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Teşekkür

The authors would like to thank the pathology team of Bursa Uludag University Faculty of Medicine for their technical contributions to HER2 and hormone receptor assessments.

HER2-Düşük Ekspresyonunun, Neoadjuvan Kemoterapi Alan HR-Pozitif / HER2-Negatif Meme Kanseri Hastalarında Patolojik Yanıta ve Sağkalıma Etkisi

Öz

Bu çalışma, neoadjuvan kemoterapi (NAKT) uygulanan hormon reseptörü (HR) pozitif/HER2 negatif meme kanseri hastalarında HER2-0 durumu ile karşılaştırıldığında HER2-düşük (IHC 1+/2+ ve negatif ISH) durumunun öngörücü ve prognostik önemini değerlendirmeyi amaçlayan retrospektif tek merkezli bir çalışmadır. Ocak 2008 – Aralık 2019 tarihleri arasında Bursa Uludağ Üniversitesi’nde NAKT alan toplam 404 HR-pozitif / HER2-negatif hasta kohortu analiz edilmiştir. Klinikopatolojik değişkenler, pCR oranı ve uzun dönem sağkalım değerlendirilmiştir. Lojistik regresyon pCR’nin bağımsız belirleyicilerini, Cox regresyon modeli ise hastalıksız sağkalımı (DFS) değerlendirmek için kullanılmıştır. Hastaların %29,0’ı (n=117) HER2-düşük, %71,0’i (n=287) HER2-0 grubundaydı. pCR oranı HER2-düşük grupta anlamlı olarak daha yüksekti (%9,4’e karşı %4,2; p=0,040). Çok değişkenli analizde HER2-düşük durumu (OR=2,88; %95 GA: 1,17–7,12; p=0,022) ve yüksek Ki-67 indeksi (OR=1,03; %95 GA:1,01–1,05; p=0,003) pCR ile bağımsız olarak ilişkiliydi. Ortanca takip süresi 110,2 ay (10,5–248,9) idi. Beş ve on yıllık DFS oranları sırasıyla %85,1 ve %73,7; genel sağkalım (OS) oranları %86,4 ve %75,3 olarak bulundu. Çok değişkenli Cox analizinde yalnızca patolojik evre DFS için bağımsız belirleyici idi (HR=2,02; %95 GA: 1,55–2,61; p<0,001), HER2 durumu anlamlı bulunmadı (HR=0,97; %95 GA: 0,66–1,43; p=0,861). Sonuç olarak, HER2-düşük durumu artmış pCR oranı ile ilişkili olmasına rağmen uzun dönem sağkalım açısından avantaj sağlamamıştır. DFS’nin en güçlü belirleyicisi patolojik evre olarak kalmıştır. Bulgularımız, HER2-low hastalığın HER2-negatif spektrum içinde biyolojik bir sürekliliği temsil ettiğini ve ayrı bir prognostik alt tip olmadığını düşündürmektedir.

Anahtar Kelimeler

HER2-düşük meme kanseri , hormon reseptör pozitif meme kanseri , neoadjuvan kemoterapi , patolojik tam yanıt , hastalıksız sağkalım

Etik Beyan

Bu çalışma, Helsinki Bildirgesi’nin etik ilkelerine uygun olarak yürütülmüş olup, Bursa Uludağ Üniversitesi Tıp Fakültesi Klinik Araştırmalar Etik Kurulu tarafından onaylanmıştır (Onay No: 2020-6/31).

Destekleyen Kurum

Yazarlar, bu araştırmanın kamu, ticari veya kar amacı gütmeyen kuruluşlardan herhangi bir mali destek almadığını beyan etmektedir.

Teşekkür

Yazarlar, HER2 ve hormon reseptör değerlendirmelerindeki teknik katkılarından dolayı Bursa Uludağ Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı ekibine teşekkür eder.

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