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

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.

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

Kaynakça

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