Neoadjuvan kemoterapi uygulanan erken evre meme kanserinde HER2-low fenotipinin tedavi yanıtı ve progresyonsuz sağkalım üzerindeki etkisi: tek merkezli retrospektif çalışma

Abstract

Amaç: Neoadjuvan kemoterapi (NAKT) uygulanan evre II–III invaziv meme kanserinde HER2-low alt tiplerinin patolojik tam yanıt (pCR) ve sağkalım sonlanımları ile ilişkisini değerlendirmek ve progresyonun bağımsız belirleyicilerini incelemek. Gereç ve Yöntemler: Akdeniz Üniversitesi Tıp Fakültesi’nde 2016-2024 yılları arasında NAKT alıp küratif cerrahi uygulanan 227 ardışık hasta retrospektif olarak analiz edildi. Demografik ve klinikopatolojik özellikler ile ER, PR, Ki-67, HER2 durumu, lenfovasküler invazyon (LVI) ve perinöral invazyon kaydedildi. Patolojik tam yanıt ( pCR ) ve Miller-Payne skoru ile; radyolojik yanıt standart kriterlere göre değerlendirildi. Sağkalım Kaplan-Meier yöntemiyle analiz edildi, gruplar log-rank testi ile karşılaştırıldı. Progresyonun bağımsız belirleyicileri çok değişkenli Cox regresyon analizi ile araştırıldı. HER2-low kavramının HER2-negatif spektrumda yorumlanması gereği dikkate alınarak, HER2-pozitif olgular dışlandıktan sonra HER2-low ve HER2-0 arasında duyarlılık analizi yapıldı. Bulgular: Ortalama yaş 50,1 yıl idi. HER2-low oranı %32,2 (%95 GA: %26,4–%38,5) ve pCR oranı %40,5 (%95 GA: %34,4–%47,0) olarak saptandı. Medyan takip süresi 43,5 ayda 5 yıllık OS %96,1 ve 5 yıllık PFS %86,6 idi. Ana analizde HER2-low ve HER2-0 grupları arasında pCR, OS ve PFS açısından anlamlı fark izlenmedi (tüm p>0,05). Çok değişkenli analizde PR pozitifliği PFS için bağımsız koruyucu faktör (HR 0,31; %95 GA 0,12–0,83), LVI varlığı bağımsız risk faktörü (HR 4,02; %95 GA 1,15–13,96) ve pCR elde edilmesi bağımsız koruyucu faktör (HR 0,20; %95 GA 0,04–0,89) olarak belirlendi. Duyarlılık analizinde de HER2-low ile HER2-0 arasında anlamlı fark gözlenmedi. Sonuç: HER2-low fenotipi tek başına pCR ve sağkalım sonuçlarını belirgin biçimde ayrıştırmazken, PR durumu, LVI ve pCR progresyon riskini daha güçlü ve bağımsız biçimde öngörmektedir.

Keywords

• meme kanseri
• HER2-low
• HER2-negatif
• neoadjuvan kemoterapi
• patolojik tam yanıt

Impact of the HER2-low phenotype on treatment response and progression-free survival in early-stage breast cancer treated with neoadjuvant chemotherapy: a single-center retrospective study

Abstract

Aim: To evaluate the association of HER2-low (IHC 1+/2+ and ISH/FISH−) versus HER2-0 (IHC 0) subtypes with pathologic complete response (pCR) and survival outcomes in patients with stage II–III invasive breast cancer treated with neoadjuvant chemotherapy (NACT), and to identify independent predictors of disease progression. Materials and Methods: A total of 227 consecutive patients who received NACT followed by curative surgery between 2016 and 2024 at Akdeniz University Faculty of Medicine were retrospectively analyzed. Demographic and clinicopathological characteristics, including ER, PR, Ki-67, HER2 status, lymphovascular invasion (LVI), and perineural invasion, were recorded. Pathologic response was assessed using pCR and the Miller–Payne grading system, while radiologic response was evaluated according to standard criteria. Survival outcomes were analyzed using the Kaplan–Meier method and compared with the log-rank test. Independent predictors of progression were investigated using multivariable Cox regression analysis. Considering that the HER2-low concept should be interpreted within the HER2-negative spectrum, a sensitivity analysis comparing HER2-low and HER2-0 tumors was performed after excluding HER2-positive cases. Results: The mean age was 50.1 years. The proportion of HER2-low tumors was 32.2% (95% CI: 26.4–38.5), and the pCR rate was 40.5% (95% CI: 34.4–47.0). With a median follow-up of 43.5 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 96.1% and 86.6%, respectively. In the primary analysis, no significant differences were observed between HER2-low and HER2-0 groups in terms of pCR, OS, or PFS (all p>0.05). In multivariable analysis, PR positivity was identified as an independent protective factor for PFS (HR 0.31; 95% CI: 0.12–0.83), whereas the presence of LVI was an independent risk factor (HR 4.02; 95% CI: 1.15–13.96). Achieving pCR was also an independent protective factor (HR 0.20; 95% CI: 0.04–0.89). Sensitivity analysis confirmed the absence of a significant difference between HER2-low and HER2-0 tumors. Conclusion: While the HER2-low phenotype alone does not clearly differentiate pCR or survival outcomes, PR status, LVI, and pCR more strongly and independently predict the risk of disease progression.

Keywords

• breast cancer
• HER2-low
• HER2-negative
• neoadjuvant chemotherapy
• pathologic complete response

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