SavedAdd your journal

Journals / Turkish Journal of Clinics and Laboratory / 2026 / Sayı: 1

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

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

Mehmet Fatih Özbay(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-3883-4364
Sertaç Vurğun(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-5326-0824
Süleyman Alkan(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0009-0003-1456-8190
Mustafa Karaca(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-3954-5273
Pages
—
Publication Date
2026-03-17
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

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.

📌 3 Key Takeaways

🎯
Objective & Hypothesis: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.
📊
Key Findings & Data: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.
💡
Conclusion & Impact: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.
🔬Design:Araştırma Makalesi
📍Scope:2016 Verileri
⚙️Variables:meme kanseri · HER2-low · HER2-negatif

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.

Özet

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.

🔖

Cite This Article

Özbay, M. F., Vurğun, S., Alkan, S., Karaca, M. (2026). 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. Turkish Journal of Clinics and Laboratory, Sayı: 1. https://doi.org/10.18663/tjcl.1853155

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (28)

  1. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA et al. Molecular portraits of human breast tumours. Nature 2000; 406: 747–52.
  2. Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med 2009; 360: 790–800.
  3. Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019; 30: 1194–220.
  4. Burstein HJ, Curigliano G, Loibl S, Dubsky P, Gnant M, Poortmans P et al. Estimating the benefits of therapy for early-stage breast cancer: The St Gallen International Consensus Guidelines 2019. Ann Oncol 2019; 30: 1674–90.
  5. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N et al. Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet 2014; 384: 164–72.
  6. Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO/CAP clinical practice guideline focused update. J Clin Oncol 2018; 36: 2105-22.
  7. Tarantino P, Hamilton E, Tolaney SM, Cortes J, Morganti S, Ferraro E et al. HER2-low breast cancer: Pathological and clinical landscape. J Clin Oncol 2020; 38: 1951–62.
  8. Schettini F, Chic N, Brasó-Maristany F, Paré L, Pascual T, Conte B et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer 2021; 7: 1.
  9. Eiger D, Agostinetto E, Saúde-Conde R, de Azambuja E. The exciting new field of HER2-low breast cancer treatment. Cancers (Basel) 2021; 13: 1015.
  10. Molinelli C, Griguolo G, Miglietta F, Nader-Marta G, Ceppi M, Bruzzone M et al. Prognostic value of HER2-low status in breast cancer. ESMO Open 2023; 8: 101614.
  11. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022; 387: 9–20.
  12. Moura Leite L, Tavares MCC, Lima MVS, Santana DM, Saldanha EF, Guimarães PT et al. HER2-low status and response to neoadjuvant chemotherapy in HER2-negative early breast cancer. Breast Cancer Res Treat 2021; 190: 155–63.
  13. Baez-Navarro X, van Bockstal MR, Jager A, van Deurzen CHM. HER2-low breast cancer and response to neoadjuvant chemotherapy: A population-based cohort study. Pathology 2024; 56: 334–42.
  14. Ilie SM, Briot N, Constantin G, Roussot N, Ilie A, Bergeron A et al. Pathologic complete response and survival in HER2-low and HER2-zero early breast cancer treated with neoadjuvant chemotherapy. Breast Cancer 2023; 30: 997–1007.
  15. Şahin AB, Karaoğlu Ç, Salı M, Özmaraşlı BE, Özçelik EE, Karaman Y et al. HER2-low expression predicts improved pathologic response but not disease-free survival in HR-positive/HER2-negative breast cancer patients receiving neoadjuvant chemotherapy. J Uludag Univ Med Fac 2025; 51: 569–75.
  16. Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M et al. Clinical and molecular characteristics of HER2-low-positive breast cancer: Pooled analysis of individual patient data from four prospective neoadjuvant clinical trials. Lancet Oncol 2021; 22: 1151–61.
  17. Kang S, Kim Y, You S, eong H, Jeong JH, Kim JE et al. Pathological complete response, long-term outcomes, and recurrence patterns in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy. Eur J Cancer 2022; 176: 30–40.
  18. de Nonneville A, Gonçalves A, Zemmour C, Sabiani L, Bannier M, Viret F et al. Pathological complete response rate and disease-free survival after neoadjuvant chemotherapy in patients with HER2-low and HER2-0 breast cancers. Eur J Cancer 2022; 172: 1–11.
  19. Zhao S, Peng J, Wang H, Liu X, Zhang Y, Zhang J. Neoadjuvant chemotherapy efficacy and prognosis in HER2-low versus HER2-zero breast cancer: A real-world study. PeerJ 2024; 12: e17492.
  20. Şen GA, Yılmaz M, Öztaş NŞ, Değerli E, Demirci NS et al. The impact of low HER2 status on response to neoadjuvant chemotherapy and disease-free survival in early-stage breast cancer. BMC Cancer 2024; 24: 13064.
  21. Çolak R, Yalçın S, Tacar SY, Gemici AA, Gergerlioglu N et al. Pathologic response and survival outcomes in HER2-low versus HER2-zero breast cancer treated with neoadjuvant chemotherapy. Medicina 2025; 61: 1168.
  22. de Moraes FCA, de Castro Ribeiro CHD, Pessôa FDDL, Chaves JR, de Souza APB, Di Felipe Ávila Alcantara D et al. Pathologic response rates in HER2-low versus HER2-zero early breast cancer patients receiving neoadjuvant therapy: A systematic review and meta-analysis. Breast Cancer Res 2025; 27: 1989.
  23. Topal A, Başak M. Evaluating the role of HER2-low versus HER2-0 status in breast cancer: Clinical and pathological implications. Eur J Res Med Sci 2024; 14: 1–10.
  24. Spring LM, Fell G, Arfe A, Sharma C, Greenup R, Reynolds KL et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: A comprehensive meta-analysis. Clin Cancer Res 2020; 26: 2838–48.
  25. An SJ, Duchesneau ED, Strassle PD, Reeder-Hayes K, Gallagher KK, Ollila DW et al. Pathologic complete response and survival after neoadjuvant chemotherapy in cT1–T2/N0 HER2+ breast cancer. NPJ Breast Cancer 2022; 8: 60.
  26. Boman C, Tranchell C, Liu X, Eriksson Bergman L, Toli MA, Bergh J et al. Prognosis after pathologic complete response to neoadjuvant chemotherapy in early-stage breast cancer. JNCCN 2025; 23: e247093.
  27. Akrami M, Meshksar A, Ghoddusi JM, Safarpour MM, Tahmasebi S, Zangouri V et al. Prognostic role of lymphovascular invasion in patients with early breast cancer. Ind J Surg Oncol 2021; 12: 671–77.
  28. Topal A, Başak M. Evaluating the role of HER2-low versus HER2-0 status in breast cancer: Clinical and pathological implications. Eur J Res Med Sci 2024; 14: 1–10.