Impact of HER2-low status on survival outcomes in patients with metastatic breast cancer treated with cdk4/6 inhibitors: A single-center experience

Öz

Aim: Cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapy are recommended as the first-line treatment for hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis. However, CDK4/6 inhibitor efficacy has been reported to differ between HER2-low and HER2-zero tumors; emerging data suggest that the therapeutic efficacy of CDK4/6 inhibitors may be reduced in HER2-low breast cancer. Therefore, we aimed to evaluate this association in a cohort of patients treated with CDK4/6 inhibitors. Material and Methods: In this single-center retrospective study, 121 patients with hormone receptor-positive, HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors between January 2019 and March 2025 were evaluated. Cases were classified as HER2-low or HER2-zero. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method. Results: Among 121 hormone receptor-positive, HER2-negative metastatic breast cancer patients treated with CDK4/6 inhibitors, 53.7% were in the HER2-zero group and 46.3% in the HER2-low group. The median follow-up duration was 28.6 months (range: 5.1-56.4 months) and the median age was 62 years (range: 33-89 years). Ribociclib was used in 68.6% and palbociclib in 31.4% of these cases. The incidence of grade 3-4 toxicities was comparable between the groups (p=0.948). There was no statistically significant difference in median PFS (31.1 vs 34.8 months, p=0.314) or OS (42.3 vs 39.9 months, p=0.946) between the HER2-zero and HER2-low groups. Ribociclib and palbociclib demonstrated similar survival outcomes across HER2 subgroups. Conclusion: The clinical significance of HER2 status in patients treated with CDK4/6 inhibitors remains unclear. In our cohort, we were unable to demonstrate an association between HER2 status and PFS or OS among patients receiving CDK4/6 inhibitor therapy.

Anahtar Kelimeler

• HR+/HER2- advanced breast cancer
• CDK4/6 inhibitor
• progression-free survival
• overall survival

Destekleyen Kurum

No financial support.

Etik Beyan

This study was conducted in accordance with Declaration of Helsinki. Ethical approval was obtained from the Local Ethics Committee of Recep Tayyip Erdoğan University.

Teşekkür

The authors sincerely thank to all patients included in the study.

CDK4/6 inhibitörleriyle tedavi edilen metastazlı meme kanseri hastalarında HER2-low durumunun sağkalım sonuçları üzerindeki etkisi: Tek merkez deneyimi

Öz

Amaç: Siklin bağımlı kinaz (CDK) 4/6 inhibitörleri, endokrin terapi ile birlikte, viseral kriz olmayan hormon reseptörü pozitif, HER2 negatif metastatik meme kanserinde birinci basamak tedavi olarak önerilmektedir. Bununla birlikte, CDK4/6 inhibitörlerinin etkinliğinin HER2-low ve HER2-zero tümörler arasında farklılık gösterdiği bildirilmiştir; ortaya çıkan veriler, CDK4/6 inhibitörlerinin terapötik etkinliğinin HER2-low meme kanserinde azalabileceğini düşündürmektedir. Bu nedenle, CDK4/6 inhibitörleri ile tedavi edilen bir hasta kohortunda bu ilişkiyi değerlendirmeyi amaçladık. Gereç ve Yöntemler: Bu tek merkezli retrospektif çalışmada, Ocak 2019 ile Mart 2025 tarihleri arasında CDK4/6 inhibitörleri ile tedavi edilen hormon reseptörü pozitif, HER2-negatif metastatik meme kanseri olan 121 hasta değerlendirildi. Hastalar HER2-low veya HER2-zero olarak sınıflandırıldı. Hastalık ilerlemesiz sağkalım (PFS) ve genel sağkalım (OS) Kaplan-Meier yöntemi kullanılarak değerlendirildi. Bulgular: CDK4/6 inhibitörleri ile tedavi edilen 121 hormon reseptörü pozitif, HER2 negatif metastatik meme kanseri hastasının %53,7'si HER2-zero grubunda ve %46,3'ü HER2-low grubundaydı. Medyan takip süresi 28,6 ay (aralık: 5,1-56,4 ay) ve medyan yaş 62 yıl (aralık: 33-89 yıl) idi. Ribosiklib %68,6'unda ve palbosiklib %31,4'inde kullanıldı. 3-4. derece toksisite insidansı gruplar arasında karşılaştırılabilir düzeydeydi (p=0,948). HER2-zero ve HER2-low grupları arasında medyan PFS (31.1’e karşı 34.8 ay, p=0,314) veya OS (42,3'e karşı 39,9 ay, p=0,946) açısından istatistiksel olarak anlamlı bir fark bulunmamıştır. Ribosiklib ve palbosiklib, HER2 alt gruplarında benzer sağkalım sonuçları göstermiştir. Sonuç: CDK4/6 inhibitörleri ile tedavi edilen hastalarda HER2 durumunun klinik önemi belirsizliğini korumaktadır. Kohortumuzda, CDK4/6 inhibitör tedavisi alan hastalarda HER2 durumu ile progresyonsuz sağkalım veya genel sağkalım arasında bir ilişki gösterilemedi.

Anahtar Kelimeler

• HR+/HER2- ileri evre meme kanseri
• CDK4/6 inhibitörü
• progresyonsuz sağkalım
• genel sağkalım

Destekleyen Kurum

Herhangi bir finansal destek alınmamıştır.

Etik Beyan

Bu çalışma Helsinki Bildirgesi'ne uygun olarak yürütülmüştür. Çalışma için Recep Tayyip Erdoğan Üniversitesi'nin Yerel Etik kurulundan onay alınmıştır.

Teşekkür

Bu çalışmaya dahil edilen tüm hastalarımıza teşekkür ederiz.

Kaynakça

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