Objective: CDK4/6 inhibitors constitute standard first-line therapy for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). We investigated real-world predictors of overall survival (OS), with particular focus on high ER expression (≥90%). Methods: In this multicenter, retrospective study, we analyzed 603 HR-positive/HER2-negative MBC patients treated with CDK4/6 inhibitors (ribociclib or palbociclib) between May 2020 and June 2024. We evaluated demographic, clinical, and pathological factors for their impact on OS using univariate and multivariate Cox regression analyses. Results: In univariate analysis, significantly longer OS was observed in endocrine therapy-naive patients (median OS: 51.0 vs. 33.3 months; p < 0.001), those without liver metastases (50.0 vs. 34.0 months; p = 0.019), bone-only metastases (57.7 vs. 40.5 months; p = 0.022), and PR-positive patients (50.0 vs. 36.0 months; p = 0.037). Patients with ER expression ≥90% showed a strong trend toward longer OS (49.0 vs. 41.0 months; p = 0.072). In multivariate analysis, endocrine therapy naivety (p = 0.045) and high ER expression (≥90%) (p = 0.031) emerged as independent predictors of superior OS. Conclusions: Our study identifies treatment naivety and exceptionally high ER expression (≥90%) as key independent predictors of prolonged OS in CDK4/6 inhibitor-treated MBC patients. These findings underscore the importance of early CDK4/6 inhibitor implementation and suggest that quantitative ER assessment may refine patient selection beyond conventional positivity thresholds.

Objective: CDK4/6 inhibitors are the standard first-line treatment for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). However, treatment response shows heterogeneity among patients. The objective of this multicentre, retrospective study is to investigate real-world parameters affecting overall survival (OS) in patients receiving CDK4/6 inhibitor therapy, particularly the effect of high oestrogen receptor (ER) expression (≥90%). Methods: A total of 603 HR-positive/HER2-negative MMK patients treated with a CDK4/6 inhibitor (ribociclib or palbociclib) from five centres were retrospectively reviewed. Age, menopausal status, metastatic status, metastatic sites, pathological subtype, HER2 status (low/negative), ER expression level (< 90% vs ≥90%), progesterone receptor (PR) status, and prior endocrine therapy (ET) or chemotherapy (CT) before CDK4/6 inhibitor were evaluated for their impact on OS using univariate and multivariate Cox regression analyses. Results: In the univariate analysis, OS was significantly longer in patients who did not receive ET prior to CDK4/6 inhibitor treatment (median OS: 51.0 months vs. 33.3 months; p< 0.01). OS was also better in patients without liver metastases (50.0 months vs. 34.0 months; p=0.019), those with bone metastases only (57.7 months vs. 40.5 months; p=0.022), and PR-positive patients (50.0 months vs. 36.0 months; p=0.037) also had better OS. OS was numerically longer in patients with ER expression ≥90% compared to those with < 90% (49.0 months vs. 41.0 months; p=0.072). In multivariate analysis, not having received ET prior to CDK4/6 inhibitor therapy (p=0.045) and high ER expression (≥90%) (p=0.031) were independently associated with better OS. Conclusion: Our study demonstrates that HR-positive/HER2-negative MBC patients who are naive to endocrine therapy prior to CDK4/6 inhibitor treatment and have high ER expression (≥90%) in their tumours derive greater OS benefit from this treatment. The ER expression level threshold of ≥90% may be proposed as a potential biomarker for predicting response to CDK4/6 inhibitor therapy. These findings necessitate further prospective studies to improve patient selection.

Background: HR (hormone receptor)-positive, HER2 (Human Epidermal Growth Factor Receptor 2)-negative metastatic breast cancer represents the majority of advanced breast cancer cases. Although CDK4/6 (cyclin-dependent kinase) inhibitors combined with endocrine therapy have become the standard first-line approach, the optimal treatment strategy after disease progression remains unclear. Methods: We conducted a multicenter retrospective study of 218 patients treated across five tertiary oncology centers in Turkey who progressed on CDK4/6 inhibitors and subsequently received either endocrine therapy (ET) or chemotherapy (CT). Results: Endocrine therapy, administered in 65 patients—most commonly with everolimus-based combinations—was associated with a significantly longer overall survival (OS) compared with CT (18.0 vs 10.0 months, p = 0.011). While progression-free survival (PFS) showed a numerical advantage for ET (6.0 vs 4.9 months), the difference did not reach statistical significance. Multivariate analysis confirmed both treatment type and de novo metastatic presentation as independent predictors of survival. Conclusion: These findings demonstrate that, in real-world clinical practice, continued endocrine therapy beyond CDK4/6 inhibitors progression yields superior survival compared to chemotherapy, particularly in patients with de novo metastatic disease. Our results support the prioritization of endocrine-based approaches over chemotherapy in this setting and underscore the urgent need for prospective trials to refine treatment sequencing strategies for this large patient population. Plain Language Summary: Hormone receptor-positive, HER2-negative metastatic breast cancer is the most common subtype of advanced breast cancer, yet the best treatment strategy after progression on CDK4/6 inhibitors remains uncertain. Many patients are switched directly to chemotherapy, which is often associated with limited benefit and significant toxicity. In this large multicenter study from Turkey, we compared endocrine therapy with chemotherapy in women whose disease progressed after CDK4/6 inhibitors. We found that patients who continued endocrine therapy, particularly with mTOR-based combinations, lived significantly longer than those who received chemotherapy. Importantly, patients who presented with de novo metastatic disease also had better survival. These findings highlight that chemotherapy may not always be the best option after CDK4/6 inhibitor failure and support the continued use of endocrine-based strategies. Our results provide real-world evidence that could influence clinical decision-making and guide the design of future prospective trials.

Objectives: Breast cancer diagnosed before the age of 40 accounts for 7% of all cases and is associated with aggressive disease. This study aimed to investigate the clinical, demographic, and pathological characteristics of young patients with breast cancer in Türkiye. Methods: A retrospective analysis was conducted on 73 patients diagnosed with breast cancer before the age of 40 at Necmettin Erbakan University between 2011 and 2020. Demographic data, clinical presentation, pathology, treatment, and recurrence/metastasis were analyzed. Results: All patients were female, with a mean age of 30.9±4.1 years. The most common symptom was a palpable breast mass (61.6%). Invasive ductal carcinoma was predominant (87.7%). The molecular subtypes were as follows: luminal, 65.8%; HER2-positive, 20.5%; and triple-negative, 13.7%. Metastasis at diagnosis occurred in 21.9% of patients, and re-currence during follow-up occurred in 23.3%. In the luminal subgroup, recurrence was more common than metastasis (82.4% vs. 43.8%, p