Background/Objectives: CDK4/6 inhibitors have changed the landscape of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC) management. It is essential to identify predictive and prognostic factors for the efficacy of CDK4/6 inhibitors. We aimed to investigate the differences in characteristics and outcomes of patients receiving first-line CDK4/6 inhibitors according to PgR status. Methods: This multicenter retrospective study included 351 patients treated with first-line CDK 4/6 inhibitors for HR-positive/HER2-negative metastatic BC. Patients were categorized based on their PgR expression levels, including the PgR-low (<20%) and PgR-high (≥20%) groups, and baseline characteristics, treatment responses, and survival outcomes were analyzed. Results: The median age was 57 years (range: 26–85). A total of 99 patients were premenopausal, and 252 patients were postmenopausal. There were 115 (32.8%) patients in the PgR-low group, while 236 (67.2%) were in the PgR-high group. The majority of patients (56.7%) presented with de novo metastatic disease. Visceral metastases presented in 44.2% of patients. Low PgR expression was significantly associated with lower estrogen receptor levels (p = 0.031), elevated Ki-67 levels (p = 0.002), a higher incidence of visceral metastases (p = 0.035), and recurrent disease (p = 0.019). In the multivariate analysis, low PgR expression was a significant independent predictor of worse progression-free survival (PFS) and overall survival (OS). Conclusions: We demonstrated that low PgR expression is independently and significantly correlated with shorter PFS and OS. These findings support low PgR expression as a valuable prognostic biomarker in metastatic BC patients treated with first-line CDK4/6 inhibitors.

Introduction: CDK 4/6 inhibitors are effectively utilized among patients with hormone-positive, HER-2-negative metastatic breast cancer. The dose reduction for these patients varies between 35% and 57% across multiple trials. We aim to clarify the characteristics of patients who had dosage reduction and the effect of this reduction on survival outcomes. Materials and Methods: The study was designed as a retrospective, multicenter study. Patients who received CDK 4/6 inhibitors in the first-line and subsequent treatment settings were grouped based on dose reductions. Progression-free survival was compared between these groups, and factors influencing dose reduction were analyzed. Results: Multivariate logistic regression study demonstrated that patients aged 65 and older, with a Charlson CI score of 2 or higher, having metastases in three or more sites, and classed as normal weight, had greater dosage reductions. Dose reduction had no impact on progression-free survival (PFS) (p = 0.114 for first-line treatment, p = 0.528 for second and subsequent-line treatment; p > 0.05). Conclusions: Regarding the absence of disparity in progression-free survival between patients with dose reduction and those without, dose reduction should not be avoided in certain patient groups to ensure therapy continuity and mitigate potential adverse effects.

Purpose: Endocrine therapy (ET) in combination with CDK 4/6 inhibitors (CDK 4/6i) is the standard treatment modality for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (mBC). There is uncertainty about the prognostic and predictive value of HER2-low status and whether HER2-low BC is an individual biologic subtype. In this study, we aimed to investigate the prognostic effect of HER2 expression status on survival in mBC patients treated with first-line ET plus CDK 4/6i. Methods: This multicenter retrospective study included patients with HR + /HER2-negative mBC cancer who were treated with first-line CDK 4/6i in combination with ET from January 2016 to March 2023. Patients were divided into two groups (HER2-low and zero), and survival and safety analyses were performed. Results: A total of 201 patients were included in this study; of these, 73 (36.3%) had HER2-low disease and 128 (63.7%) had HER2-zero. There were 135 patients (67.2%) treated with ribociclib and 66 (32.8%) with palbociclib. Most of the patients (75.1%) received aromatase inhibitors as combination-endocrine therapy. Baseline characteristics were similar between the two groups. The median follow-up was 19.1 months (range: 2.5–78.4). The most common side effect was neutropenia (22.4%). The frequency of grade 3–4 toxicity was similar between the HER2-zero and low patients (32% vs 31.5%; p = 0.939). Visceral metastases were present in 44.8% of patients. Between the HER2-low and zero groups, median PFS (25.2 vs 22.6 months, p = 0.972) and OS (not reached vs 37.5 months, p = 0.707) showed no statistically significant differences. Conclusion: The prognostic value of HER2-low status remains controversial. Our study showed no significant effect of HER2 low expression on survival in patients receiving CDK 4/6i plus ET.

Background and Objectives: Obesity is a significant risk factor for the development of breast cancer (BC) and associated poorer outcomes. A pathological complete response (pCR) with neoadjuvant chemotherapy (NACT) correlates with improved long-term prognosis in BC patients. In this study, we aimed to investigate the predictive effect of obesity on achieving pCR following NACT. Methods: This single-center retrospective study included patients with operable BC who were treated with NACT. Patients were categorized based on their pre-chemotherapy body mass index (BMI), including non-obese (<30 kg/m²) and obese (≥30 kg/m²) groups, and pathological responses to NACT were compared. Results: A total of 191 female patients were included in this study; of these, 83 (43.4%) were obese and 108 (56.6%) were in the non-obese group. Obesity was more common in postmenopausal patients, and the median age of obese patients was significantly higher compared to non-obese patients. Patients in the obese group demonstrated significantly lower pCR rates compared to the non-obese group (30% vs. 45%, p = 0.03). The histological subtype assessment indicated that only in the HR-positive/HER2-negative patients was the pCR rate significantly lower in the obese group compared to the non-obese group (11% vs. 27%, p = 0.05). According to menopausal assessment, a significant difference in pCR rates was observed only among postmenopausal patients, with rates of 29% in the obese group compared to 52% in the non-obese group (p = 0.03). In logistic regression analysis, obesity (OR: 0.52, 95% CI: 0.28–0.97; p = 0.04) and a low Ki-67 score (HR: 2.7, 95% CI: 1.37–5.53; p = 0.003) were independently associated with a decreased rate of pCR. Conclusions: The impact of obesity on achieving pCR in BC patients undergoing NACT remains controversial. Our study revealed that obesity was an independently significant negative predictive factor for achieving pCR.

Prognostic Significance of Inflammatory and Nutritional Biomarkers in Patients with Metastatic Gastric Cancer - Journal of Oncological Sciences