Tailoring advanced breast cancer treatment after cyclin-dependent kinase 4/6 inhibitors progression - real-world data analysis.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer. However, optimal treatment after disease progression is a matter of debate. We aimed to assess predictive and prognostic factors associated with the treatment outcome following CDK4/6i progression. Methods: We retrospectively analyzed patients who progressed on CDK4/6i treatment between 2018 and 2024. Treatment based on molecular findings (PIK3CA mutation), genetic findings (BRCA1/2 germline mutation), or adapted to the change in the tumor phenotype in rebiopsy (anti-HER2 therapy in the transformation to HER-2-positive disease) was grouped into tailored treatment and compared to the endocrine-based therapy and chemotherapy alone. Results: Five hundred twelve patients were treated with CDK4/6i. Two hundred patients with disease progression were enrolled in the study. Duration of response to CDK4/6i was not predictive of the response to subsequent treatment, whereas the progression in the central nervous system was the worst prognostic factor. Thirty patients were ineligible for subsequent treatment. Survival after CDK4/6i progression was significantly longer in patients eligible for tailored treatment. The median PFS in patients with tailored treatment (n=19) was 13.5 months vs. 4.9 months in patients with non-tailored therapy (n=151; p=0.045). 12-month PFS was 54.1% with tailored treatment [95% CI 24.1-76.7%] compared to 18.5% with non-tailored therapy [95% CI 11.6-26.6%]. The median OS for patients treated with a tailored approach was not reached compared to 11.5 months with non-tailored treatment (p=0.016). The 24-month OS for patients treated with a tailored approach was 80.2% [95% CI 40.3-94.8%] compared to 21.1% [95% CI 12.2-31.7%] for patients with non-tailored treatment. Conclusions: Tailoring of subsequent treatment strategy seems to be essential for achieving long-term benefit. Further studies are required, as the prognosis after CDK4/6i progression remains dismal, especially in cases affecting the central nervous system.

Clinical analysis of metaplastic breast carcinoma with distant metastases: A multi­centre experience.

Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33-87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35-70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2)+ and estrogen receptor+ were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population.

Safety and Feasibility of Radiation Therapy Combined with CDK 4/6 Inhibitors in the Management of Advanced Breast Cancer.

The addition of CDK4/6 inhibitors to endocrine therapy in advanced hormone receptor-positive HER2-negative breast cancer has led to practice-changing improvements in overall survival. However, data concerning the safety of CDK4/6i combination with radiotherapy (RT) are conflicting. A retrospective evaluation of 288 advanced breast cancer patients (pts) treated with CDK4/6i was performed, and 100 pts also received RT. Forty-six pts received 63 RT courses concurrently and fifty-four sequentially before CDK4/6i initiation (76 RT courses). Neutropenia was common (79%) and more frequent during and after concurrent RT than sequential RT (86% vs. 76%); however, CDK4/6i dose reduction rates were similar. In patients treated with CDK4/6i alone, the dose reduction rate was 42% (79 pts) versus 38% with combined therapy, and 5% discontinued treatment due to toxicity in the combined group. The risk of CDK4/6i dose reduction was correlated with neutropenia grade, RT performed within the first two CDK4/6i cycles, and more than one concurrent RT; a tendency was observed in concurrent bone irradiation. However, on multivariate regression analysis, only ECOG 1 performance status and severe neutropenia at the beginning of the second cycle were found to be associated with a higher risk of CDK4/6i dose reduction. This largest single-center experience published to date confirmed the acceptable safety profile of the CDK4/6i and RT combination without a significantly increased toxicity compared with CDK4/6i alone. However, one might delay RT for the first two CDK4/6i cycles, when myelotoxic AE are most common.

Discrepancy between Tumor Size Assessed by Full-Field Digital Mammography or Ultrasonography (cT) and Pathology (pT) in a Multicenter Series of Breast Metaplastic Carcinoma Patients.

Metaplastic breast cancer (BC-Mp) presents diagnostic and therapeutic complexities, with scant literature available. Correct assessment of tumor size by ultrasound (US) and full-field digital mammography (FFDM) is crucial for treatment planning. METHODS: A retrospective cohort study was conducted on databases encompassing records of BC patients (2012-2022) at the National Research Institutes of Oncology (Warsaw, Gliwice and Krakow Branches). Inclusion criteria comprised confirmed diagnosis in postsurgical pathology reports with tumor size details (pT) and availability of tumor size from preoperative US and/or FFDM. Patients subjected to neoadjuvant systemic treatment were excluded. Demographics and clinicopathological data were gathered. RESULTS: Forty-five females were included. A total of 86.7% were triple-negative. The median age was 66 years (range: 33-89). The median pT was 41.63 mm (6-130), and eight patients were N-positive. Median tumor size assessed by US and FFDM was 31.81 mm (9-100) and 34.14 mm (0-120), respectively. Neither technique demonstrated superiority (p > 0.05), but they both underestimated the tumor size (p = 0.002 for US and p = 0.018 for FFDM). Smaller tumors (pT1-2) were statistically more accurately assessed by any technique (p < 0.001). Only pT correlated with overall survival. CONCLUSION: The risk of underestimation in tumor size assessment with US and FFDM has to be taken into consideration while planning surgical procedures for BC-Mp.

Evaluation of health value of fats and oils.

The fat content and fatty acid composition (saturated, mono- and polyunsaturated in cis and trans configuration) in selected food products was determined. From over 2000 products investigated in recent years, results are given for some soft and hard margarines, oils and butter as well as butter-like products. It has been found that food products are distinguished by very high diversification with regard to fat content, in terms of both quantity and quality. This differentiation was particularly evident in the groups of margarines, mixed fats and confectioner's products.