Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. Aim: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. Methods: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013–2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. Results: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. Conclusions: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD.

Radiation-induced pulmonary fibrosis (RIPF) is a severe late-stage complication of radiotherapy (RT) to the chest area, typically used in lung cancer treatment. This condition is characterized by the gradual and irreversible replacement of healthy lung tissue with fibrous scar tissue, leading to decreased lung function, reduced oxygen exchange and critical respiratory deficiencies. Currently, predicting and managing lung fibrosis post-RT remains challenging, with limited preventive and treatment options. Accurate prediction of fibrosis onset and progression is therefore clinically crucial. We present a personalized in silico model for pulmonary fibrosis that encompasses tumour regression, fibrosis development and lung tissue remodelling post-radiation. Our continuum-based model was developed using data from 12 RT-treated lung cancer patients and integrates computed tomography (CT) and dosimetry data to simulate the spatio-temporal evolution of fibrosis. We demonstrate the ability of the in silico model to capture the extent of fibrosis in the entire cohort with a less than 1% deviation from clinical observations, in addition to providing quantitative metrics of spatial similarity. These findings underscore the potential of the model to improve treatment planning and risk assessment, paving the way for more personalized and effective management of RIPF.

Background: Evidence on the efficacy of alpelisib in combination with fulvestrant after progression on CKD4/6 inhibitors (CDK4/6i) is derived from a single non-comparative prospective study. Conversely, the effectiveness of everolimus plus exemestane on PIK3CA-mutant metastatic breast cancer (BC) after CDK4/6i failure has never been investigated in a prospective study. In this retrospective study, we compared alpelisib plus endocrine therapy (ET) with everolimus plus exemestane in patients with PIK3CA-mutant metastatic BC post-CDK4/6i progression. Methods: We tracked 40 patients treated with alpelisib plus ET and 22 treated with everolimus plus exemestane. We further identified 42 patients who did not harbor PIK3CA mutations (PIK3CA-wild-type group) and received everolimus as a subsequent treatment after progression on CDK4/6i. The timeframe spanned from 1st March 2020 to 30th November 2024. Results: The median progression-free survival (PFS) for the alpelisib group was 4.9 months compared to 4.5 months for the everolimus group [Hazard ratio (HR), 1.22; 95% CI, 0.65–2.28; p-value = 0.53]. The median overall survival (OS) was 9.6 months and 18.3 months for alpelisib and everolimus, respectively (HR, 0.67; 95% CI, 0.25–1.76; p-value = 0.47). Median PFS in the PIK3CA-mutant everolimus plus ET group was 4.5 months (95% CI, 2.8–6.7) compared to 5 months (95% CI, 3.5–6.9) for the PIK3CA-wild-type everolimus plus ET group (HR, 0.77; 95% CI, 0.46–1.29; p-value = 0.32). The most common side effects in the alpelisib group were hyperglycemia (57.5%), rash (27.5%), and anorexia (22.5%), while the most common side effects in the everolimus group were fatigue (40.9%) and stomatitis (27.3%). Conclusions: Our results regarding the efficacy of alpelisib plus ET were inferior to those reported in the current literature. Conversely, outcomes of everolimus plus exemestane were consistent with the current literature, denoting that the combination is an acceptable treatment option for patients with PIK3CA-mutant metastatic BC.