HR positive + HER-2 negative

In this review, we discuss the clinical and biological significance of PI3K pathway alterations in HR+/HER2- mBC, focusing on tumors that progress following endocrine therapy and CDK4/6 inhibitor treatment. We then highlight how different diagnostic strategies, including sample type, testing methodology, and timing, can improve the identification of patients who are eligible for targeted therapies and promote the effective integration of molecular diagnostics into routine clinical care.

We conducted a nationwide, cross-sectional survey to evaluate current practices and institutional readiness for PIK3CA testing in Italy, in the context of the anticipated expansion of PI3K-targeted therapies, including inavolisib...Nevertheless, persistent gaps in accreditation, heterogeneous workflows, and limited integration of liquid biopsy highlight ongoing challenges in standardization and diagnostic equity. Coordinated national strategies will be essential to ensure consistent, high-quality molecular diagnostics in HR+/HER2- MBC.

In this retrospective analysis, CT use was associated with improved DFS among patients classified as high risk, while no statistically significant association was observed in the low-risk group. These findings may help inform risk-adapted discussions and generate hypotheses for prospective validation regarding treatment selection.

P2, N=122, Completed, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Recruiting --> Completed

P3, N=400, Recruiting, Pfizer

Prompt recognition, intensive management, and drug discontinuation are critical. This is one of the first case reports to describe sustained euglycemia following severe and refractory hyperglycemia due to capivasertib therapy.

By contrast, sacituzumab govitecan is a TROP-2-targeted ADC conjugated through a hydrolysable CL2A linker to SN-38, the active metabolite of irinotecan. Clinically, trastuzumab deruxtecan has shown substantial efficacy in both HER2-positive and HER2-low breast cancer, whereas sacituzumab govitecan has demonstrated efficacy across triple-negative and hormone receptor-positive/HER2-negative breast cancers. Collectively, these agents highlight how variations in target antigen, linker chemistry, and payload potency impact ADC activity, therapeutic index, and potential strategies for sequential treatment in advanced breast cancer.

The most common regimens included capecitabine and everolimus plus exemestane. Multivariable analysis showed that younger age, prior fulvestrant use, and shorter CDK4/6i duration were associated with CHT choice...Treatment decisions are influenced by clinical history and patient characteristics. These findings underscore the need for personalized approaches and molecular profiling to guide post-CDK4/6i therapy in HR-positive/HER2-negative MBC.

In this retrospective cohort of clinically node-negative, hormone receptor-positive, HER2-negative cT1-3 breast cancer patients undergoing upfront mastectomy, omission of intraoperative frozen section (IFS) analysis was not associated with early regional recurrence during the observed follow-up. Routine IFS would likely have altered immediate surgical management in only a small minority of patients in this selected population, suggesting limited clinical utility in similar low-risk cohorts.

P3, N=300, Not yet recruiting, Rovi Pharmaceuticals Laboratories | Trial completion date: Jun 2031 --> Dec 2033 | Initiation date: May 2026 --> Aug 2026

This prospective real-world analysis shows slightly shorter median PFS and OS times compared with the pivotal trials. Patients in our analyses received alpelisib in later therapy lines, which may explain the poorer outcome.

Our findings demonstrate that integrating baseline ctDNA-derived TFx metrics with established clinical variables significantly improves risk stratification in HR-positive/HER2-negative ABC.