HER-2 negative

P=N/A, N=21, Recruiting, Parul Barry | Trial completion date: Jul 2028 --> Mar 2028 | Trial primary completion date: Dec 2026 --> Apr 2026

This benefit was confirmed in a multivariable analysis, supporting PARPi as the preferred option in eligible patients. Our findings suggest that PARPi should be prioritized in the post-CDK4/6i treatment sequence for BRCA LP/PV carriers with HR+/HER2 aBC and highlight the critical role of germline BRCA testing.

Omission of SLNB in patients with small HR-positive/HER2-negative tumors results in a missed indication for CDK4/6i in <8 % with minimal impact on recurrence.

The advent of CDK4/6 inhibitors, namely, palbociclib, ribociclib and abemaciclib, has changed the management of oestrogen receptor (ER)-positive/HER2-negative advanced breast tumours. Nonetheless, the acquired resistance to CDK4/6 inhibitors remains a major therapeutic challenge. Thus, the identification of molecular drivers involved in the resistance to these drugs is crucial for the design of novel therapeutic approaches and the selection of patient-centred strategies in various types of tumours.

P3, N=474, Completed, Istituto Oncologico Veneto IRCCS | Active, not recruiting --> Completed

P3, N=632, Completed, Fondazione Michelangelo | Active, not recruiting --> Completed

Our findings highlight triple negative HER2-low BC as a distinct subtype identifiable via standard immunohistochemistry, beyond just biomarker status. The study underscores the prognostic diversity among BC subtypes and emphasizes the importance of personalized treatment strategies.

Clinical data indicate a higher incidence of nephrotoxic adverse reactions in patients receiving CDK4/6i compared to control groups, with abemaciclib showing the highest risk ratio...Preclinical studies suggest a complex effect on renal health; while some data indicate acute nephroprotection, long-term rodent models treated with palbociclib after ischemic AKI demonstrated impaired recovery, increased renal fibrosis, and cellular senescence, indicating potentially detrimental long-term chronic effects...Furthermore, these agents are susceptible to significant drug-drug interactions, particularly with CYP3A4 inhibitors/inducers and immunosuppressants, necessitating careful dose adjustments and monitoring, especially in solid organ transplant recipients. This review consolidates current evidence regarding the renal of CDK4/6i, emphasizing the need for vigilant monitoring and a multidisciplinary approach to optimize patient outcomes.

While SLNB may be safely omitted in specific contexts, its omission carries the risk of under- and over-treatment. Our findings demonstrate that SLNB continues to guide adjuvant therapy for breast cancer patients, and thus, support the ongoing use of SLNB.

P2, N=162, Completed, MedSIR | Active, not recruiting --> Completed

CARABELA trial results suggest that 12 months of letrozole/abemaciclib may not offer similar efficacy to that of chemotherapy in achieving RCB 0-I. However, in less proliferative tumors (RS <26 or Ki-67 <30%), outcomes were comparable, suggesting that letrozole/abemaciclib could replace (neo)adjuvant chemotherapy in selected patients.

The combination therapy provides a clinically significant improvement in survival and treatment responses, even though the toxicity is increased but manageable, and requires careful prescription.