HR positive + HER-2 negative

Capivasertib, an AKT inhibitor, approved in combination with fulvestrant for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer with ≥1 PIK3CA, AKT1, and/or PTEN alterations, significantly improved progression-free survival in the CAPItello-291 phase 3 trial. However, capivasertib-associated adverse events of diarrhea, rash, and hyperglycemia may require proactive management. This article provides practical recommendations to support prevention and early intervention to optimize adherence and treatment outcomes.

Despite unchanged guideline recommendations, fewer patients started ET over time. This trend, and regional variation, suggests that a more reticent approach by physicians to initiating ET for HR+/HER2- breast cancer may be contributing to it.

Patients with PR values <20% tended to have shorter PFS, unlike the Ki-67 value, which did not demonstrate an impact on PFS. This suggests a prognostic value of PR expression levels in this scenario.

Dato-DXd offers a promising treatment option for heavily pretreated patients with HR+/HER2- breast cancer and EGFR-mutant NSCLC, providing meaningful clinical benefit with a manageable safety profile. Optimal sequencing and positioning within the rapidly shifting ADC landscape requires further investigation.

This prespecified 5-year follow-up of efficacy outcomes from NATALEE demonstrated that ribociclib + NSAI continued to reduce the risk of recurrence beyond the 3-year treatment window, supporting its use as adjuvant therapy in patients with HR-positive/HER2-negative EBC. An ongoing positive trend for improved OS in favor of ribociclib + NSAI was observed.

The simultaneous or sequential presentation of cervical and breast cancer is rare, especially under systemic treatment. The patient's cervical cancer was aggressive, and the subsequent metachronous breast cancer highlights the complex, multifactorial nature of carcinogenesis. The development of a second primary malignancy while a patient is receiving treatment for a metastatic condition is a critical clinical scenario, necessitating individualized treatment strategies, as optimal management remains unclear due to the rarity of such cases.

Ribociclib combined with aromatase inhibitors demonstrated favorable real-world effectiveness and manageable safety profiles in Vietnamese patients with hormone receptor-positive, HER2-negative metastatic breast cancer in a real-world setting.

With adequate follow-up, distant disease-free survival is a robust surrogate endpoint for predicting final overall survival outcomes in neoadjuvant RCTs for early breast cancer in most contexts. However, the distant disease-free survival surrogacy appears to be weak for the hormone receptor-positive and HER2-negative and for the hormone receptor-positive and HER2-positive molecular subtypes. These latter findings warrant further investigation in more recent RCTs enrolling higher-risk patient populations.

Materials and This retrospective analysis included 92 patients with HR+/HER2- mBC who received either ribociclib or palbociclib between 2019 and 2024 at a single tertiary care center. Given the potential for confounding by the indication/comorbidity inherent to retrospective studies, the results should be interpreted as associational. These data support the cautious use of non-essential PPIs during ribociclib therapy and underscore the need for prospective agent-specific pharmacokinetic studies.

The addition of palbociclib to NET did not impact pathologic nodal outcomes. Among those with ypN+ disease, neither LRRFI nor BCSS appears to be impacted by performance of ALND.

The prognostic value of RS in MBC appears evident; however, sex-specific thresholds may be necessary to optimize treatment stratification. Given current data limitations, male-inclusive clinical trials are needed to elucidate the predictive value of RS in men and improve personalized treatment strategies.

This review outlines the key challenges to validating and implementing ctDNA-guided early endocrine switching in routine clinical practice and discusses its potential to reshape monitoring and decision-making in metastatic hormone receptor-positive, HER2-negative breast cancer.