HER-2 negative + HR positive + BRCA mutation

Individuals reported that a key benefit of BRCA testing was the insight it provided into their treatment options, allowing for more personalized care. However, OOPC was a barrier to testing. Their choice to receive adjuvant therapy was most influenced by OOPC, followed by the tolerability of the treatment and the ability to receive a targeted therapy.

The patient achieved a remarkably prolonged progression-free survival (PFS) of 37 months on this combination therapy, representing the longest period of disease control in her metastatic course. Although eventual progression occurred (new axillary lymph node metastasis and suspected hepatic recurrence), this case demonstrates the exceptional efficacy and durable disease control achievable with Fluzoparib plus Exemestane in a pretreated patient with gBRCA2-mutated HR+/HER2-advanced breast cancer, highlighting a promising therapeutic approach for this molecularly defined population.

Characteristics, treatment patterns and outcomes were distinct among patients in China with gBRCAm eBC. Our findings support wider implementation of gBRCA testing for all patients in China with HER2-negative eBC, beyond those with triple-negative tumour subtype and/or family history of cancer, to identify more patients who may benefit from targeted therapy. Infographic available for this article.

In breast cancer expressing AKT/PIK3CA pathway alterations, drugs like alpelisib, capivasertib, and inavolisib have recently been approved, demonstrating improved PFS in this specific patient population. Recent developments of antibody-drug conjugates (ADCs) have also extended therapeutic options to previously labeled HER2-negative tumors, with drugs like trastuzumab deruxtecan (T-DXd) demonstrating efficacy in newly emerged HER2-low and HER2-ultralow pathologic subgroups, extending median overall survival to almost 2 years. Most of these drugs have paved the way for personalized medicine and opened questions around optimal sequencing of ET and application of combination therapies, which continue to be investigated through clinical trials. This review seeks to highlight current and emerging treatment strategies addressing ET resistance to improve survival outcomes for HR+ mBC patients, emphasizing the need for personalized approaches.

P2, N=30, Recruiting, Massachusetts General Hospital | Trial completion date: Dec 2025 --> Mar 2027 | Trial primary completion date: Jul 2025 --> Aug 2026

P2, N=620, Recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

These data indicated that HRR mutations had no effect on pCR in HER-2 negative patients receiving NAC regardless of hormone receptor status. BRCA1 mutation carriers have a higher rate of pCR and are more benefit from platinum-containing regimen than BRCA2 mutation carriers.

In a large dataset, T-DXd showed favorable activity for treating MBC, although outcomes for HER2-positive disease appeared worse than those observed in clinical trials. Prior SG treatment was associated with inferior outcomes with T-DXd, suggesting cross-resistance between these antibody-drug conjugates.

The safety profile was consistent with the known toxicity of both drugs. Niraparib combined with an AI has encouraging antitumor activity and a manageable safety profile in patients with AI-resistant HR-positive/HER2-negative advanced breast cancer with germline BRCA1/2 mutations.

The advancement of high-throughput sequencing technologies, coupled with the rise of targeted treatments in recent years, has facilitated a shift from conventional medical practices to individualized oncology therapeutic approaches. Our analysis presented the value of combining genetic sequencing and targeted therapy for patients with breast cancer carrying BRCA mutations and also provided the prototype of a testing model that can be utilized to promote precision medicine for better patient outcomes.

BRCA1-mutated TNBC patients with HER2-low tumors have a significantly favorable survival, highlighting the possibility of stratifying these patients into two subgroups on the basis of HER2-low status.

To improve outcomes, ovarian function suppression (OFS) with gonadotropin-releasing hormone agonists (GnRHa) added to tamoxifen or aromatase inhibitors like exemestane have shown significant disease-free survival (DFS) and, in some cases, overall survival (OS) benefits...Trials with abemaciclib and ribociclib have shown promise in high-risk EBC. For BRCA-mutant patients, the PARP inhibitor olaparib, as demonstrated in the OlympiA trial, significantly improved invasive DFS and OS when used as adjuvant therapy for one year...These advancements reflect a shift toward personalized adjuvant therapy, integrating targeted treatments like CDK4/6 inhibitors and PARP inhibitors, optimizing ET with OFS, and balancing efficacy with quality of life through de-escalation strategies. This tailored approach aims to improve long-term outcomes for HR-positive EBC patients.