^
    3d
    Treatment of breast cancer brain metastases in the era of novel drugs. (PubMed, Cancer Treat Rev)
    Tucatinib-based combinations and trastuzumab deruxtecan have demonstrated substantial intracranial activity in prospective trials, shifting the treatment paradigm by supporting systemic therapy even in the presence of active brain metastases. A major limitation remains the underrepresentation of patients with brain metastases in clinical trials. This review summarizes current evidence on systemic therapies for BCBM across subtypes and highlights the need for CNS-inclusive trials and the development of effective CNS-active treatments.
    Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA (Breast cancer early onset)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • BRCA mutation • HER-2 negative + HR positive + BRCA mutation
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki) • Tukysa (tucatinib)
    7d
    Real-World Outcomes of CDK4/6 Inhibitors in Germline BRCA1/2-Mutated Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Turkish Oncology Group (TOG) Study. (PubMed, Curr Oncol)
    Among 121 patients, 30 (24.8%) had BRCA1, 88 (72.7%) had BRCA2, and three (2.5%) had dual mutations; 66.9% received first-line therapy, with ribociclib in 69.4% and palbociclib in 29.8%. In multivariable analysis, ECOG ≥ 1 (HR 1.85; p = 0.010) and fulvestrant-based therapy (HR 1.74; p = 0.041) predicted shorter PFS; fulvestrant also predicted worse OS (HR 2.39; p = 0.008). CDK4/6 inhibitor-based therapy shows meaningful activity in gBRCAm HR+/HER2- MBC; the numerically poorer outcomes observed in BRCA2 carriers are hypothesis-generating and warrant validation in larger cohorts.
    Retrospective data • Journal • Real-world evidence • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • HR positive + HER-2 negative • HER-2 negative + HR positive + BRCA mutation
    |
    Ibrance (palbociclib) • Kisqali (ribociclib) • fulvestrant
    21d
    First-line ET plus palbociclib versus standard mono-chemotherapy in high-risk HR-positive/HER2-negative metastatic breast cancer and indication for chemotherapy: primary results from the randomized phase IV PADMA study. (PubMed, ESMO Open)
    PADMA is the first randomized multicenter study to show that palbociclib + ET as first-line treatment compared with CT also leads to improvements in TTF and PFS in predominantly postmenopausal patients with HR-positive/HER2-negative mBC.
    Clinical • P4 data • Journal • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • EGFR positive • HR positive + HER-2 negative • HER-2 negative + HR positive + BRCA mutation
    |
    Ibrance (palbociclib) • paclitaxel • capecitabine • epirubicin • vinorelbine tartrate
    1m
    A Study of Olaparib and Pembrolizumab in People With Triple Negative Breast Cancer (TNBC) or Hormone Receptor-positive HER2-negative Breast Cancer (clinicaltrials.gov)
    P2, N=6, Active, not recruiting, Memorial Sloan Kettering Cancer Center | N=23 --> 6
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • HR positive + HER-2 negative • HER-2 negative + HR positive + BRCA mutation
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib)
    1m
    Adjuvant olaparib real world data for BRCA positive, HER2-negative high-risk early breast cancer patients in the United Kingdom. (PubMed, J Oncol Pharm Pract)
    Nineteen patients had dose reductions due to adverse effects and four patients discontinued treatment early.ConclusionAdjuvant olaparib was well tolerated in our real-world UK population study, with toxicity profiles similar to the OlympiA trial. Fatigue was significantly more prevalent in the real-world cohort.
    Journal • Real-world evidence • BRCA Biomarker • PARP Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • EGFR positive • HR positive + HER-2 negative • HER-2 negative + HR positive + BRCA mutation
    |
    Lynparza (olaparib)
    2ms
    Evaluation of Talazoparib, a PARP Inhibitor, in Patients With Somatic BRCA Mutant Metastatic Breast Cancer: Genotyping Based Clinical Trial (clinicaltrials.gov)
    P2, N=30, Recruiting, Massachusetts General Hospital | Trial completion date: Mar 2027 --> Apr 2028 | Trial primary completion date: Aug 2026 --> Mar 2027
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA (Breast cancer early onset)
    |
    BRCA1 mutation • HR positive • HER-2 negative • HR positive + HER-2 negative • BRCA mutation • HER-2 negative + HR positive + BRCA mutation
    |
    Guardant360® CDx
    |
    Talzenna (talazoparib)
    3ms
    Molecular Surveillance In Early Breast Cancer Using The Tumor-Informed ctDNA Assay Myriad Genetics Precise MRD Test; A Prospective Observational Multicenter Study (The MRD Molecular Surveillance Study) (clinicaltrials.gov)
    P=N/A, N=0, Withdrawn, M.D. Anderson Cancer Center | N=300 --> 0 | Trial completion date: Dec 2033 --> Apr 2026 | Initiation date: Aug 2026 --> Apr 2026 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2031 --> Apr 2026
    Enrollment change • Trial completion date • Trial initiation date • Trial withdrawal • Trial primary completion date • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA (Breast cancer early onset)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • BRCA mutation • HER-2 negative + HR positive + BRCA mutation
    3ms
    Denosumab is associated with longer real-world progression-free survival in BRCA1/2-mutated HR+ /HER2 - breast cancer patients with bone metastases receiving CDK4/6 inhibitors: A multicenter Italian study. (PubMed, Eur J Cancer)
    In this real-world cohort, denosumab use was associated with longer rwPFS in germline BRCA1/2-mutated HR+/HER2- mBC with bone metastases.
    Clinical • Journal • Real-world evidence • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • HER-2 mutation • BRCA wild-type • HR positive + HER-2 negative • BRCA mutation • HER-2 negative + HR positive + BRCA mutation
    |
    Prolia (denosumab)
    4ms
    Molecular Surveillance In Early Breast Cancer Using The Tumor-Informed ctDNA Assay Myriad Genetics Precise MRD Test; A Prospective Observational Multicenter Study (The MRD Molecular Surveillance Study) (clinicaltrials.gov)
    P=N/A, N=300, Not yet recruiting, M.D. Anderson Cancer Center
    New trial • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA (Breast cancer early onset)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • BRCA mutation • HER-2 negative + HR positive + BRCA mutation
    6ms
    A Study of Olaparib and Pembrolizumab in People With Triple Negative Breast Cancer (TNBC) or Hormone Receptor-positive HER2-negative Breast Cancer (clinicaltrials.gov)
    P2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    HR positive • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • HR positive + HER-2 negative • HER-2 negative + HR positive + BRCA mutation
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib)
    7ms
    Real-world effectiveness of PARP inhibitors after CDK4/6 inhibitor therapy in BRCA-mutated HR-positive/HER2-negative advanced breast cancer. (PubMed, NPJ Breast Cancer)
    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.
    Journal • Real-world evidence • BRCA Biomarker • PARP Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • BRCA mutation • HER-2 negative + HR positive + BRCA mutation
    7ms
    OptiTROP-Breast01: SKB264 Injection vs Investigator Selected Regimens to Treat Locally Advanced, Recurrent or Metastatic Triple-negative Breast Cancer (clinicaltrials.gov)
    P3, N=254, Active, not recruiting, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Trial completion date: Mar 2025 --> Jun 2027
    Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    HER-2 negative • HER-2 expression • HER-2 negative + HR positive + BRCA mutation
    |
    gemcitabine • capecitabine • eribulin mesylate • vinorelbine tartrate • Jiataile (sacituzumab tirumotecan)