Benjamin Walbaum, Medical Oncologist at Pontifical Catholic University of Chile, shared a post on LinkedIn:
“Breast Cancer Weekly Newsletter – My Take from Last Week
1. Mechanisms of Resistance to Trastuzumab Deruxtecan in Breast Cancer Elucidated by Multi-omic Molecular Profiling
· Real-world multi-omic analysis of >2,700 T-DXd–treated patients.
· Higher ERBB2 (HER2) expression and lower ABCC1 expression independently associated with improved overall survival.
· Post-treatment enrichment of mutations in ERBB2, TOP1, NFE2L2, and KEAP1, suggesting biologically plausible resistance pathways.
· ABCC1-mediated drug efflux emerges as a clinically relevant, targetable resistance mechanism.
2. Neoadjuvant Abemaciclib plus Letrozole vs. Chemotherapy in HR+/HER2− Highly Proliferative Breast Cancer (CARABELA Trial)
· Phase II randomized trial comparing 12 months of letrozole/abemaciclib versus standard chemotherapy.
· Primary endpoint (RCB 0–I) not met: 13% vs. 18%, respectively.
· Tumors with Ki-67 <30% or Oncotype DX RS <26 showed comparable outcomes between endocrine-based therapy and chemotherapy.
· Higher proliferation (Ki-67 ≥30% and/or RS ≥26) favored chemotherapy.
3. A Tale of Two Trials: TAILORx and PlanB
· Unlike TAILORx, PlanB trial did not show a significant benefit of adding anthracyclines to adjuvant chemotherapy vs. TC (x6) in N0 eBC with RS≥31.
· Reinforces the need to contextualize genomic risk within trial design and treatment backbone.
4. Menopausal Hormone Therapy and Breast Cancer Risk in BRCA1/2 Pathogenic Variant Carriers
-Estrogen-only MHT was associated with a significant reduction in breast cancer risk (HR 0.37).
-No increased risk was observed with combined estrogen–progestogen therapy.
5. Capivasertib Plus Paclitaxel as First-Line Therapy for Metastatic Triple-Negative Breast Cancer (CAPItello-290)
· Capivasertib + paclitaxel did not improve overall survival compared with placebo–paclitaxel.
· No significant benefit was observed in the PIK3CA/AKT1/PTEN-altered subgroup.
6. Risk-Based vs Annual Breast Cancer Screening With Population-Based Genetic Testing (WISDOM Trial)
· Participants in the risk-based arm were assigned to one of four screening strategies based on integrated risk (genetics, clinical factors, and breast density):
· Risk-based screening was noninferior to annual screening for stage ≥IIB cancers.
· Reduced mammography numbers, but biopsy rates were not decreased.
7. Risk of QTc Prolongation, and Major Cardiovascular Adverse Events Associated With CDK4/6 Inhibitors in HR+/HER2− Breast Cancer – A Systematic Review and Meta-analysis
· Grade 3/4 QTc prolongation: RR 1.83 (95% CI 1.23–2.74), driven by ribociclib RR 1.95 (95% CI 1.27–2.98).
· VTE: RR 2.57 (95% CI 1.53–4.32), highest with abemaciclib RR 5.14 (95% CI 3.09–8.54). ”
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