Kefah Mokbel, Chair of Breast Cancer Surgery at London Breast Institute and Honorary Professor of Medicine at Cardiff University School of Medicine, shared a post on LinkedIn:
“NCCN Breast Cancer Guidelines v4.2026: What Actually Changed for Metastatic Disease
The recurrent/stage IV section (JNCCN, July 2026) has several updates that meaningfully shift decision-making – not just recycled content.
HR+/HER2+ maintenance
PATINA is now published (NEJM 2026). Adding palbociclib to maintenance endocrine + anti-HER2 therapy extends median PFS from 29 to 44 months (HR 0.75) after induction chemo. Grade ≥3 AEs 81% vs 31% – real cost, real benefit.
First-line HER2+
DESTINY-Breast09 shows T-DXd + pertuzumab beating THP outright (PFS 40.7 vs 26.9 months, HR 0.46). NCCN still keeps THP preferred – lack of crossover in the trial (a stated guideline limitation) plus higher ILD/treatment-related mortality with T-DXd (12% ILD, 3.4% grade 5 vs 0.8%) likely underpin the cautious stance.
TNBC first line
ASCENT-04/KEYNOTE-D19 (NEJM 2026) – sacituzumab govitecan + pembrolizumab vs chemo + pembrolizumab in PD-L1+ disease: PFS 11.2 vs 7.8 months (HR 0.65). Now category 1 preferred, first ADC-IO combo in this setting.
TROPION-Breast02 matures for PD-L1 CPS <10, no germline BRCA PV: datopotamab deruxtecan beats chemo on PFS (10.8 vs 5.6 months) and OS (23.7 vs 18.7 months) – now category 1 preferred in that population, on par with sacituzumab govitecan.
ESR1-mutated disease
VERITAC-2 adds vepdegestrant (PROTAC ER degrader) alongside elacestrant/imlunestrant – PFS 5.0 vs 2.1 months over fulvestrant (HR 0.58) in ESR1-mutant disease, though the trial missed its overall-population endpoint.
OS data now mature for two PI3K-pathway regimens
INAVO120 shows fulvestrant/inavolisib/palbociclib with a 7-month OS advantage (34 vs 27 months, HR 0.67). CAPItello-291’s updated analysis shows an estimated 18-month OS of 74% vs 65% with capivasertib/fulvestrant (HR 0.74) – median OS not yet reached in either arm.
Watch but not yet practice-changing
AMBRE/PADMA (SABCS 2025 preliminary) suggest CDK4/6i + endocrine can match chemo even in high-visceral-burden HR+/HER2- disease – a direct challenge to reflexive chemo-first thinking. The guideline discusses these data in narrative text but hasn’t incorporated them as a formal recommendation.
The through-line: OS data finally catching up to PFS signals, and ADC-based combinations beginning to displace conventional chemotherapy backbones in selected first-line settings (notably PD-L1-positive TNBC). The THP-vs-T-DXd/pertuzumab question is the one to watch.”
WHO Global Cancer Report 2026: Breast Cancer Survival Still Depends Too Much on Where a Woman Lives
