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AACR Annual Meeting 2026

April 17–22, 2026 · San Diego · 2418 items

After the meeting★★

Breast cancer: HER2 de-escalation, MRD, TNBC

53 people · 55 posts5 topics

Start here

Breast cancer this year is not “another HER2 drug.” Three things happened at once: first-line treatment dropping chemo (or swapping in an ADC), using tumor DNA in blood to decide whether to intensify after surgery, and new escape switches in triple-negative disease.

T-DXd hit the THP regimen that has stood for a decade. zanidatamab wants to skip chemo entirely in early HER2-positive disease — pCR 30%, enough as a de-escalation concept, not enough as a registration number. Read this chapter by separating addition from subtraction.

zanidatamab binds two HER2 domains at once (the trastuzumab and pertuzumab sites) and does not lean on chemo cytotoxicity. T-DXd is the other pole: an ADC payload pushing the first-line standard up, at the cost of interstitial lung disease.

In triple-negative disease, sacituzumab resistance was written as “protein-degradation programs plus a suppressive microenvironment,” so swapping TROP2 ADCs may only fix half the problem. MRD (NSABP-B-59) is the molecular ruler for whether to add or subtract after surgery.

Analysis

First-line HER2 is being rewritten by an ADC. De-escalation is a narrower path: less chemo, less toxicity, but a 30% pCR will not carry a large Phase 3. Do not mash both into “breast cancer is up.”

Post-COVID lymphopenia and a 2.46-fold distant-recurrence risk is a survivorship signal, not a viral thread. If the topic list only has drug names, it misses what the meeting was actually arguing.

Still open
  • Whether DESTINY-Breast09 overall survival keeps the progression-free advantage.
  • Whether chemo-free neoadjuvant has a regulatory path anyone will accept.
  • After TROP2 ADC resistance, whether to swap the payload or the target.
Key readout

T-DXd + pertuzumab · PFS HR 0.56; ILD ~12%, including 2 grade 5DESTINY-Breast09 · 1L HER2+

Records

Drug / trialReadoutSetting
T-DXd + pertuzumabtrastuzumabHER2#BREASTCANCERPFS HR 0.56; ILD ~12%, including 2 grade 5DESTINY-Breast09 · 1L HER2+
zanidatamabzanidatamabNo-chemo neoadjuvant pCR 30%NeoZanHER · below a registration bar
pumitamig#BREASTCANCERTNBC cORR 61.5%PD-L1×VEGF · also under bispecifics
NSABP-B-59#BREASTCANCER#LIQUIDBIOPSYctDNA predicted non-pCR and distant recurrencePost-neoadjuvant TNBC

Floor

Apr 23Thu
Apr 22Wed
  3. 2 more on this topicHER2 · 11
Apr 21Tue
Apr 20Mon
  8. 3 more on this topic#BREASTCANCER · 9
Apr 19Sun

Other directions

CBACBA Frontier Insights (CFI)Chinese Biopharmaceutical Association (CBA)www.cba-usa.org