Brandon Rose, MD, MPH

There was a time when treating HER2+ breast cancer was relatively simple. That time is over. And that’s great news! Not long ago, we recommended TCHP for most patients with stage II–III disease, and THP (CLEOPATRA) for those with metastatic disease. Straightforward. Almost one-size-fits-all. Within just a few years, that simplicity is gone. And that’s progress. More opportunities to spare unnecessary toxicity, tailor treatments to patients’ preferences, and move beyond rigid algorithms. To be more doctors. In early-stage disease, options now range from de-escalated THP to intensified regimens such as DB11. In metastatic disease, T-DXd/P has achieved unprecedented PFS (>3 years in the 1L setting!), with novel maintenance strategies (palbociclib or tucatinib) potentially pushing the bar even higher. Meanwhile, biomarkers are finally coming of age, from imaging to tissue and plasma. What an era to be treating HER2+ breast cancer! But more options also mean more complexity. For oncologists, and especially for patients. More knowledge needed, more discussions, more decisions to make. How do we navigate this increasingly complex landscape and choose the right treatment for the right patient? We tried to offer some guidance in our new review recently published in @NatRevClinOncol. Read it here: nature.com/articles/s41571-0… @ValenzaCarmine

✅ Changing target and payload ✅ Only changing payload 🫤 Only changing target

Switching ADC payload works. Even while keeping the same target. We previously saw it in DB02. Then in TULIP. And now in ph1 trials of novel agents. In an abstract to be presented at #SABCS26, the HER2 ADC IKS014 (caxmotabart entudotin) showed an ORR of 50% (5/10) among patients with HER2+ MBC that had previously received T-DXd. biospace.com/press-releases/…

6 years ago, I had the chance to publish a paper that would end up changing my academic life It was a review article exploring the surprising activity of certain ADCs in “HER2-low” breast cancer, a newly emerging entity whose relevance was still uncertain. We tried to connect the dots, asking if HER2-low was a subtype vs just a target, wondering whether this concept could one day translate into meaningful benefits for patients. 6 years later, that article has reached 1,000 citations. My career has gifted me more than I could ever have imagined. More importantly, what was once an intriguing scientific observation has become a clinical reality: countless patients with HER2-low breast cancer now live longer thanks to T-DXd. A reminder of how far science can take us in just a few years. Grateful to everyone who has been part of this journey! ascopubs.org/doi/10.1200/JCO…

⚡️ Concomitant publications demand extra effort from authors, reviewers and editorial team, but deliver what matters most: getting outstanding science out ASAP to advance cancer care. Glad to have handled 2 outstanding @ESMO_Open concomitant pubs by @kazuki_nozawa & @drsarahsam!

Primary results from BRIDGET ph2 trial presented by @drsarahsam and published in @ESMO_Open. Adding tucatinib to HP after an isolated intracranial PD led to impressively long PFS (59% free from PD or death at 18mo!!). Reasonable strategy from next Monday in TKI-naive patients.