Optimizing Maintenance in HER2+ Metastatic Breast Cancer: A thread

This is a rapidly evolving field: Don't forget to read out latest update summary from San Antonio Breast Cancer Symposium 2025 >

🧵 1) Welcome to a new #accredited #tweetorial on HER2+ Metastatic Breast Cancer. This tweetorial provides 0.25 AMA PRA Category 1 Credits. #CME.

Before commencign this activty, the statement of accreditation and disclosures can be found at https://app.medall.org/articles/1-l-her-2-hr-mbc-cme-material-and-disclosures This program has been supported by an independent medical education grant from Pfizer and is delivered in joint providership with AffinityCE

After you have read the thread you can claim CME credit here.

So... How much do you know about #HER2Positive MBC? 🤔

In #HER2Positive MBC, maintenance therapy should sustain disease control while reducing toxicity and improving quality of life. Let’s dive into the shift from CLEOPATRA’s model to current de-escalation trials #MedOnc

We asked Prof Mark Pegrum to share his thoughts about how the evidence on HER2+ MBC maintenance evolved from the CLEOPATRA trial to today? 👇

5. What is the role of endocrine therapy ± CDK4/6 inhibitors in HE2R+/HR+ MBC 1L setting?

Well, first it’s important to understand ER/HER2 crosstalk: HER2 signaling confers resistance to endocrine intervention. 💡Growth factor signalling activates ER in the absence of oestrogen via downstream HER2 signal transduction molecules 💡Activated cytoplasmatic ER dimerizes and translocates to the nucleus, induces transcription or ER-dependent genes

6. But interestingly - its bidirectional: ER-pathway as an escape mechanism to HER2-inhibition 💡 HER2 signalling down-regulates ER-regulated transcription – resistance to endocrine therapy 💡 HER2 inhibition results in activation of ER-regulated – compensatory mechanism for tumor growth and survival 💡 Superior inhibition of tumour growth by parallel blockade of HER2 and ER pathways

7. Key Studies: ✅PATINA ✅PERTAIN ✅monarcHER

8. Prof. Rupert Bartsch shared with us a little of the background - Why add CDK4/6 inhibitor therapy in HER2+ MBC?’

9. 💊 #CDK46i in #HER2Positive MBC - #PATINAStudy ✔️ AFT-38 PATINA: #CDK46i as part of 1L maintenance ✔️ #Palbociclib + anti-HER2 and ET 🆚 anti-HER2 and ET ✔️ Improved PFS with #palbociclib (p=0.0074)

10. 💊 #CDK46i in #HER2Positive MBC - #DESTINYBreast07Trial ✔️ #DESTINYBreast07: #T-DXd ± #pertuzumab in 1L #HER2Positive MBC ✔️ PFS rates higher with #T-DXd + #pertuzumab ⚠️ Diarrhea rate higher ✔️ Published Phase 3 DESTINY-Breast09 will provide definitive data

11. 🔎Now let’s explore maintenance in first-line #HER2Positive MBC some more, with somes Cases👇#OncoTwitter #MedOnc

12)❓Which therapy would you choose in this case?

13. Dr Sarah Sammons discussed this case recently at a MedAll Grand Rounds:

14. 🔎What about multidrug maintenance strategies? Let’s look at another case 👇 #CaseBasedLearning #OncoTwitter #MedOnc #ClinicalCase

13. ❓Which therapy would you choose for this patient?

14. In relation to this case, Dr Sarah Sammons explained at our recent grand round the PATINA trial for ER+, HER2+ MBC:

15. Thank you for participating in this tweetorial! We hope you are as excited about the future of #HER2+ MBC as we are!

Claim your FREE credit NOW at https://forms.gle/67KdtDe4bweNjyCB8 and follow us for more CE/#CME!