Do you ever utilize an anthracycline based regimen rather than a non-anthracycline based regimen for patients with locally advanced HER2 positive breast cancer?

I do not use a lot of AC-THP except in a few cases where we had multicentric or multifocal locally advanced breast cancer that had both HER2+ and HER2- disease concurrently so we had to "cover our bases" for both disease types so to speak. For straightforward HER2+ disease, the 3-year EFS data from the TRAIN-2 phase 3 trial (van der Voort et al., PMID 34014249) showed nonanthracycline treatment with dual HER2 blockade had similar pCR rates (~67%) to anthracycline containing therapy, same 3 year EFS (92.7 and 93.6% for anthracycline vs. non-anthracycline), same OS, but more febrile neutropenia for anthracycline chemo, more EF declines >10% and under 50% EF with anthracycline vs non-anthracycline (7.7% vs. 3.2%), and 2 leukemias in the anthra...

That is a very interesting question!

Yes, I sometimes use the AC-THP as opposed to TCHP, though my use has decreased over time. I have used it most often in those with life threatening visceral disease where I feel a need to obtain as rapid a response as possible. I have used it less and less as neoadjuvant therapy - not for any reason based on data, but based on subjective ease of using this approach.

I can't claim that either approach is superior, and patient factors and comorbidities may factor into this. In some ways, I think of this as a "Coke versus Pepsi" choice. Both are similar, but people may have strong preferences.

There is very little reason to use an anthracycline for HER2 positive breast cancer and is best to avoid the unnecessary added risk from cardiac toxicity. I have also seen dose dense AC being used for HER2 positive disease, a practice that should be unequivocally discouraged.

The one specific situation worth mentioning that I will use adriamycin for HER2+ breast disease is for a pregnant patient.

For inflammatory Her 2+ breast cancer, I have used Dose Dense AC - THP.

I agree that in 2023, there are very few reasons to use anthracyclines in HER2-positive breast cancer, given the increasing body of literature (as cited by colleagues above) showing equivalent outcomes and lesser risk for cardiotoxicity and secondary leukemias. However, I like to remind myself that in many of the trials evaluating non-anthracycline-based regimens such as TRAIN-2, patients with extensive nodal involvement (N3 disease) and inflammatory breast cancer were not adequately represented. As such, I still discuss these uncertainties with patients in this situation, and in younger and fit patients, without excess cardiac risk, I still favor AC-THP. Not because of any data showing it is superior, but rather because of the absence of d...

I agree with others that in most circumstances, anthracycline use should be abandoned. I also agree with Dr. @Dr. First Last that in the setting of Her2 heterogeneity, it should be considered. I would only add one more circumstance that I would at least discuss with colleagues and your pathologist.

In Her2 IHC 2+ cases where the Her2/CEP17 ratio is less than 2, but the copy number is greater than 6, these are categorized as Her2 positive. These fall into CAP group 3. On examination of the literature, patients in this group seem to fall out into 2 groups: those who are non amplified and those who are amplified with a much higher copy number and are referred to by some as group 3N and group 3A (Press et al., The American Journal of Hematolog...