DR LOVE: Just to finish out the anthracycline story, you referenced UCLA. And, of course, at the last San Antonio meeting, your colleague, Dennis Slamon, presented the follow-up for the BCIRG-006 trial that had a nonanthracycline arm in it. Any comments on that follow-up data and how you approach the issue of anthracyclines with HER2-positive disease?

DR HURVITZ: Yes. I mean, that was 10-year follow-up data, very clean, very little dropout or crossover in that study. So it’s a very clean data set, 3,200 patients. And what it showed was, now again, it wasn’t a noninferiority design, which is what all of the people who don’t like that study say, However, that said, the 2 trastuzumab-based arms were significantly better than the nontrastuzumab-based arm. And there was no statistically significant difference between the 2 trastuzumab arms, ACTH or TCH.

If you actually look at the highest-risk patients, 4 lymph nodes or more positive, the 2 arms are neck and neck. They’re essentially the same with one another. So if your theory is that the highest-risk patients really need an anthracycline, it doesn’t hold water. The survival was similar between the 2 trastuzumab-based arms. But you are seeing a number of patients who had cardiac events that prevented them from even getting to the trastuzumab because the cardiac event occurred during the AC regimen, you have more leukemia/myelodysplasia events.

Dennis always puts that final slide, that therapeutic index slide, adding up the DFS events and then adding in the cardiomyopathy and leukemia/myelodysplasia. They’re pretty much neck and neck when you look at them. So I don’t feel that the use of an anthracycline in that setting is beneficial. I don’t think that we have any data to say that it’s adding much outside of toxicity. Where I will use it, and I have used it in a few patients, being at a large center, I see outliers. I’ve treated a few pregnant women with AC for 4 cycles to get them to their delivery so that then, after the delivery, we can give TH.

DR LOVE: Hmm. So is it the issue of taxane in pregnancy?

DR HURVITZ: And trastuzumab. It’s not safe enough to give in pregnancy. There’s been some problems with amniotic fluid with the use of trastuzumab. And then the taxanes, I’m not convinced of their safety looking at the literature in pregnancy.

DR LOVE: So it sounds like you don’t use anthracyclines very much. And I’m curious. ASCO just came out with guidelines about HER2-positive disease. I thought they came on pretty strong, pro-anthracycline. Was that your read?

DR HURVITZ: Yes, although consensus statements are funny, because it’s a bunch of thought leaders, people who treat this disease and look at the literature. But it’s not without bias. And I think we all have our biases. I mean, I started this session by telling you I’m from UCLA, so you know what my biases are already. But I do think that anthracyclines are very effective drugs, very effective cancer drugs.

But when we are dealing in the curative setting, we have to keep in mind that, based on those early Bernie Fisher studies and the earliest chemo trials, anywhere from 40% to 70% of patients are cured by surgery alone, depending on the population you’re looking at; lymph node-positive, triple-negative. So we are overtreating a vast number of patients with the chemotherapy that we’re using.

And if we are picking patients and giving everyone anthracyclines and putting them at risk of heart failure and long-term cardiac toxicity, which has been underappreciated by the lack of long-term follow-up in these clinical trials, I have a real problem with that. So I think it’s important for us to be honest with patients about their risk of recurrence and the relative benefits and what we know and don’t know.

Genomic assays and (neo)adjuvant treatment decision-making

Early-stage breast cancer in the adjuvant and neoadjuvant settings

Management of metastatic breast cancer (mBC)

CDK4/6 inhibitors for the treatment of breast cancer

Checkpoint inhibitors and other novel immunotherapeutic approaches to breast cancer

Triple-negative and BRCA mutation-positive breast cancers