Chemo, Targeted Drugs Extremely Efficacious in HER2-Positive Breast Cancer

Presurgical treatment with paclitaxel, Herceptin (trastuzumab) and Perjeta (pertuzumab) led to a clearance of circulating tumor DNA (ctDNA; cancer DNA detected on blood tests) in patients with HER2-positive breast cancer, according to findings from the phase 2 DAPHNe trial that were presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Researchers on the study were analyzing if ctDNA clearance, indicating that there was no detectable cancer on the blood test, could be predictive of response rate at surgery. However, they found that the paclitaxel, Herceptin and Perjeta regimen was so effective that most patients experienced ctDNA clearance at surgery, regardless of whether or not they still had remaining tumors at the time of surgery.

“When we use chemotherapy plus HER2-targeted drugs in truly HER2-positive breast cancer, we see incredible efficacy of those regimens,” study author Dr. Andienne G. Waks, associate director of Breast Oncology Clinical Research at the Dana-Farber Cancer Institute in Boston, said in an interview about the findings. “And so, we didn't see the correlation with the outcomes that we expected because in fact, what our results suggested is that the treatment worked really well for everyone.”

Transcript:

That was our hypothesis. We thought that if somebody cleared their ctDNA, they'd be more likely to have a pathologic complete response at surgery, and if they didn't, that they'd be more likely to have residual disease. We thought it would distinguish between outcomes, certainly at surgery, maybe even long-term.

In the end in this particular cohort — and this surprised us — that's not what we found. We found actually that, at least as measured by ctDNA, the 12 weeks of treatment worked so well, that almost everyone cleared their detectable ctDNA, regardless of whether they had disease left at surgery or not, which I think is a testament which is different from what's been found in hormone receptor-positive HER2-negative breast cancer and triple-negative breast cancer.

I think it's a testament to the fact that HER2-positive breast cancer is different. When we use chemotherapy plus HER2-targeted drugs in truly HER2-positive breast cancer, we see incredible efficacy of those regimens. And so, we didn't see the correlation with the outcomes that we expected because in fact, what our results suggested is that the treatment worked really well for everyone. And that's congruent with what we've now seen in long-term follow up for this patient population, which is that there has only been one recurrence, one local recurrence in breast after about five years of follow up at this point.

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