Paolo Tarantino, MD, Dana-Farber Cancer Institute, Boston, MA, discusses discoveries made in the genomic characterizations and treatment landscape of HER2-low, HER2-zero, and HER2-positive breast cancers, at the 2022 San Antonio Breast Cancer Symposium in San Antonio, TX.

Transcript

Hello, I'm Paolo Tarantino, advanced research fellow from Dana-Farber Cancer Institute, and I'm so excited to be here at San Antonio with so much exciting news in breast oncology.

I would like first to touch upon one field that I've been working on in the past years. That is the HER2-low breast cancer field, and we had a dedicated session in San Antonio this year on HER2-low breast cancer. We saw many interesting pieces of data out, and the way we contributed at Dana-Farber is looking at the genomics of HER2-low in more than 1000 patients with HER2 non-amplified tumors. We compared genomic findings in HER2-low and HER2-zero breast cancer. We found that there was no major genomic difference between these 2 cohorts when you account for estrogen receptor expression, because we know that in this cohort of HER2 non-amplified tumors it is the estrogen receptor that really makes the difference.

It's our more receptor-positive and triple negative tumors that are different in terms of biology and prognosis. What we are learning is that HER2-low is not really a distinct subtype. This is what we saw from our large Dana-Farber cohort. Similar findings were reported in other studies, so it was very comforting to see the overall picture being once again that HER2-low is not a distinct biologic subtype. Although clinically it's still very important to remember that HER2-low breast cancer in a metastatic setting can now be treated with a novel antibody drug conjugate that is FDA approved, trastuzumab deruxtecan, that improves survival. It is clinically an important subset, but we still need to work a lot on it. And there is a randomized trial DESTINY Breast06 that is ongoing that might show that not only HER2-low but also certain HER2-zero tumors may respond and derive benefit from trastuzumab deruxtecan.  We're all waiting for this data, hopefully next year or in general in the near future.

The other field I would like to touch upon is HER2-positive breast cancer, specifically small node-negative, HER2-positive breast cancer. We know that this subset, the treatment for these tumors, the adjuvant treatment was defined based on the APT trial, a study led by Sara Tolaney [MD, MPH] at Dana-Farber. They looked at outcomes with trastuzumab deruxtecan and after 7 years these outcomes were outstanding. At this congress, Sara Tolaney will present the 10-year outcomes and HER2DX [genomic tool] results. I'll have the opportunity to present another trial, a follow-up trial, that looked at T-DM1 [trastuzumab emtansine] compared to trastuzumab and paclitaxel in terms of toxicity and the outcome with T-DM1. We will report the 5-year outcomes in patients with stage 1, HER2-positive breast cancer treated with adjuvant T-DM1.

What we have observed in stage 1, HER2-positive breast cancer treated with adjuvant T-DM1 for 1-year is outstanding disease-free survival rate of 97% at 5 years, 98.3% relapse-free interval rate and only 3 distant recurrences among 383 patients treated with this regimen, telling us it's highly effective. We also applied the HER2DX genomic tool to look if we could identify a population with a higher risk of recurrence. Indeed, there was about 6% of the patients in the trial that are up to 20% risk of recurrence. They were identified as high risk by this genomic tool, HER2 DX, whereas most of the other population were low risk for the tool at less than 2% risk of recurrence.

We hope in the future that HER2DX might help to refine treatment tailoring for these patients. But I would say it's really reassuring to see outstanding long-term outcomes, both with trastuzumab and paclitaxel, but also with T-DM1, which allows the patients to have a treatment with less alopecia, with less neutropenia, and in general with a better quality of life.

And now there is another trial attempt 2.0, that is looking at a shorter duration of T-DM1. We hope we can make it equally effective, but even better tolerated for our patients with small HER2-positive breast cancer. Thank you.

Source:

Tarantino P, Gupta H, Hughes M, et al. “Comprehensive genomic characterization of HER2-low breast cancer.” Presented at: San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract HER2-05

Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: Final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. Published online: April 02, 2019. doi:10.1016/S1470-2045(23)00051-7