The Impact of HER2-low Status on Prognosis in Hormone Receptor-Positive Metastatic Breast Cancer Treated With a Targeted Therapy Plus Endocrine Therapy

The Impact of HER2-low Status on Prognosis in Hormone Receptor-Positive Metastatic Breast Cancer Treated With a Targeted Therapy Plus Endocrine Therapy

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Jason Mouabbi, MD, The University of Texas MD Anderson Cancer Center, discusses his presentation from the 2022 San Antonio Breast Cancer Symposium on survival outcomes among patients with hormone receptor-positive, HER2-negative metastatic breast cancer treated with targeted therapies in combination with endocrine therapy, based on HER2 expression.

Transcript:

I'm Jason Mouabbi. I'm an Assistant Professor in the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center.

And it's my privilege today to discuss with you one of the abstracts I'll be presenting titled, “Histology-Based Survival Outcomes in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer Treated with Targeted Therapies in Combination with Endocrine Therapy, Based on HER2 Expression.”

So a little bit of background. The efficacy of trastuzumab deruxtecan, also known as Enhertu, in the HER2-low hormone receptor-positive metastatic breast cancer has been practice-changing. However, when it was first presented and then approved, we were all caught off-guard, given that prior to that study, HER2-low had not been well-characterized in metastatic breast cancer and we did not know whether HER2-low is a separate entity.

Since the presentation of the DESTINY-Breast04 study at ASCO '22, there have been a number of conflicting data about the prognostic value of HER2-low status in hormone receptor-positive metastatic breast cancer, patients who were treated with target therapies, especially those who were treated with CDK4/6 inhibitor.

In fact, there was three papers published back to back around the same time. One paper showed that patients with HER2-low status treated with CDK4/6 inhibitor had better outcomes compared to those who do not express HER2 at all, also known as HER2-0. There was another paper that came out showing the opposite, the total opposite, showing that patients with HER2-low had inferior outcomes, when exposed to CDK4/6 inhibitor in combination with endocrine therapy compared to the other group. And there was also a third group of studies that showed absolutely no impact on prognosis based on the HER2-low status.

Also, HER2-low has not been characterized based on histology. So we don't know if the same thing is true for ductal histology vs the lobular histology.

So the goal of our study was twofold. The first fold was that there was need for more data to better characterize HER2-low in hormone receptor-positive, HER2-negative metastatic breast cancer, and HER2-low implication on prognosis when treated with endocrine therapy in combination with targeted therapies, especially CDK4/6 inhibitors. The second goal was the need for HER2-low characterization in different histologies. And here, we're talking about the invasive ductal carcinoma compared to the invasive lobular carcinoma.

So what we did, we did an observational analysis or review on our MD Anderson Cancer Center breast cancer database, and we looked for patients with hormone receptor positive, HER2-negative metastatic breast cancer treated with endocrine therapy plus a targeted therapy. Patients were divided into three groups. So we looked at them in all histologies, in the ductal histology or IDC group and in the lobular histology or ILC group.

So we identified 1,649 patients, 64% of them has low expression of HER2, labeled as HER2-low. And 36% were nonexpressors of HER2, or HER2-0. And 68% of those patients were treated with CDK4/6 inhibitors.

Our study showed, and the poster will highlight that, that there was no statistically significant differences in clinical pathological characteristics between HER2-low and HER2-0 patients. So all of the characteristics were divided equally between those with no statistical significance between any differences.

And when you look at outcomes, and the two outcomes we’re looking for are progression-free survival and overall survival, there was no statistical difference between HER2-low and HER2-0 groups when treated with a targeted therapy in combination with endocrine therapy, especially in the ones who received CDK4/6 inhibitor plus endocrine therapy in the first-line setting. Also, we found the same finding regardless of histology.

So the conclusion of our study is that HER2-low status did not have a significant impact on prognosis in hormone receptor-positive metastatic breast cancer treated with a targeted therapy plus endocrine therapy, including those who are treated with first-line therapy of CDK4/6 inhibitors plus endocrine therapy.

This study, between all the three studies I talked about in my introduction, this is the largest between them all. It has the most numbers. We had more than 1,500 patients, where the other studies only had about less than 100 patients, each one of them.

So this is the most comprehensive study, the biggest study that does not support HER2-low as a separate entity and it does not support HER2-low as a prognostic entity in metastatic HR-positive or HER2-negative breast cancer.

Mouabbi J, Raghavendra AS, Bassett R, et al. Histology-based survival outcomes in HR+/HER2- metastatic breast cancer treated with targeted therapies plus endocrine therapy based on HER2 expression. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX and virtual. Abstract P5-02-30.