Transcript Related Guidelines

HR+/HER2- Metastatic Breast Cancer That Becomes Resistant to Endocrine Therapy

Kathy D. Miller, MD · Indiana University School of Medicine


October 19, 2022

Editor’s Note: The US Food and Drug Administration (FDA) has approved the antibody-drug conjugate trastuzumab deruxtecan, the first infusion therapy approved for the treatment of patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or for patients whose cancer has returned during adjuvant chemotherapy or within 6 months of completing it. The FDA approval was based on the significant results of the DESTINY-Breast04 trial.[1]

Key Takeaways:

  • Patients with hormone receptor positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer who become resistant to hormone therapy have a wealth of chemotherapy options available to them. 

  • Based on the results of the DESTINY-04 study, fam-trastuzumab deruxtecan (trastuzumab deruxtecan) significantly improved response rates, progression-free survival (PFS), and overall survival in patients who have tumors that are HER2 low (1+ or 2+ by IHC) and have had at least one previous chemotherapy when compared with several standard chemotherapy single agents.

  • Data presented at the American Society for Clinical Oncology (ASCO) 2022 meeting comparing sacituzumab govitecan (currently approved and available for patients with triple-negative disease) reported significant improvements in PFS compared with standard, single-agent chemotherapy. 

  • As data accumulates, we will be able to further classify patients with hormone refractory breast cancer and treat them accordingly.

This transcript has been edited for clarity.

Hormone therapy is the mainstay of treatment for patients with hormone receptor–positive HER2-negative breast cancer. But at some point, it will be clear that those patients are resistant to hormone therapy, and they will need to move on to chemotherapy. Now, they have a wealth of chemotherapy options available to them. And those options have now expanded. So first, we need to reconsider their HER2 status. And this will require us to go back to their original pathology or the most recent pathology.

Often, when HER2 is tested, the details get lost in our clinical notes. Patients who were 1 plus or 2 plus by immunohistochemistry, negative by FISH testing, in our clinic notes are often now just listed as HER2-negative. But those patients would be eligible for treatment with fam-trastuzumab deruxtecan.[2,3] And based on the results of the DESTINY-04 study in patients who'd had at least one previous chemotherapy, that agent significantly improved response rates, progression-free survival, and overall survival compared to several standard chemotherapy single agents.[4]

So first, go back and look at the HER2 status. See if fam-trastuzumab should be on your radar. We also have another antibody drug conjugate to consider that would be available for all of those patients. We saw results at the ASCO 2022 meeting comparing sacituzumab govitecan, a trope 2–targeted antibody drug conjugate currently approved and available for patients with triple-negative disease, now also showing significant improvements in progression-free survival compared to standard, single-agent chemotherapy.[5] Now, this also was in patients who had had one previous chemotherapy for metastatic disease, but provides another option for patients, and an option with a bit more activity than other chemotherapy.

This is a great time for our patients when they become hormone refractory with more options, and ones that will require us to begin to break this group into those that are HER2 truly negative, IHC-0, or those that are HER2 low 2+, 1+ but FISH-negative, because their options are now different.


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