Brock Underscores Need to Reclassify Patients With HER2-Negative Metastatic Breast Cancer

With the advent of HER2-low classification, patients with metastatic breast cancer who were previously labeled as HER2-negative may need reevaluation to see if they are eligible for treatment with HER2-directed therapies such as fam-trastuzumab deruxtecan-nxki (Enhertu), according to La-Urshular Brock, MSN, FNP-BC, CNM.

Brock, a family nurse practitioner and certified midwife who works at Emory Healthcare in the Medical Oncology Department and specializes in breast and gynecologic oncology, recently presented on HER2-low status as part of the nursing track at the 40th Annual Miami Breast Cancer Conference®. Following the conference, she spoke with Oncology Nursing News® to recount key takeaways from her presentation.

HER2 is expressed on the receptor breast cells and play a role in the growth of breast cells. Immunohistochemistry (IHC) is commonly used to assess HER2 status along with in situ hybridization (ISH) testing. The IHC test detects HER2 protein overexpression, whereas the ISH testing detected HER2 gene amplification.¹

Moreover, according to Schettini et al, in a sample of 2485 patients with hormone receptor–positive disease, 63% had HER2-low disease, and in a sample of 620 patients with triple-negative breast cancer, 34% had HER2-low disease.² According to Brock, these findings signify the prevalence of this new classification among patients with breast cancer patients.

Oncology Nursing News: What is HER2-low status and at what time points should testing for HER2 status be done in patients?

Brock: HER2-low status is a new category in metastatic breast cancer. We define HER2-low by looking at the IHC assay. If it comes back as it IHC 1+ or IHC 2+, with the ISH negative, [we] consider that to be HER2-low. Previously, we considered the IHC 1+ as being [HER2] negative. So that is where this new category comes into treating metastatic breast cancer.

We should be testing for HER2-low in the metastatic setting. We could test for it when [patients] are newly diagnosed as metastatic. If we’re getting a tissue biopsy at that point, we could test then, and [investigate] whether or not they have HER2-low status. If there is no biopsy at that point, it can always be checked later. Whether it be at their time progression, after they’ve had that first line of treatment, or even after that second line of treatment, you can always go back and look at what their HER2 status was in the very beginning.

There really isn’t a specific time of when you should check, and, as we know, HER2 status can change over time [as] someone [is] being treated, but if someone is getting a tissue [biopsy] at diagnosis, then that would be the best time.

Could you discuss the outcomes for DESTINY-Breast04 (NCT03734029), and how it has changed the standard of care for these patients?³

In DESTINY-Breast04, [investigators] were looking at progression-free survival [PFS] for patients in the hormone receptor–[positive] setting who were HER2-low, as well as the PFS of the overall population, which [included] hormone receptor–positive, as well as triple-negative [disease]. These were significant clinical findings.

In the HER2-positive group, there was [approximately] a 10.1-month PFS improvement vs the [control] treatment arm group with physicians’ choice therapy. This shows a longer time for PFS, as well as overall survival in all the groups as well [and] gives us a pivotal finding that [supports] trastuzumab deruxtecan, the first known [effective] treatment for HER2-low metastatic breast cancer.

What is the implication for patients who had previously been classified as having HER2-negative disease?

For patients who would [have been] considered HER2 negative, now 2 new tools can go in your toolbox. Patients feel better and a little bit more comfortable knowing that there’s something else out [there]. Usually their concern is: ‘How many more treatment lines are there before I have to wonder about what is going to happen to me?’

With [the DESTINY-Breast04 data], patients who were considered HER2-negative now have another medication that we can use. It’s going to, hopefully, provide them that [additional] 10 months or possibly even longer, in keeping them from progressing and having to change treatments.

What are some of the unique adverse effects that are associated with HER2-directed therapies?

When we’re looking at the overall treatment, we know that the adverse effect that causes people to discontinue treatment would be the interstitial lung disease [ILD], or pneumonitis. So, that’s the biggest one. In DESTINY-Breast04, they saw approximately 12.1% of patients experienced this.² When patients do experience [ILD], we have to hold the medication and start them on steroids for treatment.

The next things that were the most common, in terms of having a dose reduction, were fatigue and nausea. We have found that pretreating patients can help, but those are the 2 biggest adverse effects for dose modifications.

What you [also] have to think about with these HER2 medications is the heart. We don’t want to forget about left ventricular function dysfunction in patients—there was approximately a 4.8% [incidence] of left ventricular dysfunction in the DESTINY-Breast04 trial.

Is there anything else that you’d like oncology nurses to know?

Just thinking about trastuzumab deruxtecan, now we have a new set of patients [with breast cancer] that we need to consider [for] this medication. Before [this treatment] was strictly just for metastatic breast cancer patients with HER2-positivity.

But now we really can open this up to patients who are HER2-low, meaning, we really do need to go back and check their status. That’s going to be helpful for all of us to look through patient records, that is going to be important. So, if a patient has been metastatic for a while, it is easy for us [as] nurses or advanced practice providers to go back and look and say, now I need to start recording the HER2 status [and] really make sure they are negative, with IHC of 0. [We can consider] are they actually HER2-low? [Are there tests] ICH 1+ or IHC 2+ with ISH negative?

I think it’s going to be really important for us to go back and make sure that we are reclassifying our metastatic breast cancer patients.

Editor’s Note: Brock is a speaker for Curio Science.

References

1. Brock L. HER2 low: a new category in breast cancer. Poster presented at: 40th Annual Miami Breast Cancer Conference; March 2-5, 2023; Miami Beach, FL.
2. Schettini F, Chic N, Brasó-Maristany F, et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer. 2021;7(1):1. doi:10.1038/s41523-020-00208-2
3. Modi S, Jacot W, Yamashita T; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-Low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690