What Is HER2-Low Breast Cancer?

October 07, 2022 by Chelsea Backler MSN, APRN, AGCNS-BC, AOCNS®, VA-BC

Human epidermal growth factor receptor 2 (HER2) proteins (https://_www.cancer.gov/publications/dictionaries/cancer-terms/def/her2-neu) are involved in normal cellular growth and are found on the surface of all breast cells. Approximately 20% of breast cancers (https://www.bcrf.org/blog/her2-low-breast-cancer-explained/) are HER2 positive, meaning they have high levels of HER2 protein, and those cancers typically grow and metastasize more quickly than other types of breast cancer.

An Emerging Designation

Historically, HER2 status has been binary: positive (3+ immunohistochemical [IHC] score) or negative (0 or 1+ IHC score). However, a subgroup of patients has borderline scores (2+), which clinicians and scientists have recently termed “HER2-low breast cancer.” An estimated 55% of breast cancers are classified as HER2 low (https://www.bcrf.org/blog/her2-low-breast-cancer-explained/). Historically, patients with HER2-low breast cancer have not responded as favorably to HER2-targeted therapies and have had few treatment options available—that is, until a new therapy was approved (https://voice.ons.org/news-and-views/fda-approves-fam-trastuzumab-deruxtecan-nxki-for-her2-low-breast-cancer) in August 2022.

A Promising Treatment Option

Researchers for the DESTINY-Breast04 (https://www.nejm.org/doi/pdf/10.1056/NEJMoa2203690) trial studied patients with HER2-low (defined as 1+ IHC or 2+ with negative results on in situ hybridization) metastatic breast cancer who previously received one or two lines of chemotherapy. The trial included patients with both hormone (estrogen or progesterone) receptor- (HR-) positive and negative cancers. Study participants received either fam-trastuzumab deruxtecan (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761139s022lbl.pdf) or the physician’s choice of chemotherapy. Results demonstrated a significantly lower risk of disease progression and death in the patients treated with fam-trastuzumab deruxtecan compared to those treated with chemotherapy.

The media heralded the findings as “unheard of (https://www.nytimes.com/2022/06/07/health/enhertu-breast-cancer-chemotherapy.html) and “practice changing (https://www.bloomberg.com/opinion/articles/2022-06-06/enhertu-breast-cancer-drug-from-astrazeneca-and-daiichi-sankyo-is-a-breakthrough?leadSource=uverify%20wall)” for treating metastatic breast cancer. A group of patients with traditionally poor responses to available therapies now has a treatment option that could significantly extend survival—including patients with triple-negative breast cancer (https://www.bcrf.org/blog/her2-low-breast-cancer-explained/) (one third of which are also HER2 low).

Future Opportunities

The DESTINY-Breast04 trial paved the way for an effective treatment for HER2-low breast cancer, with future studies of the agent planned (https://www.cancer.gov/news-events/cancer-currents-blog/2022/enhertu-her2-low-breast-cancer) for patients with earlier stage HER2-positive and HER2-low cancers. Researchers are also investigating whether fam-trastuzumab deruxtecan could prevent breast cancer from metastasizing (https://www.cancer.gov/news-events/cancer-currents-blog/2022/enhertu-her2-low-breast-cancer).

The study findings will also shift how metastatic breast cancers are classified (https://www.cancer.gov/news-events/cancer-currents-blog/2022/enhertu-her2-low-breast-cancer) so patients in the HER2-low category can be identified and properly treated. Current methods don’t always accurately identify patients who fit into the HER2-low category, but research is underway to develop new tests to detect lower HER2 levels.

What Oncology Nurses Should Know

The U.S. Food and Drug Administration (FDA) approved fam-trastuzumab deruxtecan (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-low-breast-cancer) on August 5, 2022, for HER2-low breast cancer. It is indicated for adults with unresectable or metastatic HER2-low breast cancer who have previously received chemotherapy or developed disease recurrent within six months of completing adjuvant chemotherapy. The medication is administered via IV infusion every three weeks, and the prescribing information contains a black box warning (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761139s022lbl.pdf) for interstitial lung disease, pneumonitis, and embryo-fetal toxicity as well as other adverse effects.

Patients should discuss with their care team fam-trastuzumab deruxtecan’s current indications and whether it could be effective for their specific type of breast cancer. Oncology nurses should provide patients with education about HER2 testing for tumors (https://www.ons.org/genomics-taxonomy/biomarker-testing) and why it helps determine precise treatment, especially in the HER2-low population who have fewer treatment options. Clinical trials for HER2-low breast cancer are ongoing (https://clinicaltrials.gov/ct2/results?cond=HER2-low&term=&cntry=&state=&city=&dist=), and nurses should inform qualified patients about the opportunity to enroll.

Read ONS Voice’s oncology drug reference sheet for fam- (https://voice.ons.org/news-and-views/oncology-drug-reference-sheet-fam-trastuzumab-deruxtecan-nxki)trastuzumab deruxtecan (https://voice.ons.org/news-and-views/oncology-drug-reference-sheet-fam-trastuzumab-deruxtecan-nxki) for more information about the treatment.

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