HER2-Negative Breast Cancer

“These BRCA1/2 mutations are not frequent, but if you find these patients, a PARP [poly (ADP-ribose) polymerase] inhibitor may be something to consider. We can now make the case that more patients should be getting genetic testing.” 

—William J. Gradishar, MD, FACP, FASCO

The systemic treatment of HER2-negative breast cancer is largely governed by whether the patient is hormone receptor–positive or –negative. In the past several years, the treatment landscape was essentially revolutionized by the emergence of the cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in the hormone receptor–positive subset and by immunotherapy for patients with hormone receptor–negative, HER2-negative tumors. In contrast, the more recent advances have been tweaks that help escalate treatment where necessary and de-escalate it whenever possible. 

Some of these small but important changes to the guidelines were reviewed at the conference by William J. Gradishar, MD, FACP, FASCO, Chief of the Division of Hematology and Oncology and the Betsy Bramsen Professor of Breast Oncology at Northwestern University Feinberg School of Medicine and Director of Robert H. Lurie Comprehensive Cancer Center’s Maggie Daley Center for Women’s Cancer Care, Chicago.

The NCCN Guidelines for HER2-Negative Breast Cancer, focusing on systemic therapy, include the following updates:

- For HER2-negative, hormone receptor–positive, BRCA-mutated early breast cancer, adjuvant olaparib (with endocrine therapy) can be considered in patients with residual disease.

- For HER2-negative, hormone receptor–positive early breast cancer with high-risk characteristics, 2 years of adjuvant abemaciclib can be considered in conjunction with endocrine therapy.

- For triple-negative early breast cancer with high-risk characteristics, adjuvant pembrolizumab is a preferred option (following neoadjuvant pembrolizumab).

- For patients with triple-negative breast cancer and residual disease after neoadjuvant therapy, capecitabine can be useful as maintenance.

- For HER2-positive early breast cancer, adjuvant therapies listed as useful in certain circumstances include neratinib, paclitaxel/trastuzumab/pertuzumab, and ado-trastuzumab emtansine.

- For locally recurrent or metastatic HER2-negative disease, paclitaxel plus bevacizumab has been removed as an option.

- For locally recurrent or metastatic HER2-positive disease, a new second-line option, cited as “preferred,” is fam-trastuzumab deruxtecan-nxki. This drug can also be considered as first-line therapy in select patients.