Breast Cancer Coverage from Every Angle

Update on Systemic Therapies for Breast Cancer: ‘Pragmatic Decision-Making’ Still Needed

By: Joseph Cupolo
Posted: Tuesday, January 5, 2021

During the NCCN 2020 Virtual Annual Conference, William J. Gradishar, MD, of Northwestern University, informed listeners about practice-changing interventions for metastatic breast cancer, and how these interventions have been incorporated into the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer (NCCN Guidelines®). He noted that decision-making starts with breast cancer subtype, with appropriate therapeutic choices based on whether a tumor is HER2-positive, estrogen receptor–positive, or triple-negative and BRCA-mutated. Highlights of this presentation were published in JNCCN–Journal of the National Comprehensive Cancer Network.

Regarding HER2-positive disease, a recent addition to the NCCN Guidelines, fam-trastuzumab deruxtecan-nxki (T-DXd), gained FDA approval late in 2019. “As an antibody-drug conjugate, T-DXd is similar to T-DM1,” noted Dr. Gradishar. “However, because the payload is a topoisomerase-1 inhibitor, there is a higher drug-to-antibody ratio, a potentially greater antitumor effect, and potentially a bystander effect that may produce broader killing.” However, although most adverse events with this new agent are mild, he noted that a black box warning about interstitial lung disease requires vigilance on the part of clinicians.

Dr. Gradishar also provided therapeutic updates on estrogen receptor–positive breast cancer, including the PI3K inhibitor alpelisib and triple-negative and BRCA-mutated breast cancer. “Triple-negative breast cancer strikes fear in patients,” Dr. Gradishar commented. “Olaparib and talazoparib have both been shown to improve progression-free survival in patients with germline BRCA mutations and are considered options for these patients. However, the benefit of these drugs is optimized when they are given earlier in the course of metastatic disease rather than later.”

In closing, Dr. Gradishar asked listeners what could be done to improve the cure rate in metastatic breast cancer. “This will require finding and treating smaller metastases (and eliminating disparities that lead to delayed diagnosis and treatment), developing the right drugs for the right patients (teasing out the subtypes), understanding the effect of prior therapies and the best options for current treatment, and using an increasing array of molecular markers to make decisions.”

Disclosure: For Dr. Gradishar’s disclosures, visit

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