Pathway Optimization in Early Breast Cancer: Biomarkers, Therapies, and Shared Decision-Making

In this interview, Erika P Hamilton, MD, discusses advancements in clinical pathways for early breast cancer, including the role of genomic assays, emerging therapies such as CDK4/6 inhibitors and immunotherapy, targeted treatments for HER2-positive and triple-negative subtypes, and the importance of biomarkers and shared decision-making in optimizing patient outcomes.

Erika P Hamilton, MD, is a board-certified medical oncologist and the Director of Breast Cancer Research at Sarah Cannon Research Institute. She specializes in breast cancer treatment and research.

What are the most significant advancements in the treatment pathways for early breast cancer in recent years?

Erika P Hamilton, MD: Genomic assays to determine a person’s individual risk of cancer recurrence have been the biggest advancement in hormonally driven breast cancer. These assays allow us to personalize the treatment plan for the individual patient in front of us and ultimately spare many women the need for chemotherapy. For triple-negative breast cancer, the approval of immunotherapy for early breast cancer has improved cure rates by harnessing the body’s own immune cells to fight cancer in combination with traditional chemotherapy.

What emerging therapies show the most promise for improving outcomes in early breast cancer?

Dr Hamilton: We have recent data for two CDK4/6 inhibitors in early breast cancer. We are still following these trials in terms of long-term follow up, but both are already showing improved cure rates when added to traditional estrogen blockers. This represents a big advancement in cure rates for our most common type of breast cancer.

Can you discuss advancements in targeted therapies for early breast cancer, particularly for HER2-positive or triple-negative subtypes?

Dr Hamilton: The most notable advancements for triple-negative breast cancer are immunotherapy and PARP inhibitors. Immunotherapy can be used in all higher-risk triple-negative cancers to harness the body’s own infection-fighting cells to fight cancer cells. PARP inhibitors are a targeted option for a subset of patients facing cancer who have a mutation in the hereditary breast cancer genes BRCA1 or BRCA2. These are pills that can be taken at home after surgery that decrease the chance of recurrence.

Among HER2-positive cancer, we have many targeted agents that take advantage of the cancer’s dependence on the HER2 protein. Trastuzumab, a HER2 targeted antibody, has been in use since the 1990s, but pertuzumab is a newer antibody given in combination with trastuzumab that also improves cure rates. For patients who have residual disease after chemotherapy and surgery, we have an antibody-drug conjugate T-DM1 that improves cure rates. Antibody-drug conjugates can be thought of as a “smart bomb,” it uses an antibody-honing mechanism to deliver chemotherapy right to the cancer cell while sparing healthy cells.

What emerging biomarkers are showing promise in predicting recurrence risk or treatment response in early breast cancer?

Dr Hamilton: Large panel assays, such as Oncotype, Mammaprint, and Prosigna, are already in use to help us predict recurrence. However, Ki-67 has become a much more important marker of recurrence than it used to be. Ki-67 is a measurement of what percentage of cells in a person’s cancer are actively dividing and can give us a good idea of how aggressive the cancer is. We use Ki-67 to predict which patients with hormonally driven breast cancer may derive benefit from CDK4/6 inhibitors in particular.

How does shared decision-making impact adherence to clinical pathways in early breast cancer, especially for patients with unique clinical or genetic profiles?

Dr Hamilton: We all participate in shared decision-making every day. We explain what we know about someone’s cancer and how their age and genetics play into the chance their cancer comes back. Then we can better discuss, and quantify, the interventions at our disposal, such as chemotherapy, endocrine therapy, immunotherapy, targeted agents, etc., and how we want to use these to decrease risk. Trial data about how much each intervention decreases risk is very important to quantify perceived benefit for an individual patient and whether the side effects, etc., of that therapy are “worth it” for the benefit.