Dr Premji on Exciting Advancements in Breast Cancer Therapy

In recognition of October as Breast Cancer Awareness Month, Sarah Premji, MD, assistant director of Breast Cancer Research at Sarah Cannon Research Institute (SCRI), discusses exciting advancements in the treatment landscape of breast cancer.

Watch part 1 of Dr Premji's interview.

The landscape of breast cancer treatment is undergoing a rapid and exciting transformation, driven by advancements across several key areas. An expert perspective highlights five particularly impactful avenues of research and clinical development that promise to revolutionize care for patients.

A major focus lies in enhancing the efficacy of targeted therapies for estrogen receptor-positive (ER-positive) breast cancer by overcoming acquired resistance. While drugs like CDK4/6 inhibitors have demonstrated a significant benefit, including the prolongation of overall survival in the first-line metastatic setting, resistance eventually develops. Identifying the molecular mechanisms driving this resistance is paramount. The field is seeing the emergence of entirely new drug classes designed to address this challenge. These include novel selective estrogen receptor degraders (SERDs) and selective estrogen receptor modulators (SERMs), which aim to better block or degrade the estrogen receptor. Furthermore, innovative proteolysis-targeting chimeras (PROTACs) represent a sophisticated approach to drug design. The ultimate goal of these efforts is to significantly delay the need for traditional, more toxic treatments like chemotherapy, improving the patient's quality of life and treatment duration.

In the HER2-positive breast cancer space, the utilization of antibody-drug conjugates (ADCs) has been a significant breakthrough. ADCs act like "guided missiles," delivering potent chemotherapy directly to the HER2-expressing cancer cells, thus minimizing systemic toxicity. Research continues to explore even more novel HER2-targeting agents to improve patient outcomes further.

For triple-negative breast cancer (TNBC), which is typically aggressive and lacks common therapeutic targets, the focus is heavily on leveraging the body's own immune system. This includes the strategic use of immunotherapies and the development of vaccines. A critical area of investigation is the precise understanding and manipulation of tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment. By learning how to better activate these immune cells, researchers aim to turn an immunosuppressive environment into one that is receptive to an effective anti-tumor response.

Two other themes cut across the entire spectrum of breast cancer. The first is the innovative use of circulating tumor DNA (ctDNA) and other novel technologies to gain a deeper understanding of tumor biology. Current efforts are focused on integrating complex information, such as single-gene variant allele fractions (VAFs), the emergence of new alterations, and polyclonality (the presence of multiple different cancer cell clones). The ability to non-invasively track these features in real-time allows for a more sophisticated understanding of tumor evolution and helps scientists design smarter, more targeted therapeutic strategies.

The second crucial area is the right-sizing of therapies—a commitment to tailoring treatments to each individual patient. This personalization is key to reducing toxicities while simultaneously improving treatment outcomes. Crucially, this approach must be coupled with robust programs for survivorship and supportive care to address the long-term physical and emotional needs of those living with and beyond breast cancer. This holistic approach ensures that medical progress translates into meaningful, sustained improvements in patients' lives.

Read the full interview with Dr Premji.