Sara M. Tolaney, MD, MPH, Chief of Breast Oncology at Dana-Farber Cancer Institute, welcomed participants to the Contemporary Cancer Network program focused on novel therapeutic approaches for personalized breast cancer treatment.

Dr. Tolaney outlined that breast cancers are traditionally classified into hormone receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-positive, and triple-negative subtypes. Hormone receptor-positive cancers comprise approximately two-thirds of breast cancers. HER2-positive and triple-negative subtypes each represent 15-20% of cases. Historically, triple-negative disease was associated with the worst prognosis, but outcomes for HER2-positive cancers are now similar to HER2-negative cancers with anti-HER2 therapies.

A subset of breast cancers are classified as HER2-low, with low levels of HER2 expression between HER2-negative and -positive cancers. HER2-low cancers represent 50% of breast cancers and, while not considered a prognostic indicator, have therapeutic implications.

Major therapeutic advances have improved patient outcomes across breast cancer subtypes, including anti-HER2 therapies for HER2-positive disease, CDK4/6 inhibitors and PARP inhibitors for hormone receptor-positive tumors, and immunotherapies for triple-negative cancers. However, early-stage cancers still have a risk of relapse, highlighting the need for biomarkers to guide personalized treatment approaches and optimize outcomes while mitigating toxicities.

Ongoing research is focused on developing biomarkers and tailored treatment strategies. One evolving area is detection of minimal residual disease (MRD) using circulating tumor DNA (ctDNA) assays, which can identify residual cancer cells and risk of relapse. These assays, such as the monarchE test, may guide adjuvant treatment decisions in the future.

Multiple clinical trials are underway evaluating novel targeted therapies and immunotherapies in various settings. For example, the phase 3 NATALEE study is assessing the PD-L1 inhibitor Tecentriq following chemotherapy in high-risk early breast cancer. The OlympiA trial demonstrated a benefit for the antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) versus standard-of-care chemotherapy in HER2-low metastatic breast cancer. And the KEYNOTE-522 trial is evaluating pembrolizumab plus chemotherapy in triple-negative breast cancer.

In conclusion, while outcomes have improved dramatically, personalized approaches are needed to optimize results, prevent overtreatment, and improve cure rates in breast cancer. Biomarkers and selective use of novel therapies show promise in achieving these goals.

*Video synopsis is AI-generated and reviewed by Cancer Network editorial staff.