CDK4/6 inhibitors have emerged as a game-changing treatment for hormone receptor-positive (HR+) breast cancer, significantly improving progression-free survival and overall survival when combined with endocrine therapy1. This combination is now the standard first-line treatment for both pre- and postmenopausal women. In the HER2-targeted therapy realm, trastuzumab deruxtecan (Enhertu) has been approved for HER2-positive secondary breast cancer, while datopotamab deruxtecan shows promise for HR+, HER2-low or negative breast cancer2. These advancements offer new hope for patients with specific breast cancer subtypes, potentially delaying the need for chemotherapy and improving quality of life.

Immunotherapy has emerged as a promising approach in breast cancer treatment, with checkpoint inhibitors leading the charge. Pembrolizumab (Keytruda) has been approved for certain patients with triple-negative breast cancer, particularly those with tumors larger than 2 centimeters1. This treatment is typically administered alongside neoadjuvant chemotherapy and then continued as monotherapy after surgery. Researchers are also exploring novel combinations to enhance the efficacy of checkpoint inhibitors. A notable example is a three-drug combination involving a histone deacetylase inhibitor and two checkpoint inhibitors, which has shown promising results in advanced HER2-negative breast cancer, with a 25% overall response rate and an impressive 40% response rate in triple-negative cases2.

Adding ribociclib to standard hormone therapy has shown significant benefits for patients with stage 2 or 3 HR-positive, HER2-negative early breast cancer. This combination reduced the risk of cancer recurrence by 25%, with three-year invasive disease-free survival rates of 90.4% compared to 87.1% for hormone therapy alone1. The treatment also improved distant disease-free and recurrence-free survival rates. These findings, presented at ASCO 2024, suggest that ribociclib plus endocrine therapy could become a new standard treatment option for a broader population of early-stage breast cancer patients1.

Significant progress has been made in treating metastatic breast cancer, with advances in this area accounting for nearly one-third of the decrease in annual breast cancer deaths from 1975 to 20191. For triple-negative breast cancer, researchers are developing novel therapies such as antibody-drug conjugates. One promising example is a tailored drug that links cetuximab, targeting the EGFR protein, with a CDK-blocking drug, potentially offering a more targeted approach with fewer side effects2. These advancements are particularly crucial for triple-negative breast cancer, which accounts for 15% of all diagnosed cases and is known for its aggressiveness and resistance to traditional therapies2.

Emerging treatments for metastatic breast cancer are showing promise in improving patient outcomes and quality of life. Antibody-drug conjugates, such as ado-trastuzumab emtansine (Kadcyla), trastuzumab deruxtecan (Enhertu), and sacituzumab govitecan (Trodelvy), are FDA-approved and target specific cancer cells by combining antibody therapy with chemotherapy1. Selective estrogen receptor degraders (SERDs) like fulvestrant (Faslodex) and elacestrant (Orserdu) are also approved for hormone receptor-positive metastatic breast cancers, with additional SERDs under study1. Advances in immunotherapy include a two-pronged approach that sensitizes the tumor microenvironment and activates T cells, showing potential in preclinical models to eliminate metastatic tumors and prevent recurrence4. Furthermore, the use of circulating tumor DNA and artificial intelligence in cancer imaging is being explored to diagnose metastatic disease earlier and guide treatment sequencing, potentially leading to more effective disease control and longer survival2.