Dr Tripathy on the HER2+ Breast Cancer Treatment Paradigm

Debu Tripathy, MD, professor, chairman, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the current state of the HER2-positive breast cancer treatment paradigm.

Treatment approaches for patients with HER2-positive breast cancer vary depending on the disease’s clinical stage at presentation, Tripathy begins. Initially, patients are assessed to determine their clinical stage based on tumor size and lymph node involvement through imaging, according to Tripathy. For patients diagnosed with clinical stage I disease, a de-escalated treatment strategy is typically employed to minimize toxicity, he explains. The phase 2 APT trial (NCT00542451) demonstrated notable disease control rates with adjuvant paclitaxel plus trastuzumab (Herceptin) in patients with clinical stage I breast cancer, Tripathy emphasizes. Upon confirmation of stage I disease post-surgery, these patients received de-escalated therapy consisting of 12 weeks of weekly paclitaxel combined with trastuzumab, followed by a full year of trastuzumab, Tripathy states. If the tumor was hormone receptor (HR)–positive, endocrine therapy was also administered concurrently, Tripathy says. This tailored approach allows for effective treatment and minimizes the use of more aggressive therapies, Tripathy notes.

Conversely, patients with disease beyond clinical stage I are candidates for neoadjuvant therapy, he continues. This treatment approach aims to shrink the tumor, potentially enabling less extensive surgery with a higher likelihood of breast preservation and reduced lymph node involvement, Tripathy elucidates, adding that neoadjuvant regimens often involve more intensive treatments, such as taxane-based chemotherapy combined with dual antibody therapy.

Furthermore, some oncologists opt for neoadjuvant platinum-based chemotherapy in addition to taxanes and dual antibody therapy, he expands. The role of platinum agents in the neoadjuvant setting remains somewhat unclear due to the lack of definitive randomized trials, according to Tripathy. Notably, the achievement of a pathologic complete response (pCR) to frontline therapy plays a critical role in subsequent treatment decisions, Tripathy says. Patients who achieve pCR in both the primary tumor and lymph nodes continue dual antibody therapy for 1 year alongside endocrine therapy for HR-positive cases, Tripathy notes. In contrast, patients who do not achieve pCR may undergo treatment with ado-trastuzumab emtansine (Kadcyla) administered over 14 cycles every 3 weeks to complete the year of therapy, he concludes.