Personalizing Breast Cancer Neoadjuvant and Adjuvant HER2-Targeted Therapy
Debu Tripathy, MD, University of Texas, MD Anderson Cancer Center at Houston, discussed the basic requirements of personalizing therapy.
Understanding breast cancer, which patients may be more vulnerable to long-term effects, and who benefits the most are just some of the ways oncologists can design the best personalized neoadjuvant and adjuvant human epirdermal growth factor receptor 2 (HER2)-targeted therapy, according to a session at the virtual 38th Annual Miami Breast Cancer Conference® (MBCC).
Debu Tripathy, MD, University of Texas, MD Anderson Cancer Center at Houston, discussed the basic requirements of personalizing therapy, which includes:
- Knowledge of the natural history of the disease.
- Known effective therapies, or differential impact of several therapy options.
- Characterized toxicities, including vulnerable populations and risk factors.
- Clinical or biomarker factors that predict benefit.
- Risk-adapted or biomarker-adapted trials that demonstrate differential benefits and safety.
Tripathy mentioned how trials can help inform new standards that allow for de-escalation or escalation from the beginning or in “real time” of the patient’s course of treatment.
“We can design a single-arm trial with a statistical plan,” Tripathy said. “If we see a good enough outcome, we might be able to adopt them into our practice.”
Specifically, Tripathy noted the differences in adaptive therapy and the escalation and de-escalation in HER2-positive early-stage breast cancer. When adjuvant and node negative, there is T1/smaller T2 or paclitaxel plus trastuzumab used, or TCH is considered for larger node-negative. When it is node positive, one should consider chemotherapy with trastuzumab plus pertuzumab, Tripathy said.
Further, neoadjuvant is the best for T2-positive/N1-positive, according to Tripathy, which involves chemotherapy with trastuzumab plus pertuzumab. Following this, surgery is considered and PCR (trastuzumab +/- pertuzumab) versus no PCR (TDM-1 every 3 weeks x 14) is looked at. For a higher risk (hormone-receptor-positive), neratinib should be considered.
Tripathy also discussed the physiology of trastuzumab-related cardiac dysfunction. Trastuzumab is an antibody that targets HER2 proteins, and since HER2 is expressed at low levels on adult myocytes, it can lead to a stress-induced progressive wall dilatation, which is thinning and decreased contractility, according to Tripathy. In a cultured mytocyte, the myopathic changes from trastuzumab and other HER2 being absent and can be reversed with neuregulin 2b.
Tripathy D. Personalizing Neoadjuvant and Adjuvant HER2-Targeted Therapy. Virtual 38th Annual Miami Breast Cancer Conference®. Accessed March 5, 2021.