Dr Tolaney on Standard Frontline Treatment Approaches in HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, associate director, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute; associate professor, medicine, Harvard Medical School, discusses standard-of-care frontline treatment approaches for patients with HER2-positive breast cancer.

When patients are initially diagnosed with HER2-positive breast cancer, their oncologists’ first goal should be to determine the size of the tumor and whether lymph nodes are clinically involved, Tolaney begins. Patients with tumors smaller than 2 cm and no lymph node involvement typically undergo upfront surgery, she says. Patients with stage I or II disease have the option to instead receive paclitaxel plus trastuzumab (Herceptin) or ado-trastuzumab emtansine (T-DM1; Kadcyla), Tolaney explains.

However, patients with tumors greater than 2 cm or lymph node involvement should receive neoadjuvant therapy, Tolaney emphasizes. This preoperative therapy typically consists of 6 cycles of docetaxel plus carboplatin, trastuzumab, and pertuzumab (Perjeta; TCHP) or TCHP plus anthracyclines, although Tolaney notes that most oncologists have stopped using anthracyclines. 

At the time of surgery, patients are assessed for response to neoadjuvant therapy, she adds. In the adjuvant setting, patients with residual disease usually receive 14 doses of T-DM1, whereas those who achieve a pathologic complete response typically continue to receive the HER2-directed therapy they received in the neoadjuvant setting to complete 1 year of therapy, Tolaney reports. All frontline treatment decisions account for patients’ initial clinical anatomic risk profiles, she concludes.

In 2019, T-DM1 was approved by the FDA in the adjuvant setting for the treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant treatment with trastuzumab plus chemotherapy. In the pivotal phase 3 KATHERINE trial (NCT01772472), T-DM1 reduced the risk of invasive breast cancer recurrence or death from any cause by 50% compared with trastuzumab (HR, 0.50; 95% CI, 0.39-0.64; P < .0001).