PEOPLE WITH EARLY-STAGE HER2-positive breast cancer often start treatment with a combination of chemotherapy and HER2-targeted therapies, such as Herceptin (trastuzumab), before having surgery to remove any signs of cancer. Using treatments before surgery is an approach known as neoadjuvant therapy. After surgery, patients typically continue taking Herceptin to reduce the chance that cancer will come back or grow.  

Now, a final analysis of the KATHER INE study, published Jan. 15, 2025, in the New England Journal of Medi cine, confirms that people who have signs of cancer after neoadjuvant treatment can benefit from Kadcyla (trastuzumab emtansine, or T-DM1) instead of Herceptin. Kadcyla is an antibody-drug conjugate that links chemotherapy with an antibody that binds to HER2 proteins on cancer cells to deliver chemotherapy directly to the cancer. 

The study included 1,486 participants with HER2-positive breast cancer who received neoadjuvant therapy but had evidence of disease in their breast or lymph nodes in the surgically removed tissue. Of the patients who received Kadcyla after surgery, 80.8% were alive and free of disease after seven years, compared with 67.1% in the group that was treated with Herceptin after surgery. In addition, the overall survival after seven years was 89.1% with Kadcyla, compared with 84.4% in the Herceptin group.  

People have a higher risk for recurrence if neoadjuvant HER2-directed therapy and chemotherapy do not eliminate invasive cancer in the breast and axillary lymph nodes at surgery, says Charles E. Geyer Jr., a medical oncologist at UPMC Hillman Cancer Center in Pittsburgh and the study’s corresponding author. These most recent findings confirm the long-term benefit of Kadcyla, building on the results from an earlier 2018 primary analysis that established Kadcyla as the standard of care for these high-risk patients, Geyer says.  

“If all the cancer is gone after surgery, also known as a complete pathologic response, the risk of recurrence is low, and trastuzumab [Herceptin] is continued to complete a year of therapy because it worked well in the individual patients,” Geyer says. “If invasive cancer is present, trastuzumab didn’t work optimally, so a switch is made to T-DM1 [Kadcyla].”  

These findings demonstrate that treatment escalation with Kadcyla for patients at high risk of recurrence can improve survival, says Virginia Kaklamani, a medical oncologist at the Mays Cancer Center at UT Health in San Antonio who was not involved in the study. People who took Kadcyla experienced more side effects than those who took Herceptin. Many patients who experienced neuropathy—characterized by numbness and pain in the arms or legs—during earlier chemotherapy treatment often experience this same side effect while taking Kadcyla, Kaklamani says.  

“This can be an issue since patients may have neuropathy from the previous chemotherapy they have received,” Kakla mani says. “However, the majority of patients receiving T-DM1 [Kadcyla] in this setting can complete their treatment.” 

Other clinical trials are exploring whether different treatments, including another antibody-drug conjugate called Enhertu (trastuzumab deruxtecan) that has shown promise in controlling brain metastases in metastatic disease, might also be effective in extending survival after surgery in HER2-positive breast cancer. Whether or not this drug or others could further improve outcomes “is an important question being addressed” in those trials, Geyer says.