Perioperative HER2 targeted treatment in early stage HER2-positive breast cancer

Abstract

Although human epidermal growth factor receptor 2 (HER2)-positive breast cancer was associated with poor prognosis, it has been changed after the development of trastuzumab. There has been great progress in perioperative HER2-targeting treatment, and investigations of several novel drugs and their combinations are ongoing. Adjuvant trastuzumab with or without pertuzumab for 1 year in combination with concomitant chemotherapy has become a standard treatment in high-risk node-negative tumors or node-positive HER2-positive early breast cancer patients without residual disease or who have not received neoadjuvant treatment. For low-risk HER2-positive early breast cancer patients, adjuvant paclitaxel and 1-year trastuzumab are possible alternatives. For residual disease after neoadjuvant treatment, adjuvant trastuzumab emtansine (T-DM1) for 14 cycles is a standard treatment. Non-anthracycline chemotherapy with dual anti-HER2 targeting of trastuzumab and pertuzumab represents one of the preferred neoadjuvant regimens to achieve higher pathologic complete response (pCR) rates and better clinical outcomes. Further research is needed to develop and validate potential biomarkers to predict pCR, which could help escalate or de-escalate anti-HER2 therapy. Trials incorporating novel agents such as T-DM1, trastuzumab deruxtecan (T-DXd), and immune checkpoint inhibitors and trying to de-escalate treatments in neoadjuvant setting are ongoing. In the future, tailored treatments such as no adjuvant therapy, various HER2-directed therapies alone with chemotherapy, combinations of various HER2-directed therapies and chemotherapy, addition of immune checkpoint inhibitors, and omission of surgery will be individualized in HER2-positive early breast cancer patients.

Smart drug delivery systems to overcome drug resistance in cancer immunotherapy

“…Further, cancer cells become resistant to topoisomerase II through a variety of mechanisms 33 due to mutations in the topoisomerase II gene. In addition, human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor of the EGFR family, is overexpressed in 30% of patients with breast cancer, and resistance can develop following long-term use of inhibitors targeting this receptor 34 .…”

Somatic mutations in a multigene panel and impact on prognosis based on TP53 status in Chinese HER2‐positive patients undergoing neoadjuvant therapy: A single‐institution retrospective cohort

“…Neoadjuvant therapy (NAT) has become a standard clinical practice used to downsize the tumor and increase the breast‐conserving surgery rate 4 . The addition of herceptin on top of chemotherapy increased the pathological complete response (pCR) rate to 38%, 5 and after intervention with both herceptin and pertuzumab, the pCR rate increased to approximately 70% 6 . However, 30%–60% of patients with early HER2‐positive BC cannot achieve pCR after NAT.…”

“… 4 The addition of herceptin on top of chemotherapy increased the pathological complete response (pCR) rate to 38%, 5 and after intervention with both herceptin and pertuzumab, the pCR rate increased to approximately 70%. 6 However, 30%–60% of patients with early HER2‐positive BC cannot achieve pCR after NAT. More biomarkers to predict efficacy and more therapeutic targets are needed.…”