Factors Influencing HER2 Discordance in Nonmetastatic Breast Cancer and The Role of Neoadjuvant Therapy

Abstract

Objective: The rates of and the factors influencing HER2 discordance in patients receiving neoadjuvant therapy for breast cancer are investigated. Methods: This study retrospectively examines the rates of HER2 and hormone receptor discordance between the biopsy and postoperative resection specimens of 400 female early-stage breast cancer patients. Results: One hundred and thirty-three (33.3%) patients had received neoadjuvant therapy. The rate of HER2 discordance between biopsy and resection specimens was 1.7% in the control group and 5.3% in the neoadjuvant therapy group (p = 0.018). The rate of HER2 discordance was higher in younger patients and in patients with T1 tumors in the neoadjuvant therapy group. Conclusion: Neoadjuvant therapy, age <40 years and smaller tumor size were independent risk factors for HER2 discordance.

Incidence and prognostic impact of HER2‐positivity loss after dual HER2‐directed neoadjuvant therapy for HER2+ breast cancer

“…Several studies that have investigated the impact of neoadjuvant HER2‐targeted treatment with trastuzumab alone plus chemotherapy report a HER2 discordance rate ranging from 7% to 43% from the time of core biopsy to surgery 7–19 . However, there are few studies that report the discordance rate after neoadjuvant dual HER2‐targeted treatment plus chemotherapy, the current standard‐of‐care.…”

“…Nevertheless, it appears that clinically meaningful differences in IDFS were not observed for patients with HER2 concordant disease and HER2 discordant disease after neoadjuvant treatment. Previous studies are inconsistent regarding whether the loss of HER2 amplification after neoadjuvant treatment is associated with worse outcomes 7–9,11–15,17–20 . For example, Branco et al report the 5‐year IDFS and 5‐year OS of patients who retained HER2 amplification after neoadjuvant treatment is 70% and 84%, respectively, and 21% and 50% for patients whose residual tumors lost HER2 amplification ( p = 0.02 and p < 0.001) 8 .…”

“…Several studies that have investigated the impact of neoadjuvant HER2‐targeted treatment with trastuzumab alone plus chemotherapy report a HER2 discordance rate ranging from 7% to 43% from the time of core biopsy to surgery. 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 However, there are few studies that report the discordance rate after neoadjuvant dual HER2‐targeted treatment plus chemotherapy, the current standard‐of‐care. In one retrospective analysis of 130 patients treated with neoadjuvant dual HER2‐targeted therapy plus chemotherapy, Ferraro et al reported a HER2 discordance rate of 52%, although only 25 patients were eligible for analysis.…”

“…Previous studies are inconsistent regarding whether the loss of HER2 amplification after neoadjuvant treatment is associated with worse outcomes. 7 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 For example, Branco et al report the 5‐year IDFS and 5‐year OS of patients who retained HER2 amplification after neoadjuvant treatment is 70% and 84%, respectively, and 21% and 50% for patients whose residual tumors lost HER2 amplification ( p = 0.02 and p < 0.001). 8 In contrast, Wetzel et al found no difference in 5‐year recurrence‐free survival and OS for patients with HER2‐positive residual disease compared to patients with HER2‐negative residual disease.…”

“…Studies have shown that the incidence of HER2 discordance after neoadjuvant trastuzumab with chemotherapy ranges from 7% to 47%, but evidence is mixed regarding whether the loss of HER2‐positivity after neoadjuvant systemic treatment impacts disease‐free recurrence and survival. 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 The impact of HER2‐positivity loss with neoadjuvant dual HER2‐targeted therapy with chemotherapy, the current standard‐of‐care, is not well described.…”