Molecular biomarker discordances of breast cancer before and after neoadjuvant chemotherapy: Are they related to neoadjuvant chemotherapy or intratumoral heterogeneity and is there any clinical significance?

Autor: Cengiz Yilmaz, Demet Kocatepe Cavdar
Rok vydání: 2022
DOI: 10.21203/rs.3.rs-1515575/v1
Popis: PURPOSE: To investigate the frequency, clinical significance, and causes of molecular discordances between tru-cut biopsy and residual tumor in patients with breast cancer who received neoadjuvant chemotherapy (NACTx). METHODS: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) statuses; hormone expression levels; Ki-67 index; and tumor grade in tru-cut biopsy before NACTx and in the residual tumor after NACTx were evaluated and compared using the Wilcoxon signed-rank test.RESULTS: The study included 102 women. Histopathologically, approximately 70% of the patients were partially responsive and 30% were unresponsive. The concordance and discordance rates between tru-cut biopsy and residual tumor were 95.1% vs. 4.9% (p = 0.180) for ER, 97.1% vs. 2.9% (p = 0.083) for PR, and 89.2% vs. 10.8% (p = 0.763) for HER2. Following NACTx, 15% of hormone receptor (HR)-negative patients and 5.7% of HER2(−) patients became positive, requiring adjuvant treatment. In particular, 18% of triple-negative patients became HR(+) and 12% became HER2(+). HER2 loss was detected in 40% HER2(+) patients. Ki-67 and PR expression significantly decreased in pathologically responsive patients (p = 0.001 and p = 0.004) and tumor grade increased in pathologically unresponsive patients (p = 0.034).CONCLUSION: NACTx alone cannot explain receptor discordance observed in breast cancers. HER2 loss and decreased PR expression levels are mainly associated with NACTx; whereas the receptor status turning positive, which has clinical significance for adjuvant treatment, is primarily associated with intratumoral heterogeneity. Therefore, immunohistochemical re-staining for biomarkers should be performed in residual tumors.
Databáze: OpenAIRE