Biomarker Alteration after Neoadjuvant Endocrine Therapy or Chemotherapy in Estrogen Receptor-Positive Breast Cancer

Abstract

In estrogen receptor (ER)-positive breast cancer, changes in biomarker expression after neoadjuvant therapy indicate the therapeutic response and are prognostic. However, there is limited information about the biomarker alteration caused by neoadjuvant endocrine therapy in ER-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. We recruited ER-positive/HER2-negative breast cancer patients who received neoadjuvant chemotherapy (NCT), neoadjuvant endocrine therapy (NET), or sequential neoadjuvant endocrine-chemotherapy (NECT) at Peking University Cancer Hospital from 2015 to 2021. A total of 579 patients had paired immunohistochemistry information in both diagnostic biopsy samples and post-neoadjuvant therapy surgical samples. Through a paired comparison of the immunohistochemical information in pre-treatment and post-treatment samples, we found that progesterone receptor (PR) expression reductions were more frequent than ER expression reductions (70.8% vs. 35.2%) after neoadjuvant therapy. The percentage of patients who had a decreased Ki-67 index in the post-operative samples was similar in the three groups (79.8% vs. 79.7% vs. 78.4%). Moreover, PR losses caused by NET were related to low baseline PR expression (p = 0.001), while we did not find a significant association between PR losses and Ki-67 reductions (p = 0.428) or ER losses (p = 0.274). All three types of neoadjuvant therapies caused a reduction in ER, PR, and Ki-67 expression. In conclusion, we found that PR loss after NET was only significantly related to low baseline PR expression, and there is no significant difference in the extent of prognostic factor change including Ki-67 and ER between the PR loss and non-loss groups.

Morphological and molecular changes of oestrogen receptor‐positive breast cancer following bridging endocrine therapy: a United Kingdom multicentre study

“…AIs therefore had a significant suppressive effect on PR expression. A reduction in PR expression following standard endocrine therapy was previously reported, 8,27 and might imply resistance to endocrine treatment. Ohara et al showed that PR-negative status was independently associated with shorter survival following AIs adjuvant therapy.…”

Nomograms for Predicting Disease-Free Survival Based on Core Needle Biopsy and Surgical Specimens in Female Breast Cancer Patients with Non-Pathological Complete Response to Neoadjuvant Chemotherapy

“…Alterations in ER, PR, HER2, Ki67, and p53 have been reported following NAC treatment, with widely varying results from series to series [ 18 , 19 , 21 , 35 , 36 ]. Considering that these biomarkers may change after NAC, we included ER, PR, HER2, Ki67, and p53 both before and after treatment in the pre-NAC and post-NAC multivariate analysis, respectively.…”

“…The purpose of this study was to fill this research gap by developing and evaluating novel nomograms for predicting disease-free survival (DFS) based on core needle biopsy and surgical specimens in female BC patients with a non-pCR to NAC. A biopsy at diagnosis and post-NAC residual tumors in patients without a pCR can show discrepancies in receptor status (from negative to positive or vice versa) and changes in biomarker expression [ 18 , 19 ]. Discordances in ER, PR, HER2, Ki67, and p53 can indicate chemosensitivity or chemoresistance as well as have clinical implications for the prognosis and adjuvant therapy [ 18 , 20 , 21 , 22 ].…”

Changing the phenotype of breast cancer in the process treatment: literature review

“…Сообщалось, что первичная химиотерапия преимущественно убивает недифференцированные РЭ / РПотрицательные или HER2-положительные [16] опухолевые клетки, таким образом, в значительной степени оставляя РЭ / РП-положительные или HER2-отрицательные опухолевые клетки.…”