Impact on survival of estrogen receptor, progesterone receptor and Ki-67 expression discordance pre- and post-neoadjuvant chemotherapy in breast cancer.

Yuqin Ding,Dehong Zou,Wenju Mo,Fanrong Zhang,Xiangming He,Chengdong Qin,Yurong Zheng,Xiaowen Ding,Hongjian Yang,Hongdan Qian,Kaijing Ding,Xingfei Yu,William B Coleman

doi:10.1371/journal.pone.0231895

Abstract

PurposeTo investigate whether estrogen receptor (ER), progesterone receptor (PR) and Ki-67 expression discordance before and after neoadjuvant chemotherapy (NAC) correlates with prognosis and treatment of breast cancer patients.MethodsThe study cohort included 482 breast cancer patients at the Zhejiang Cancer Hospital from January 1, 2008, to December 31, 2018. Core needle biopsies and excised tissue biopsies pre- and post-NAC were obtained. Immunohistochemistry was used to determine ER, PR and Ki-67 status. The relationship between biomarker discordance before and after NAC and clinicopathological features was compared retrospectively.ResultsER (n = 482), PR (n = 482) and Ki-67 (n = 448) expression was assessed in the same lesion pre- and post-NAC. Discordance in the three markers pre- and post-NAC was observed in 50 (10.4%), 82 (17.0%) and 373 (77.4%) cases, respectively. Positive-to-negative PR expression changes were the most common type of discordance observed. The risk of death in patients with a PR positive-to-negative conversion was 6.58 times greater than for patients with stable PR expression. The risk of death in patients with increased Ki-67 expression following NAC treatment was 2.05 times greater than for patients with stable Ki-67 expression.ConclusionBreast cancer patients showed changes in ER, PR and/or Ki-67 status throughout NAC, and these changes possibly influenced disease-free survival and overall survival. A switch to negative hormone receptor expression with increased Ki-67 expression following NAC could be indicators of a worse prognosis. Biomarker expression investigations following NAC may potentially improve patient management and survival.

Highlights

Neoadjuvant chemotherapy (NAC) is increasingly used for breast cancer treatment, neoadjuvant endocrine therapy is administered based on the presence of biomarkers such as estrogen receptor (ER), progesterone receptor (PR) and Ki-67 [1]
ER (n = 482), PR (n = 482) and Ki-67 (n = 448) expression was assessed in the same lesion pre- and post-neoadjuvant chemotherapy (NAC)
1194 patients were initially identified for inclusion in the study, we excluded patients who were unevaluable for immunohistochemical (IHC) analyses, who had another primary cancer or bilateral primary breast cancer at the time of initial diagnosis

Summary

Introduction

Neoadjuvant chemotherapy (NAC) is increasingly used for breast cancer treatment, neoadjuvant endocrine therapy is administered based on the presence of biomarkers such as estrogen receptor (ER), progesterone receptor (PR) and Ki-67 [1]. Endocrine therapy often provides a benefit to patients with ER-positive and/or PR-positive hormonedependent breast cancer [4, 5]. Several small studies have revealed a lack of stability of HR and/or Ki-67 biomarker expression during tumor progression in breast cancer [4, 6, 7]. It is currently unknown how NAC modulates these biomarkers. If therapy-predictive biomarkers change throughout NAC, investigating biomarker expression in lesions before and after NAC could provide additional important information that could improve patient treatment management

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Conclusion