Impact of hormone receptor, HER2, and Ki-67 status conversions on survival after neoadjuvant chemotherapy in breast cancer patients: a retrospective study

Abstract

Background: The discordance of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 cell nuclear proliferation antigen status in patients with locally advanced breast cancer pre-and post-neoadjuvant chemotherapy (NAC) is quite common. This study aimed to assess the frequency of changes in receptor status after NAC in patients with invasive ductal breast cancer and the prognostic impact of such changes. Methods:The study comprised 670 patients who were diagnosed with invasive ductal breast carcinoma and treated with both NAC and surgery from 2012-2017. Hormone receptor (HR; including ER and PR), HER2, and Ki-67 status was assessed before NAC and in residual invasive tumor cells of the surgical specimens. The prognostic impact of receptor conversions in breast cancer patients treated with NAC was evaluated in this retrospective study.Results: The conversion of ER was related to overall survival (OS; P=0.008) and disease-free survival (DFS; P=0.004). Patients whose ER status was always positive had the best prognosis, and those who were always negative had the worst prognosis. Similar results were also found for PR status, as the conversion of PR status was also related to OS (P<0.001) and DFS (P<0.001). At the same time, the conversion of Ki-67 status was related to OS (P=0.042) and DFS (P=0.037), and patients whose Ki-67 status was ≤20% persistently after NAC had the best survival among the 4 groups, while those whose Ki-67 status changed from ≤20% to >20% after NAC had the worst survival. Nevertheless, there was no statistical significance in the conversion of HER2 status. In multivariate Cox regression analyses, PR conversion and post-neoadjuvant pathological lymph node stage (ypN) were independent prognostic factors for DFS (P=0.008, <0.001) and OS (P=0.002, <0.001).Conclusions: Changes in receptor status between pre-treatment and residual disease after NAC are common. Moreover, these alterations have an impact on the survival outcome of invasive ductal breast cancer patients. Thus, receptor status should be re-evaluated routinely before and after NAC to guide individualized treatment.

Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions

“…To our knowledge, no prospective randomized trials have been performed addressing this issue. Although there is still no consensus or guideline indicating biomarkers routine retesting in residual tumors [23], we are in accordance with previous authors who recommend that biomarkers should be retested, especially in hormone receptors or HER2-negative cases, since these could represent false-negative results in the initial biopsy [1][2][3][4]7,10,20,21].…”

“…The changes in tumor pathological characteristics and biomarkers expression after neoadjuvant therapy are widely debated in the literature. They could directly affect decisions regarding adjuvant therapy [ 2 , 19 ].…”

“…Invasive breast carcinomas (IBC) treatment involves local control (surgery and radiotherapy), usually associated with systemic therapies, guided by tumor stage, histological characteristics and tumor biomarkers status, including hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]), human epidermal growth factor receptor 2 (HER2) and Ki67 status, which are assessed in all new breast cancer cases by immunohistochemical staining (IHC). These prognostic and predictive factors give information about clinical outcome and predict response to specific therapies, thus influence the best individual treatment decision [1][2][3].…”

“…Systemic therapies can be administered before (neoadjuvant) and/or after surgical resection (adjuvant). Neoadjuvant chemotherapy (NACT) is used as the initial treatment for patients with inoperable tumors, for operable tumors to downstage and allow more conservative surgical excisions (both in the breast and in the axilla), for early-stage tumors (especially triple-negative and HER2-positive), and in highly proliferative tumors, as they show better response to systemic therapy [1][2][3][4][5]. Information about response to neoadjuvant therapy response also allows adjuvant therapy decision.…”

“…In metastatic IBC, the American Society of Clinical Oncology and College of American Pathologists (ASCO/ CAP) guidelines recommend re-biopsy of breast cancer metastases to re-evaluate ER, PR, and HER2 status [9]. Although several authors have reported pathological changes in residual tumors, there is still no consensus if biomarkers should be retested in post-NACT samples and if these changes should be considered in the adjuvant setting [1][2][3][4]7,8,10].…”