Receptor Status after Neoadjuvant Therapy of Breast Cancer: Significance and Implications

Abstract

Neoadjuvant chemotherapy (NACT) is now established in routine management of early breast cancer. Alterations in oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) following NACT are reported, with wide variation in results across series. In larger series, changes in ER status are identified in 5–23%, whilst changes in PR status are more frequent (14.5–67%). HER2 status changes less frequently with loss being more common than gain, and higher rates of change with immunohistochemistry are observed compared to in situ hybridization and following HER2-targeted therapy compared with chemotherapy alone. Triple negative is the most stable molecular subtype with combined ER, and HER2-positive cancers show the highest rate of change. Neoadjuvant endocrine therapy is used less commonly than NACT, and whilst loss of ER is rare, changes in PR status can occur in up to 40% of cases. There is relatively little published data on the impact of change in receptor status on survival outcomes. In patients whose tumours become ER or HER2 positive post-NACT, endocrine or anti-HER2 therapy can be initiated, although evidence from clinical trials is lacking. Most guidelines do not currently recommend routine retesting; however it should be considered in some circumstances.

Immunohistochemical Evaluation of Candidate Biomarkers for Fluorescence-Guided Surgery of Myxofibrosarcoma Using an Objective Scoring Method

“…All patients in our cohort had ≥50% stainable tumor cells (according to the EORTC-STBSG), which could explain why preoperative therapy did not significantly affect TEM-1, PDGFR-α, and VEGF-A expression [ 28 ]. From other types of cancer, such as breast and pancreatic cancer, we know that IHC staining patterns change after neoadjuvant therapy, but for TEM-1 in MFS, this remains largely unknown [ 38 , 39 ]. Although our analysis of the preoperative therapy effect did not have sufficient statistical power to draw conclusions, de Gooyer et al also state that preoperative radiotherapy did not significantly influence TEM-1 expression in MFS tissue [ 23 ].…”

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.…”

Preoperative considerations and benefits of neoadjuvant chemotherapy: insights from a 12-year review of the Hong Kong Breast Cancer Registry

“…Neoadjuvant chemotherapy can cause changes in ER, PR, and HER2 statuses, as well as the Ki-67 level, in patients with invasive breast cancer. 26,27 A possible explanation for this phenomenon is that chemosensitive cancer cells are destroyed by chemotherapy, whereas chemoresistant cells survive; such a change could alter the receptor status. Furthermore, because ER, PR, and HER2 are highly interdependent, a change in one receptor could lead to changes in the other receptors.…”