Neoadjuvant Therapy for Breast Cancer as a Model for Translational Research

Abstract

Neoadjuvant therapy, where patients receive systemic therapy before surgical removal of the tumour, can downstage tumours allowing breast-conserving surgery, rather than mastectomy. In addition to its impact on surgery, the neoadjuvant setting offers a valuable opportunity to monitor individual tumour response. The effectiveness of standard and/or potential new therapies can be tested in the neoadjuvant pre-surgical setting. It can potentially help to identify markers differentiating patients that will potentially benefit from continuing with the same or a different adjuvant treatment enabling personalised treatment. Characterising the molecular response to treatment over time can more accurately identify the significant differences between baseline samples that would not be identified without post-treatment samples. In this review, we discuss the potential and challenges of using the neoadjuvant setting in translational breast cancer research, considering the implications for improving our understanding of response to treatment, predicting therapy benefit, modelling breast cancer dormancy, and the development of drug resistance.

Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκβ interplay

“…Proper staging is critical for determining the appropriate clinical treatment course and surgical planning. Neoadjuvant therapies, where patients receive systemic therapy before surgical removal of the tumor, can downstage tumors allowing breast-conserving surgery, rather than mastectomy [91,95]. The effectiveness of standard and/or potential new therapies can be tested in the neoadjuvant pre-surgical setting [91].…”

“…The effectiveness of standard and/or potential new therapies can be tested in the neoadjuvant pre-surgical setting [91]. It can potentially help to identify markers differentiating patients that will potentially benefit from continuing with the same or a different adjuvant treatment enabling personalised treatment [95].…”

Effect of COL4A1 Expression on the Survival of Neoadjuvant Chemotherapy Breast Cancer Patients

“…e varying roles of the different regimens used as neoadjuvant chemotherapy need to be investigated, as it is currently unclear which treatment regimen suits best [14]. Prior to the surgical removal of the tumors, patients receive neoadjuvant chemotherapy and can downstage tumors allowing breast-conserving surgery, rather than mastectomy and setting offers a valuable opportunity to monitor individual tumor response [15]. Prior to the surgical removal of the tumors, patients receive neoadjuvant chemotherapy, can downstage tumors allowing breast-conserving surgery, rather than mastectomy and setting which offers a valuable opportunity to monitor individual tumor response [15].…”

“…Prior to the surgical removal of the tumors, patients receive neoadjuvant chemotherapy and can downstage tumors allowing breast-conserving surgery, rather than mastectomy and setting offers a valuable opportunity to monitor individual tumor response [15]. Prior to the surgical removal of the tumors, patients receive neoadjuvant chemotherapy, can downstage tumors allowing breast-conserving surgery, rather than mastectomy and setting which offers a valuable opportunity to monitor individual tumor response [15]. In 42 patients who received neoadjuvant chemotherapy, the expression level of COL4A1 in the tumor, as assessed by immunohistochemistry, was not associated with age (Table 2), but was highly positively correlated with stage status (P � 0.046).…”

Genomic and Expression Analyses Define MUC17 and PCNX1 as Predictors of Chemotherapy Response in Breast Cancer

“…Neoadjuvant chemotherapy (NAC) also provides a powerful research opportunity since matched primary tumour samples from before (diagnostic biopsies) and after therapy (resections) may be available. With respect to chemotherapy response, a relevant hypothesis is that tumour cells that remain post-NAC have characteristics associated with therapy resistance, while characteristics lost from tumour cells in the matched pre-NAC sample are associated with sensitivity; therefore, comparative analysis of these matched samples can give insights into both resistance and sensitivity (11). Based on this hypothesis, investigators have examined expression pre-NAC and post-NAC and identified individual molecules such as bFGF (12), families of molecules such as xenobiotic drug pumps (13), or pathway-level gene expression changes (14) that were associated with relative resistance.…”