Study of markers of biogenesis and response to therapy in inflammatory and locally advanced breast cancer

Danial, Irini (2023). Study of markers of biogenesis and response to therapy in inflammatory and locally advanced breast cancer. University of Birmingham. M.Sc.

Preview

Danial2023MScByRes.pdf
Text - Accepted Version
Available under License All rights reserved.
Download (992kB) | Preview

Abstract

Background: One of the subtypes of locally advanced breast cancer (LABC), known as inflammatory breast cancer (IBC), is considered rare but profoundly aggressive. Traditionally, this disease was consistently fatal; nevertheless, with the induction of chemotherapy and carefully coordinated multimodality treatment, the prognosis of the patients has enhanced.

The study aims to examine the feasibility of predicting response to neoadjuvant chemotherapy by studying the expression of specific molecular markers CD151, CD68, and CD3 in IBC and LABC in clinical tissue samples and correlates the expression of these markers with disease-free survival and overall survival rate.

Method: Patients diagnosed with breast cancer regardless of the type were identified from the oncology database in the duration from January 2006 to December 2015. We also collaborated with other hospitals in the UK and outside the UK, e.g. Japan, to get reasonable IBC cases to conduct the study. Only patients who were treated primarily with neoadjuvant chemotherapy (NACT) 6-months prior to the surgery were included in this study.

Patients were divided into three groups based on the type of cancer. Group 1; included patients with locally advanced breast cancer, group 2; included patients with inflammatory breast cancer, and group 3; included the rest of the patients (neither IBC nor LABC). In our study, we focused on group 1 and group 2, aiming to predict the response of neoadjuvant chemotherapy by studying the expression of two tumour microenvironment markers: CD3 and CD68 and one marker of tetraspanins family CD151.

Statistical analyses were used to determine if the expression of the markers (CD151, CD3, and CD68) show a significant association with overall and disease-free survival, as well as response to neoadjuvant chemotherapy and other factors. Results: From 2006 to 2015, there were 1347 patients reviewed, with a mean age of 54.5 years (range 28 to 81 years). There were 327 patients that met the inclusion criteria. The total number of final cohorts was comprised of 301 cases. Group 1; patients with a diagnosis of locally advanced breast cancer (LABCs), included 43 patients. Group 2; patients with a diagnosis of inflammatory breast cancer (IBCs), included 96 patients. Group 3, patients were neither IBC nor LABC included 162 patients, but this group was excluded from this study. In locally advanced breast cancer (group1), statistically significant findings showed a higher percentage of CD3 that was associated with complete pathological response, increased Disease-Free Survival (DFS), and HER2 positive subtype. In addition, a significant association between complete pathological response and HER2 subtype tumour was noted. On the other hand, inflammatory breast cancer (group 2) showed some potential association between increased Overall Survival (OS), complete pathological response to chemotherapy, and increased expression of CD3.

In locally advanced breast cancer (group 1), although a higher percentage of CD68 was significantly associated with a higher grade of cancer, it was noted in inflammatory breast cancer (group 2) that a higher percentage of CD68 was correlated with a better response to NACT. Also, in group 1, a significant correlation was noted between histological tumour type and response to NACT. Furthermore, invasive ductal carcinoma including (NST and micro-papillary) had a better response to neoadjuvant chemotherapy than invasive lobular carcinoma. Also, in-group 1, significant alteration in receptor markers after treatment with neoadjuvant chemotherapy was noted, thus crucially altering potential adjuvant therapy. In inflammatory breast cancer (group 2), there was a correlation with a significant value between complete pathological response and over-expression of CD151 and overall survival. In addition, there was a significant correlation between the patient's age and over-expression of CD151 and CD3 as women >50 years were found to have a higher expression of both markers compared to women <50 years.

The greater nodal burden was significantly associated with poor response to NACT and greater nodal metastasis, which was inversely correlated with HER2 positive subtype tumour in both locally advanced breast cancer and inflammatory breast cancer.

Conclusions: Identifying reliable predictive prognostic markers for the outcome is essential to developing our understanding of IBC and LABC which will improve treatment outcomes. Nevertheless, identifying reliable, informative, and uniform endpoints is a crucial first step to increasing confidence in the value of neoadjuvant chemotherapy.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):