Abstract

Objective::To investigate the level of three drug resistance proteins; P-glycoprotein 1 (P-gp), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and aldehyde dehydrogenase isoform 1 (ALDH1) expression and their relationship to metastasis, recurrence and survival in advanced breast cancer patients that received neoadjuvant chemotherapy.Methods:This study is a combination of prospective and retrospective cohort study involving one hundred and thirty one cases of advanced stage invasive breast cancer that have received neoadjuvant chemotherapy. Initial biopsy specimens (incisional biopsy or core biopsy) were taken from paraffin blocks. Immunohistochemistry (IHC) was used to detect P-gp, NF-κB, and ALDH1 expression. Prospectively analysed patients were followed for five years and evaluated for recurrence and death.Results:The expression of P-gp has no significant statistical correlation to metastases (p = 0.659), recurrence (p = 0.862) and survival (p = 0.835) in advanced stage breast cancer patients who received neoadjuvant chemotherapy. Similarly, ALDH1 was not correlated to metastases (p=0.120), recurrence (p = 0.186) and survival (p = 0.254) statistically. We found that NF-κB expression showed a significant correlation to metastases (p=0.004), recurrence (p = 0.016) and overall survival (p = 0.041) in advanced stage breast cancer patients after neoadjuvant chemotherapy.Conclusion:NF-κB expression is a potential marker that can be used to assess or to predict increasing risk of metastases, recurrence and survival in advanced stage breast cancer patients who receive neoadjuvant chemotherapy.

Highlights

  • GLOBOCAN data issued by the International Agency for Research on Cancer World Health Organization showed that the incidence of new breast cancer in Indonesia were 48.998 cases (16.4 %) (GLOBOCAN, 2012)

  • We found that NF-κB expression showed a significant correlation to metastases (p=0.004), recurrence (p = 0.016) and overall survival (p = 0.041) in advanced stage breast cancer patients after neoadjuvant chemotherapy

  • This study investigated all three components: P-glycoprotein (P-gp), which is part of ABC transporter, expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) that plays a role in the regulation of apoptosis and aldehyde dehydrogenase isoform 1 (ALDH1) which a functional marker of cancer stem/progenitor cells as critical components related to breast cancer metastases, recurrence and patient survival

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Summary

Introduction

GLOBOCAN data issued by the International Agency for Research on Cancer World Health Organization showed that the incidence of new breast cancer in Indonesia were 48.998 cases (16.4 %) (GLOBOCAN, 2012). Estimation for absolute number of breast cancer cases was 61.682. The domestic health survey by the Ministry of Health showed that the death rate for breast cancer is increasing, from 1.4% in 1972, 3.4% in 1980, 4.3% in 1986 and to 4.4% in 1992. The prevalence of locally advanced breast cancer in Indonesia is estimated to be higher than neighbouring countries. There are limited data describe the prevalence and outcome of locally advanced breast cancer. Ramli (2015) found that from all cases of local advanced stage breast cancer, 23% were operable stage IIIA and 40% were inoperable stage IIIB There are limited data describe the prevalence and outcome of locally advanced breast cancer. Ramli (2015) found that from all cases of local advanced stage breast cancer, 23% were operable stage IIIA and 40% were inoperable stage IIIB

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