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http://dx.doi.org/10.14456/apjcp.2016.219/APJCP.2016.17.8.4089

Predictive Value of the Pattern of β-Catenin Expression for Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients  

Elsamany, S (Oncology, King Abdullah Medical City)
Elemam, O (Oncology, King Abdullah Medical City)
Elmorsy, S (Pharmacology, Faculty of Medicine, Cairo University)
Alzahrani, A (Oncology, King Abdullah Medical City)
Abbas, MM (Pathology, King Abdullah Medical City)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.8, 2016 , pp. 4089-4093 More about this Journal
Abstract
Purpose: This study aimed to explore the association of ${\beta}-catenin$ expression pattern with pathological response after neoadjuvant chemotherapy in breast cancer (BC) patients. Materials and Methods: In this retrospective exploratory study, data for 50 BC patients who received neoadjuvant chemotherapy were recorded. ${\beta}-catenin$ expression in tumours was assessed using immunohistochemistry and classified as either membranous or cytoplasmic according to the pattern of staining. Distributions of different clinico-pathological parameters according to ${\beta}-catenin$ expression were assessed using the Chi-square test. Logistic regression analysis was used to assess any relation of the pattern of ${\beta}-catenin$ expression with the pathological response. Results: Cytoplasmic ${\beta}-catenin$ expression was detected in 34% of BCs. Among our cases, 52% were hormonal receptor (HR)-positive, 24% were HER2-positive, 74% were clinical stage III and 74% received both anthracycline and taxane-based chemotherapy. Patients with cytoplasmic expression were more commonly younger than 40 years at diagnosis (cytoplasmic, 41.2% vs. no cytoplasmic expression, 12.1%, p=0.03). By doing t-test, cytoplasmic ${\beta}-catenin$ expression was linked with a higher body mass index compared to membranous-only expression ($mean{\pm}SD$ $33.0{\pm}4.47$ vs. $29.6{\pm}6.01$, respectively, p=0.046). No significant associations were found between ${\beta}-catenin$ expression and other parameters such as HR and HER2 status, or clinical stage. Complete pathological response (pCR) rate was twice as great in patients with membranous expression but without statistical significance (membranous-only, 33.3% vs. cytoplasmic, 17.6%, OR= 2.3, 95% CI= 0.55-9.87, p=0.24). Conclusions: This study suggests that cytoplasmic ${\beta}-catenin$ expression may be linked with lower probability of achieving pCR after neoadjuvant chemotherapy. These data need to be validated in a larger cohort of patients.
Keywords
${\beta}-catenin$; breast cancer; neoadjuvant chemotherapy;
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1 Sinnberg T, Menzel M, Ewerth D, et al (2011). ${\beta}$-Catenin signaling increases during melanoma progression and promotes tumor cell survival and chemoresistance. PLoS ONE, 6, 23429.   DOI
2 van der Hage J, van de Velde C, Julien J, et al (2001). Preoperative chemotherapy in primary operable breast cancer: results from the european organization for research and treatment of cancer trial 10902. J Clin Oncol, 19, 4224-37.   DOI
3 Wong SC, Lo SF, Lee KC, et al (2002). Expression of frizzled related protein and Wnt-signalling molecules in invasive human breast tumours. J Pathol, 196, 145-53.   DOI
4 Xu WH, Liu ZB, Yang C, et al (2012). Expression of dickkopf-1 and beta-catenin related to the prognosis of breast cancer patients with triple negative phenotype. PLoS ONE, 7, 37624.   DOI
5 Bear H, Anderson S, Smith R, et al (2006). Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: national surgical adjuvant breast and bowel project protocol B-27. J Clin Oncol, 24, 2019-27.   DOI
6 Bertolo C, Guerrero D, Vicente F, et al (2008). Differences and molecular immunohistochemical parameters in the subtypes of infiltrating ductal breast cancer. Am J Clin Pathol, 130, 414-24.   DOI
7 Chung GG, Zerkowski MP, Ocal IT, et al (2004). beta-Catenin and p53 analyses of a breast carcinoma tissue microarray. Cancer, 100, 2084-92.   DOI
8 Bukholm IK, Nesland JM, Karesen R, et al (1998). E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol, 185, 262-6.   DOI
9 Chan DSM, Vieira AR, Aune D, et al (2014). Body mass index and survival in women with breast cancer- systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol, 25, 1901 - 1914.   DOI
10 Chau WK, Ip CK, Mak AS, et al (2012). c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/b-catenin-ATPbinding cassette G2 signaling. Oncogene, 10, 103.
11 Fisher B, Bryant J, Wolmark N, et al (1998). Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol, 16, 2672-85.   DOI
12 Clevers H (2006). Wnt/beta-catenin signaling in development and disease. Cell, 127, 469-80.   DOI
13 Cortazar P, Zhang L, Untch M, et al (2014). Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet, 384 , 164-72.   DOI
14 Dolled-Filhart M, McCabe A, Giltnane J, et al (2006). Quantitative in situ analysis of beta-catenin expression in breast cancer shows decreased expression is associated with poor outcome. Cancer Res, 66, 5487-94.   DOI
15 Dawood S, Broglio K, Gonzalez-Angulo AM, et al (2008). Prognostic Value of Body Mass Index in Locally Advanced Breast Cancer. Clin Cancer Res, 14, 1718-25.   DOI
16 Fanelli MA, Montt-Guevara M, Diblasi AM, et al (2008). P-Cadherin and ${\beta}$-catenin are useful prognostic markers in breast cancer patients; ${\beta}$-catenin interacts with heat shock protein Hsp27. Cell Stress Chaperones, 13, 207-20.   DOI
17 Geyer FC, Lacroix-Triki M, Savage K, et al (2011). ${\beta}$-Catenin pathway activation in breast cancer is associated with triplenegative phenotype but not with CTNNB1 mutation. Mod Pathol, 24, 209-31.   DOI
18 Hess K, Anderson K, Symmans W, et al (2006). Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast can. J Clin Oncol, 24, 4236-44.   DOI
19 Jiang Y, Zou L, Zhang C, et al (2009). PPARgamma and Wnt/- Catenin pathway in human breast cancer: expression pattern, molecular interaction and clinical/prognostic correlations. J Cancer Res Clin Oncol, 135, 1551-9.   DOI
20 Khramtsov AI, Khramtsova GF, Tretiakova M, et al (2010). Wnt/beta-catenin pathway activation is enriched in basallike breast cancers and predicts poor outcome. Am J Pathol, 176, 2911-20.   DOI
21 Li S, Sun Y, Li L (2014). The expression of ${\beta}$-catenin in different subtypes of breast cancer and its clinical significance. Tumor Biol, 35, 7693-8.   DOI
22 Lin SY, Xia W, Wang JC, et al (2000). Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin D1 expression and cancer progression. Proc Natl Acad Sci USA, 97, 4262-6.   DOI
23 Lopez-Knowles E, Zardawi SJ, McNeil CM, et al (2010). Cytoplasmic localization of beta-catenin is a marker of poor outcome in breast cancer patients. Cancer Epidemiol Biomarkers Prev, 19, 301-9.   DOI
24 Nelson WJ, Nusse R (2004). Convergence of Wnt, beta-catenin, and cadherin pathways. Science, 303, 1483-7.   DOI
25 Nolen B, Marks J, Ta’san S, et al (2008). Serum biomarker profiles and response to neoadjuvant chemotherapy for locally advanced breast cancer. Breast Cancer Res, 10, 45.
26 Pedersen KB, Nesland JM, Fodstad O, et al (2002). Expression of S100A4, E-cadherin, alpha- and beta-catenin in breast cancer biopsies. Br J Cancer, 87, 1281-6.   DOI
27 Prasad CP, Gupta SD, Rath G, et al (2007). Wnt signaling pathway in invasive ductal carcinoma of the breast: relationship between beta-catenin, dishevelled and cyclin D1 expression. Oncol, 73, 112-117.   DOI
28 Rouzier R, Perou C, Symmans W, et al (2005). Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res,11, 5678-85.   DOI
29 Prosperi JR, Goss KH (2010). AWnt-ow of opportunity: targeting the Wnt/beta-catenin pathway in breast cancer. Curr Drug Targets, 11, 1074-88.   DOI