(P118) Metadherin Overexpression Is Associated With Improved Locoregional Control After Mastectomy

Publication
Article
OncologyOncology Vol 28 No 1S
Volume 28
Issue 1S

Breast cancer patients who develop a recurrence in the chest wall after mastectomy represent a high-risk subgroup that may benefit from early identification and more aggressive treatment. Traditional clinicopathologic factors have been proven useful for prognosis, but there remains a need to identify molecular markers with prognostic significance.

Sibo Tian, BA, Atif Khan, MD, Bruce G. Haffty, MD, Sinae Kim, PhD, Meena Moran, MD, Neil K. Taunk, MD, Hao Wu, PhD, Sharad Goyal, MD; Robert Wood Johnson Medical School; The Cancer Institute of New Jersey

Background: Breast cancer patients who develop a recurrence in the chest wall after mastectomy represent a high-risk subgroup that may benefit from early identification and more aggressive treatment. Traditional clinicopathologic factors have been proven useful for prognosis, but there remains a need to identify molecular markers with prognostic significance. Metadherin (MTDH) is an oncogene that is overexpressed in all cancers studied so far. It has been linked to multiple pathways, including PI3K/Akt, NFkB, and Wnt/ β-catenin, and is a key mediator of proliferation, metastasis, and chemoresistance. MTDH, while normally absent from human breast tissue, is overexpressed in 44% of primary breast tumors. The purpose of this study is to evaluate the association between MTDH expression and locoregional recurrence in a cohort of breast cancer patients treated with mastectomy.

Patients and Methods: We retrospectively identified 22 patients who developed a locoregional recurrence as the first or only site of failure after mastectomy and had paraffin-embedded tissue blocks from the primary tumor available. These patients were case control–matched to 28 patients who were disease-free at last follow-up. They were matched with respect to age (± 3 yr) and follow-up duration (< 5 or ≥ 5 yr). All patients initially presented with 0–3 positive nodes, and none received postmastectomy RT. Tumor blocks were assembled into a tissue microarray, and MTDH expression was analyzed by immunohistochemical methods and then quantified electronically based on the intensity of staining. Conditional logistic regression was used to test the relationship between each variable and the risk of locoregional recurrence.

Results: Immunohistochemical analysis revealed primarily cytoplasmic expression of MTDH, and 26 of 49 (53.1%) patients were positive for MTDH overexpression. Higher levels of MTDH expression were significantly associated with lower Ki67 expression (P = .006). Lower MTDH expression was linked to the triple-negative phenotype (P = .0027). In a univariate conditional logistic regression, lower MTDH expression was strongly linked to higher odds of locoregional recurrence (odds ratio [OR] = 0.062; 95% confidence interval [CI], 0.008–0.477; P = .0076).

Conclusions: We demonstrate, using a matched case-control design, that MTDH overexpression is significantly associated with improved locoregional control after mastectomy in a cohort of patients presenting with 0–3 positive nodes.

Articles in this issue

(P113) Age and Marital Status Are Associated With Choice of Mastectomy in Patients Eligible for Breast Conservation Therapy
(P112) Single-Institution Experience With Intrabeam IORT for Treatment of Early-Stage Breast Cancer
(P110) Breast Cancer Before Age 40: Current Patterns in Clinical Presentation and Local Management
(P111) Accelerated Partial-Breast Irradiation With Multicatheter High-Dose-Rate Brachytherapy: Feasibility and Results in a Private Practice Cohort
(P115) Breast Cancer Laterality Does Not Influence Overall Survival in a Large Modern Cohort: Implications for Radiation-Related Cardiac Mortality
(P117) Anatomical Variations and Radiation Technique for Breast Cancer
(P116) Bilateral Immediate DIEP Reconstruction and Postmastectomy Radiotherapy: Experience at a Tertiary Care Institution
(P118) Metadherin Overexpression Is Associated With Improved Locoregional Control After Mastectomy
(P119) Effect of Economic Environment on Use of Postlumpectomy Radiation Therapy for Stage I Breast Cancer
(P120) Immediate Versus Delayed Reconstruction After Mastectomy in the United States Medicare Breast Cancer Patient
(P121) Trend in Age and Racial Disparities in the Receipt of Postlumpectomy Radiation Therapy for Stage I Breast Cancer: 2004–2009
(P122) Streamlining Referring Physicians Orders With ‘Reflex Testing’ Significantly Decreases Time to Resolution for Abnormal Screening Mammograms
(P123) National Trends in the Local Management of Early-Stage Paget Disease of the Breast
(P124) Effect of Inhomogeneity on Cardiac and Lung Dose in Partial-Breast Irradiation Using HDR Brachytherapy
(P125) Breast Cancer Outcomes With Anthracycline-Based Chemotherapy for Residual Disease Burden After Full-Dose Neoadjuvant Chemotherapy and Surgery Followed by Radiation Treatment
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