Prognostic significance of transforming growth factor β receptor II in clinical stage III breast cancer patients - a pilot study

Article type: Research Article

Authors: Refaat, Sherif^{a; b} | Shamaa, Sameh^{a; b} | Elkhodary, Tawfik^{a; b} | Atwan, Nadia^{c; d} | Ghazy, Hayam^{a; b} | Akl, Tamer^{a; b} | Abdelwahab, Khaled^{e; f} | Foda, Abd AlRahman Mohammad^{c; d} | El-Badrawy, Adel^g | Emarah, Ziad^{a; b;}

Affiliations: [a] Medical Oncology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt | [b] Medical Oncology Unit, Oncology Center, Mansoura University, Mansoura, Egypt | [c] Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt | [d] Pathology Department, Oncology Center, Mansoura University, Mansoura, Egypt | [e] Surgery Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt | [f] Surgical Oncology Unit, Mansoura Oncology Center, Mansoura University, Mansoura, Egypt | [g] Radiology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt

Correspondence: [*] Corresponding author: Ziad Emarah, MD, PhD, Medical Oncology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, 35516 Mansoura, Egypt. Tel.: +20 1003530926; E-mail: ziadomara@mans.edu.eg. ORCID: https://orcid.org/0000-0003-0622-2598

Abstract: BACKGROUND:Transforming growth factor–β (TGFβ) has a dual function in breast cancer, having a tumor suppressor activity in early carcinomas while enhancing tumor metastasis in advanced breast carcinoma. Consequently, the prognostic role of TGFβ and its signaling cascade in breast cancer remain unclear. OBJECTIVE:To investigate the relationship between TβRII expression, clinic-pathological characteristics, and prognostic significance of TβRII expression in clinical stage III breast cancer. METHODS:Biopsy from the primary tumor was obtained from 30 newly diagnosed clinical stage III breast cancer patients before receiving any therapy. Expression of TβRII, ER, PR, Her2 and Ki-67 was assessed by immunohistochemistry. RESULTS:TβRII expression was positive in 66.7% of cases and was significantly associated with advanced nodal stage and distant metastases. After a median follow up of 42.3 months, TβRII was associated with poor disease-free survival and it was an independent factor for predicting the poor outcome for breast cancer patients, especially in node positive tumors, ER/PR positive and Her2-negative tumors. CONCLUSIONS:These findings suggest the usage of therapeutic drugs that target TGFβ in advanced breast cancer patients may be effective. Nevertheless, blockage of the tumor promoting and sparing of the tumor suppressor effect of TGFβ pathway should be taken into consideration. We suggest that these therapies might have more benefit in ER and PR positive tumors.

Keywords: TβRII, transforming growth factor–β, breast cancer

DOI: 10.3233/BD-201009

Journal: Breast Disease, vol. 40, no. 2, pp. 75-83, 2021