TP 53 status and estrogen receptor-beta in triple negative breast cancer management in Africa: Time to rethink regime management of triple negative breast cancer and save more lives in Nigeria.

Abstract

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). Although Estrogen receptor alpha (ESR1) is now routinely used in typing breast cancers in most of Eastern Nigeria, where it is used as a major prognostic and predictive factor in treatment outcome.1,2 ESR1 negative breast cancer remains a significant subtype contributing to (38.4%) and usually the predominant triple negative breast cancers.1,2 For these patients no further treatment is given after surgery and neoadjuvant chemotherapy and radiotherapy. A comparative study done by Wright et al.3 shows that comparatively by 50 weeks after diagnosis and management survival probability of triple negative breast cancers in Nigeria; fall from 1 to 0.3, while in UK survival probability only falls from 1.0 to 0.6 (twice as good). By 100 weeks it has flattened to 0.1 in Nigeria and in UK 0.353. Although the differences can be explained in part by our late presentations, poorer health care systems and lack of good health insurance. We note that Adding Transcription factor 53 status as well as the estrogen receptor beta status evaluation only for triple negative breast cancers will make a significant difference in survival. Estrogen receptor beta (ESB2) shares structural homology at DNA and ligand binding domains (98% and 56%, respectively) with (ESR1) the major type of estrogen receptor in breast cancer.4,5 ESR2 functions and expression patterns are different from ESR1 and is widely expressed in both basal and luminal epithelial cells.6–8 The precise role of ESR2 in breast cancer is unclear, with both antiproliferative and proliferative roles described.9,10 The mechanisms for these opposing actions of ESR2 in breast tumorigenesis have not been fully elucidated.11 Mukhopadhyay et al.12 provides an explanation for the dual nature of ESR2 function in triple-negative breast cancer (TNBC) related to its interactions with TP53 status (wildtype or mutant). In wild-type TP53-expressing cells, silencing of ESR2 augmented apoptosis, whereas its over expression resulted in increased proliferation. Opposite effects were observed following silencing or overexpression of ESR2 in mutant TP53 cells, suggesting the important role of TP53 status in determining ESR2’s function. Mechanistically, ESR2-mutant TP53 interaction mediates sequestration of mutant TP53, leading to the TP73 activation and antiproliferative effects. Treatment with tamoxifen (4-hydroxy tamoxifen) also increases ESR2 expression and reactivates TP73 in mutant TP53 cells, providing an TP 53 status and estrogen receptorbeta in triple negative breast cancer management in Africa: Time to rethink regime management of triple negative breast cancer and save more lives in Nigeria