More Than Meets the Eye - A Case of Breast Cancer Switching from Being Luminal-Androgen-Receptor-Positive to Being Hormone-Receptor-Positive

Sep 24, 2026

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Triple-negative breast cancer (TNBC) represents about 15% of all breast cancers and typically shows aggressive behavior with poor prognosis. Four TNBC molecular subgroups have been defined, including luminal androgen receptor (LAR), which is marked by androgen receptor expression and gene patterns resembling luminal tumors, yet with an unresolved clinical course. This case describes a recurring LAR TNBC that shifts phenotype during disease progression, developing strong estrogen receptor expression after initial LAR diagnosis and demonstrating limited responses to multiple therapies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

TNBC definition, prevalence, and heterogeneity

Molecular subtypes (Lehmann; Burstein)

Detailed Case Description

medicina Case Report More Than Meets the Eye: A Case of Breast Cancer Switching from Being Luminal-Androgen-Receptor-Positive to Being Hormone-Receptor-Positive Federica Martorana 1, *, Giuseppe Di Grazia 2, Giovanni Nunzio Rosano 3, Giada Maria Vecchio 3, Chiara Conti 2, Sabrina Nucera 2, Gaetano Magro 3 and Paolo Vigneri 1,4 Citation: Martorana, F.; Di Grazia, G.; Rosano, G.N.; Vecchio, G.M.; Conti, C.; Nucera, S.; Magro, G.; Vigneri, P. More Than Meets the Eye: A Case of Breast Cancer Switching from Being Luminal-AndrogenReceptor-Positive to Being Hormone-Receptor-Positive. Medicina 2023, 59, 1875. [https://](https://)[ ](https://)[doi.org/10.3390/medicina59101875](doi.org/10.3390/medicina59101875) Academic Editor: Maria Rosaria De Miglio Received: 27 September 2023 Revised: 16 October 2023 Accepted: 20 October 2023 Published: 22 October 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; [paolo.vigneri@unict.it](paolo.vigneri@unict.it) 2 Department of Human Pathology “G. Barresi”, University of Messina, 98131 Messina, Italy; [giuseppedigrazia25@gmail.com](giuseppedigrazia25@gmail.com) (G.D.G.); [conchiara9@gmail.com](conchiara9@gmail.com) (C.C.); [sabrinanuc@libero.it](sabrinanuc@libero.it) (S.N.) 3 Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, Anatomic Pathology, University of Catania, 95123 Catania, Italy; [giovanninunziorosano@gmail.com](giovanninunziorosano@gmail.com) (G.N.R.); [giadamariavecchio@gmail.com](giadamariavecchio@gmail.com) (G.M.V.); [gmagro@unict.it](gmagro@unict.it) (G.M.) 4 Humanitas Istituto Clinico Catanese, University Oncology Department, 95045 Catania, Italy * Correspondence: [federica.martorana@unict.it](federica.martorana@unict.it); Tel.: +39-095-3781949 Abstract: Triple-negative breast cancer (TNBC) represents about 15% of all breast cancers and is usually characterized by aggressive clinical behavior and a poor prognosis. Four TNBC subgroups have been previously deﬁned with different molecular proﬁles: (i) luminal androgen receptor (LAR),(ii) mesenchymal (MES),(iii) basal-like immunosuppressed (BLIS) and (iv) basal-like immune-activated (BLIA) . Among these, LAR is characterized by the expression of the androgen receptor (AR), and exhibits genomic characteristics that resemble luminal breast cancers, with a still undeﬁned prognosis and clinical behavior. Here, we report a case of a woman affected by recurring LAR TNBC, which underwent phenotypic changes throughout its natural history. After the initial diagnosis of LAR breast cancer, the patient experienced local recurrence with strong expression of the estrogen receptor. Due to this ﬁnding, she started treatment with a CDK4/6-inhibitor and an aromatase inhibitor, followed by oral vinorelbine, both with dismal outcomes. Then, she received everolimusand exemestane, which determined temporary disease stabilization. An extensive NGS analysis of tumor tissue showed PIK3CA and HER2 mutations. Our case is consistent with previous reports of LAR breast cancer and underlines the potential utility of re-biopsy and molecular testing in breast cancer (BC), especially in rare subtypes. Keywords: breast cancer; triple-negative breast cancer; luminal androgen receptor; molecular testing; PIK3CA; everolimus 1. Introduction Triple-negative breast cancer (TNBC) is deﬁned by the lack of hormone receptors (HR) and epidermal growth factor receptor 2 (HER2) overexpression or ampliﬁcation [1] . TNBC accounts for 15% of all breast cancers and is usually characterized by aggressive clinical b

FAQs

What is the main clinical issue discussed in the case report?

The report describes a recurring TNBC case with luminal androgen receptor (LAR) features that undergoes phenotypic switching during its natural history, including later strong estrogen receptor expression.

How does LAR TNBC differ at the molecular and biological level?

LAR TNBC is characterized by androgen receptor (AR) expression and a gene expression profile resembling luminal breast cancers, with enrichment of mutations such as PIK3CA, and clinical behavior and prognosis that remain undeﬁned.

Why is re-biopsy and molecular testing emphasized?

Because phenotypic changes and actionable molecular alterations can emerge over time, the case supports the potential utility of re-biopsy and molecular testing to better characterize rare TNBC subtypes.

Sep 24, 2026

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