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

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 everolimus and 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.

Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies

“…Luminal Androgen Receptor (LAR) Subtype: The LAR subtype of TNBC is characterized by the expression of androgen receptor (AR) and luminal-associated genes, such as FOXA1 and GATA3 ( 31 ). These Tumors often display luminal-like features and are less proliferative compared to other TNBC subtypes ( 32 ).…”