The Spectrum of Triple-Negative Breast Disease

Abstract

Triple-negative breast cancer is viewed clinically as an aggressive subgroup of breast cancer. In fact, most triple-negative breast cancers are poor-prognosis tumors with a complex genomic landscape. However, triple-negative disease is vastly heterogeneous, encompassing multiple entities with marked genetic, transcriptional, histologic, and clinical differences, with neoplasms in this group ranging from low to high grade. Among the less common low-grade triple-negative lesions, two large subgroups, both with a rather indolent behavior, can be distinguished: a low-grade triple-negative breast neoplasia family, which includes nonobligate precursors of triple-negative breast cancer, and, despite being low-grade, harbors the complex genomic landscape of usual triple-negative breast cancer, and the salivary gland-like tumors of the breast, lacking all the cardinal molecular features of conventional triple-negative breast cancer and underpinned by specific fusion genes or hotspot mutations, which may be of diagnostic and possibly therapeutic utility. Progression to high-grade triple-negative breast cancer likely occurs in both subgroups but at different rates. In this review, we describe the heterogeneity of triple-negative disease, focusing on the histologic and molecular features of the low-grade lesions. Recognition that triple-negative breast cancer is an operational term and that triple-negative disease is heterogeneous and includes low-grade forms driven by distinct sets of genetic alterations is germane to the successful implementation of precision medicine.

High rate of PIK3CA mutations but no TP53 mutations in low‐grade adenosquamous carcinoma of the breast

“…Recently Geyer et al . have reported on the existence of a ‘low‐grade triple‐negative breast neoplasia family’ featuring microglandular adenosis/atypical microglandular adenosis as non‐obligate precursors of TNBC, and acinic cell carcinomas as low‐grade forms of TNBC with the potential to transform into conventional high‐grade TNBCs.…”

Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple‐negative breast cancer

“…Patients with triple‐negative breast cancer (TNBC), which is negative for ER, PR, and HER2 expression, account for 15%‐20% of all breast cancer patients . TNBC is generally considered to be more aggressive and have a worse prognosis compared to other subtypes of breast cancer . Due to the absence of well‐defined molecular targets, there is no definitely effective molecular target therapy for TNBC .…”

Impact of biomarkers and genetic profiling on breast cancer prognostication: A comparative analysis of the 8th edition of breast cancer staging system

“…However, TNBCs comprise a heterogeneous group with varied genetic, histologic, and clinical features, ranging from low grade, locally aggressive neoplasm with low if any metastatic potential, to high‐grade BCs developing visceral metastasis within 2‐3 years from diagnosis and having a highly aggressive behavior. () Despite the histopathologic and clinical heterogeneity in TNBCs, the TNM + Biomarkers system does not account for the biologic diversity and less aggressive behavior of some special types of TNBCs, such as adenoid cystic carcinoma. All that said, our patient cohort did not include significant number of special histologic subtypes of TNBCs.…”