Triple negative breast cancer: special histological types and emerging therapeutic methods

Abstract

Triple negative breast cancer (TNBC) is a complex and malignant breast cancer subtype that lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), thereby making therapeutic targeting difficult. TNBC is generally considered to have high malignancy and poor prognosis. However, patients diagnosed with certain rare histomorphologic subtypes of TNBC have better prognosis than those diagnosed with typical triple negative breast cancer. In addition, with the discovery and development of novel treatment targets such as the androgen receptor (AR), PI3K/AKT/mTOR and AMPK signaling pathways, as well as emerging immunotherapies, the therapeutic options for TNBC are increasing. In this paper, we review the literature on various histological types of TNBC and focus on newly developed therapeutic strategies that target and potentially affect molecular pathways or emerging oncogenes, thus providing a basis for future tailored therapies focused on the mutational aspects of TNBC.

Keywords: Triple negative breast cancer; androgen receptor; immunotherapy; pathological subtype; targeted therapy.

Figure 1

Representative H&E images of rare triple negative breast cancer. (A) Adenoid cystic carcinoma (400×). Most adenoid cystic carcinoma cells surround spherules of basement membrane material constituting pseudolumina. (B) Secretory carcinoma (400×). Abundant intracellular and extracellular secretory material is a typical feature of secretory carcinoma. (C) Acinic cell carcinoma (400×). An example of acinic cell carcinoma with abundant clear cytoplasm. (D) Carcinoma with apocrine differentiation (400×). The example shows cells with abundant, granular, intensely eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli (type A cells). (E) Microglandular adenosis (100×). Haphazard proliferation of small round glands with open lumina composed of a single layer of flat to cuboidal epithelial cells is seen. (F) Carcinoma arising in microglandular adenosis (100×). Carcinoma arising in microglandular adenosis shows a more complex and disordered architecture. (G) Low-grade adenosquamous carcinoma of the breast (200×). The example shows well-developed glandular and tubular formation closely admixed with solid nests of squamous cells on a spindle-cell background. (H) Low-grade fibromatosis-like metaplastic carcinoma (200×). An example of low-grade fibromatosis-like metaplastic carcinoma composed of deceptively bland-looking spindle cells arranged in wavy, interlacing fascicles is shown.

Figure 2

A model showing current therapeutic strategies that could be combined with other therapies. The therapeutic strategies include AR-inhibitors, PI3K/AKT/mTOR inhibitors, AMPK inhibitors, and immunotherapy.