Triple-Negative Apocrine Breast Carcinoma Has Better Prognosis despite Poor Response to Neoadjuvant Chemotherapy

Abstract

Apocrine carcinoma is a rare subtype of invasive ductal breast cancer that shows apocrine differentiation and largely triple-negative immunohistology. Triple-negative breast cancers are known to have more aggressive clinical courses. However, unlike most other subtypes, it is reported that triple-negative apocrine carcinoma (TNAC) has a better prognosis. Due to the scarcity of reported studies, our knowledge regarding its clinical behavior, prognosis and response to therapy is very limited. In this study, we retrospectively retrieved 41 triple-negative apocrine carcinoma cases from our breast cancer database, with an average follow-up of 32.8 months. It was found that TNAC had a poorer response to neoadjuvant therapy but a better prognosis than other nonapocrine types of triple-negative breast cancer. Meanwhile, TNAC has a low proliferative nature, as indicated by its low Ki-67 index. An updated analysis of the Surveillance, Epidemiology, and End Results database showed that chemotherapy did not improve breast-cancer-specific survival in TNAC patients. Our results suggest that TNAC is a special subtype of triple-negative breast cancer with a better short-term prognosis despite poor response to neoadjuvant chemotherapy.

Proteomics Landscape of Triple-Negative Apocrine Breast Carcinoma Reveals Molecular Mechanisms of Tumorigenesis and Characteristics of Chemo-insensitivity

“…TNAC is a rare type of TNBC indicated by unique morphology and protein markers. Previous studies have shown that TNAC typically expresses protein AR and EGFR while lacking ER, PR, and Ki67 2,5,7,10,11 . Current mass spectrometry proteomics data align with the protein expression observations from IHC (Figure 1 and Figure S4).…”

“…The Formalin-fixed paraffin-embedded (FFPE) blocks used in this study were obtained from Peking University Cancer Hospital in Beijing, China, with approval from the hospital's ethical committee under reference number 2020KT113. The cells were stained using Hematoxylin and Eosin (H&E), and the expression of protein markers such as ER, PR, and HER2 was evaluated using immunohistochemical staining (IHC), as described in a previous publication 7 . Out of the 31 invasive TNAC cases, 10 still contained accompanying DCIS lesions; therefore, invasive, DCIS, and adjacent normal tissues (~10 μm thick) were carefully dissected from the FFPE blocks on a macroscopic level.…”

“…Additionally, TNAC tumor tissues typically express low Ki67 and strong androgen receptor (AR), indicating a low proliferation rate and potential for treatment using AR-targeted drugs 5 . TNAC usually responds poorly to chemotherapy [6][7][8] , but has a better prognosis than non-apocrine triple-negative breast cancer (NA-TNBC) 5,[9][10][11][12] . Due to the low clinical incidence, there is limited research on characterizing TNAC using both genomic and proteomic sequencing data.…”

“…Regarding chemo-exemption for TNBC patients, the development of immunotherapy, including pembrolizumab, and new drug targets such as AR, offers potential alternatives [24][25][26][27] . Increasing evidence suggests that TNAC patients might not benefit from chemotherapy, leading to discussions about identifying molecular biomarkers to screen for TNAC patients to exclude from chemotherapy [6][7][8] .…”

Biomarker Alteration after Neoadjuvant Endocrine Therapy or Chemotherapy in Estrogen Receptor-Positive Breast Cancer

“…The IHC staining procedure was conducted as described in our previous study [ 15 ]. Antibody information was as following: ER (SP1, Roche, 1 µg/mL), PR (1E2, Roche, 1 µg/mL), HER2 (4B5, Ventana, 6 µg/mL), Ki-67 (M1B1, Zhongshan Jinqiao, working concentration), and EGFR (EP22, Jinbiaoyatu, working concentration).…”