TROP2, androgen receptor, and PD‐L1 status in histological subtypes of high‐grade metaplastic breast carcinomas

Abstract

High-grade metaplastic breast carcinoma (HG-MBC) is a rare subtype of invasive breast carcinoma, mostly triple-negative. Metaplastic carcinomas are less responsive to neoadjuvant chemotherapy and are associated with a worse outcome than invasive carcinomas of no special type. Methods: Clinicopathological characteristics and immunophenotype were retrospectively assessed in a series of 65 patients diagnosed with HG-MBC between 2005 and 2017 at the Curie Institute (antibody panel: oestrogen receptor [ER], progesterone receptor [PR], androgen receptor [AR], human epidermal growth factor receptor 2 [HER2], programmed death ligand-1 [PD-L1], and trophoblast cell surface antigen 2 [TROP2]). Results: The median age at diagnosis was 59.5 years. Six (9%) patients had metastatic disease at diagnosis. Among the nonmetastatic patients receiving neoadjuvant therapy, 26% (5/19) achieved pathological complete response. Most tumours were pT1/pT2 (77%) and 12% were pN+. Histological subtypes (mixed, squamous, mesenchymal, and spindle cell) were 40%, 35.5%, 15.5%, and 9%, respectively. Tumourinfiltrating lymphocytes were low or moderate except when squamous differentiation was present. Most tumours were triple-negative (92%). AR and TROP2 were positive in 34% and 85% of the cases, respectively. PD-L1 was positive in tumour cells in 18% (cutoff: 1% of positive tumour cells) of the cases and in tumour-infiltrating immune cells in 40% (cutoff: 1% of tumour area) of the cases. Notably, spindle cell and mesenchymal metaplastic breast carcinomas were mostly PDL1-negative. Lastly, 21 (32.3%) cases were HER2-low, all being HER2 1+, with no HER2 2+. Conclusion: Metaplastic breast carcinoma could benefit from tailored therapeutic strategies adapted to the phenotypic specificities of histological subtypes.

Discrepancy between Tumor Size Assessed by Full-Field Digital Mammography or Ultrasonography (cT) and Pathology (pT) in a Multicenter Series of Breast Metaplastic Carcinoma Patients

“…Currently, BC-Mp is often considered to respond poorly to treatment [ 7 ]. However, other studies indicate higher HER2-positive status than in our cohort, increased programmed cell death ligand-1 (PDL1) positivity, and the presence of specific somatic tumor mutations and germline mutations like Breast Cancer susceptibility gen1 mutation [ 34 , 35 , 36 , 37 , 38 ]. This suggests the potential for targeted and possibly more effective systemic treatment, including neoadjuvant systemic approaches.…”

Clinical analysis of metaplastic breast carcinoma with distant metastases: A multi‑centre experience

“…The data did not reveal any prognostic significance associated with the histologic subtype of BC-Mp, aligning with findings reported by certain researchers ( 18 , 19 ) but in contrary to results published by others ( 34 , 35 ). Emerging data indicate that the expression of proteins serving as potential targets for novel therapies is associated with histological subtypes ( 36 ). Therefore, this factor warrants re-evaluation in the context of clinical trials or cohort studies of patients treated recently.…”

“…Pembrolizumab, when used in combination with chemotherapy, received approval from Food and Drug Administration for treating metastatic TNBC displaying positive programmed death ligand 1 (PD-L1) expression (combined positive score ≥10) as shown in the KEYNOTE-355 study ( 44 , 45 ). Numerous reports have emphasized the notable expression of PD-L1 in metaplastic breast carcinomas, observed in 40–50% of cases ( 36 , 46 ). This suggests a potential for enhanced effectiveness of immunotherapy-based treatments within this subgroup.…”

“…In these trials, TROP-2 expression did not exhibit predictive value within the patient populations, which was likely attributable to the consistently elevated expression levels observed. Furthermore, it has been reported that patients with mBC also exhibit heightened TROP-2 expression ( 36 ).…”

Case report: Successful treatment of a rare HER2-positive advanced breast squamous cell carcinoma

“…Additionally, the use of PD-L1/PD-1 immune checkpoint blockade therapy shows promise. Suzanne’s study revealed that PD-L1 expression was positive in tumor cells in 18% of the enrolled high-grade MpBC cases and in tumor-infiltrating immune cells in 40% of the cases ( Chartier et al, 2023 ). Sylvia and Anita separately reported a case of pCR achieved through a combination of chemotherapy and Pembrolizumab in MpBC ( Adams, 2017 ; Gul et al, 2023 ).…”