ABSTRACT
Secretory carcinoma is a special-type breast carcinoma underpinned by a recurrent t(12;15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion. Immunohistochemistry (IHC) using a pan-TRK antibody has been recently shown to help identify NTRK rearrangements in other tumor types. The purpose of this study was to assess the diagnostic utility of pan-TRK IHC in secretory carcinoma of the breast. Pan-TRK IHC was performed using a rabbit monoclonal antibody on whole sections of 24 breast secretory carcinomas and tissue microarray sections of other breast carcinoma types (n=203) and histologic mimics (n=15). Cases were assessed for staining intensity and localization. The 24 patients with secretory carcinoma had a median age of 44 years and a median tumor size of 1.0 cm. ETV6 fluorescence in situ hybridization was positive in all cases tested (n=20). Twenty-three cases (95.8%) showed staining with pan-TRK, which was exclusively nuclear in 19, primarily nuclear with weak cytoplasmic staining in 3, and primarily cytoplasmic with focal nuclear staining in 1. The nuclear staining was diffuse in 17 and at least focally strong in 17. The only pan-TRK negative case was a core biopsy with limited tumor. Among the 203 nonsecretory carcinomas, 21 (10.3%) showed focal, weak nuclear staining in <5% of tumor cells and 1 (0.5%) showed focal membranous staining. All histologic mimics were negative. In conclusion, diffuse and/or at least focally strong nuclear pan-TRK staining is a sensitive and specific marker for secretory carcinoma of the breast.
Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms, Male/enzymology , Breast Neoplasms/enzymology , Carcinoma/enzymology , Gene Fusion , Immunohistochemistry , Receptors, Nerve Growth Factor/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms, Male/genetics , Breast Neoplasms, Male/pathology , Carcinoma/genetics , Carcinoma/pathology , Female , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Paris , Predictive Value of Tests , Proto-Oncogene Proteins c-ets/genetics , Receptors, Nerve Growth Factor/genetics , Repressor Proteins/genetics , United States , Young Adult , ETS Translocation Variant 6 ProteinABSTRACT
OBJECTIVE: To evaluate the effectiveness and tolerability of neoadjuvant chemotherapy with weekly paclitaxel in combination with weekly carboplatin area under curve 2 followed by anthracycline chemotherapy. PATIENTS AND METHODS: This is a retrospective review of electronic medical records of patients (Nâ¯=â¯32) with stage 1c-III triple-negative breast cancer. Patients received neoadjuvant chemotherapy with paclitaxel 80â¯mg/m2 once per week for 12 weeks in combination with carboplatin area under curve 2 once per week for 12 weeks (wP + wCb), followed by a standard anthracycline regimen including either doxorubicin 60â¯mg/m2 and cyclophosphamide 600â¯mg/m2 every 2 or 3 weeks, or epirubicin 90â¯mg/m2 and cyclophosphamide 600â¯mg/m2 every 3 weeks for four cycles with myeloid growth factor support. RESULTS: Most patients (91%) received all 12 cycles of wP + wCb, and 88% received all four planned cycles of anthracycline chemotherapy. Of the patients, 84% completed all planned therapies. The complete pathologic response rate was 60%. In terms of hematologic toxicity, 96% of the patients experienced grade ≥3 leucopenia, 40% grade ≥3 anemia, and 15% grade ≥3 thrombocytopenia, and neutropenic fever was seen in 22% of the patients. CONCLUSION: The combination of neoadjuvant chemotherapy with wP + wCb before anthracycline chemotherapy can be tolerated by patients with triple-negative breast cancer. Complete pathologic response rates were comparable with those historically seen. Careful selection of patients is fundamental as this regimen is associated with a high incidence of hematologic toxicity.
