Differential Response of Immunohistochemically Defined Breast Cancer Subtypes to Anthracycline-Based Adjuvant Chemotherapy with or without PaclitaxelReport as inadecuate




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Background

The aim of the present study was to investigate the efficacy of adjuvant dose-dense sequential chemotherapy with epirubicin, paclitaxel, and CMF in subgroups of patients with high-risk operable breast cancer, according to tumor subtypes defined by immunohistochemistry IHC.

Materials and Methods

Formalin-fixed paraffin-embedded FFPE tumor tissue samples from 1,039 patients participating in two adjuvant dose-dense sequential chemotherapy phase III trials were centrally assessed in tissue micro-arrays by IHC for 6 biological markers, that is, estrogen receptor ER, progesterone receptor PgR, HER2, Ki67, cytokeratin 5 CK5, and EGFR. The majority of the cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A ER-PgR-positive, HER2-negative, Ki67low; luminal B ER-PgR-positive, HER2-negative, Ki67high; luminal-HER2 ER-PgR-positive, HER2-positive; HER2-enriched ER-negative, PgR-negative, HER2-positive; triple-negative TNBC ER-negative, PgR-negative, HER2-negative; and basal core phenotype BCP TNBC, CK5-positive and-or EGFR-positive.

Results

After a median follow-up time of 105.4 months the 5-year disease-free survival DFS and overall survival OS rates were 73.1% and 86.1%, respectively. Among patients with HER2-enriched tumors there was a significant benefit in both DFS and OS log-rank test; p = 0.021 and p = 0.006, respectively for those treated with paclitaxel. The subtype classification was found to be of both predictive and prognostic value. Setting luminal A as the referent category, the adjusted for prognostic factors HR for relapse for patients with TNBC was 1.91 95% CI: 1.31–2.80, Wald-s p = 0.001 and for death 2.53 95% CI: 1.62–3.60, p<0.001. Site of and time to first relapse differed according to subtype. Locoregional relapses and brain metastases were more frequent in patients with TNBC, while liver metastases were more often seen in patients with HER2-enriched tumors.

Conclusions

Triple-negative phenotype is of adverse prognostic value for DFS and OS in patients treated with adjuvant dose-dense sequential chemotherapy. In the pre-trastuzumab era, the HER2-enriched subtype predicts favorable outcome following paclitaxel-containing treatment.



Author: George Fountzilas , Urania Dafni, Mattheos Bobos, Anna Batistatou, Vassiliki Kotoula, Helen Trihia, Vassiliki Malamou-Mitsi, Spyr

Source: http://plos.srce.hr/



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