triple-negative breast cancer: a new perspective on biomarkers

Conditions: Triple Negative Breast Neoplasms; Triple Negative Breast Cancer

Summary: a single-institutional cohort to determine the prevalence of new immunohistochemical panel in advanced triple-negative submitted to neoadjuvant chemotherapy and its association with response and survival.

background/rationale: triple negative breast cancer (tnbc) is known to be a heterogeneous disease, and different molecular sub-classifications are proposed based in specific biomarkers as immunohistochemical (ihc) expression of the androgen-receptor (ar), epidermal growth factor receptor (egfr), cytokeratin 5/6 (ck5/6), cytokeratin14 (ck14), cytokeratin 17 (ck17), clusters of differentiation 117 (cd 117), p53, ki67 level, programmed cell death-ligand 1 (pd-l1) and pd-l2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes (pd-1+, foxp3+, cd 4+ or cluster designation 8 (cd8 +), cd 3+, cluster of differentiation 56 (cd56+), cluster designation 68 (cd68+) or cd 14+). predicting response and survival to neoadjuvant treatment of locally advanced triple-negative breast cancer remains a major challenge. many doubts still prevail over the role of new biomarkers in predicting different outcomes for tumors with the same stage and morphological characteristics. objectives and hypotheses: primary objective: to evaluate the association of the intratumoral lymphocytic infiltrate (tils) status profile in the core biopsy with complete pathological response (cpr) outcomes to neoadjuvant chemotherapy and progression-free survival (pfs). secondary objectives: to evaluate the association of the others biomarkers expression profile and the quality of tils with pfs and cpr. to determine the prevalence of a large immunohistochemical panel (ar, egfr, ck5/6, ck14, ck17, cd 117, p53, ki67 level, pd-l1 and pd-l2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes pd-1+, foxp3+, cd 4+ , cd8 +, cd 3+, cd56+, cd68+ and/or cd 14+), before and after neoadjuvant chemotherapy. to determine if the negativation of biomarkers after the systemic treatment is associated with cpr and pfs. methods: study design: a cohort with retrospective data collection and sectional analysis of pathological material. data source(s): medical records and pathological material. study population: women with locally advanced triple negative breast cancer consecutively enrolled at brazilian national cancer institute (inca) submitted to neoadjuvant treatment and subsequently operated. exposure(s): status of specified biomarkers. outcome(s): complete pathologic response and progression free survival and sample size estimations: with a type i error of 5% and study power of 80%, it is estimated that 155 patients are needed. statistical analysis: statistical analysis will be performed using spss (version 18.0 for windows, statistical package for social science (spss) inc., chicago, il). survival curves will be constructed using the kaplan-meier method.

Eligibility criteria:
inclusion criteria: * women older than 18 years * locally advanced tnbc (t3-4, any node, m0; any tumor, n1-3, m0) * patients submitted to anthracycline and taxane-based neoadjuvant chemotherapy and then operated between january 2010 and december 2014 at the brazilian national cancer institute. exclusion criteria: * patients with metastatic breast cancer; * other non-epithelial histologies of breast cancer; * pure ductal carcinoma in situ diagnoses are not eligible. * patients with scarce material for immunohistochemistry; * other primary synchronous or anachronistic tumors in the breast or other sites; * no prior immunotherapeutic, chemotherapeutic or antiandrogenic drugs allowed * patients treated with alternative neoadjuvant chemotherapy regimens (not based on anthracycline and taxane) or with only hormone therapy; * patients who received chemotherapy or who were operated outside the inca.

Keywords: neoadjuvant chemotherapy predictive biomarkers prognostic biomarkers complete pathological response tumor infiltrating lymphocytes pd-l1 pd-l2