ABSTRACT
PURPOSE: Hormone receptor (HR)-positive breast cancer (BC) shows a poor response to neoadjuvant chemotherapy (NACT). New treatment targets like the Cyclin D1-CDK4/CDK6 complex are promising adjuvant/post-neoadjuvant therapeutic strategies. Evaluating Cyclin D1 overexpression in residual tumor could recognize those patients that benefit most from such post-neoadjuvant treatment. In this study, we determined Cyclin D1 expression in residual BC after NACT. Secondary aims were to correlate Cyclin D1 expression levels with clinicopathological parameters and to assess its prognostic value after NACT. METHODS: We retrospectively assessed the nuclear expression of Cyclin D1 on tissue microarrays with residual tumor from 284 patients treated in the neoadjuvant GeparTrio (n = 186) and GeparQuattro (n = 98) trials. Evaluation was performed with a standardized immunoreactive score (IRS) after selecting a cut-off value. RESULTS: A high expression level (IRS ≥ 6) of Cyclin D1 was found in 37.3% of the assessed specimens. An increased Cyclin D1 expression was observed in HR-positive tumors, compared to HR-negative tumors (p = 0.02). Low Cyclin D1 levels correlated with clinical tumor stage 1-3 (p = 0.03). Among patients with HR-positive/Her2-negative tumors and high Cyclin D1 expression, a better disease-free survival (DFS) was graphically suggested, but not significant (p = 0.21). CONCLUSION: Our study demonstrates a measurable nuclear expression of Cyclin D1 in post-neoadjuvant residual tumor tissue of HR-positive BC. Cyclin D1 expression was not prognostic for DFS after NACT. Our results and defined cut-off suggest that the marker can be used to stratify tumors according to protein expression levels. Based on this, a prospective evaluation is currently performed in the ongoing Penelope-B trial.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Breast Neoplasms/therapy , Breast/pathology , Cyclin D1/metabolism , Adult , Biomarkers, Tumor/analysis , Breast/cytology , Breast/surgery , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cell Nucleus/metabolism , Cyclin D1/analysis , Disease-Free Survival , Female , Gene Expression Profiling/methods , Humans , Mastectomy , Middle Aged , Neoadjuvant Therapy/methods , Neoplasm, Residual , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Tissue Array Analysis/methodsABSTRACT
BACKGROUND: There is a lack of uniform criteria for the diagnosis and management of tuberculosis (TB) in children in Cali, Colombia. Addressing TB in children is a challenge in this setting, under both programmatic and research conditions. OBJECTIVES: To facilitate the diagnostic assessment of TB in a paediatric cohort of TB household contacts. METHODS: A diagnostic and management algorithm (DMA) was used to assess children exposed to adult TB cases, according to clinical and epidemiological findings and under programmatic conditions. On the basis of diagnostic tests, cases were classified as TB exposure, TB infection, suspected TB, possible TB or confirmed TB and then submitted to a management plan. This was a prospective pilot study nested within a national cohort study of the transmission dynamics of Mycobacterium tuberculosis, undertaken in Colombia during 2005-2008. RESULTS: During 24 months of follow-up, 54 of 217 children met the criteria for assessment by DMA, 18 of whom (33%) were considered to be TB incident cases (new TB cases among household contacts). The main clinical findings were failure to thrive and cough lasting >21 days. Only one case was smear-positive and culture-confirmed TB. TB treatment was given to 16 children and they demonstrated clinical and radiographic resolution at follow-up. Conducting the study under programmatic conditions demonstrated barriers to accessing competent radiological evaluation, correct interpretation of the tuberculin skin test, and proper specimen collection. CONCLUSION: Structured assessment using DMA facilitated the detection of incident TB cases. The study identified potential barriers to addressing childhood TB in Cali.
