ABSTRACT
The androgen receptor (AR) has been shown to be of potential prognostic importance in retrospective cohorts. We evaluated immunohistochemical AR expression on a tissue microarray of 673 core biopsies from primary breast cancer patients treated with neoadjuvant docetaxel/doxorubicin/cyclophosphamide (TAC) chemotherapy in the prospective GeparTrio phase-III trial. AR was detected in 53.2% of tumours. Lowest AR expression was detected in triple-negative breast cancers (TNBC) with 21.2%. Highest AR expression was observed in Luminal A-like tumours with 67%. In AR-positive tumours, pathological complete response (pCR) rate was 12.8% compared to 25.4% in AR-negative tumours (P < 0.0001). In multivariate analysis, AR independently predicted pCR (OR 1.86; 95% CI [1.16-2.79] P = 0.0086). Overall patients with an AR-positive tumour had a significant better disease-free (DFS) (AR-positive 78.9% vs. AR-negative 72.5%; log-rank P = 0.0329) and overall survival (OS) (88.8% vs. 82.7%; log-rank P = 0.0234) than those with AR-negative tumours. Stratified analysis revealed that in the TNBC subgroup, but not in the other subgroups defined by ER, PgR and HER2, AR expression predicted a better DFS (AR-positive 85.7% vs. AR-negative 65.5% log-rank P = 0.0544) and OS (95.2% vs. 76.2%; log-rank P = 0.0355). Within the non-pCR subgroup, AR positivity selected a group with a significant better DFS (P = 0.045) and OS (0.021) but not within the pCR group. Patients with an AR-negative tumour have a higher chance of achieving a pCR than those with an AR-positive one. But, patients with AR-positive tumours have a better survival especially if they did not achieve a pCR.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Lobular/metabolism , Neoadjuvant Therapy , Receptors, Androgen/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/mortality , Carcinoma, Lobular/pathology , Clinical Trials, Phase III as Topic , Cyclophosphamide/administration & dosage , Disease-Free Survival , Docetaxel , Doxorubicin/administration & dosage , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , Prospective Studies , Randomized Controlled Trials as Topic , Taxoids/administration & dosageABSTRACT
CASE REPORT: A 75-year old female was admitted to the intensive care unit because of a respiratory insufficiency during a bronchoscopy. Extubation was done rapidly. Two months before, the patient suffering from breast cancer without metastases underwent a radical mastectomy. Thoracic x-ray presented a progressive shadow. Differential diagnoses took into consideration neoplastic, infectious or immunologic causes. The following day the patient suffered from dyspnea. A cardiopulmonary resuscitation was without success. Obduction revealed a honeycomb lung. Histology presented an idiopathic lung fibrosis.
Subject(s)
Idiopathic Pulmonary Fibrosis/diagnosis , Aged , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Bronchoscopy , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Critical Care , Disease Progression , Fatal Outcome , Female , Humans , Idiopathic Pulmonary Fibrosis/pathology , Lung/pathology , Lymphocytosis/pathology , Mastectomy , Neoplasm Staging , Postoperative Complications/diagnosis , Postoperative Complications/pathology , Pulmonary Alveoli/pathology , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Tomography, X-Ray ComputedABSTRACT
Our aim was to determine the spectrum and accumulation of mutations in surveillance biopsies from Barrett's mucosa of individual patients during follow-up. We performed loss of heterozygosity (LOH) analysis of six recently described tumor suppressor genes relevant for the carcinogenesis of Barrett's adenocarcinoma from laser-microdissected, paraffin-embedded biopsy samples of Barrett's mucosa without or with low-grade dysplastic change. 118 biopsy samples from 26 patients were taken during surveillance programs in time intervals ranging between 6 and 51 months. We found no significant increase in LOH events at least in a 51-month interval. In two patients, Barrett's adenocarcinoma was diagnosed 6 months after the first diagnosis of Barrett's mucosa. Six of 26 patients did not show LOH. The remaining patients exhibited a striking variation of LOH patterns and accumulations in biopsy samples during follow-up. From our microsatellite marker panel, we were not able to define a single surrogate marker that could serve as a potential biomarker, indicating an increased risk of progression to Barrett's adenocarcinoma. However, LOH combinations, especially APC/p16(INK4) or APC/p53, deserve attention as putative biomarkers in future studies. Our results raise important questions regarding the biological dynamics of mutations in Barrett's mucosa in addition to the influence of sampling, especially with regard to the number of biopsies taken from Barrett's mucosa.
