Prognostic Role of Human Epidermal Growth Factor Receptor 2 Status in Premenopausal Early Breast Cancer Treated With Adjuvant Tamoxifen

BackgroundHormone therapy is the most prescribed systemic therapy for patients with breast cancer (BC). Some patients fail to respond to tamoxifen; one pathway seems to involve human epidermal growth factor receptor 2 (HER2) overexpression. To better understand this matter, we reviewed our single-center experience of premenopausal patients who were chemotherapy naive and treated with 5 years of tamoxifen for early-stage BC by focusing on estrogen receptor (ER), progesterone receptor, HER2 status, and Ki-67 proliferative index.Patients and MethodsWe reviewed 425 patients treated with tamoxifen for early-stage BC. Previous solid tumors, age less than 18 years, BC recurrences or contralateral tumor, tamoxifen discontinuation, adjuvant chemotherapy, and a follow-up shorter than 6 months were considered exclusions criteria of the study.ResultsAt a mean follow-up of 8.1 years, the mean (SD) time to local relapse was 6.7 ± 3.6 years; range, 2.0-10.7 years), whereas the mean (SD) time to distant metastases was 4.7 ± 2.3 years; range, 2.2-8.8 years). HER2 status did not influence local relapse–free survival (log-rank test, 0.40), distant metastases–free survival (log-rank test, 0.72), and overall survival rate (log-rank test, 0.87).ConclusionsResistance to tamoxifen is a complex trait, and its pathway is still unclear; in patients with BC, a multidisciplinary approach is highly recommended. In our experience, we did not find a statistically significant difference in tamoxifen treatment efficacy according to HER2 status.     

Intraperitoneal mesh prosthesis metastasis from pancreatic cancer,after laparoscopic hernia repair

Introduction There are very few case reports of metastasis on a mesh prosthesis following laparoscopic hernia repair in the literature and its incidence is completely unknown.

Case report A 76-year-old male patient presented in December 2013 with a suspicious malignant lesion of the pancreatic tail on the MRI. He was also complaining of a painful mass in the right para-rectal area. An exploratory laparoscopy performed in December 2013 revealed microscopic whitish peritoneal implants in the left hypochondrium and a massive metastasis involving a mesh prosthesis placed é years before in the right para-rectal area. The pathology report of biopsies of the mesh confirmed a metastasis compatible with a pancreatic tumor.

Discussion Possible modes of metastasis and limited published data to date on mesh prosthesis metastasis are presented. This situation can be assimilated to port-site metastasis after laparoscopy.

Conclusion A mesh prosthesis metastasis after laparoscopic hernia repair is very rare.     

The ups and downs of somatic cell nucleus transfer (SCNT) in humans

Achieving successful somatic cell nuclear transfer (SCNT) in the human and subhuman primate relative to other mammals has been questioned for a variety of technical and logistical issues. Here we summarize the gradual evolution of SCNT technology from the perspective of oocyte quality and cell cycle status that has recently led to the demonstration of feasibility in the human for deriving chromosomally normal stem cells lines. With these advances in hand, prospects for therapeutic cloning must be entertained in a conscientious, rigorous, and timely fashion before broad spectrum clinical applications are undertaken.     

Pleuro-pneumo-phreno-pericardiectomy with pericardial and diaphragmatic plasty]

Aim of the paper is to evaluate 43 extrapleural pneumonectomy performed from 1988 to May 2000. Criteria for extrapleural pneumonectomy were pleural biopsy by thoracoscopy, potentially completely resectable unilateral disease by computed tomography and predicted postresection forced expiratory volume >1,3 L/sec. The resections regarded 33 pleural mesothelioma, 9 pleural lung-carcinosis and 1 pleural melanoma effusion. The perioperative mortality rate was 2,2% (1 death) and morbidity 21,4%.     

Concurrent chemotherapy with carboplatin + 5-fluorouracil and radiotherapy in advanced squamous cell head and neck carcinoma: a retrospective single institution's study.

AIMS AND BACKROUND: The purpose of the study was to analyze the long-term follow-up of a single institution's experience with a regimen of concomitant carboplatin + 5-fluorouracil (CBDCA + 5-FU) infusion and radiotherapy. STUDY DESIGN: Fifty-eight patients with locally advanced squamous cell head and neck cancer treated with combined chemoradiotherapy between March 1990 and October 1998 were reviewed retrospectively. According to the TNM tumor staging, 6 patients had stage II, 21 stage III and 31 stage IV tumors. The chemotherapy regimen consisted of the combination of 5-FU and CBDCA, for a total of 3 cycles. Both drugs were given as 4-day continuous intravenous infusions during the first and fourth week of radiation therapy: 5-FU at 1000 mg/m2 per day and CBDCA at 75 mg/m2 per day. Radiation was given in single daily fractions of 1.8 to 2 Gy, to a total dose of 66 to 70 Gy. RESULTS: After the completion of chemotherapy and radiotherapy, 34 patients (58.6%) achieved clinical and radiological (computerized tomography and/or magnetic resonance imaging) complete remission, 15 patients (25.9%) partial remission >50%, 5 patients (8.6%) partial remission <50%, and 4 patients (6.8%) had no response. Toxicity was intensive but tolerable. After a median follow-up of 25 months, overall survival and recurrence-free survival estimated for the whole patient population was 52% at 3 years, and the median length of recurrence-free survival was 23 months. CONCLUSIONS: Our regimen combining standard single daily fraction radiation with the conventional dose of CBDCA and 5-FU was given without dose modification regardless of the severity of the adverse effects. It gave a clinical complete response at the primary site in 58.6% of patients. With a 52% projected 3-year overall survival, our series compares favorably with similar studies in the literature. Therefore, our results with concomitant CBDCA/5-FU infusion and radiotherapy are encouraging and suggest that CBDCA can be substituted for cisplatin with a good therapeutic index.     

HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples

Background Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations.Methods Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR.Results We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples.Conclusions We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.Subject terms: Diagnostic markers, Biliary tract cancer     

Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer

We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy. The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; ≥50% stromal) and correlated with distant disease-free survival. Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N = 209) were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (hazard ratio [HR] = 1.27 p interaction = 0.014 [DCN], HR = 1.58, p interaction = 0.027 [PLAU], HR = 1.71, p interaction = 0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR = 0.73 p interaction = 0.47 [DCN], HR = 0.71, p interaction = 0.73 [PLAU], HR = 0.84; p interaction = 0.36 [HER2STROMA]). Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC <50%). In conclusion, reactive stroma in HER2-positive/ER-negative early breast cancer tumors may predict resistance to adjuvant trastuzumab therapy.     

Molecular basis of beta-thalassemia intermedia in a southern Italian region (Puglia).

We investigated the molecular bases for a mild phenotype by alpha-, beta- and gamma-globin gene analyses in 22 patients with transfusion-independent thalassemia intermedia (15) or a late-presenting form of thalassemia major (7) originating from Puglia, a region of southern Italy. Twenty-two patients with thalassemia major served as controls. The beta+ IVS-I nt 6 of the beta-globin gene and the C----T substitution at position -158 5' of the G gamma-globin gene were detected more frequently in patients with thalassemia intermedia or late-presenting thalassemia major considered together as compared to those affected by typical transfusion-dependent thalassemia major. Three of 15 patients with thalassemia intermedia had the triple alpha-globin gene arrangement in the heterozygous (2) or homozygous state (1) in association with heterozygous beta zero-thalassemia. From these results, we may conclude that the inheritance of a mild beta-thalassemia allele such as the beta+ IVS-I nt 6 mutation, in the homozygous or heterozygous state, the coinheritance with homozygous beta zero-thalassemia of the -158 (C----T) G gamma gene promoter mutation and the presence of heterozygous beta-thalassemia/triple alpha-globin gene arrangement are the most common reasons accounting for the development of attenuated forms of beta-thalassemia in Puglia.