BIRC5 (survivin): a pejorative prognostic marker in stage II/III breast cancer with no response to neoadjuvant chemotherapy.

PURPOSE: Neoadjuvant systemic therapy (NAC) is currently used in the treatment of stage II/III breast cancer. Pathological complete response as a surrogate endpoint for clinical outcomes is not completely validated for all subgroups of breast cancers. Therefore, there is a need for reliable predictive tests of the most effective treatment. METHODS: We used a combination of predictive clinical, pathological, and gene expression-based markers of response to NAC in a prospective phase II multicentre randomized clinical trial in breast cancer patients, with a long follow-up (8 years). This study concerned the subpopulation of 188 patients with similar levels of pathological response rates to sequential epirubicin/cyclophosphamide and docetaxel to determine predictive marker of pCR and DFS. We used a set of 45 genes selected from high throughput analysis and a standardized RT-qPCR. We analyzed the predictive markers of pathological complete response (pCR) and DFS in the overall population and DFS the subpopulation of 159 patients with no pCR. RESULTS: In the overall population, combining both clinical and genomic variables, large tumor size, low TFF1, and MYBL2 overexpression were significantly associated with pCR. T4 Stage, lymphovascular invasion, negative PR status, histological type, and high values of CCNB1 were associated with DFS. In the no pCR population, only lymphovascular invasion and high values of BIRC5 were associated with DFS. CONCLUSIONS: We confirm the importance of ER-related and proliferation genes in the prediction of pCR in NAC-treated breast cancer patients. Furthermore, we identified BIRC5 (survivin) as a main pejorative prognostic factor in patients with breast cancers with no pCR. These results also open perspective for predictive markers of new targeted therapies.

p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes.

BACKGROUND: We hypothesized that, among molecular subclasses of breast cancer, p53 status may have a differential predictive value for the efficacy of anthracyclines/alkylating agents-based regimen. We analysed the efficacy of a preoperative combination between 5-fluorouracil, anthracyclines and cyclophosphamide according to both p53 status and molecular classification. PATIENTS AND METHODS: Oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) expression and p53 status were determined by immunohistochemistry in 293 samples from two different centres. A logistic regression model was used for multivariate analysis of predictors for pathological complete response (pCR). RESULTS: p53 immunostaining (54%) was associated with high grade (P = 0.002) and ER negativity (P = 0.04). p53 was detected in 59% of triple-negative tumours (ER-/PgR-/HER2-, n = 120 patients). In the overall population, pCR (9.6%) was independently predicted by high tumour grade (P = 0.002) and ER/PgR/HER2 triple negativity (P = 0.0004), but not by p53 status (P = 0.12). p53 immunostaining was associated with a trend for a higher rate of pCR in triple-negative tumours [relative risk (RR) = 2.5, 95% confidence interval (CI) = 0.8-7.5, P = 0.09], but not in non-triple-negative tumours (RR = 0.73, 95% CI = 0.16-3.3, P = 0.69). CONCLUSION: p53 status may have a different predictive value for efficacy of anthracycline/alkylating agents-based regimen in each molecular subclass, a result which may explain the different results reported in literature.

Quantitative assessment of cell viability and apoptosis in cultured epidermal autografts: application to burn therapy.

Cultured epidermal autografts (CEA) have been used in the treatment of burns for almost two decades but the clinical results are still inconsistent. In a group of 37 patients with extensive burn wounds admitted to the University Hospital of Lausanne, CEA take ranged between 10 and 100% with a mean of 65%. To investigate CEA efficacy in burns, twelve CEA preparations were tested for their biological properties with particular emphasis on the balance between cell viability and apoptosis. Apoptosis was evaluated by in situ end-labeling (TUNEL), detection of DNA fragments in CEA extracts and analysis of caspase-3 activity. All CEA samples displayed a high cell viability (> 90%) and a low apoptosis rate (< 6%). However, several biological parameters including the activity of transglutaminase showed wide interindividual variability suggesting that CEA therapeutic efficacy could be partly determined by intrinsic biological factors.

[Hypertrophic scars and keloids: which therapeutic options today?]. / Cicatrices hypertrophiques et chéloïdes: quelles options thérapeutiques aujourd'hui?

Hypertrophic scars and keloids are a hyperproliferative response of connective tissue to trauma. Histologically the difference between the two is that keloids invade normal tissue whereas hypertrophic scars remain confined within the original wound. A variety of treatments have been proposed, which we will review according to their efficiency. Prevention of pathological scarring will also be discussed, and we will present our current attitude to treat these scars. As a surgical treatment for keloids, we have been using the intralesional technique which we think gives better results.

[Breast augmentation: indications, types of prostheses, surgical techniques, complications, results]. / L'augmentation mammaire: indications, types de prothèses, techniques opératoires, complications, résultats.

Augmentation mammaplasty is one of the most frequent surgical procedures in plastic surgery. The indications and techniques are precise and should be closely observed. Silicone gel implants are still used in Europe and multiple epidemiologic studies have failed to demonstrate an association between silicone breast implants and autoimmune disease. After a short historical review, we will present the indications, techniques and complications. As capsular contracture is the main complication, we shall discuss the latest issues. Data was collected on a group of patients using a systematic questionnaire and clinical follow-up. Patients' satisfaction is optimal in the absence of capsular contracture. We are convinced that silicone breast implants have an appropriate texture and give excellent aesthetic results. We are satisfied with silicone breast implants and continue to think that this device has an appropriate texture and gives excellent aesthetic results.

[Principles of physics and application of the laser in plastic surgery]. / Principes physiques et application du laser en chirurgie esthétique.

Recent advances in laser technology have expanded the surgeon's possibilities to treat various cutaneous lesions, as well as proposing a new tool for skin rejuvenation. Review of the basic physical principles of laser energy then overview of the different lasers used in plastic surgery as well as some of their clinical applications.