Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane-based chemotherapy in operable triple-negative breast cancer: identification of biologically defined signatures predicting treatment impact.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors for some of which the epithelial growth factor receptor (EGFR) pathway may play an important role. We investigated the efficacy and toxicity of an anti-EGFR antibody (panitumumab) combined with a standard neoadjuvant anthracycline-taxane-based chemotherapy in patients with operable, stage II-III, TNBC. PATIENTS AND METHODS: Treatment in this multicentric neoadjuvant pilot study consisted of panitumumab (9 mg/kg) for eight cycles q.3 weeks combined with four cycles of 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC100: 500/100/500 mg/m(2)) q.3 weeks, followed by four cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Following therapy, all patients underwent surgical resection. Pathologic complete response (pCR) in assessable patients was the main end point while clinical response, toxicity and ancillary studies were secondary end points. Paraffin-embedded and frozen tumor samples were systematically collected with the aim to identify predictive biomarkers of efficacy and resistance in order to select biologically defined subpopulations for potential further clinical development of the anti-EGFR antibody. RESULTS: Sixty patients were included with 47 assessable for pathologic response. The pCR rates were 46.8% [95% confidence interval (CI): 32.5% to 61.1%] and 55.3% [95% CI: 41.1% to 69.5%] according, respectively, to Chevallier and Sataloff classifications. The complete clinical response (cCR) rate was 37.5%. Conservative surgery was carried out in 87% of cases. Toxicity was manageable. The association of high EGFR and low cytokeratin 8/18 expression in tumor cells on one hand and high density of CD8+ tumor-infiltrating lymphocytes on the other hand were significantly predictive of pCR. CONCLUSIONS: Panitumumab in combination with FEC100 followed by docetaxel appears efficacious, with acceptable toxicity, as neoadjuvant therapy of operable TNBC. Several biomarkers could help define large subsets of patients with a high probability of pCR, suggesting a potential interest to further develop this combination in biologically defined subgroups of patients with TNBC. CLINICAL TRIAL NUMBER: NCT00933517.

[Cancer and nipple discharge]. / Cancer et écoulement par le mamelon.

The authors, in a retrospective study, have looked at the clinical and paraclinical parameters that suggest that a cancer may be present when there is a nipple discharge. By using logistic regression on these criteria a model has been able to be constructed with four variables (bloody discharge, and associated palpable tumour, a suspicious mammographic appearance and atypical or proliferating cells in cytology). The probability of a cancer being present varies between three per thousand when none of the four variables are present to 99.1% when all four are present. A first outline of the therapy that can be used is suggested.

[Ovarian cysts. The respective role of clinical examination, echography, biological markers and cytology]. / Kyste de l'ovaire. Places respectives de l'examen clinique de l'échographie, des marqueurs biologiques et de la cytologie.

The authors assess the value of clinical examinations and para-clinical examinations carried out when an ovarian cyst is discovered. They try to find out whether a diagnosis of the aetiology is possible before the operation and particularly whether the cystic forms of cancer can be detected pre-operatively. The study is concerned with a retrospective assessment of 358 patients. The first line of investigation was seen to be ultrasound which is effective in 91% of cases. When the level of CA-125 is above 35 U/ml that suggests that there may be a malignant neoplasm present. The test is sensitive to about 78.6% and specific at 76%. 96 cysts were considered to be benign using clinical and para-clinical examinations and were punctured under ultrasound control or laparoscopically. The cytology could not be interpreted in 15%. Only one borderline tumour of the ovary was found. 25.3% of cysts that had been aspirated recurred and this is a high figure. Given these figures, the authors suggest a diagnostic and therapeutic program for ovarian cysts.

[Epidemiology, diagnostic approach, prognostic factors of ovarian cystadenocarcinoma]. / Epidémiologie, moyens diagnostiques, facteurs pronostiques des cystadénocarcinomes de l'ovaire.

The number of ovarian cancers is increasing and a parallel increase has been observed in the mortality rate of this disease. Epidemiological surveys have elicited contributing factors such as feeding habits, environmental, individual and familial factors. The ovary being a deep-seated organ, the diagnosis is difficult and rests on physical examination and, chiefly, ultrasonography. The prognosis is poor, with an overall survival rate of about 30 p. 100 at five years.

[Scarred uterus: management]. / L'utérus cicatriciel: conduite à tenir.

Uterine rupture was seen in a total of 1.1 per cent of 10,012 pregnancies involving scarred uteri. Rupture frequency during pregnancy was estimated as 0.4 per cent, although this is doubtless an underestimate due to the occasionally asymptomatic nature of the condition. Maternal mortality was nil. Fetal mortality related to uterine rupture was also nil, but psychomotor backwardness was seen in one case of uterine rupture after completion of 30 weeks of pregnancy. These results and those of the literature show that maternal and fetal risks linked to uterine rupture are significant during pregnancy and very small during confinement. The indications for systematic prophylactic cesarean section are discussed. An increased frequency of uterine tests could decrease the overall rate of cesarean sections without danger to mother or baby.

[Second-trimester abortion: a difficult, unresolved problem]. / L'avortement du deuxième trimestre: un problème difficile, non résolu.

The authors review the various methods proposed for the late evacuation of the uterus. They report their experience of intra-amniotic injection of prostaglandins and, more recently, the use of extra-amniotic injections. They have found this latter technique to be unsatisfactory. Evacuation following dilatation under local anaesthetic, despite a few complications, appears to be effective... but the problem is far from being resolved.