Compliance to genomic test recommendations to guide adjuvant chemotherapy decision-making in the case of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, in real-life settings.

BACKGROUND: Genomic tests are a useful tool for adjuvant chemotherapy decision-making in the case of hormone receptor-positive (HR+), and human epidermal growth factor receptor 2-negative (HER2-) breast cancer with intermediate prognostic factors. Real-life data on the use of tests can help identify the target population for testing. METHODS: French multicentric study (8 centers) including patients, all candidates for adjuvant chemotherapy for HR-positive, HER2-negative early breast cancer. We describe the percentage of tests performed outside recommendations, according to the year of testing. We calculated a ratio defined as the number of tests required to avoid chemotherapy for one patient, and according to patient and cancer characteristics. We then performed a cost-saving analysis using medical cost data over a period of 1 year from diagnosis, calculated from a previous study. Finally, we calculated the threshold of the ratio (number of tests required to avoid chemotherapy for one patient) below which the use of genomic tests was cost-saving. RESULTS: A total of 2331 patients underwent a Prosigna test. The ratio (performed test/avoided chemotherapy) was 2.8 [95% CI: 2.7-2.9] in the whole population. In the group following recommendations for test indication, the ratio was 2.3 [95% CI: 2.2-2.4]. In the case of non-abidance by recommendations, the ratio was 3 [95% CI: 2.8-3.2]. Chemotherapy was avoided in 841 patients (36%) following the results of the Prosigna test. The direct medical costs saved over 1 year of care were 3,878,798€ and 1,718,472€ in the group of patients following test recommendations. We calculated that the ratio (performed test/avoided chemotherapy) needed to be under 6.9 for testing to prove cost-saving. CONCLUSION: The use of genomic testing proved cost-saving in this large multicentric real-life analysis, even in certain cases when the test was performed outside recommendations.

[Surgery or not on an atypical breast lesion? Taking anxiety into account in shared decision support from a prospective cohort of 300 patients]. / Opérer ou non une lésion atypique du sein ? Prise en compte de l'anxiété dans l'aide à la décision partagée à partir d'une cohorte prospective de 300 patientes.

INTRODUCTION: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions (ABL)". Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. METHODS: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. RESULTS: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, P<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). CONCLUSION: Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.

Lanreotide Autogel 90 mg and lymphorrhea prevention after axillary node dissection in breast cancer: a phase III double blind, randomized, placebo-controlled trial.

AIM: The aim of this study was to assess the efficacy of Lanreotide Autogel 90 mg PR to prevent lymphorrhea after axillary dissection in breast cancer. METHODS: A Phase III double-blind, randomized, placebo-controlled trial was performed between April 1st, 2008, and December 31st, 2010. The primary endpoint was the lymphorrhea volume (ml) in the axillary drain during the first four postoperative days. The secondary end points were the number of days until axillary drain removal, hospital stay duration (days), lymphorrhea volume (ml) up to days 15, 30 and 180, number of cases with seroma aspiration and number of seroma aspirations, evaluation of wound, arm pain and mobility on days 15, 30 and 180. RESULTS: A total of 148 patients were recruited for the study. Altogether 145 patients were randomized and analysed on an intention-to-treat basis. On the day before surgery 73 patients received the placebo and 72 patients received lanreotide. At four postoperative days, there was a tendency towards a reduction of the lymphorrhea volume in the lanreotide group (median 292 ml, range 1-965 ml) as compared to the placebo group (median 337 ml, range 0-1230 ml), although it was not statistically significant (p = 0.18). There was no significant difference for the secondary end points. In the group with axillary dissection performed alone (n = 24), the lymphorrhea volume was shown to be significantly reduced in the lanreotide group, (p = 0.035) as compared to the placebo group. CONCLUSION: Our study did not identify any overall significant reduction of lymphorrhea on lanreotide.

Oncogramme responses of breast tumour cells treated with herceptin correlate with HER2/C-ERB B2 pathological status.

BACKGROUND: Among targeted therapies, Herceptin is a monoclonal antibody successfully used on patients with breast cancer expressing Human Epidermal Growth Factor Receptor-2 (HER2 receptors). Oncogramme is a method developed to predict anticancer activity of molecules and thus individualize chemotherapeutic strategies. Before this ex vivo test enters clinical validation, it was desirable to correlate breast cancer cell responses to Herceptin observed through Oncogramme with HER2 expression by these cells. MATERIALS AND METHODS: Breast tumour fragments were dissociated and obtained cells were cultured in defined medium. After Herceptin treatment, cytotoxicity was detected by cell death analysis, and responses compared to tumour HER2 status were determined by pathologists. RESULTS: Cell responses to increasing doses of Herceptin obtained with Oncogramme were in correlation with HER2 expression. CONCLUSION: Comparison between Herceptin responses obtained with Oncogramme and HER2 status of breast tumour cells confirmed that Oncogramme is a reliable method for prediction of patient cell sensitivity to anticancer drugs.

Oncogramme, a new promising method for individualized breast tumour response testing for cancer treatment.

BACKGROUND: Breast cancer is the most widely spread cancer in the world, attracting much research and individualized tumour response testing (ITRT) methods are now used to individualize patient chemotherapeutic administrations. A new ITRT method was developed with optimized processing. MATERIALS AND METHODS: Breast tumour fragments were separated and the cells seeded in a foetal calf serum-free defined medium. After various chemotherapeutic treatments, cytotoxicity was determined by cell death detection with calcein acetoxymethyl and ethidium homodimer labelling. RESULTS: The culture medium allowed breast tumour cell proliferation in culture, while preventing fibroblastic cell survival. Moreover, the cell death analysis gave rise to a chemoresistance profile called an Oncogramme, with statistically significant values. CONCLUSION: The Oncogramme is a new ITRT method which can predict patient cell sensitivities to chemotherapeutics and should be validated by a new phase I clinical trial.

[Low invasion in sentinel lymph node according to the European Working Group In Breast Screening Pathology (EWGBSP) recommendations and non sentinel invasion risk in breast cancer]. / Atteinte minime du ganglion sentinelle selon les recommandations de l'European Working Group in Breast Screening Pathology (EWGBSP) et risque d'atteinte non sentinelle dans le cancer du sein.

OBJECTIVE: Because of variability in histopathological interpretations in studies, it's difficult to elucidate the risk of non-sentinel lymph node involvement in case of sentinel node nanometastases (lesions not larger than 0.2 mm) and micrometastases (lesions not larger than 2 mm but larger than 0.2 mm) in breast cancer. In this study, we have evaluated this risk according to the European Working Group for Breast Screening Pathology (EWGBSP) recommendations. PATIENTS AND METHODS: Among patients who underwent sentinel lymph node dissection between February 2001 and April 2008 in our unit, we reviewed the files of patients who had sentinel lymph node involvement smaller than 2mm. A second interpretation of all sentinel lymph node sections was made according to the EWGBSP recommendations. Each patient had complete axillary dissection. RESULTS: Among 608 patients who had sentinel lymph node dissection for breast cancer, 72 (11.84%) had sentinel lymph node involvement smaller than 2 mm (27 pN0i+ and 45 pN1mi). The percentage of pN1mi patients who had non sentinel involvement is 8.89%. None of pN0i+ patients had non sentinel involvement. DISCUSSION AND CONCLUSION: After making a minimal sentinel lymph node involvement strict interpretation according to EWGBSP restrictive recommendations, nanometastases rate was smaller. Any non sentinel involvement was detected in case of sentinel lymph node nanometastases.

Axillary recurrence after negative sentinel lymph node biopsy under local anesthesia in breast cancer.

UNLABELLED: The procedure known as sentinel lymph node biopsy (SLNB) under local anesthesia (LA) allows surgical teams to avoid the uncertainties of frozen tissue examination and to perform axillary dissection on patients who have been informed of the risks of lymph node invasion prior to the procedure. OBJECTIVE: In the absence of studies that assess the risk of obtaining false negatives during SLNB under LA, we believed it would be relevant to do a study of the safety of SLNB under LA to ensure that the risk of axillary recurrence is as low as with SLNB carried out in the traditional manner under general anesthesia. Through the experience of the Department of Gynecological Surgery at the Limoges CHU, we were able to assess the risk of axillary recurrence after SLNB under LA. MATERIALS AND METHODS: Between July 2001 and November 2008, 319 SLNB under LA was performed in cases of invasive breast cancer. Axillary dissection was done in 125 cases. In total, 194 patients underwent SLNB with no lymph node invasion and without additional axillary dissection. Follow-up was monitored until May 30, 2008. RESULTS: With a median follow-up period of 39.5 months, there were no patients with axillary recurrence. We recorded 6 local recurrences and 3 distant metastases. CONCLUSION: With an experienced team, SLNB under LA is a procedure that does not expose patients to a greater risk of axillary recurrence than SLNB carried out in the traditional manner under general anesthesia.

[Pleural metastases of sclerosing epithelioid fibrosarcoma]. / Métastases pleurales d'un fibrosarcome épithélioïde sclérosant.

Sclerosing epithelioid fibrosarcoma is a rare tumor recently described. The histological presentation can be confused with certain soft tissue benign tumors and certain sarcomas. Metastatic spread is usually late in the natural course of the disease. We report a case of recurrent sclerosing epithelioid fibrosarcoma with pleural metastases which developed ten years after surgical resection of the primary tumor. The tumor was formed by small uniform round epithelioid cells with a clear cytoplasm. The tumor cells were strongly positive for vimentin. This clinical case is discussed in light of other cases reported in the literature.

Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?

This study evaluated by immunohistochemistry (IHC) immune cell response during neoadjuvant primary systemic therapy (PST) with trastuzumab in patients with HER2-positive primary breast cancer. In all, 23 patients with IHC 3+ primary breast cancer were treated with trastuzumab plus docetaxel. Pathological complete and partial responses were documented for nine (39%) and 14 (61%) patients, respectively. Case-matched controls comprised patients treated with docetaxel-based PST without trastuzumab (D; n=23) or PST without docetaxel or trastuzumab (non-taxane, non-trastuzumab, NT-NT; n=23). All surgical specimens were blind-analysed by two independent pathologists, with immunohistochemical evaluation of B and T lymphocytes, macrophages, dendritic cells and natural killer (NK) cells. Potential cytolytic cells were stained for Granzyme B and TiA1. HER2 expression was also evaluated in residual tumour cells. Trastuzumab treatment was associated with significantly increased numbers of tumour-associated NK cells and increased lymphocyte expression of Granzyme B and TiA1 compared with controls. This study supports an in vivo role for immune (particularly NK cell) responses in the mechanism of trastuzumab action in breast cancer. These results suggest that trastuzumab plus taxanes lead to enhanced NK cell activity, which may partially account for the synergistic activity of trastuzumab and docetaxel in breast cancer.

[Hybrid Capture 2 vs HPV Consensus kit: comparison of 2 assays for human papillomavirus detection and typing]. / Comparaison de deux techniques de détection et de typage des papillomavirus humains: Hybrid Capture 2 et HPV Consensus kit.

BACKGROUND: Many laboratories use the DNA Hybrid Capture 2 HPV-high risk assay (Digene) to detect and type oncogenic HPV. The aim of this work was to compare this assay with a new HPV genotyping assay: HPV Consensus kit (Argène). Actually, this assay is not commercially available. MATERIALS AND METHODS: Ninety-four cervical samples were tested with both the routine assay Hybrid Capture 2 and the HPV Consensus kit. Discordant results were analysed by amplification with a nested PCR and sequencing of amplified products. RESULTS: Only 81 results could be analysed concerning the oncogenic risk. The overall concordance was 92,6%. But we find 13 "generic" results with the HPV Consensus kit, the generic probe including high risk and low risk genotypes. CONCLUSION: HPV Consensus kit results showed a better detection sensitivity for this assay than Hybrid Capture 2 assay. Nevertheless, "generic" results give no information about the oncogenic risk of the HPV detected in a sample.

[MRI evaluation of primary chemotherapy response in breast cancer]. / Evaluation par IRM de la réponse à la chimiothérapie d'induction dans les cancers du sein.

The aim of this work was to evaluate the value of contrast enhanced MRI for determination of response to neoadjuvant chemotherapy (type FEC) in breast cancer according to two parameters: size of the enhancing tumor and the maximum relative enhancement curve (MRC) in the same tumor area. Twenty women with breast cancer (15 invasive ductal carcinomas and 5 invasive lobular carcinomas) T2 (n = 8) or T3 (n = 12) were evaluated by physical examination and MRI after a minimal of three courses of FEC and prior to surgery. Data from physical examination and imaging studies were compared to histopathological findings. Physical examination estimated correctly the residual tumor size in 45% of cases and MRI in 60% with 3 false negative cases. Among evaluated patients with MRI measurable residual tumor, tumor size was underestimated in 69% of the cases and overestimated in 31% of the cases. A MRC flattening was observed in 5 cases among the patients with a partial response or clinical stable disease correlated with a poor cellular density in the microscopic findings. MRI monitoring of chemotherapy response can be useful for guiding surgery. Therefore, underestimation of the residual tumor size and false negative rate are remaining problems.

[How to avoid the uncertainties of intraoperative examination of the sentinel lymph node in breast cancer?]. / Comment éviter les aléas de l'examen extemporané du ganglion sentinelle dans le cancer du sein?

The sentinel lymph node procedure is now admitted by many teams for axillary evaluation in the early stage of breast cancer. The classical technique consists in an intraoperative examination of the sentinel lymph node under general anaesthesia during tumorectomy, deciding whether or not complete axillary lymphadenectomy must be done. Intraoperative examination seems to us to have a poor predictive value. In the case of a false positive, the surgeon would perform lymphadenectomy unnecessarily, while a false negative would mean that the patient would have to be re-operated for lymphadenectomy once the definitive results have become available. For all these reasons, we propose the detection of the sentinel lymph node under local anaesthesia and to await its definitive analysis before carrying out tumorectomy on the patient and axillary lymphadenectomy if necessary under general anesthesia. Hence, we consider that the best way to avoid the uncertainties of an intraoperative examination of the sentinel lymph node is not to carry out intraoperative examinations.

Detection of the sentinel lymph node under local anaesthesia in early-stage breast cancer: feasibility study in a series of 78 unselected patients.

AIMS: To evaluate the feasibility of excision of the sentinel lymph node under local anaesthesia in early-stage breast cancer. METHODS: Sentinel lymph node detection under local anaesthesia was carried out on all patients presenting with breast cancer at Stage T0, T1 or T2 < 3 cm and N0, M0. The lymph node was mapped using a radioisotope and patent blue dye and lymphoscintigraphy was routinely performed. No premedication was given, and local anaesthesia was carried out with xylocaine. The patients underwent tumorectomy one week later under general anaesthesia, with or without complete axillary dissection, depending on the results of the definitive histopathological examination of the sentinel lymph node. RESULTS: 78 patients underwent this procedure over a period of 20 months. The procedure was successful in 76 out of the 78 patients, with one failure in mapping and one failure in detection (detection rate = 97.4%). The mean time to detection was 21 min (range: 6-45). It was unnecessary to interrupt the procedure due to patient discomfort in any of the cases. One allergic reaction to patent blue dye was noted and required corticosteroid therapy without interruption of the procedure. The time to detection was correlated with the experience of the surgeon carrying of the procedure, the patient's body mass index and the number of labelled lymph nodes found at lymphoscintigraphy. CONCLUSION: We have shown that it is feasible to detect the sentinel lymph node under local anaesthesia in an unselected population. Using this procedure, patients can undergo surgery with the knowledge of their axillary lymph node status while at the same time avoiding the uncertainties of an intraoperative examination of the sentinel lymph node--a source of many false negatives, particularly in the event of micrometastases.

How to avoid the uncertainties of intraoperative examination of the sentinel lymph node in breast cancer?

Numerous researchers have confirmed the diagnostic relevance of the sentinel lymph node (SLN) examination in breast carcinoma. Many technical problems are analyzed which are correlated with the intraoperative examination of the SLN and its sensitivity and specificity. In order to avoid the incidence of false positive or false negative intraoperative diagnoses, the authors propose the examination of SLN under local anesthesia, awaiting its definitive analysis before carrying out tumorectomy and/or axillary lymphadenectomy.

[Colon cancer in pregnancy]. / Cancer colique et grossesse.

Colon cancers arise only rarely in the course of a pregnancy. Yet colon obstruction, perforation and metastatic spread seem to occur more frequently in this setting than with the average colon cancer. Perhaps this is due to the immunotolerance which accompanies pregnancy. No case of epidermoid (squamous cell) cancer of the colon has been previously described in a pregnant woman. This conjunction has a catastrophic prognosis: the diagnosis of colon tumor is delayed since symptoms are masked by the pregnancy, and epidermoid colon cancer is a particularly aggressive lesion. A major sub-diaphragmatic surgical procedure can be performed with reasonable safety to mother and fetus. Radiotherapy is contraindicated. Neo-adjuvant chemotherapy can be administered although the risks to the fetus are not well known. During the first trimester, a therapeutic abortion can be proposed to optimise the treatment of the mother. During the second and third trimesters, treatment of the mother exposes the fetus to the risk of malformations or premature delivery; delay in maternal treatment in hopes of prolonging the pregnancy in order to obtain a viable neonate diminish the chances of maternal survival.

[Benign mesothelioma of the uterus. Clinical and histopathological aspects and evidence of its mesothelial origin. Apropos of 1 case]. / Le mésothéliome bénin de l'utérus. Aspects cliniques, histopathologiques et évidences de son origine mésothéliale. A propos d'un cas.

Benign mesothelioma is a rare tumor nearly always find in relation to the genital tract. We report the case of a 47-year, old woman admit in the gynecologic department for metrorragia. The tumor was composed of irregular tubules between smooth muscle cells, lined by flattened or cuboidal cells without nuclear atypia or mitoses. The tumor cells express cytokeratins and vimentin. Histologically, differential diagnosis can be made with adenocarcinoma or vascular proliferation like lymphangioma, hemangioma or angiomyoma. Clinical outcome is always favourable without recurrence or malignant transformation.

Orthotopic and heterotopic autografts of frozen-thawed ovarian cortex in sheep.

Freezing ovarian cortex is a new option to preserve the fertility of young patients undergoing cancer treatment or in women facing premature menopause. However, the best way to use this banked tissue remains unclear. The function of heterotopic and orthotopic autografts of frozen-thawed ovarian cortex of sheep was compared in the present study. Fresh and frozen-thawed fragments of ovarian cortex were autografted on the uterine horn of six ewes (orthotopic grafts) and under the skin of the belly in nine ewes (heterotopic grafts). In both orthotopic and heterotopic grafts, the resumption of follicular growth and ovulation was monitored. In orthotopically grafted ewes, fertility was recorded. Oocytes from both types of grafts were collected, matured and fertilized in vitro. In both fresh and frozen-thawed grafts follicular growth resumed normally; preantral and antral follicles were first detectable 4 and 10 weeks respectively following grafting but only 5% of the primordial follicles appeared to have survived. This confirms that grafting procedures are more deleterious for follicle survival than cryopreservation. Although ovulation resumed in most ewes, none of the ewes grafted orthotopically became pregnant at a synchronized mating. Seven months following grafting, oocytes could be collected from heterotopic and orthotopic grafts, matured and some of them fertilized, but none developed to the blastocyst stage. Heterotopic grafting may be an alternative to orthotopic grafting to preserve fertility provided follicle survival in the grafts is markedly improved.

Double maternal seroconversion to cytomegalovirus and Toxoplasma gondii.

BACKGROUND: We report the first case of a double maternal seroconversion for Toxoplasma gondii (TG) and cytomegalovirus (CMV) diagnosed during pregnancy. CASE: One case is reported of a female patient referred for seroconversion in response to TG in the 27th week of gestation. A search for foetal involvement revealed signs of non-specific foetal infection without any TG-related lesions. Tests were carried out for another foeto-maternal infectious disease and maternal seroconversion in response to CMV was discovered with virus in the amniotic fluid. The foetus developed hydrocephalus and intracranial calcifications and the pregnancy was terminated at the parents' request. CMV-induced multiple organ involvement without any signs of Toxoplasma gondii-related involvement were noted in the foetus. CONCLUSIONS: This case indicates that a search should be made for another infectious disease likely to involve the foetus when non-specific signs of infection in the foetus are present, even though maternal seroconversion has been recognized.