Purpose Fertility issues are of great concern for young women undergoing treatment for breast cancer (BC). Fertility preservation (FP) protocols using controlled ovarian stimulation (COS) with letrozole have been widely used with overall good results. However, letrozole cannot be used in every country in this context. This study aimed to assess the efficacy of tamoxifen for COS in women with early BC undergoing FP. Methods This multicentric prospective study included patients aged 18-40, diagnosed with stage I, II and III invasive BC, undergoing tamoxifen-COS before adjuvant or neoadjuvant chemotherapy (NAC). The primary endpoint was the efficacy of tamoxifen-COS protocol evaluated by the number of oocytes collected and vitrified. Secondary endpoints included the time interval before chemotherapy, breast cancer (BC) recurrence rates, and reproductive outcomes. Results Ninety-five patients were included between 2014 and 2017, aged 31.5± 4 years on average. 37.9% received NAC and 62.1% received adjuvant chemotherapy. FP procedure was successful in 89.5% of the cycles. The mean number of collected and vitrified oocytes was 12.8±7.9 and 9.8±6.2, respectively. The mean duration of COS was 10.4±1.9 days. Median time before chemotherapy initiation was 3.6 weeks (IQR 3.1;4.1) for women receiving NAC. Five-year relapse-free and overall survival rates were in-line with those expected in this population. Twenty-one women had spontaneous full-term pregnancies, while 5 underwent IVF cycles with frozen-thawed oocytes, without pregnancy. Conclusion Tamoxifen-COS protocols appear to be feasible before adjuvant or NAC treatment in young BC patients and efficient in terms of oocyte yield.

Purpose The objective of this study is to evaluate predictors for attendance in a home-based adapted physical activity (APA) program for women with breast cancer during chemotherapy and radiotherapy treatment. Methods This retrospective study was based on two prospective studies (SAPA and APAC), including a total of 73 patients with localized breast cancer during their treatment period. The same APA program lasting 27 weeks was proposed and registered. It consisted of three physical activity sessions (two aerobic and one strength training) per week. The predictors (age, height, body weight, body mass index (BMI), VO2peak, 6-min walking test distance (6MWT), fatigue ( MFI), quality of life (EORTC-QLQ), anxiety and depression (HADS), and previous physical activity (IPAQ)) were evaluated before the APA program. Results According to the multivariate regression analysis, the baseline 6MWT distance and quality of life were predictive of good attendance in the APA program. The univariate analysis showed that initial VO2peak, body weight, BMI, and fatigue influenced attendance in the APA program. Conclusions This study helps to better understand the profile of patients who would be participative or non-participative in an APA program. 6MWT distance and quality of life accounted for 19% of attendance in an APA program before the start of treatment. These correlations between the initial predictors of women with breast cancer and their attendance in the APA program during their treatment period make it possible to adapt physical activity professional practices to these patients.

In 1st-line trials, the relative Progression Free Survival (PFS) benefit of adding CDK4/6 inhibitors to AI was consistent across all subgroups of patients (pts), including those with lower ER expression. However, little is known about the absolute PFS obtained under CDK4/6i and AI in pts with low ER expression and whether PR and HER2 expression impact PFS in this setting. PADA-1 is a phase III trial (NCT03079011) testing the clinical utility of ESR1mut detection in blood in ER ≥ 10% HER2- MBC pts receiving 1st- line Pal + AI. We investigated the association of locally-assessed ER (%), PR (%) and HER2 (0,1+,2+) IHC expression on the most recent tumor sample with PFS under Pal + AI. Of 1017 pts, 12 (1.2%), 34 (3.5%), 181 (18.5%) & 751 (76.8%) had an ER% expression of [10-20%], [21-50%], [51-80%] & [81-100%], respectively. N=249 pts (29.2%), 148 (17.3%), 186 (21.8%) & 270 (31.6%) had a PR% of [0-20%], [21-50%], [51-80%] & [81-100%], respectively (Allred scores will be presented). Available HER2 IHC scores were 0 & 1+/2+ in 357 (54.6%) & 296 (45.4%) pts, respectively. In univariate analysis, after a mFU of 28.1 months and 527 PFS events (51.8%) under Pal + AI, mPFS in pts with [10-50%], [51-80%] & [81-100%] ER IHC were 14.1, 21.6 & 30.1 months, respectively. mPFS in pts with [0-50%], [51-80%] & [81-100%] PR IHC were 20.6, 27.1 and 42.6 months, respectively. Longer PFS were observed in HER2(1/2+) vs (0) MBC (HR=0.79 [0.64;0.98]). In multivariate analysis, aside standard prognostic factors (PS, age, visceral disease, number of metastatic site, DMFI), both ER% and PR% had an independent prognostic impact: each +10% gain in ER% was associated with a reduced 10% risk of PFS event under Pal + AI (HR=0.90, 95%CI [0.84;0.96], p=0.002); each +10% gain in PR% was associated with a reduced 8% risk of PFS event under Pal + AI (HR=0.92, 95%CI [0.90;0.95], p<0.001). ER and PR IHC % have significant, independent and similar impact on PFS achieved under 1st line by Pal + AI. The 14.1 months absolute mPFS obtained among pts with ER IHC <50% suggests that CDK4/6i + AI remains a good treatment option in this patient population.

The rise of oral cancer therapies induced new strategies to facilitate continuity of care and better quality of life for patients. We presented here the functioning of a multiple health professionals oral therapy center through a prospective program of coordination's nurses (CNs). This is a prospective monocentric program of CNs role in management of patient with oral treatment in Limoges hospital (May 2015 - June 2018). All patients whatever the stage of cancer and oral therapies were supported in this center. 287 patients with a median age of 67 years (26-89 years) were included. 76% were in metastatic situation (44% in first line). For the vast majority (88%), the first contact with CNs took place on the day of the physician's consultation (duration of 60± min). There was no difference in consultation time regardless of high-risk patient situations (cancer or social characteristics) or home distance from the hospital. During the follow-up, CNs made 2,719 calls (i.e.10 min) to verify adherence and to make educational training. je l'exprimerais plutot par patient the call programming is dependant of Drug They received 833 specific calls from patients (70%). The main reason was management of side effects. 1,069 follow-up visits were made to assess side effects (49.2%) in non-scheduled mode. CNs got also phone contacts with all healthcare professionals in charge of patients (calls received and done) like general practitioner (n = 323) or city nurse (n= 270) or pharmacist (n= 306). CNs spend 5 hours per patient for 3 months of treatment (i.e. 25 min/day) and organize scheduled hospitalization in the department of oncology (54%). We show the interest and real-life work in a specific oral therapy center within oncology department with the role of CNs to facilitate the global health care of the patients.

Abstract Background. Past twenty years, clinical research focuses on the fatigue and the place of physical activity during the treatment of women with breast cancer. Use of cardiopulmonary exercise test (CPET) for determination of peak oxygen consumption (VO2peak) provides the gold standard assessment of aerobic capacity. Our first pilot study was designed to evaluate the effects of a training program during chemotherapy in women with breast cancer showed a significant improvement of VO2peak after treatment (1). So, we performed a phase III study, to assess the effects of a home-based adapted physical activity (APA) program in women treated by adjuvant or neoadjuvant chemotherapy and radiotherapy for breast cancer versus control group (without APA). The main criterion was cardiopulmonary function, measured by VO2peak, at 27 weeks after radio-chemotherapy (RT-CT) between the 2 groups. Methods. Participants were randomized into 2 groups: Arm A (aerobic and strength training) during the 27 weeks of treatment (RT-CT); Arm B (control group). This study included 3 assessments phases (T0: before RT-CT; T1: week 27; and T2: final evaluation at the 54th week). These assessments included: cardiopulmonary exercise test (CPET) with maximal oxygen uptake test (VO2peak), 6 Minutes Walking Test (6MWT) and health-related quality of life. The APA program consisted in 2 sessions of endurance (walking and/or cycling) and 1 session of resistance (elastic band) per week. Training endurance intensity was based on the first ventilator threshold and coached by a specialist. Results. Forty-four subjects were included from June 2012 to June 2013. At baseline (T0), the average age was 52,3 ± 11,7 years for Arm A versus 48,8 ± 8 years for Arm B. Before treatment VO2peak was 23,2 ± 4,9 ml.kg-1.min-1 for Arm A and 22,9 ± 5,4 ml.kg-1.min-1 for Arm B. After treatment (T1), VO2peak was significantly different between the two groups (3.5 ml.kg-1.min) with 24.6 ± 5 ml.kg-1.min-1 vs 20.97 ± 4.8 ml.kg-1.min-1 for Arm A and Arm B respectively (P = . 048). Walking distance on 6MWT improved by 19,7m (P = .016) for training group and decreased by 20,7m (P = .043) for control group. At 6 months (T2), VO2peak was not different between the two groups (P = .069). Arm A continued to increase (26,2 ± 5,6 ml.kg-1.min-1) while Arm B recovered his baseline value (22,3 ± 5,6 ml.kg-1.min-1). Similar results was showed in 6MWT, compared with T1, the two Arms A and B increased by 12,9m (P = .063) and 17,6m (P = .27) respectively. Conclusion. Home-based APA program improved aerobic function and exercise capacity during RT-CT. The exercise during treatment is feasible, safe, and provides a real benefit of physical fitness. In addition, this activity has been performed at home. Keywords. Cardiorespiratory Fitness, VO2peak, Breast Cancer, Adjuvant or Neoadjuvant Chemotherapy, Physical Function, Adapted Physical Activity. Reference. 1. F.Vincent JL.Labourey, S.Leobon, MT.Antonini, S. Lavau-Denes, N. Tubiana-Mathieu. Effects of a home-based walking training program on cardiorespiratory fitness in breast cancer patients receiving adjuvant chemotherapy a pilot study. Eur J Phys Rehabil Med. 2013 Jun;49(3):319-29. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-10.

AIM OF THE STUDY:To detect hereditary non-polyposis colorectal cancer (HNPCC) patients with a strategy combining clinical selection (patient age at onset of cancer less than 50 years or family history of HNPCC tumors) and microsatellite instability typing plus immunohistochemistry, leading to mismatch repair (MMR) germline mutation analysis. METHODS:Tumors were screened for microsatellite instability (MSI) and for hmlh1 and hmsh2 immunohistochemical expression. Germline mutation analysis was performed to search for MLH1 and MSH2 mutations in patients with MSI-High and MSI-Low tumors. RESULTS:197 adenocarcinomas were studied: 164 patients were< or =50 years old, 33 were older than 50 years but had a family history of HNPCC tumors. Fifty tumors (25.4%) were MSI-High, 10 were MSI-Low (5.1%), and 130 were MS-Stable (66%). MSI typing was inconclusive in 7 (3.5%). Immunohistochemistry screening was performed on 165 tumors: sensitivity was 63.6%, specificity was 99%. Germline mutation analysis was performed in 33/60 MSI-High or Low tumors: 23 mutations were noted (70% of the tested patients). CONCLUSION:This proposed strategy of determining microsatellite instability in young colorectal cancer patients or in patients with a family history of HNPCC tumors led to an increased frequency in the detection of MMR germline mutations.

The purpose of this work was to determine the response rate and toxicity of a combination of Carmustine and Cisplatin administered before radiation in patients with newly diagnosed high grade astrocytoma. A good response rate has been published with this association in primary cerebral high grade tumor. This protocol was administered in a homogeneous population of 37 adult patients with measurable tumor on magnetic resonance imaging (MRI) or CT scan. After biopsy or subtotal resection, the patients received BCNU 40 mg/m2/d and CODP 40 mg/m2/d, for 3 days every 28 days for 3 cycles. Evaluation was performed before each cycle. Radiation therapy began 4 weeks after completing the chemotherapy or immediately if there was evidence of tumor progression on chemotherapy. Seven out of 37 (19%) demonstrated tumor regression with a median duration to progression of 11 months. Median survival was 6 months. Myelosuppression was the predominant but manageable toxicity. This work indicated that the first chemotherapy protocol gave poor results in a homogeneous group of patients, with bad prognosis.

OBJECTIVE:Dysmetabolic hepatosiderosis is a recently described entity, which reunites iron overloads associated with polymetabolic syndromes, steatosis and steato-hepatitis. The aim of this study was to specify the relationship between iron overload, polymetabolic syndrome, HFE mutations of primary hemochromatosis and steatosis.METHOD:This was a 5-year retrospective study of 51 patients hospitalised and/or seen in consultation, non-alcoholic, presenting with hyperferritinemia associated with a polymetabolic syndrome and/or hepatic steatosis.RESULTS:Patients mean age was of 53 +/- 12 years with a sex ratio M/F of 5.4. Metabolic disorders were found in 97% of the non-steatosis patients (overweight: 40%, perturbed sugar metabolism: 47%, dyslipidemia: 79.5%). Hyperferritinemia was constant but moderate (513.4 +/- 280.3 ng/ml). Transferrin saturation was predominantly normal (0.44 +/- 0.17). The hepatic enzymes were normal or only slightly perturbed. Steatosis was revealed by sonography in 62% of cases. The hepatic iron overload, documented in 6 patients by hepatic needle biopsy, was discreet (concentration/age ratio of 1.64 +/- 0.19). Among the 59% patients screened for the HFE gene, 40% were positive for C282Y and/or H63D. There was no correlation between ferritin levels and iron parameters, polymetabolic syndrome parameters and hepatic enzymes. The HFE mutations had no influence on the iron parameters.CONCLUSION:Dysmetabolic hepatosiderosis must be know by hospital practitioners because of their prevalence in cases of hyperferritinemia and their therapeutic incidence.

Les phages λ irradiés aux UV ont une survie dépendant de l'état physiologique des bactéries. Si ces bactéries sont aussi irradiées, les phages sont réactivés et un grand nombre de mutants apparaissent. Toutefois les bactéries irradiées perdent très rapidement, en fonction de la dose, leur capacité de multiplier les phages λ (même non irradiés). Cette perte de capacité peut cependant être réparée par la présence de plusieurs phages.Plusieurs phages inactivés par les UV placés dans la même bactérie peuvent se réactiver. Cependant l'efficacité de cette réactivation est beaucomp plus faible que pour le phage T2.Ces faits sont discutés et analysés dans l'hypothèse que les phages tempérés ont, une partie tout au moins, de leur génome plus on moins homologue à une partie du génome de la bactérie, de sorte que des croisements entre phages et bactéries peuvent se produire.The survival of U.V.-irradiated λ-phages depends on the physiological state of the bacteria. If these bacteria are also exposed to U.V. irradiation, the phages are reactivated and a large number of mutants appear. Irradiated bacteria, however, very rapidly lose their capacity to multiply the λ-phages (even non-irradiated ones), as a function of the irradiation dose. This loss of ability can, however, be restored by the presence of several phages.Several U.V.-inactivated phages, when placed among the same bacteria, can reactivate themselves. The efficacy of this reaction is, however, far weaker than in the T2 phage.The above facts are discussed and analysed from the hypothesis that at least part of the genom of the temperate phages is more or less homologous with a part of the bacterial genom, so that crossing between phages and bacteria is possible.