GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients

International audienceGenetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46x10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16x10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors

Early objective response may not be a prognostic factor of survival for patients with metastatic urothelial carcinoma: from a retrospective analysis of a cohort of 113 patients

International audienceBackground: This study aims to better define prognostic factors for patients with metastatic urothelial carcinoma (mUC), and to identify patients who will benefit from first-line cisplatin-based chemotherapy. We test the hypothesis that early objective response (EOR), defined as the occurrence of an objective response following 2 or 3 courses of chemotherapy, could be a prognostic factor for overall survival (OS) and thus be used to guide treatment decisions. Data from 113 patients with evaluable mUC receiving first-line cisplatin-based treatment between January 2004 and December 2006 was collected retrospectively from prospectively-maintained databases across seven French cancer centers. Clinical factors potentially associated with survival and EOR were analyzed in univariate and multivariate analysis. Results: One hundred three patient records were complete and available for inclusion in the multivariate model. Four factors were independently associated with OS: Performance status 1 and 2 (HR 2.3 [95 % CI 1.3–3.9], p = 0.002; HR 3.4 [95 % CI 1.6–7.2], p = 0.001 respectively); presence of visceral metastases (HR 2.2 [95 % CI 1.3–3.9], p = 0.004); abnormal hemoglobin levels (HR 1.7 [95 % CI 1.01–2.8], p = 0.045); disease progression (HR 10.1 [95 % CI 4.2–24.1], p < 0.001)

Comparison of 18FDG-PET/CT and conventional follow-up methods in colorectal cancer: A randomised prospective study

International audienceA surveillance program was performed in colorectal cancer (CRC) patients after surgery, to diagnose asymptomatic recurrence

Nutritional advice in older patients at risk of malnutrition during treatment for chemotherapy: a two-year randomized controlled trial.

We tested the effect of dietary advice dedicated to increase intake in older patients at risk for malnutrition during chemotherapy, versus usual care, on one-year mortality.We conducted a multicentre, open-label interventional, stratified (centre), parallel randomised controlled trial, with a 1∶1 ratio, with two-year follow-up. Patients were aged 70 years or older treated with chemotherapy for solid tumour and at risk of malnutrition (MNA, Mini Nutritional Assessment 17-23.5). Intervention consisted of diet counselling with the aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d, by face-to-face discussion targeting the main nutritional symptoms, compared to usual care. Interviews were performed 6 times during the chemotherapy sessions for 3 to 6 months. The primary endpoint was 1-year mortality and secondary endpoints were 2-year mortality, toxicities and chemotherapy outcomes.Between April 2007 and March 2010 we randomised 341 patients and 336 were analysed: mean (standard deviation) age of 78.0 y (4·9), 51.2% male, mean MNA 20.2 (2.1). Distribution of cancer types was similar in the two groups; the most frequent were colon (22.4%), lymphoma (14.9%), lung (10.4%), and pancreas (17.0%). Both groups increased their dietary intake, but to a larger extent with intervention (p<0.01). At the second visit, the energy target was achieved in 57 (40.4%) patients and the protein target in 66 (46.8%) with the intervention compared respectively to 13 (13.5%) and 20 (20.8%) in the controls. Death occurred during the first year in 143 patients (42.56%), without difference according to the intervention (p = 0.79). No difference in nutritional status changes was found. Response to chemotherapy was also similar between the groups.Early dietary counselling was efficient in increasing intake but had no beneficial effect on mortality or secondary outcomes. Cancer cachexia antianabolism may explain this lack of effect.ClinicalTrials.gov NCT00459589

Panel gene profiling of small bowel adenocarcinoma, results from the NADEGE prospective cohort

International audienceSmall bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. The NADEGE cohort has enrolled 347 patients with all stage SBA from 2009 to 2012. Next generation sequencing investigates the presence of 740 hotspot somatic mutations in a panel of 46 genes involved in carcinogenesis. The mismatch repair (MMR) status was assessed by immunochemistry. We have collected 196 tumour samples and 125 had conclusive results for mutation analysis. The number of mutations was 0 in 9.6% of tumours, only 1 in 32.0%, 2 in 26.4% and ≥ 3 in 32.0%. Altogether, at least one genomic alteration was observed in 90.4% of tumour. The most frequent genomic alteration was in KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%) genes. KRAS mutations were more frequent in synchronous metastatic tumours than in localized tumours (72.7% vs 38.2%, P = 0.003). There was no significant difference in the mutation rates according to primary location for the most frequently altered gene. ATM, FGFR3 and FGFR1 gene alterations were associated with Lynch syndrome and IDH1 mutations with Crohn disease. dMMR tumours were associated with younger age, localized tumours, less KRAS but more SMARCB1 mutations. No genomic alteration was associated with overall survival. There is a trend for better survival in patient with dMMR tumours. In conclusion, there is a different genomic alteration profile in SBA according to predisposing diseases. No association between genomic alterations and prognoses was observed except for a trend of better prognoses associated with dMMR

Trabectedin in combination with doxorubicin for first-line treatment of advanced uterine or soft-tissue leiomyosarcoma (LMS-02): a non-randomised, multicentre, phase 2 trial

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Small bowel adenocarcinoma: Results from a nationwide prospective ARCAD‐NADEGE cohort study of 347 patients

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Randomized phase 2 neoadjuvant trial evaluating anastrozole and fulvestrant efficacy for postmenopausal, estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer patients: Results of the UNICANCER CARMINA 02 French trial (UCBG 0609)

International audienceBACKGROUND:Treatment strategies for locally advanced breast cancer in elderly patients too frail to receive neoadjuvant chemotherapy and the introduction of new classes of drugs in the early 2000s have led to the consideration of endocrine therapy as a neoadjuvant treatment for younger hormone receptor (HR)-positive, postmenopausal patients not eligible for primary breast-conserving surgery (BCS).METHODS:This was a multicenter, phase 2, randomized trial designed to evaluate as its primary objective the clinical response rate after up to 6 months of neoadjuvant endocrine therapy (NET) alone in HR-positive/human epidermal growth factor receptor 2 (HER2)-negative patients with 1 mg of anastrozole (arm A) or 500 mg of fulvestrant (arm B). Secondary objectives included the BCS rate, tumor response assessment (breast ultrasound and magnetic resonance imaging), pathological response (Sataloff classification), safety profile, relapse-free survival (RFS), and predictive markers of responses and outcomes.RESULTS:From October 2007 to April 2011, 116 women (mean age, 71.6 years) with operable infiltrating breast adenocarcinoma (T2-T4, N0-N3, M0) were randomized to receive anastrozole or fulvestrant. The clinical response rates at 6 months were 52.6% (95% confidence interval [CI], 41%-64%) in arm A and 36.8% (95% CI, 25%-49%) in arm B. BCS was performed for 57.6% of arm A patients and 50% of arm B patients. The RFS rates at 3 years were 94.9% in arm A and 91.2% in arm B. The Preoperative Endocrine Prognostic Index status was significantly predictive of RFS. Both treatments were well tolerated.CONCLUSIONS:Both drugs are effective and well tolerated as NET in postmenopausal women with HR-positive/HER2-negative breast cancer. NET could be considered a treatment option in this subpopulation. Cancer 2016;122:3032-3040. © 2016 American Cancer Society