Background: Advances in screening and treatment have reduced mortality from breast cancer. Once the disease progresses to metastasis, survival is limited. We have initiated the SToRM clinical cohort to study the contribution of the patient's genetic background to clinically relevant phenotypes in metastasis. Methods: 1502 women were included in SToRM at metastatic progression from March 2012 to May 2014. A genome wide association study was carried out in 1250 patients, using the Illumina HumanCore Exome chip set. This chip set is composed of over 250,000 variants designed to capture common variation across the genome, as well as over 200,000 variants in coding regions. Patients are followed through contact with their clinical team to capture information regarding their treatment and survival. SToRM is designed to complement the SIGNAL/PHARE cohort of over 10,000 early breast cancer patients. Results: Delay between primary diagnosis and metastasis (average 58.5 months (±73.5)), and tumor type (luminal like (n = 747), HER2 + (n = 249), triple negative (n = 194), is available for SToRM patients. As of April 2017, 875 deaths are reported. As expected, survival probability is highly correlated with tumor type (p = 2.27x10−38), with triple negative patients showing median survival after metastatic diagnosis of less than 24 months, while median survival for luminal and HER2+ patients is longer than 36 months. Overall, no variants show associations with survival. There are, however, borderline associations between a number of variants and survival among triple negative and HER2+ patients. As of July 2017, median follow-up in SIGNAL is 3.8 years, and 7 years in PHARE, 1497 patients have progressed, and 154 deaths have been reported. Conclusions: Genetic variants are important factors of risk for developing breast cancer. We have just begun to scratch the surface of the wealth of data that the SIGNAL/PHARE and SToRM clinical cohorts provide with respect to genetics and response to treatment and survival among breast cancer patients. Understanding how genetic variants influence outcomes may lead to better understanding of breast cancer in general. Furthermore, genetic variants associated with response to treatment may be used as stratification variables in future clinical trials. Clinical trial identification: SToRM: NCT01460186, SIGNAL/PHARE: NCT00381901/RECF1098 Legal entity responsible for the study: SToRM: Centre Léon Bérard, SIGNAL/PHARE: INCa Funding: Foundation Cancer de Sein-Parlons On!, INCa Disclosure: All authors have declared no conflicts of interest.

BACKGROUND Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV NCT01303679.

Abstract Background : The quality of life of couples which one of the members is affected by a cancerous pathology at a relatively young age is important to evaluate in global care. No questionnaire specifically addresses some thematic proper to young women (ex education, desire for a child(s), couple relationship), problems which are yet important for young women suffering from breast cancer. Besides, no questionnaire evaluates the partner's quality of life in this particular context, even if he is frequently the first source of support for the woman (Vanlemmens et al., 2012). Objectives : The main objective was to create a particular and specific tool for measuring the impact of breast cancer on the quality of life of young women (< 45 years of age) with non-metastatic disease and the quality of life of their partners. This work presents the psychometric validation of two questionnaires for patient and partner consisted of items comparable to the semantic level. Methods: We followed the different steps to construct a quality of life tool. After preliminary non-directive interviews and identification of relevant items, we administered the questionnaires on a wide sample of 546 young breast cancer patients and 497 partners. Psychometric testing assessed the hypothesized scale structure based on an examination of item-scale correlation, scale reliability by testing for internal consistency using Cronbach's alpha coefficient, construct validity with inter-scale correlations. Results : Items analyses indicate a good internal consistency of both questionnaires (superior to .75). This questionnaire includes 37 items. The factorial structure highlights 8 factors : 1) management of children and of everyday life, 2) negative affectivity and apprehension about future, 3) feeling of couple cohesion, 4) financial difficulties, 5) body image and sexual life, 6) deterioration with close relations, 7) sharing and support of close relations, and 8) management of the professional life..This structure explains respectively 56% for the patients and 58% for the partners of the total variance. As expected, convergent validity showed strong correlations with Kalicou scales and quality of life measures (QLQC-30 and QLQBR-23). Conclusions: Overall psychometric results for the 2 Kalicou questionnaires confirmed them as valid questionnaires for breast cancer patients and partners. This study will allow the clinicians to have a measurement tool for subjective real-life experience of young breast cancer women and their partner. These questionnaires will also allow comparisons according to the stage and study the interactions of couple. This tool should help to identify modifications of the subjective quality of life. The objective is to improve the medical, psychological and social care for patients and their partner, with a systemic, dynamic approach. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-07.

Exportin 1 (XPO1), also known as chromosome maintenance 1 protein (CRM1), is the main transporter for hundreds of proteins like tumor suppressors, growth regulatory factors, oncoprotein mRNAs and others. Its upregulation leads to the inactivation of the tumor suppressor anti-neoplastic function in many cancers and logically is associated with poor prognosis. Selective inhibitors of nuclear export (SINE) are a new generation of XPO1 inhibitors that are being investigated as a promising targeted anti-cancer therapy. Selinexor is the first generation of SINE compounds that is being evaluated in many clinical trials involving solid tumors and hematological malignancies with its two approved indications for relapsed multiple myeloma and relapsed diffuse large B-cell lymphoma. Here, we comprehensively review the current knowledge of selinexor and next generations of the SINE compounds in lymphoid and myeloid malignancies.