Introduction: Therapy-related myeloid neoplasms (t-MN) are associated with extremely poor clinical outcomes in otherwise long-term cancer survivors. t-MN accounts for ~20% of cases of myeloid neoplasms and is expected to rise due to the increased use of chemotherapy/radiotherapy (CT/RT) and improved cancer survivorship. Historically, t-MN was considered a direct consequence of DNA damage induced in normal hematopoietic stem cells (HSC) by DNA damaging cytotoxics. However, these studies have largely ignored the bone marrow (BM) microenvironment and the effects of age and concurrent/previous cancers. Aim: We performed an exhaustive functional study of mesenchymal stromal cells (MSC) obtained from a comparatively large cohort of t-MN patients and carefully selected control populations to evaluate the long-term damage induced by cytotoxic therapy to BM microenvironment and its impact on malignant and normal haematopoiesis. Methods: Four different cohorts were used: (1) t-MN, in which myeloid malignancy occurred after CT/RT for a previous cancer (n=18); (2) patients with multiple cancer and in which a myeloid neoplasm developed following an independent cancer which was not treated with CT/RT (MC-MN; n=10); (3) primary MN (p-MN; n=7) untreated and without any prior cancer or CT/RT; (4) age-matched controls (HC; n=17). Morphology, proliferation, cellular senescence, differentiation potential and γH2AX DNA damage response was performed. Stem/progenitor supportive capacity was assessed by co-culturing haematopoietic stem cells on MSC feeder-layer in long-term culture initiating assay (LTC-IC). Cytokine measurements were performed using 38-plex magnetic bead panel (Millipore) and RNA sequencing libraries were prepared with Illumina TruSeq Total RNA protocol for 150bp paired-end sequencing on a NextSeq500 instrument. Functional enrichment analysis was performed using EnrichR software. Results: MSC cultured from t-MN patients were significantly different from HC, p-MN and MC-MN MSC according to multiple parameters. They exhibited aberrant morphology consisting of large, rounded and less adhesive cells compared to typical spindle-shaped morphology observed with controls. MSC from myeloid neoplasm also showed impaired proliferation, senescence, osteo- and adipogenic differentiation with t-MN MSC showing the greatest differences. DNA repair was dramatically impaired compared to p-MN and HC (Fig.1A). Importantly, these aberrant t-MN MSC were not able to support normal or autologous in vitro long-term haematopoiesis (Fig.1B). The biological characteristic and poor haematopoietic supportive capacity of MSC could be "cell-intrinsic" or driven by an altered paracrine inflammatory microenvironment. Interestingly, several inflammatory cytokines were higher in t-MN compared with marrow interstitial fluid obtained from p-MN patients (Fig.1Ci) and many of these including Fractalkine, IFNα2, IL-7 and G-CSF were also significantly higher in t-MN MSC conditional media (Fig.1Cii). Together, this data suggest that t-MN microenvironment is distinct from p-MN with paracrine production of pro-inflammatory milieu that may contribute to poor HSC supportive capacity. Preliminary whole transcriptome analysis revealed differential gene expression between t-MN and HC (Fig.1Di) and p-MN MSC. Importantly, the deregulated genes play critical role in cell cycle, DNA damage repair, and cellular senescence pathways explaining phenotypical characteristic of t-MN MSC (Fig.1Dii). Moreover CXCL12 expression, a key regulator of haematopoiesis, was significantly lower in t-MN compared to HC (p=0.002) and p-MN MSC (p=0.009), thus explaining poor HSC supportive capacity. The key difference between the p-MN, MC-MN and t-MN is prior exposure to CT/RT. To study this we obtained MSC from two t-MN patients for whom we had samples at the time of their primary cancer, post high-dose chemotherapy and at the time of t-MN. MSC displayed aberrant proliferation and differentiation capacity after high-dose cytotoxic therapy (2 to 4 years prior to developing t-MN) and remained aberrant at t-MN diagnosis (Fig.1E). Conclusions: BM-MSC from t-MN patients are significantly abnormal compared with age-matched controls and typical myeloid neoplasm. Importantly, prior CT/RT leads to long-term irreversible damage to the BM microenvironment which potentially contributes to t-MN pathogenesis. Disclosures Hughes: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hiwase:Novartis Australia: Research Funding.

Background. - Studies of survival after myocardial infarction (MI) are often based on intention to treat analyses of controlled trials. Objectives. - Describe long-term survival after MI in France. Methods. - Six-year cohort study of patients recruited within 3 months after MI. Primary outcome was all-cause death. Vital status was verified in the national death registry. Analysis used Cox models with time-dependent variables and propensity scores. Results. - Five thousand five hundred and twenty-seven (5527) subjects were included, 62.1 +/- 13 years old, 77.6% male, 9.6% smokers, 16.7% diabetic, 13.3% with previous MI. Up to 99% of patients were initially prescribed secondary prevention drugs (aspirin and/or other antiplatelet agents, beta-blockers, statins or other lipid-lowering agents, angiotensin converting enzyme inhibitors or angiotensin receptor blockers); 73% had all four classes. Overall 6-year mortality was 13.1% [95% confidence interval 12.3 to 14.0%], 2.34 per hundred patient-years (%PY); 49% returned all or all but one of the possible questionnaires (compliant [C]), 50.8% did not (non-compliant [NC]). The main predictors for death were non-compliance with study protocol (death rates NC 2.98% PY, C 1.69%PY, hazard ratio (HR) 3.13 [2.63-3.57]); increasing age at inclusion (HR up to 15.7 [10.7-23.2] for age >= 80); diabetes (1.39 [1.17-1.65]); smoking atinclusion (1.76 [1.27-2.44]), previous MI (1.46 [1.22-1.75]). Beta-blockers (0.79 [0.64-0.96]), statins (0.68 [0.51-0.90]), and enrolment in physical rehabilitation programs (0.74 [0.62-0.89]) were associated with a lower death rate. Conclusion. - Association of mortality with non-compliance to study protocol probably indicates general non-compliance with prevention. Analyses of treatment effects were hindered by paucity of events and of unexposed patients. (C) 2019 Societe francaise de pharmacologie et de therapeutique. Published by Elsevier Masson SAS. All rights reserved.

The behavioral goals of the coronary patient require active management by the cardiologist. Every smoker must be clearly informed about the cardiovascular consequences of smoking and the major benefits of smoking cessation. The only advice to "quit smoking" is not enough. Validated "treatments" (cognitive-behavioral therapy, nicotine replacement therapy, varenicline, bupropion) must be used, with a precise strategy and prolonged follow-up. All drugs assistance can be prescribed in coronary patients and nicotine replacement therapy can even be used just after a myocardial infarction. Nutrition plays a significant role in cardiovascular prevention. Counseling today is based on solid evidence, although evidence is harder to obtain than with drugs. It should no longer be advisable only to "suppress cooked fats and starches" because these recommendations are unclear and/or false. Today we need positive food-based benchmarks and complex dietary patterns in which fruits and vegetables, fish, whole grains, pulses, nuts, olive oil and a diet closed to the Mediterranean diet. Dairy products have their place. Sugary foods should be limited especially in case of overweight and metabolic syndrome. Physical activity is part of good nutrition. Indeed, the fight against a very sedentary lifestyle and physical inactivity in coronary and heart failure patients is part of the lifelong treatment of these patients. The cardiologist and the general practitioner must be much more involved in their prescription and education to hope for good compliance.

Abstract Background: Prognostic factors have been used for years to determine the benefit of adjuvant chemotherapy in breast cancer. However, reporting of the size and grade of the tumor are affected by interobserver variability in reporting. This can result in a change in the results of adjuvant online and an impact on decision making of chemotherapy. On the contrary, genomic testing such as oncotype Dx is reproducible. The purpose of our study was to assess the effect of pathological discordance on the adjuvant online results on a cohort of patients who also underwent oncotype Dx testing. Materials and Methods: A total of 143 patients' histologies were included in this study. The results of the Phase III WSG-Plan B trial concerning central vs. local grade discrepancy rates were utilized to randomly change the grade of the tumors. 61 percent of grade 1 cancers were upgraded to grade 2 and 2% upgraded to grade 3. 4 percent of grade 2 cancers were downgraded to grade 1 and 26% were upgraded to grade 3. 1 percent of grade 3 cancers were downgraded to grade 1 and 25% were downgraded to grade 2. Likewise, change was made in the size of the tumor in 20 percent of patients. 8 to 10mm, 18-20, 28-30, and 48-50mm changed to 11, 21, 31 and 51mm respectively. 11-13mm, 21-23, 31-33, and 51-53mm was changed to 10, 20, 30, and 50mm. Ten percent of patients had the ER and Her 2 status changed. Results: The simulation results showed that when the grade was only altered, the spearman correlation of the predicted 10 year mortality on adjuvant online with the original data was significantly changed from 1 to a result of 0.788. When the changed size was additionally added, the coefficient was 0.836. With the altered ER status, the result was 0.749 and with the Her 2 change, the spearman correlation was minimally changed to 0.742. The scattergrams showed a large number of outliers when the alteration in size was added to the altered grade. Conclusion: Our simulation study confirms that with minimal changes in the clinical parameters because of the lack of perfect correlation between pathologist's results, there is a significant difference in the 10 year predicted mortality on adjuvant online. This is one step further in understanding the lack of correlation between adjuvant online and oncotype Dx, and the inconsistency of chemotherapy decision making with the sole use of adjuvant online. Citation Format: Khawaja S, Thomas D, Udayasankar S, Munir A, Huws A, Sharaiha Y, Holt S. A simulation study depicting the inconsistency of adjuvant online compared to genomic testing when determining the benefit of chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-03-12.

Abstract Background: In the Western World, it has been stated that breast cancers detected on a screening program are indolent. There have been many recent publications stating that breast screening is overdiagnosing and therefore overtreating patients with breast cancer. With the advent of genomic testing, it can now be determined which patients have an aggressive tumor requiring systemic chemotherapy. We therefore conducted a retrospective study in the UK on patients having oncotype DX testing in both screen detected and symptomatic cancers. Materials and Methods: Patients in our institution undergoing oncotype DX testing for invasive breast cancer which was ER positive and node negative were part of this study. The detection of the breast cancer was documented as either a screening case or a symptomatic one. The recurrence scores of the oncotype DX testing was then compared in the screening versus the symptomatic cohort. Results: 155 patients were included in this study. They underwent Oncotype DX testing between 2008 to 2016. The age of the patients ranged from between 31 years to 78 years. Eighty-nine patients were reported to have a low recurrence score; 45 had an intermediate score; and 21 had a high result. Fifty eight patients were screen detected, while 97 patients were symptomatic presentations. In the screening population, 32 patients had a low recurrence score; 22 had an intermediate result and 4 had a high recurrence score resulting in the latter groups being considered for chemotherapy. In the symptomatic cohort, 57 had a low recurrence score; 23 had an intermediate result; and 17 had a high score. Conclusion: The results of our study depict that even patients in a screeining cohort will have a high number of intermediate recurrence scores and some with a high recurrence score. This shows that the hypothesis that screening detects a majority of breast cancers which are indolent not requiring further systemic treatment should be looked at again in light of our results with genomic testing. Citation Format: Khawaja S, Parab A, Thomas D, Huws A, Munir A, Udayasankar S, Sharaiha Y, Holt S. A comparison of oncotype DX recurrence scores in a screen detected vs a symptomatic cohort of patients with breast cancer: A UK experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-21.

Background: We have previously reported on the impact of oncotype Dx testing in decision making for adjuvant therapy in early stage breast cancer patients with oestrogen receptor (ER)-positive and axillary lymph node-negative disease. The primary objective of this study was to determine the long term recurrence outcome in these patients.

Abstract Introduction: A synthetic 2D mammogram (C-view) can be created by combining the individual optimally enhanced 1mm slices of a digital breast tomosynthesis (DBT). Studies show that screening with 2D mammography and DBT increases the cancer detection rate by about 40% and reduces the recall rate by about 25% but it doubles the x-ray exposure to the patient and reading time for the radiologist compared to standard 2D screening. The use of a synthetic 2D instead of a standard 2D film may theoretically overcome these problems by avoiding a second exposure and presenting the detail normally available in DBT in one picture. The hypothesis we wished to test is, "if the synthetic 2D is normal/benign, is there any advantage in also viewing the DBTs?" Method: We prospectively collected data on 2500 unselected cases presenting symptomatically or at follow up, all of whom underwent DBT on a Hologic® Dimensions machine. From the 3D data sets synthetic 2D mammograms were constructed (Hologic C-view). One breast radiologist with 13 years experience of interpreting mammograms and 5 years with DBTs was asked to review the 2D synthetic mammograms (CC and MLO) and report them before then reviewing the DBTs and issuing a final report. The mammograms were reported M1 to M5 using the standard BIRADs criteria. The BIRADs scores for each breast were recorded prospectively. Similarly the breast density as assessed by eye was recorded (fatty/average density/dense). Results: 2500 patients were studied between October 2013 and October 2014. The average age of the women was 58.4 years (range 28-95). Of these some were under follow up after mastectomies so in total there were 4589 individual mammogram sets reported. Table 1 summarises the correlation between the synthetic 2D and DBT reports. BIRADS Classification - Synthetic 2D v DBT Synthetic 2D M1M2M3M4M5 M115874000 M2827051510DBTM32810140 M4015480 M5001396 The correlation is very close, but there were 11 patients in whom the synthetic 2D was reported normal or benign (M1 or M2) but the DBT was reported as M3. Of these 10 were benign on assessment and one malignant. There was one patient reported as M2 on synthetic 2D but M4 on DBT. Assessment confirmed malignancy. Sixteen cases reported as suspicious of malignancy (M3/4) by synthetic 2D were subsequently downgraded to benign after review of the DBT. We estimate that 2D mammography alone would have detected only 68 of the 94 detected by synthetic 2D. Of the 4589 examinations, 1131 (25%) were assessed as fatty, 1851 (40%) as average density and 1607 (35%) as dense. One cancer was missed in an averagely dense and one in a dense breast. Conclusion: In a symptomatic and follow up clinic, our study suggests that much radiologist's time and x-ray exposure to the patient could be saved by using synthetic 2D mammograms rather than using 2D/3D combinations. Only if the synthetic 2D is reported M3, 4 or 5 is it necessary to review the DBT. Whilst a similar trial is required to confirm these findings in a screening population, this trial suggests that synthetic 2D mammography could be cost effective compared to combination 2D/3D. Citation Format: Holt SD, Sharaiha YM, Moalla A, Williams HR, Thomas D, Huws AM. A comparison of the diagnostic performance of 2D synthetic mammography versus digital breast tomosynthesis in 2500 patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S1-09.

Objective To document interactions during the antenatal consultation between parents and neonatologist that parents linked to their satisfaction with their participation in shared decision making for their infant at risk of being born at the limit of viability. Methods This multiple-case ethnomethodological qualitative research study, included mothers admitted for a threatened premature delivery between 200/7 and 266/7 weeks gestation, the father, and the staff neonatologist conducting the clinical antenatal consultation. Content analysis of an audiotaped post-antenatal consultation interview with parents obtained their satisfaction scores as well as their comments on physician actions that facilitated their desired participation. Results Five cases, each called a “system—infant at risk”, included 10 parents and 6 neonatologists. From the interviews emerged a blueprint for action by physicians, including communication strategies that parents say facilitated their participation in decision making; such as building trustworthy physician-parent relationships, providing "balanced" information, offering choices, and allowing time to think. Conclusion Parent descriptions indicate that the opportunity to participate to their satisfaction in the clinical antenatal consultation depends on how the physician interacts with them. Practice implications The parent-identified communication strategies facilitate shared decision making regarding treatment in the best interest of the infant at risk to be born at the limit of viability.

L'étude EOLE a pour objectif principal d'évaluer l'impact en situation réelle des traitements à visée cardiovasculaire recommandés dans la prévention secondaire de l'infarctus du myocarde (IDM) sur la mortalité totale à six ans. L'objectif de cette analyse est d'étudier l'impact de la non-réponse aux auto-questionnaires attendus (AQ) sur la mortalité totale. EOLE est une cohorte observationnelle nationale de patients présentant un IDM récent, inclus par des cardiologues hospitaliers et libéraux et suivis pendant six ans, avec des AQ patients de suivi à compléter à 6 mois, 2, 3, 4, 5, et 6 ans. Le statut vital des patients a été obtenu à partir du registre national des décès, complété par les informations du cardiologue participant ou à défaut du médecin traitant ou du patient/famille. L'exposition aux traitements de prévention secondaire recommandés (bêtabloquants, aspirine, autres antiagrégants plaquettaires [AAP], statines seules, inhibiteurs de l'enzyme de conversion [IEC] seuls, supplémentation pharmacologique en oméga 3) à l'inclusion était définie comme tout traitement prescrit par le cardiologue et/ou déclaré par le patient, et à chaque suivi comme tout traitement déclaré par le patient. Le risque relatif (HR) de non-réponse aux AQ attendus sur la mortalité à six ans a été évalué avec un modèle de Cox en tant que variable dépendante du temps, ajusté sur l'âge, le sexe, les facteurs de risque cardiovasculaire à l'inclusion et l'exposition à chacun des traitements de prévention secondaire recommandés à l'inclusion (les auto-questionnaires étant attendus uniquement pour les patients non décédés et non sortis étude). Sur les 5527 patients inclus, 49,2 % étaient répondants (réponse à tous les AQ attendus) et 50,8 % non-répondants (≥ 1 non-réponse à un AQ attendu). Comparés aux non-répondants, les répondants étaient à l'inclusion plus âgés (63 ± 12 versus 61 ± 14 ans), avec un peu plus d'hommes (79 % versus 77 %), plus de retraités (59 % versus 49 %), moins d'obèses (IMC ≥ 30, 18 % versus 20 %), moins de fumeurs (6 % versus 13 %), moins de diabétiques (15 % versus 19 %), moins d'antécédent d'IDM (12 % versus 14 %). L'exposition aux traitements de prévention secondaire recommandés était élevée dans les deux groupes : bêtabloquant 90,7 % et 88,7 %, antiagrégant plaquettaire 99,6 % et 99,3 %, statine 96,9 % et 94,8 %, IEC/ARAII 83,2 % et 81,7 %, oméga 3 17,3 % et 14,3 %, respectivement. La mortalité totale à six ans était de 13,1 % (IC95 % [12,3 %–14,1 %]) pour l'ensemble de la cohorte. Le HR ajusté pour les non-répondants était de 3,2 (IC95 % [2,7–3,7]). Cette analyse montre un impact majeur de la non-réponse aux AQ attendus sur la mortalité à six ans dans le post-IDM. Ceci implique que les méthodes d'imputation des données manquantes usuelles, comme la LOCF ou imputations multiples, ne permettraient pas d'estimer valablement l'exposition, basée sur les AQ, des traitements de prévention secondaire au cours du temps.

L'étude EOLE a pour objectif principal d'évaluer l'impact en situation réelle des traitements à visée cardiovasculaire recommandés dans la prévention secondaire de l'infarctus du myocarde (IDM) sur la mortalité totale à six ans (bêtabloquants, aspirine, autres antiagrégants plaquettaires [AAP], statines seules, inhibiteurs de l'enzyme de conversion [IEC] seuls, supplémentation pharmacologique en oméga 3 [Om3]). Les premiers résultats de l'analyse finale montrent une mortalité totale à six ans moins importante qu'attendue, avec une question sur le niveau de surmortalité par rapport à la population générale de même sexe et âge. Estimer la mortalité totale de la cohorte EOLE et le ratio standardisé de mortalité (SMR) par rapport à la population générale de même sexe et âge. EOLE est une étude de cohorte observationnelle nationale de patients présentant un IDM récent (≤ 3 mois), inclus par des cardiologues hospitaliers et libéraux et suivis pendant six ans. Le statut vital des patients a été obtenu à partir du registre national des décès, complété par les informations du cardiologue participant ou à défaut du médecin traitant ou du patient/famille. L'exposition aux traitements de prévention secondaire recommandés à l'inclusion était définie comme tout traitement prescrit par le cardiologue et/ou déclaré par le patient. La méthode de Kaplan-Meier a été utilisée pour estimer la probabilité de la mortalité totale à six ans. Le calcul du SMR tient compte des années de suivi et a été standardisé sur l'âge, et le sexe à partir des données nationales de mortalité de l'Insee pour l'ensemble de la cohorte, ainsi que pour les hommes et les femmes, avec l'intervalle de confiance à 95 % (IC95 %) et le test de Breslow et Day. Entre mai 2006 et juin 2009, 596 cardiologues ont inclus 5523 patients analysables : âge médian 61,0 ans, 77,6 % d'hommes, 9,6 % de fumeurs, 16,7 % de diabétiques, 44,6 % avec de l'hypercholestérolémie, 43,6 % d'hypertendus, et 8,1 % avec une FEVG < 40 %. À l'inclusion, 97,5 % étaient exposés à l'aspirine, 92,1 % aux statines seules, 91,1 % aux AAP, 89,8 % aux bêtabloquants, 70,3 % aux IEC seuls, et 15,7 % aux Om3. La mortalité totale à six ans était de 13,1 % (IC95 % [12,3 %–14,1 %]) avec un taux d'incidence de 23,4 pour 1000 personnes–années suivies. Le SMR de la cohorte EOLE par rapport à la population générale était de 1,11 [1,03–1,20] (p = 0,005), 1,05 [0,97–1,15] (p = 0,24) pour les hommes et 1,29 [1,12–1,48] (p < 0,001) pour les femmes. Les premiers résultats de l'analyse finale de l'étude EOLE montrent un niveau d'exposition à la plupart des traitements de prévention secondaire recommandés à l'inclusion très élevé avec un taux relativement modéré de mortalité à six ans (13,1 %). Cette mortalité reste un peu supérieure à celle de la population générale, de façon non significative pour les hommes et significative pour les femmes, mais loin de la surmortalité post-infarctus de la fin des années 1990. Cette relativement faible mortalité couplée à un niveau très élevé d'exposition complique les analyses usuelles d'une cohorte exposés–non exposés.

OBJECTIVE: Vacuum-assisted breast biopsy (VABB) has replaced surgical biopsy for the assessment of mammographic abnormalities that are not evident clinically and or on ultrasound examination. The aim of this study was to determine the indications for, and accuracy of, vacuum-assisted breast biopsy (VABB) performed using digital breast tomosynthesis (DBT) guidance. (Hologic® Dimensions, Affirm guidance and Eviva handsets). MATERIALS AND METHODS: Design: Retrospective medical record and histopathologic review. Patients and method: We introduced DBT guided VABB in June 2014 having previously investigated such patients using the prone table technique. This is a review of the first 66 consecutive patients investigated using this technique up to April 2105. The following information was reviewed: Indication for VABB, (mammographic classification M1-5, type of abnormality – calcifications/mass/distortion), complications of the procedure itself, (failure to complete, infection, haematoma), the result of the multidisciplinary team (MDT) review of imaging/pathologic correlation and the outcome for the patient. RESULTS: In one case it proved impossible to locate the lesion and this patient has been excluded from further analysis. The mean age of the patients was 57 years (30-80years). VABB was proposed for patients with lesions initially reported as highly suspicious (M5) 4 patients (6%), suspicious (M4) in 18 patients (28%), intermediate (M3) in 37 patients (57%) or benign (M2) in 6 patients (9%). Mean size of the lesion was 13mm (range 3-100mm). Forty-four patients (68%) presented with micro calcifications, 14 (21%) with distortions in and 7 (11%) with masses. There were no complications (infection or haematoma) that required further management following the procedure. Review by the MDT agreed that all biopsies were adequate and removed representative tissue from the lesion (No B1s). Review showed that the histology was benign and consistent in 30 (46%) patients all of whom were discharged to routine screening. 19 (29%) cases were reported as B3 (ADH, flat atypia, LCIS or ALH) in whom all the calcifications had been removed in 13 (20%) and the patients discharged and 6 (9%) went to open biopsy for residual calcifications all of whom were benign on final analysis. There was one (1.5%) radial scar reported as B4 that went to open excision and proved benign. 15 (23%) proved malignant (B5a, B5b) and went on to definitive treatment (with one patient entered into the LORIS low risk DCIS trial). The procedure is quicker, more accurate (related to the higher resolution and larger window of the receptor plate) and involves less radiation exposure (often involving only one DBT exposure) when compared to performing the same procedure on the Hologic Platinum prone table. CONCLUSION: DBT-guided VABB is an accurate, convenient and safe procedure. Citation Format: Munir A, Moalla A, Williams HR, Thomas D, Huws AM, Holt SD. A review of 66 consecutive patients investigated for mammographic abnormalities by digital tomosynthesis guided vacuum assisted breast biopsy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-02-02.

OBJECTIVE: Vacuum-assisted breast biopsy (VABB) has replaced surgical biopsy for the assessment of mammographic abnormalities that are not evident clinically and or on ultrasound examination. The aim of this study was to determine the indications for, and accuracy of, vacuum-assisted breast biopsy (VABB) performed using digital breast tomosynthesis (DBT) guidance. (Hologic® Dimensions, Affirm guidance and Eviva handsets). MATERIALS AND METHODS: Design: Retrospective medical record and histopathologic review. Patients and method: We introduced DBT guided VABB in June 2014 having previously investigated such patients using the prone table technique. This is a review of the first 66 consecutive patients investigated using this technique up to April 2105. The following information was reviewed: Indication for VABB, (mammographic classification M1-5, type of abnormality – calcifications/mass/distortion), complications of the procedure itself, (failure to complete, infection, haematoma), the result of the multidisciplinary team (MDT) review of imaging/pathologic correlation and the outcome for the patient. RESULTS: In one case it proved impossible to locate the lesion and this patient has been excluded from further analysis. The mean age of the patients was 57 years (30-80years). VABB was proposed for patients with lesions initially reported as highly suspicious (M5) 4 patients (6%), suspicious (M4) in 18 patients (28%), intermediate (M3) in 37 patients (57%) or benign (M2) in 6 patients (9%). Mean size of the lesion was 13mm (range 3-100mm). Forty-four patients (68%) presented with micro calcifications, 14 (21%) with distortions in and 7 (11%) with masses. There were no complications (infection or haematoma) that required further management following the procedure. Review by the MDT agreed that all biopsies were adequate and removed representative tissue from the lesion (No B1s). Review showed that the histology was benign and consistent in 30 (46%) patients all of whom were discharged to routine screening. 19 (29%) cases were reported as B3 (ADH, flat atypia, LCIS or ALH) in whom all the calcifications had been removed in 13 (20%) and the patients discharged and 6 (9%) went to open biopsy for residual calcifications all of whom were benign on final analysis. There was one (1.5%) radial scar reported as B4 that went to open excision and proved benign. 15 (23%) proved malignant (B5a, B5b) and went on to definitive treatment (with one patient entered into the LORIS low risk DCIS trial). The procedure is quicker, more accurate (related to the higher resolution and larger window of the receptor plate) and involves less radiation exposure (often involving only one DBT exposure) when compared to performing the same procedure on the Hologic Platinum prone table. CONCLUSION: DBT-guided VABB is an accurate, convenient and safe procedure. Citation Format: Munir A, Moalla A, Williams HR, Thomas D, Huws AM, Holt SD. A review of 66 consecutive patients investigated for mammographic abnormalities by digital tomosynthesis guided vacuum assisted breast biopsy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-02-02.

Introduction: A synthetic 2D mammogram can be created by combining the individual optimally enhanced 1mm slices of a digital breast tomosynthesis (DBT). Theoretically this could help overcome the problems associated with standard 2D mammograms (superimposition of structures hiding small cancers) and the significantly increased reading time and decreased conspicuity of microcalcifications associated with DBT. It may avoid the need for the double x-ray exposure required for combination 2D and DBT currently being suggested to maximise the specificity and sensitivity of mammography. The hypothesis we wished to test is, the synthetic 2D is normal, is there any advantage to looking at the DBTs as well? Method: We have reviewed 1000 consecutive cases presenting symptomatically or to our follow up clinic all of which underwent DBT on a Hologic Dimensions machine. From the 3D data sets synthetic 2D mammograms were constructed (Hologic C-view technology). One breast radiologist with 12 years experience of interpreting mammograms and more recently 4 years experience in interpreting DBTs was asked to first review the 2D synthetic mammograms (each breast CC and MLO) and report them before then reviewing the DBTs and issuing a final report. The mammograms were reported M1 to M5 using the standard BIRADs criteria. The BIRADs scores for each breast were recorded prospectively and entered into a database. Results: 1000 consecutive patients were studied between October 2013 and March 2014. The average age of the women was 58.1 years (range 29 to 92). Of these some were under follow up after mastectomy so in total there were 1871 individual mammogram sets reported. Table 1 summarises the correlation between C-view and DBT reporting. The correlation between the two modalities is very close, but importantly there was only one patient in whom the C-view was reported normal or benign (M1 or M2) but the DBT reported a possible abnormality (M3). However, 31 cases reported as suspicious or malignant M3, 4 or 5 by C-view were subsequently downgraded to benign after review of the DBT. Conclusion: In a symptomatic and follow up clinic, our study suggests that much radiologist’s time and x-ray exposure to the patient could be saved by using synthetic 2D mammograms derived from the DBT data rather than using separate 2D studies. Only if the C-view is reported M3, 4 or 5 is it necessary to review the DBT but for all these patients the DBT is already available without further x-ray exposure or recall. Citation Format: Simon DH Holt, Ali Moalla, Helen R Williams, Khaldoun MY Nadi, Anita M Huws, Amrita Gurung, Daniel Thomas, Yousef M Sharaiha. Can synthetic 2D mammography be used to select patients in whom there is no need to review the digital breast tomosynthesis from which they were constructed? A review of 1871 consecutive mammogram sets of patients presenting symptomatically or for follow [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-01-01.

Telomere shortening is common in bone marrow failure syndromes such as dyskeratosis congenita (DC), aplastic anemia (AA) and myelodysplastic syndromes (MDS). However, improved knowledge of the lineage-specific consequences of telomere erosion and restoration of telomere length in hematopoietic progenitors is required to advance therapeutic approaches. We have employed a reversible murine model of telomerase deficiency to compare the dependence of erythroid and myeloid lineage differentiation on telomerase activity. Fifth generation Tert-/- (G5 Tert-/-) mice with shortened telomeres have significant anemia, decreased erythroblasts and reduced hematopoietic stem cell (HSC) populations associated with neutrophilia and increased myelopoiesis. Intracellular multiparameter analysis by mass cytometry showed significantly reduced cell proliferation and increased sensitivity to activation of DNA damage checkpoints in erythroid progenitors and in erythroid-biased CD150hi HSC, but not in myeloid progenitors. Strikingly, Cre-inducible reactivation of telomerase activity restored hematopoietic stem and progenitor cell (HSPC) proliferation, normalized the DNA damage response, and improved red cell production and hemoglobin levels. These data establish a direct link between the loss of TERT activity, telomere shortening and defective erythropoiesis and suggest that novel strategies to restore telomerase function may have an important role in the treatment of the resulting anemia.

Few studies have assessed the real-life impact of secondary prevention drugs on all-cause mortality postmyocardial infarction (MI), especially in countries with low incidence of MI. The objective of this interim analysis after 3.5-year of follow-up was to assess the real-life all-cause mortality impact of drugs reimbursed for MI secondary prevention in France: acetylsalicylic acid (ASA), antiplatelet agents (APA), beta-blockers (ß-), angiotensin-converting enzyme inhibitors (ACEI), statins, and omega-3 supplementation (Om3)