Incidence and outcome of brain and/or leptomeningeal metastases in HER2-low metastatic breast cancer in the French ESME cohort.

BACKGROUND: Breast cancer (BC) is the second most common cancer that metastasizes to the brain. Particularly up to half of patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (mBC) may develop brain metastases over the course of the disease. Nevertheless, little is known about the prevalence and the outcome of brain and leptomeningeal metastases (BLMM) in HER2-low BC. We compared the cumulative incidence of BLMM and associated outcomes among patients with HER2-low, HER2-negative (HER2-) and HER2+ mBC. PATIENTS AND METHODS: This cohort study was conducted from the Epidemiological Strategy and Medical Economics (ESME) mBC database and included patients treated for mBC between 2012 and 2020 across 18 French comprehensive cancer centers and with known HER2 and hormone receptor (HR) status. The cumulative incidence of BLMM after metastatic diagnosis was estimated using a competing risk methodology with death defined as a competing event. RESULTS: 19 585 patients were included with 6118 (31.2%), 9943 (50.8%) and 3524 (18.0%) being HER2-low, HER2- and HER2+ mBC, respectively. After a median follow-up of 48.6 months [95% confidence interval (CI) 47.7-49.3 months], BLMM were reported in 4727 patients: 1192 (25.2%) were diagnosed with BLMM at first metastatic diagnosis and 3535 (74.8%) after metastatic diagnosis. Multivariable analysis adjusted for age, histological grade, metastases-free interval and HR status showed that the risk of BLMM at metastatic diagnosis was similar in patients with HER2- compared to HER2-low mBC [odds ratio (OR) (95% CI) 1.00 (0.86-1.17)] and higher in those with HER2+ compared to HER2-low [OR (95% CI) 2.23 (1.87-2.66)]. Similar results were found after metastatic diagnosis; the risk of BLMM was similar in HER2- compared to HER2-low [subdistribution hazard ratio (sHR) (95% CI) 1.07 (0.98-1.16)] and higher in the HER2+ group [sHR (95% CI) 1.56 (1.41-1.73)]. CONCLUSIONS: The prevalence and evolution of BLMM in HER2-low mBC are similar to those in patients with HER2- tumors. In contrast to patients with HER2+ mBC, the prognosis of BLMM remains dismal in this population.

Capecitabine efficacy after cycline-dependent-kinase 4/6 inhibitor plus endocrine therapy in metastatic hormone receptor-positive breast cancer.

BACKGROUND: The combination of endocrine treatment with cycline-dependent-kinase 4/6 inhibitor is the new standard of treatment in hormone receptor-positive HER2 negative metastatic breast cancer. The optimal subsequent treatment after CDK4/6 inhibitor remain unclear. As recommended by standard guidelines, capecitabine, an oral chemotherapy is a therapeutic option in endocrine resistant metastatic breast cancer. The objective of this study was to evaluate capecitabine efficacy after disease progression under combination of ET and CDK4/6 inhibitor in a hormone receptor positive metastatic breast cancer population. PATIENTS AND METHODS: Patients progressing under CDK 4/6 inhibitor plus ET and treated with capecitabine, between January 2016 and December 2020, were retrospectively included. Primary endpoint was time to treatment failure (TTF) on capecitabine. Logistic regression were used to identify predictive factors: exclusive bone versus visceral metastases, first-line versus ≥ 2 lines of combination therapy, aromatase inhibitor (AI) versus fulvestrant. RESULTS: Fifty-six patients with a 62-year median age (IC95% 42-81) were analyzed. The CDK 4/6 inhibitor and ET combination was prescribed in first-line setting in 26 patients (46%). Twenty-five patients (44%) had exclusive bone metastasis. Median TTF was 6.1 months. Six patients discontinued capecitabine due to toxicity. Outcomes were not significantly different regardless of metastases localization, ET, and treatment line of the combination of CDK 4/6 inhibitor and ET. Median PFS was 7.1 months. Median OS was 41.3 months. CONCLUSION: Compared to other data of capecitabine prescribed in patients with hormonal resistant MBC, this retrospective study suggests that capecitabine remains effective after CDK 4/6 inhibitor plus ET progression, regardless of therapeutic-line setting and metastases localization. MICRO ABSTRACT: Cycline dependant kinase 4/6 inhibitor plus endocrine therapy have become the standard of care in metastatic hormone receptor positive (HR+) breast cancer (BC). Few data reported the optimal subsequent therapy after progression under the combination. Capecitabine is a therapeutic option in endocrine resistant HR+/HER2- metastatic breast cancer. Data evaluating efficacy of capecitabine after disease progression on endocrine therapy plus cycline-dependant kinase 4/6 inhibitor are poor. This study showed a 6.1-month median time to treatment failure on capecitabine. Capecitabine remained effective regardless of therapeutic-line setting and metastases localization.

Efficacy of front-line treatment for hormone receptor-positive HER2-negative metastatic breast cancer with germline BRCA1/2 mutation.

BACKGROUND: Efficacy of endocrine therapy in HR+/HER2- metastatic breast cancer could differ depending on the presence of BRCA1/2 germline mutation. METHODS: The ESME metastatic breast cancer platform (NCT03275311) is a French real world database. Multivariable models including a time-varying approach and landmark analyses assessed the association between time-dependent gBRCA status (categorised as gBRCAm, gBRCAwt (wild type), and untested), overall survival (OS), and first-line progression-free survival (PFS1). RESULTS: A total of 170 patients were gBRCAm carriers, 676 gBRCAwt, and 12,930 were untested at baseline. In the multivariable analysis, gBRCAm carriers overall had a lower OS compared to gBRCAwt (adjusted HR [95% CI] 1.26 [1.03-1.55]). gBRCAm patients treated with front-line endocrine therapy had lower adjusted OS (adjusted HR [95% CI] = 1.54 [1.03-2.32]) and PFS1 (adjusted HR [95% CI] 1.58 [1.17-2.12]) compared to gBRCAwt patients. However, for patients who received frontline chemotherapy, neither OS nor PFS1 differed between gBRCAm carriers and the other groups (HR versus gBRCAwt for OS: 1.12 [0.88-1.41], p = 0.350; PFS1: 1.09 [0.90-1.31], p = 0.379). CONCLUSION: In this large cohort of HR+/HER2- MBC patients treated in a pre-CDK4/6 inhibitors era, gBRCAm status was associated with a lower OS and lower PFS following first-line endocrine therapy, but not following first-line chemotherapy.

A propensity score-weighted study comparing a two- versus four-weekly pegylated liposomal doxorubicin regimen in metastatic breast cancer.

PURPOSE: A 4-weekly schedule of pegylated liposomal doxorubicin (PLD) has been approved for the treatment of metastatic breast cancer (MBC). Phase II trials have suggested interest in a 2-weekly regimen. This study aimed to compare the efficacy and safety of these two schedules. METHODS: Data from MBC patients treated with PLD between 2011 and 2021 were retrospectively collected. The objective was to demonstrate the noninferiority of the 2-weekly versus the 4-weekly schedule in terms of 6-month progression-free survival (PFS). The prespecified noninferiority margin was calculated as 1.20. A propensity score to receive either schedule was estimated using a gradient boosting algorithm. Survival analyses using Cox regression models weighted by the propensity score were performed to compare the schedules. RESULTS: Among the 192 patients included, 96 (50%) underwent each schedule. The median number of previous systemic therapies was 4 (IQR, 3 to 6). Anthracyclines were previously given in early breast cancer in 63.9% of patients. The median follow-up was 10.0 months (IQR, 5.0 to 20.1). A comparable distribution of adverse events was observed. The median PFS was 3.2 months (95% CI, 2.9 to 3.9), and the median overall survival was 12.1 months (95% CI, 10.8 to 14.9). The weighted hazard ratio for PFS was 1.12 (90% CI, 0.82 to 1.54), including the noninferiority boundaries. CONCLUSION: PLD appeared to be a well-tolerated drug in this heavily pretreated MBC population. The efficacy and safety of the 2-weekly schedule did not provide any advantage, suggesting no interest in changing the registered regimen.

Enrollment of older metastatic breast cancer patients in first-line clinical trials: 9-year experience of the large-scale real-life multicenter French ESME cohort.

PURPOSE: Older cancer patients are underrepresented in clinical trials. We aimed to evaluate the enrollment of older women aged 70 years old (yo) or over with metastatic breast cancer (MBC) in clinical trials. METHODS: We used the national Epidemio-Strategy and Medical Economics MBC Data Platform, a French multi-center real-life database. We selected MBC women over 70yo, without central nervous system metastases, with at least one line of systemic treatment, between January 1st, 2008 and December 31st, 2016, and had no other cancer in the 5 years before MBC. The primary objective was to evaluate the proportion of patients enrolled in clinical trials according to their age. Secondary objective was to identify variables associated with enrollment in older ones. RESULTS: 5552 women were aged ≥ 70 (median 74yo; IQR 72-77). 14,611 were less than 70. Of the older ones, 239 (4%) were enrolled in a clinical trial during first line of treatment, compared with 1529 (10.5%) for younger ones. Multivariable analysis of variables predicting for enrollment during first line of treatment in older patients were younger age (OR 0.50 [95%CI 0.33-0.76] for the 80-85yo class; OR 0.17 [95%CI 0.06-0.39] for the 85yo and more class), good ECOG Performance Status (PS 0-1) (OR 0.15 [95%CI 0.08-0.27] for the PS 2-4 class), HER2 + disease (OR 1.78 [95%CI 1.27-2.48]), type of treatment (chemotherapy/targeted therapy/immunotherapy OR 5.01 [95%CI 3.13-8.18]), and period (OR 1.65 [95%CI 1.22-2.26] for 2012-2016, compared to 2008-2011). CONCLUSION: In this large database, few older MBC patients were enrolled in a trial compared with younger ones.

De novo metastatic breast cancer in patients with a small locoregional tumour (T1-T2/N0): Characteristics and prognosis.

INTRODUCTION: The estimated rate of de novo metastatic breast cancer (dnMBC) at the time of diagnosis is between 5 to 12%. International guidelines recommend metastatic work-up (MWU) only in women with advanced breast cancer. The purpose of this study was to describe the characteristics and prognosis of patients with dnMBC diagnosed without an initial indication for MWU. METHODS: We conducted a retrospective, comparative study in dnMBC patients selected from the ESME-MBC cohort. Patients were treated in France between 2008 and 2016. We compared two populations: patients in whom dnMBC was diagnosed by staging although not indicated by guidelines (non-guideline staging [NGS]) and those in whom dnMBC was diagnosed by guideline staging (GS). RESULTS: During the study period, 22,463 patients with MBC were included in the ESME cohort. Among them, 6698 were dnMBC patients. In 247 of these patients (6% of dnMBC and 1% of the overall population), dnMBC was diagnosed by non-guideline staging. Women in this group were significantly younger (57 vs. 59 years, p = 0.02) and had fewer metastatic sites at diagnosis than dnMBC-GS patients. The two groups were not significantly different in terms of the other characteristics. Overall survival (OS) and progression-free survival (PFS) were better in the dnMBC-NGS group than in the dnMBC-GS group. The impact on survival was confirmed by univariate and multivariate analysis (HR 1.83 [1.31-2.57], p < 0.01). CONCLUSION: This study provides the first description of a very specific population. These patients with dnMBC-NGS were younger and more likely to have oligometastatic disease with a better prognosis.

Metastatic inflammatory breast cancer: survival outcomes and prognostic factors in the national, multicentric, and real-life French cohort (ESME).

BACKGROUND: Primary inflammatory breast cancer (IBC) is a rare and aggressive entity whose prognosis has been improved by multimodal therapy. However, 5-year overall survival (OS) remains poor. Given its low incidence, the prognosis of IBC at metastatic stage is poorly described. MATERIALS AND METHODS: This study aimed to compare OS calculated from the diagnosis of metastatic disease between IBC patients and non-IBC patients in the Epidemiological Strategy and Medical Economics database (N = 16 702 patients). Secondary objectives included progression-free survival (PFS) after first-line metastatic treatment, identification of prognostic factors for OS and PFS, and evolution of survival during the study period. RESULTS: From 2008 to 2014, 7465 patients with metastatic breast cancer and known clinical status of their primary tumor (T) were identified (582 IBC and 6883 non-IBC). Compared with metastatic non-IBC, metastatic IBC was associated with less hormone receptor-positive (44% versus 65.6%), more human epidermal growth factor receptor 2-positive (30% versus 18.6%), and more triple-negative (25.9% versus 15.8%) cases, more frequent de novo M1 stage (53.3% versus 27.7%; P < 0.001), and shorter median disease-free interval (2.02 years versus 4.9 years; P < 0.001). With a median follow-up of 50.2 months, median OS was 28.4 months [95% confidence interval (CI) 24.1-33.8 months] versus 37.2 months (95% CI 36.1-38.5 months) in metastatic IBC and non-IBC cases, respectively (P < 0.0001, log-rank test). By multivariate analysis, OS was significantly shorter in the metastatic IBC group compared with the metastatic non-IBC group [hazard ratio = 1.27 (95% CI 1.1-1.4); P = 0.0001]. Survival of metastatic IBC patients improved over the study period: median OS was 24 months (95% CI 20-31.9 months), 29 months (95% CI 21.7-39.9 months), and 36 months (95% CI 27.9-not estimable months) if diagnosis of metastatic disease was carried out until 2010, between 2011 and 2012, and from 2013, respectively (P = 0.003). CONCLUSION: IBC is independently associated with adverse outcome when compared with non-IBC in the metastatic setting.

Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases in a large real-life database.

BACKGROUND: Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high morbidity/mortality rates. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models. METHODS: The Epidemiological Strategy and Medical Economics (ESME) MBC database (NCT03275311) includes all consecutive patients who have initiated treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan-Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots. RESULTS: Of the 22 266 patients included in the database between 2008 and 2016, 312 received IT therapy and were selected for our analysis. Compared with non-IT-treated patients, IT-treated patients were younger at MBC relapse (median age: 52 years versus 61 years) and more often had lobular histology (23.4% versus 12.7%) or triple-negative subtype (24.7% versus 13.3%) (all P < 0.001). Median OS was 4.5 months [95% confidence interval (CI) 3.8-5.6] and 1-year survival rate was 25.6%. Significant prognostic factors associated with poorer outcome on multivariable analysis were triple-negative subtype (hazard ratio 1.81, 95% CI 1.32-2.47), treatment line ≥3 (hazard ratio 1.88, 95% CI 1.30-2.73), ≥3 other metastatic sites (hazard ratio 1.33, 95% CI 1.01-1.74) and IT cytarabine or thiotepa versus methotrexate (hazard ratio 1.68, 95% CI 1.28-2.22), while concomitant systemic therapy was associated with better OS (hazard ratio 0.47, 95% CI 0.35-0.62) (all P < 0.001). We validated two previously published prognostic scores, the Curie score and the Breast-graded prognostic assessment, both with C-index of 0.57. CONCLUSIONS: MBC patients with LM treated with IT therapy have a poor prognosis. We could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used.

Subpolar North Atlantic western boundary density anomalies and the Meridional Overturning Circulation.

Changes in the Atlantic Meridional Overturning Circulation, which have the potential to drive societally-important climate impacts, have traditionally been linked to the strength of deep water formation in the subpolar North Atlantic. Yet there is neither clear observational evidence nor agreement among models about how changes in deep water formation influence overturning. Here, we use data from a trans-basin mooring array (OSNAP-Overturning in the Subpolar North Atlantic Program) to show that winter convection during 2014-2018 in the interior basin had minimal impact on density changes in the deep western boundary currents in the subpolar basins. Contrary to previous modeling studies, we find no discernable relationship between western boundary changes and subpolar overturning variability over the observational time scales. Our results require a reconsideration of the notion of deep western boundary changes representing overturning characteristics, with implications for constraining the source of overturning variability within and downstream of the subpolar region.

Evolution of overall survival and receipt of new therapies by subtype among 20 446 metastatic breast cancer patients in the 2008-2017 ESME cohort.

BACKGROUND: Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. PATIENTS AND METHODS: We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2-; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). RESULTS: The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2- MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2- and TNBC cohorts, respectively, whatever YOD. CONCLUSION: OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed.

CinéBreast-factors influencing the time to first metastatic recurrence in breast cancer: Analysis of real-life data from the French ESME MBC database.

PURPOSE: The Time to First Metastatic Recurrence (TFMR) could be considered as an indirect reflection of the tumour growth kinetics which plays an important role in cancer. Molecular subtypes such as expression of estrogen receptor are known predictive factors of TFMR. The CinéBreast study aimed to identify predictive factors of the time to TFMR. METHODS: The French Epidemiological Strategy and Medical Economics (ESME) Metastatic Breast Cancer (MBC) Database (NCT03275311) was used, which contains data from a cohort of metastatic breast cancer patients from 2008 to 2016 using retrospective data collection. It is a national multi-centre database. The impact of TFMR on overall survival (OS) since first metastasis was also evaluated. RESULTS: Among 16 702 patients recorded in the ESME MBC database, 10 595 had an initially localised breast cancer with hormone receptor (HR) and HER2 status available, with a metastatic recurrence. Median follow up was 56 months. Median TFMR was 59 months (<24: 20%, 24-60: 31%, 60-120: 25%, >120: 24%). HER2+ and TNBC were respectively 4 times and 12 times (p < 0.0001) more likely to have a recurrence within 2 years when compared to the luminal subgroup. Short TFMR and HR-/HER2-subtype significantly correlated with a poor OS in multivariate analysis. Some patients with MBC (20% in HER2+, 10% in ER+/HER2-and <5% in the ER-/HER2-) were long-term survivors in all 3 subgroups. CONCLUSIONS: In this large-scale real-life data study, patients with a TNBC metastatic recurrence had a shorter TFMR. Short TFMR significantly correlated with worse overall survival.

Differential impact of endocrine therapy and chemotherapy on quality of life of breast cancer survivors: a prospective patient-reported outcomes analysis.

BACKGROUND: In early breast cancer (BC), there has been a trend to escalate endocrine therapy (ET) and to de-escalate chemotherapy (CT). However, the impact of ET versus CT on the quality of life (QoL) of early BC patients is unknown. Here, we characterize the independent contribution of ET and CT on patient-reported outcomes (PROs) at 2 years after diagnosis. PATIENTS AND METHODS: We prospectively collected PROs in 4262 eligible patients using the European Organization for Research and Treatment of Cancer QLQ-C30/BR23 questionnaires inside CANTO trial (NCT01993498). The primary outcome was the C30 summary score (C30-SumSc) at 2 years after diagnosis. RESULTS: From eligible patients, 37.2% were premenopausal and 62.8% postmenopausal; 81.9% received ET and 52.8% CT. In the overall cohort, QoL worsened by 2 years after diagnosis in multiple functions and symptoms; exceptions included emotional function and future perspective, which improved over time. ET (Pint = 0.004), but not CT (Pint = 0.924), had a persistent negative impact on the C30-SumSc. In addition, ET negatively impacted role and social function, pain, insomnia, systemic therapy side-effects, breast symptoms and further limited emotional function and future perspective recovery. Although CT had no impact on the C30-SumSc at 2-years it was associated with deteriorated physical and cognitive function, dyspnea, financial difficulties, body image and breast symptoms. We found a differential effect of treatment by menopausal status; in premenopausal patients, CT, despite only a non-significant trend for deteriorated C30-SumSc (Pint = 0.100), was more frequently associated with QoL domains deterioration than ET, whereas in postmenopausal patients, ET was more frequently associated with QoL deterioration, namely using the C30-SumSc (Pint = 0.004). CONCLUSION(S): QoL deterioration persisted at 2 years after diagnosis with different trajectories by treatment received. ET, but not CT, had a major detrimental impact on C30-SumSc, especially in postmenopausal women. These findings highlight the need to properly select patients for adjuvant ET escalation.

Surgery for no palpable testis before the age of one year: a risk for the testis?

INTRODUCTION: Surgery for undescended testis is now commonly recommended before the age of one year. However, the risk of testicular atrophy or miss location after surgery at a young age has not been clearly evaluated. OBJECTIVE: The objective of this study is to evaluate the rate of testicular atrophy after surgery for non-palpable testis before the age of one year. MATERIALS: Fifty-five patients operated between 2005 and 2014 for non-palpable testes were reviewed for clinical and ultrasound (US) evaluation. Median follow-up after surgery was of 68.5 months (range 26-130 months). The median age at surgery was of months (5-12 months). Eight patients (14.5%) had bilateral non-palpable testis; thus, 63 testes were evaluated. At surgery, 38 (60%) testes were located in the high inguinal canal; 25 (40%), in the abdominal cavity. Orchiopexy was performed with preservation of the testicular vessels for 58 testes. Fowler-Stephens (FS) procedure was performed for 5 testes. Testicular location was clinically evaluated, and testicular volume was measured using a standard sonogram technique in our pediatric radiology department. Ratio comparing the volume of the descended testis to the spontaneously scrotal located testis was calculated in unilateral forms. RESULTS: After surgery, testes had scrotal location in 62 cases and inguinal location in one case. Seven cases of atrophy were confirmed after US control (11%), more frequently (odds ratio, OR 11.68 [1.9-72.5]) in abdominal testis (24%) than in inguinal testis (2.6%). Atrophy testicular was more frequent with FS technique (OR 7.1 [1.3-40.1]), but the population was weak (N = 5). Median volume ratio for unilateral form was 0.88 [0-1.8]; 14 patients presented a ratio greater than 1. DISCUSSION: The influence of the young age at surgery and the risk of post operative testicular atrophy had not been clearly evaluated. The term of 'no palpable testis' supports an heterogeneous group mixing abdominal and extra-abdominal testis sharing a uniform clinical presentation. Our rate of atrophy in the group of abdominal testes (24%) and inguinal testes (2.6%) is similar to the literature, which concerns older patients. The long-term sonogram assessment demonstrated a good development of the testis after surgery, especially in inguinal cases. CONCLUSION: Surgery for no palpable testis before the age of one year does not lead to a superior risk of testicular atrophy compared with surgery at an older age and allows a good development of the testis.

[Assessment of astigmatism associated with the iris-fixated ARTISAN aphakia implant: Anterior fixation versus posterior fixation, study of postoperative follow-up at one year]. / Évaluation de l'astigmatisme associé à l'implant ARTISAN Aphakia fixé à l'iris en face antérieure versus face postérieure : étude du suivi postopératoire sur un an.

PURPOSE: The goal of our retrospective, single-center study of a case series was to compare the total, corneal, and internal astigmatism, and the visual acuity at one year after combined or stand-alone surgery consisting of iris fixation of an iris-claw intraocular lens (ARTISAN aphakia) in aphakic patients, according to whether the lens was fixated to the anterior (n=21) or posterior (n=51) surface of the iris. RESULTS: We did not find a significant difference between these two types of fixation for any of the studied variables. The surgically induced astigmatism was 1.67 D at 176° in group A versus 1.19 D at 11° in group P. CONCLUSION: Although this surgery creates additional corneal astigmatism, it has not been proven that it differs depending on the type of fixation of the iris-claw. If we adhere to the notion that the posterior fixated iris-claw decreases the risk of endothelial decompensation in case the implant becomes disenclavated, then reverse iris fixation of the iris-claw makes sense.

[A series of 20 cases of endogenous endophthalmitis]. / Description et devenir d'une série de 20 endophtalmies endogènes.

BACKGROUND: The purpose of this case series was to evaluate both the visual and systemic prognosis of patients with endogenous endophthalmitis. MATERIAL AND METHODS: We reported a series of 20 cases of endogenous endophthalmitis occurring between 2012 and 2015 at the university medical center in Toulouse. RESULTS: The mean age was 67 (±43.3) years with a male predominance (n=11). The site of entry was found in 14 cases (87.5%). In 11 cases (69%), the causative agent was a bacterium; a fungal infection was found in five cases. Visual acuity after maximal medical and surgical treatment was limited to "no light perception" in 7 cases (35%), "hand motion" in 2 cases (10%), "finger counting" in 3 cases (15%) and 10/10 in 2 cases (10%). One case had no final data. The main site of entry was found to be associated endocarditis (n=7), central venous line or venipuncture (n=6). The main local complications were retinal detachment (n=6), cataract (n=5) and choroidal neovascularization secondary to scarring (n=2). CONCLUSIONS: Endogenous endophthalmitis is associated with poor visual prognosis. It is also often associated with systemic complications that may be life-threatening.

[Acute generalized exanthematous pustulosis induced by phloroglucinol]. / Pustulose exanthématique aiguë généralisée induite par le phloroglucinol (Spasfon®).

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a severe drug eruption. We report herein the first case of AGEP induced by phloroglucinol (Spasfon®). PATIENTS AND METHODS: A 27-year-old pregnant woman developed a febrile exanthematous pustulosis eruption three days after treatment with intravenous phloroglucinol and paracetamol for nephritic colic. She had no previous history of psoriasis. The laboratory workup showed hyperleukocytosis with neutrophilia. A cytobacteriological sample of the pustules was negative. Skin biopsy revealed marked neutrophilic and leukocytoclastic vasculitis. Reintroduction of phloroglucinol after delivery resulted in the same clinical symptoms within a few hours of intake. A diagnosis of phloroglucinol-induced AGEP was made on the basis of intrinsic imputability of I4 (S3 C3) using the imputability criteria of Begaud et al. The outcome was favorable after withdrawal of the drug. DISCUSSION: To the best of our knowledge, this is the first case of phloroglucinol-induced AGEP confirmed by reintroduction of the drug.

[Atypical intradermal smooth-muscle neoplasm]. / Tumeur musculaire lisse atypique dermique.

BACKGROUND: We report herein a case of atypical intradermal smooth-muscle neoplasm. PATIENT AND METHODS: A 58-year-old man presented with a painless pinkish-white chest nodule ongoing for two years. Histopathology revealed a proliferation of intradermal smooth-muscle cells. Some atypia and 5 mitoses were seen in the most mitotic fields. The histopathologist suggested a diagnosis of "atypical intradermal smooth-muscle neoplasm". DISCUSSION: Atypical intradermal smooth-muscle neoplasm is part of a spectrum extending from skin leiomyoma to leiomyosarcoma. The prognosis consists chiefly in risk of local recurrence. The terminology is not currently accepted by WHO but nevertheless offers an alternative to inappropriate diagnosis of sarcoma, which carries psychological and social impact.

Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab.

Background: We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab. Patients and methods: Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System. Results: From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value. Conclusion: In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials.