Possible association between viral infection and poor survival of the corneal graft after penetrating keratoplasty in patients with congenital corneal opacity: a cohort study

2022 ◽  
pp. bjophthalmol-2021-320031
Author(s):  
Sen Miao ◽  
Qi Lin ◽  
Xu Li ◽  
Lu Zhao ◽  
Zhiqiang Pan

BackgroundCongenital corneal opacity (CCO) is a rare disorder. Penetrating keratoplasty (PK) is the main surgical option for CCO, but many factors affect graft survival. Therefore, this study aimed to perform a virological examination of CCO specimens after PK to explore the relationship between virological factors and graft survival after PK.MethodsThis prospective study included consecutive patients (<6 months of age) diagnosed with CCO and treated with PK at Beijing Tongren Hospital from August 2017 to January 2018. Next-generation sequencing was used to detect viral DNA in the CCO specimens. The survival of the primary graft was analysed using the Kaplan-Meier method.ResultsOverall, 24 eyes of 24 infants were treated with PK during the study period. The mean age at surgery was 4.8±1.1 months. Epstein-Barr virus DNA was detected in two specimens, varicella-zoster virus DNA in one specimen, herpes simplex virus DNA in three specimens and cytomegalovirus DNA in one specimen. In the virus-positive group, only one (14.3%) graft remained clear during follow-up. In contrast, in the virus-negative group (n=17), 13 (76.5%) grafts were still clear at the last follow-up. The mean survival of the grafts in the virus-positive group was significantly shorter than in the virus-negative group (11.0±9.8 months vs 27.1±7.7, p<0.001).ConclusionThe presence of viral DNA in CCO specimens might be associated with poor graft survival after PK.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1936-1936
Author(s):  
Myoung Joo Kang ◽  
Yoo Jin Cho ◽  
Heui June Ahn ◽  
Shin Kim ◽  
Dae Ho Lee ◽  
...  

Abstract Abstract 1936 Poster Board I-959 Introduction: Epstein-Barr virus (EBV) is well-known as an etiologic agent of lymphoproliferative disorders. Almost all types of sporadic non-Hodgkin's lymphoma (NHL) of both B-cell and T-cell origins have been demonstrated to have EBV-infected tumor cells. However, the prognostic significance of EBV viral load has not been established yet. Methods: To monitor quantitative EBV DNA load, real time quantitative PCR of EBV BZLF1 DNA was done using RealArt® EBV LC PCR reagents (Artus) from whole blood samples drawn from newly diagnosed NHL patients at the time of diagnosis and during the follow-up. Results: Between July 2006 and March 2009, a total of 233 patients (including 120 [51.5%] diffuse large B-cell lymphoma [DLBCL]; 18 [7.7%] natural killer (NK)/T-cell lymphoma; and 11 [4.7%] peripheral T-cell lymphoma, unspecified) were reviewed and analyzed. Among them, 33 (14%) patients, had a detectable EBV DNA (positive group) while 200 (85%) patients did not (negative group). Those in positive group had a more advanced disease and a higher LDH level than those in negative group (P=0.003 and 0.007, respectively). With a median follow up of 11.3 months (range 1.2-34.9), 14 (42.4%) of the 33 patients in positive group had a progressive or relapsed disease while 30 (15%) of the 200 patients in negative group did (P<0.001). One-year overall survival (OS) rate was 72.5% in positive group while that was 82.9% in negative group (log-rank P=0.001). Interestingly, conversion to negative EBV DNA during the follow-up was associated with a lower probability of progressive or relapsed disease (P=0.004). NK/T-cell lymphoma patients having an EBV DNA survived shorter than those having not. However, in DLBCL patients, there was no difference in survival between those having an EBV DNA and those not. Conclusions: The presence of EBV DNA at diagnosis and the negative conversion of EBV DNA during the follow-up might have prognostic significance in patients with NHL. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 102 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Hamed AlArrayedh ◽  
Louis Collum ◽  
Conor C Murphy

Background/aimTo report the outcome of penetrating keratoplasty (PKP) in Irish patients with congenital hereditary endothelial dystrophy (CHED).MethodsA retrospective case series review of patients with CHED who underwent PKP was conducted. The outcomes of PKP in 14 patients with CHED at the Royal Victoria Eye and Ear Hospital in Dublin from 1978 to 2013 were described following case note review. The main outcome measures were best-corrected visual acuity (BCVA) and graft survival.ResultsThirty-three corneal transplants were performed, which included 32 PKPs and one Descemet’s stripping endothelial keratoplasty. Twenty-four eyes underwent primary corneal grafts and nine eyes had regrafts. The graft survival rates at final follow-up were 37.5% and 33% in the primary graft and regraft groups, respectively. Preoperative BCVA was 20/200 or worse in all patients. At the final postoperative visit, the BCVA was 20/80 or better in four eyes following primary PKP, 20/160 in one eye following regrafting and was 20/200 or worse in all other eyes. The mean time to graft failure was 16 months (range 0–37 months). The mean follow-up time was 101 months (range 12–252 months). Fifty per cent of the patients continue to attend for follow-up.ConclusionsThis study has demonstrated a poor outcome from PKP for CHED in this Irish cohort. This arises from a combination of dense amblyopia and a high risk of graft failure in the long term.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5328-5328
Author(s):  
Mehmet Gunduz ◽  
Pinar Ataca ◽  
Mehmet Ozen ◽  
Erden Atilla ◽  
Sinem Civriz Bozdag ◽  
...  

Abstract Introduction Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), FMS-like tyrosine kinase 3 tyrosine kinase domain (FLT3-TKD) and nucleophosmin1 gene (NPM1) are most frequent mutations found in patients with AML. In this study, we aimed to identify the prognostic value of FLT3 and NPM1 mutations in our AML patients. Method We retrospectively evaluated 121 patients who had been diagnosed based on the WHO AML diagnosis criteria, between 2007 and 2014 in the Department of Hematology at Ankara University. FLT3 and NMP 1 mutations were detected by Polymerase chain reaction (PCR) amplification method. The overall survival (OS) and relapse-free survival (RFS) due to FLT3 and NMP1 mutations were analyzed using Kaplan Meier method and Long-Rank. P<.05 was considered statistically significant. Results Of the 121 patients, 50 (41%) were female and 71 were male (59%). The mean diagnosis age of AML in the female patients was 50.52 ± 2.23, whereas the mean diagnosis age in the male patients was 50.62 ± 2.15. 115 of 121 patients (95%) received cytarabine (ARA-C) and an anthracycline ("7+3" protocol) as an remission induction therapy while 6 of the patients (5%) haven't received any therapy because of older age and poor performance status. 33 of 121 patients (33%) got cytarabine (ARA-C) and an anthracycline ("7+3" protocol) as a reinduction therapy. 67 of 121 patients (55%) were followed by consolidation therapy with high-dose ARA-C. Allogeneic stem cell transplantation (ASCT) was performed in 31 of 121 patients (31%) during follow-up. The donors were relatives in 21 of 31 patients (68%) while 10 ASCT were from unrelated donors (32%). 32 of 121 patients (26%) were dead during follow-up. The FLT3 and NMP1 mutations were studied from peripheral blood in 27 of 121 patients (22%) while in 94 of 121 (78%) patients samples from bone marrow were used. 27 of 121 patients (22%) had NMP1 mutation positive whereas 22 of 121 patients (18%) had FLT3 mutation positive. In 4 of 22 patients were FLT3-TKD positive others were FLT3-ITD positive.The FLT3 positive patients are significantly older than FLT3 negative patients (P<.05) Due to flow cytometric analysis, 17 of 121 patients (14%) were considered as low risk. 3 of 17 low risk patients had FLT3 mutation positive (18%) and 2 of them were diagnosed as AML M3 (12%). The median OS in FLT3 mutation positive group was 17.93 ± 13.86 months, whereas the median OS was 15.03±14.90 months in FLT3 mutation negative group. In NMP mutation positive patients the median OS was 14.53±13.03 months while in NMP mutation negative groups the median OS was 15.85±15.20 months. The median RFS in FLT3 mutation positive group was 13.38±11.59 months, whereas the median RFS was 11.98±12.79 months in FLT3 mutation negative group. In NMP mutation positive patients the median RFS was 12.26±12.11 months while in NMP mutation negative groups the median RFS was 12.23±12.73 months. In subgroup analysis, the median OS in FLT3-ITD mutation positive group was 15.34±13.03 months while 14.29±14.65 months of median OS was detected in FLT3-ITD negative patients. On the other hand, the median RFS was 10.10±9.32 months in FLT3-ITD positive patients and 11.46±12.40 months in FLT3-ITD negative patients. Neither FLT3 mutation (FLT3-ITD or both FLT3-ITD and FLT3-TKD) nor NMP mutation positive patients are statistically different from FLT3 or NMP mutation negative patients due to OS and RFS (P>.05)(Figure 1)(Figure 2). Conclusion In previous studies, FLT3-ITD mutation predicted an unfavorable prognosis whereas mutation in NPM1 gene was associated with favorable prognosis. Unexpectedly we detected no difference in either OS or RFS in FLT3 or NPM1 gene mutated patients. Figure 1. Kaplan Meier Curve of OS in FLT3 positive and negative group(dashed curve FLT3 positive). Figure 1. Kaplan Meier Curve of OS in FLT3 positive and negative group(dashed curve FLT3 positive). Figure 2. Kaplan Meier Curve of RFS in FLT3 positive and negative group (dashed curve FLT3 positive). Figure 2. Kaplan Meier Curve of RFS in FLT3 positive and negative group (dashed curve FLT3 positive). Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 681.1-681
Author(s):  
L. Garzanova ◽  
L. P. Ananyeva ◽  
O. Koneva ◽  
O. Desinova ◽  
O. Ovsyannikova ◽  
...  

Background:Rituximab (RTX) is a new option in the treatment of systemic sclerosis (SSc) [1]. There is not enough data on changes in the level of autoantibodies and their clinical significance during RTM therapy. There are only a few reports on the higher efficiency of RTX in patients (pts) with SSc positive for anti-topoisomerase-1 antibodies (a-Topo-1), therefore the study of this issue might be interested.Objectives:To compare clinical parameters and B-lymphocytes (B-lymph) level in SSc pts depending on the presence or absence of a-Topo-1 during RTX therapy with prospective long-term follow-up.Methods:This study included 88 pts with SSc. The mean follow-up period was 26,3±10,7 months. The mean age was 47years (17-71), female-73 pts (83%), the diffuse cutaneous subset of the disease had 50 pts (57%). Symptoms of the interstitial lung disease (ILD) were observed in 70 pts (80%). The mean disease duration was 5,9±4,8 years. The cumulative mean dose of RTX was 2,9±1,1 grams. All patients received prednisone at a dose of 11,7±4,4 mg, immunosuppressants received 42% of them. There were 63 pts positive for a-Topo-1 and 25 pts - negative. The pts of the compared groups did not differ in the main demographic and clinical parameters, excepting lung involvement. In a-Topo-1 positive group 55 (87%) pts had ILD and only 15 (60%) – in a-Topo-1-negative group (p=0,02). The results at baseline and at the end of the follow up are presented in the form of mean values and changes in parameters (delta).Results:Considering the entire cohort, an improvement of almost all outcome parameters was found. When a-Topo-1 positive and a-Topo-1-negative pts were analyzed separately, we observed a significantly higher decrease in the activity score, depletion of B-lymph, an increase in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) in a-Topo-1 positive group of pts (table 1).Table 1.Changes of the main outcome parameters depending on the presence of a-Topo-1 on RTX therapy.Parametersa-Topo-1positive ptsa-Topo-1negative ptsPDelta Activity score (EScSG-AI)1,790,90,001Delta Rodnan skin score (mRSS)4,95,2NSDelta B-lymphocytes (absolute count)0,2120,1930,001Delta FVC*, %8,646,460,001Delta DLCO**, %2,860,0320,001*FVC - forced vital capacity % predicted, **DLCO - diffusion capacity for carbon monoxide % predictedThe a-Тopo-1 level decreased from 174,2±50,1 to 148,1±66,1 units/ml (p=0,0009). In this group, a-Тopo-1 became negative in 5 pts (7,9%). The disappearance of a-Topo-1 positivity was accompanied by a more pronounced decrease in mRSS (delta mRSS=7,4) and a higher depletion of B-lymph. There was a higher cumulative dose of RTX (4±1,4grams) in this 5 pts compared with the pts who sustained a-Topo-1 positivity. There was a moderate negative statistically significant correlation between the a-Topo-1 and the total dose of RTX (r=-0,298, p=0,017). A moderate negative statistically significant correlation was found between the a-Topo-1 and FVC (r=-0,322, p=0,009).Conclusion:In our study, the a-Topo-1 level significantly decreased during RTX therapy in Russian pts. The decrease in a-Topo-1 titers correlated with the total dose of RTX and was accompanied by a decrease in mRSS, disease activity index and an increase in FVC and DLCO. A higher efficacy of RTX in the a-Topo-1 positive group with prevalence of ILD was revealed, therefore a-Topo-1 positivity could be considered as a predictor of a better response to RTX therapy.References:[1]Jordan S, et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis.2015;74:1188–94.Doi:10.1136/annrheumdis-2013-204522.[2]Ebata S, Yoshizaki A, et.al. Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti-topoisomerase I-positive systemic sclerosis-associated interstitial lung disease. J Dermatol.2019.Nov;46(11):1006-1013.doi:10.1111/1346-8138.15079.Disclosure of Interests:None declared


2014 ◽  
Vol 86 (4) ◽  
pp. 325 ◽  
Author(s):  
Saverio Forte ◽  
Pasquale Martino ◽  
Silvano Palazzo ◽  
Matteo Matera ◽  
Floriana Giangrande ◽  
...  

Introduction: The intrarenal resistance index (RI) is a calculated parameter for the assessment of the status of the graft during the follow-up ultrasound of the transplanted kidney. Currently it is still unclear the predictive value of RI, also in function of the time. Materials and Methods: We retrospectively investigated the correlation between the RI and the graft survival (GS) and the overall survival (OS) after transplantation. We evaluated 268 patients transplanted between 2003 and 2011, the mean followup was 73 months (12-136). The RI was evaluated at 8 days, 6 months, 1 year and 3 years. The ROC analysis was used to calculate the predictive value of RI and the Kaplan Mayer curves was used to evaluated the OS and PS. Results: The ROC analysis, correlated to the GS, identified a value of RI equal to 0.75 as a cut-off. All patients was stratified according to the RI at 8 days (RI ≤ 0,75: 212 vs RI &gt; 0.75: 56), at 6 months (RI ≤ 0.75: 237 vs RI &gt; 0.75: 31), at 1 year (RI ≤ 0.75: 229 vs RI &gt; 0.75: 39) and at 3 years (RI ≤ 0.75: 224 vs RI &gt; 0.75: 44). The RI showed statistically significant differences between the two groups in favor of those who had an RI ≤ 0.75 only at 8 days and at 6 moths (p = 0.0078 and p = 0.02 to 8 days to 6 months) on the GS. On the contrary, we observed that the RI estimated at 1 year and 3 years has not correlated with the GS. The same RI cut-off was correlate with PS after transplantation. We observed that there are no correlations between the RI and OS. Conclusions: The RI proved to be a good prognostic factor on survival organ when it was evaluated in the first months of follow- up after transplantation. This parameter does not appear, however, correlate with OS of the transplanted subject.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Yasuyuki Iguchi ◽  
Kazumi Kimura ◽  
Jyunya Aoki ◽  
Kazuto Kobayashi ◽  
Kenichiro Sakai ◽  
...  

Background and Purpose Our aim is to investigate the diagnostic utility of diffusion weighted magnetic resonance imaging (DWI) for transient ischemic attack (TIA), not only admission but also 24 h after first study. Methods We prospectively enrolled TIA patients who were admitted within 24 h of onset. We examined trans-thoracic echocardiography, 24 h Holter electrocardiography, and carotid duplex ultrasonography in order to give the best medication. All of patients received DWI immediately after admission. At first, when we observed hyper-intense lesion considered as ischemia, additional DWI examination was not conducted. When there was no hyper-intense lesion on initial DWI study, we conducted follow-up DWI 24 h after initial examination. We defined a recurrence of ischemic event as an occurrence of symptomatic ischemic stroke or TIA at 3 months after onset. Regarding initial DWI study, we compared proportional frequency of recurrence between patients with ischemic lesion (i-positive group) and without any lesion (i-negative group), and also compared recurrence rate between patients with ischemic lesion on initial and/or follow-up studies (if-positive group) and without any lesion on both studies (if-negative group). Results We registered 100 TIA patients (men; 63, median age; 74 years, ABCD2 score <3; 32). On initial DWI study, 34 patients had ischemic lesion (i-positive group) and 66 had no lesion (i-negative group). Among 66 patients of i-negative group, 12 (19%) had hyper-intense lesion in follow-up study. Finally, there were 46 patients in if-positive group and 54 in if- negative. Recurrence ischemic event occurred in 19 (19%) of 100 patients. There was no significant difference of recurrence rate between i-positive and i-negative groups (27% vs. 16%, p=0.172). However, recurrence rate was significantly higher in if-positive group than these of if-negative group (29% vs. 12%, p=0.024) Conclusions New ischemic lesions on follow up DWI appeared in approximately 20% of TIA patients who did not have ischemic lesion on initial DWI. Only initial DWI but initial and follow-up DWI was important role of predicting the recurrence of ischemic events in TIA patients.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Inge Derad ◽  
Johanna Busch ◽  
Martin Nitschke ◽  
Malte Ziemann

Abstract Background and Aims Posttransplant kidney survival depends on several risk factors. A careful immunogenetic matching and the absence of HLA donor specific antibodies (DSA) seem to determine the longevity of the transplant. Method Screening the presence of donor specific HLA antibodies in our posttransplant outpatients was implemented in 2010 (every 6 months in case of DSA free patients for two years, then yearly, and every 3 months in case of DSA + patients for two years, then twice a year). At the same time a treatment protocol was implemented, omitting reduction of immunosuppressive drugs in case of newly detected DSA, and most important with preventing steroid withdrawal in this case.The present single center study reports the long-term survival and kidney function from patients undergoing HLA-screening after transplantation between 2010 and 2016 with a follow-up until 2018. Using a Kaplan-Meier analysis patients without HLA antibodies (no HLA-ab), with HLA antibodies but without DSA (NDSA), and with donor-specific HLA antibodies (DSA) were compared by logrank-testing. Results A full dataset was obtained from 318 patients. The mean overall survival (patients and organ function) didn´t differ between the three groups, p=0.318: no HLA-ab 7.2 years (95%confidence interval 6.7;7.6), NDSA 6.6 (5.9;7.2), DSA 6.8 (6.1;7.5), overall 7.0 (6.6;7.3), events are given in Table1. Whereas the mean patient survival didn´t differ between the groups (p=0.715), the mean death-censored graft survival differed significantly, p=0.008, with a reduced transplant survival in the patients with HLA antibodies but without donorspecific antibodies: no HLA-ab 8.0 years (95%confidence interval 7.7;8.3), NDSA 7.0 (6.4;7.6), DSA 7.6 (7.1;8.2), overall 7.7 (7.4;8.0), numbers are given in Table1. Conclusion In conclusion, the presence of HLA antibodies was associated with a reduced transplant survival. Patients with HLA antibodies had a worse survival than patients with DSA undergoing HLA screening with a personalised immunosuppressive regimen. Immunosuppressive regimen of the groups, as well as other known risk factors of graft survival have to be further analysed. The results of these multivariate analyses have to be awaited to determine whether the risk for graft loss inferred by HLA antibodies is independent from other factors.


2009 ◽  
Vol 19 (4) ◽  
pp. 535-543 ◽  
Author(s):  
Leopoldo Spadea ◽  
Massimo Saviano ◽  
Angela Di Gregorio ◽  
Domenico Di Lodovico ◽  
Fabio De Sanctis

Purpose To evaluate in a long-term period the effectiveness and safety of topographically guided two-step laser in situ keratomileusis (LASIK) and standard LASIK technique in the correction of refractive errors after successful penetrating keratoplasty (PKP) for keratoconus. Methods At least 2 years after PKP and 6 months after removal of all sutures, 15 eyes of 15 patients (Group 1; mean manifest refraction spherical equivalent (MRSE) −7.23 D ± 3.42 SD) were submitted to standard LASIK and 15 eyes of 15 patients (Group 2; mean MRSE −4.37 D ± 1.97 SD) to a topographically guided two-step LASIK procedure (first the flap and at least 2 weeks later the laser ablation). In all cases, a superior hinged corneal flap (160 μm/9.5 mm) was created. Results After a follow-up of 36 months, in Group 1 the mean uncorrected visual acuity (UCVA) was 0.51 logarithm of the minimum angle of resolution (logMAR) ± 0.41 SD and the mean best-corrected visual acuity (BCVA) was 0.03 logMAR ± 0.05 SD, with a mean MRSE of −1.57 D ± 2.65 SD. In Group 2, the mean UCVA was 0.28 logMAR ± 0.24 SD and the mean BCVA was 0.01 logMAR ± 0.03 SD, with a mean MRSE of −0.07 D ± 1.00 SD. In both groups, no complications were observed. Conclusions After a long follow-up period, both topographically guided two-step LASIK and standard LASIK could be considered effective and safe tools in the correction of refractive errors after successful PKP for keratoconus.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Michał Ciszek ◽  
Bartosz Foroncewicz ◽  
Krzysztof Mucha ◽  
Dorota Żochowska ◽  
Bogna Ziarkiewicz-Wróblewska ◽  
...  

Objective. Presence of anti-HLA antibodies has a well-known impact on kidney grafts survival; however their role in liver transplantation has not been fully elucidated. We conducted a 7-year prospective study to show correlation between presence of anti-HLA and anti-MICA antibodies and liver graft survival.Methods. Blood samples from 123 liver transplant recipients were collected during patients routine visits. Time from transplantation to blood sample collection was different for each patient. Blood samples were tested for anti-HLA (separately class I and II) and MICA antibodies using Luminex assays.Results. There were 32 (26%) patients with positive anti-HLA and 37 (30%) with positive anti-MICA antibodies. Graft loss occurred in 7 cases (23%) in anti-HLA positive group compared to 20 (22%) in anti-HLA negative group (P=ns) and in 8 cases (22%) in anti-MICA positive group but 19 (23%) in anti-MICA negative group (P=ns). No correlations were detected between presence of antibodies and acute graft rejection (AGR). Presence of any antibodies (anti-HLA or anti-MICA antibodies) correlated with late graft rejection (P=0.04).Conclusion. Presence of anti-HLA or anti-MICA had no impact on long-term liver graft survival; however, detection of any antibodies was correlated with episodes of late graft rejection.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11017-11017
Author(s):  
R. Wesolowski ◽  
T. K. Choueiri ◽  
L. Rybicki ◽  
A. G. Shealy ◽  
G. Casey ◽  
...  

11017 Background: Since the BRCA gene is responsible for excisional DNA repair, we hypothesized that breast cancer patients with BRCA mutation would be more susceptible to the induction of second malignancies following chemotherapy treatment than breast cancer patients who tested negative for BRCA mutations. Methods: Breast cancer patients tested for BRCA1 and BRCA2 mutations at the Cleveland Clinic were identified and evaluated for history of neoadjuvant or adjuvant chemotherapy and for the occurrence of subsequent non-breast primary invasive cancer. Patients with inadequate follow-up and those with inoperable disease at diagnosis were excluded from the analysis. Fisher’s exact test was used to compare different cohorts. The IRB at Cleveland Clinic approved the study. Results: Of 115 identified breast cancer patients tested for BRCA mutations, 77 met the inclusion criteria. Twenty-seven of these patients carried BRCA1 or BRCA2 mutations and 50 tested negative for these mutations. Twelve patients (44%) in the BRCA positive group and 8 patients (16%) in the BRCA negative group underwent prophylactic oophorectomy. Median follow-up for the two groups was 53.5 months (75 months in the BRCA positive group and 48.5 months in the BRCA negative group). Median age at diagnosis was 42 years (40.5 years in the BRCA positive group and 44.5 in the BRCA negative group). In the BRCA positive group 3 of 25 patients (12%) treated with chemotherapy developed second malignancies (ovarian cancer, transitional cell cancer in urinary tract and renal cell carcinoma) compared with none of the 2 patients who did not get chemotherapy (p= 1.0). In the BRCA negative group, 2/34 patients (6%), treated with chemotherapy developed second cancers compared with 2/16 patients (12%), who were not treated with chemotherapy (p=0.58). Cancers in the BRCA negative group included two bladder carcinomas in the chemotherapy treated patients and in the non-chemotherapy group, non-small cell lung cancer, uterine, ovarian, endometrial and peritoneal cancers. Conclusions: At more than 4-years of follow up, chemotherapy in operable breast cancer patients was not associated with an increase in the risk of secondary malignancy or with a differential effect on this endpoint by BRCA mutation status in this retrospective study. No significant financial relationships to disclose.


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