Recently, phase I studies with novel antibody drug conjugates targeting HER2 suggested benefit in HER2-low patients -defined as immunohistochemistry(IHC) +1 or +2 FISH/ISH non-amplified, with advanced breast cancer(BC). Data on the prognostic value of HER2-low in early stage disease is scarce. The purpose of this study was to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy(NACT) and survival outcomes in early stage HER2negative BC. MethodsRecords from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. Primary objective was to compare differences between pathologic complete response(pCR) and relapse free survival(RFS) in luminal HER2-low/HER2-0 and triple negative(TNBC) HER2-low/HER2-0. Results855 non-HER2-positive patients were identified. Median follow-up was 59 months. 542 had luminal BC (63.4%) and 313 TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal tumors, 145 had HER2 IHC+1 (26.8%) and 91 IHC+2/ISH non-amplified (16.8%). In TNBC, only 36 had HER2 IHC+1 (11.5%) and 13 IHC+2/ISH non-amplified (4.2%). Among luminal/HER2-low and luminal/HER2-0 population, there was a high proportion of clinical T3/4 (61.5% vs 69.2%, p=0.053), node positive (74.2% vs 66.3%, p=0.27) and stage III tumors (63.1% vs 65%, p=0.51). The same was true TNBC/HER-low as compared to TNBC/HER2-0, despite a non-statistically significant higher cT4 among TNBC/HER-low (32.7% vs. 19.3%, p=0.17). pCR was 13% in luminal/HER2-low versus 9.5% in luminal/HER2-0 (p=0.27), and 51% in TNBC/HER2-low versus 47% in TNBC/HER2-0 (p=0.64). 5y RFS was 72.1% in luminal/HER2-low and 71.7% in luminal/HER2-0 (p=0.47), and 75.6% in TNBC/HER2-low versus 70.8% in TNBC/HER2-0 (p=0.23). HER2-low status was not associated with RFS in multivariate analysis (HR 0.83, 95%CI 0.6-1.11, p=0.21). ConclusionOur data does not support HER2-low as a biologically distinct BC subtype, with no predictive effect on pCR after NACT nor prognostic value on survival outcomes.

Background The aim of this study was to report the prevalence and mortality associated with anticoagulant-related nephropathy (ARN) through a systematic review of the literature. Methods Electronic searches were conducted in the Medline and EMBASE databases, and manual searches were performed in the reference lists of the identified studies. The studies were selected by two independent researchers, first by evaluating the titles and abstracts and then by reading the complete texts of the identified studies. Case series, cross-sectional studies, cohort studies and case–control studies reporting the prevalence and factors associated with ARN were selected. The methodological quality was assessed using the Newcastle–Ottawa scale. Meta-analyses of the prevalence of ARN and 5-year mortality using the random effects model were performed when possible. Heterogeneity was assessed using the I2 statistic. Results Five studies were included. Prevalence of ARN ranged from 19% to 63% among the four included cohort studies. Meta-analysis of these resulted in high heterogeneity [I2 96%, summary effect 31%; 95% confidence interval (CI) 22–42%]. Subgroup meta-analysis yielded an ARN prevalence of 20% among studies that included patients with fewer comorbidities (I2 12%; 95% CI 19–22%). In a direct comparison, meta-analysis of the 5-year mortality rate between anticoagulated patients who had experienced ARN and anticoagulated patients without ARN, patients with ARN were 91% more likely to die (risk ratio = 1.91; 95% CI 1.22–3; I2 87%). Risk factors for ARN that were reported in the literature included initial excessive anticoagulation, chronic kidney disease, age, diabetes, hypertension, cardiovascular disease and heart failure. Conclusions ARN studies are scarce and heterogeneous, and present significant methodological limitations. The high prevalence of ARN reported herein suggests that this entity is underdiagnosed in clinical practice. Mortality in patients with ARN seems to be high compared with patients without this condition in observational studies.

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e18043 Background: Neoadjuvant chemotherapy (NACT), followed by interval debulking surgery (IDS), is a possible approach to patients with stages IIIC and IV epithelial ovarian cancer who are most likely to have suboptimal results with upfront surgery. Delay in initiation of adjuvant chemotherapy has been associated with worse outcomes. Our study aimed to evaluate whether time from NACT to surgery (TNS) and from surgery to adjuvant chemotherapy (TSA) were associated with survival outcomes and with platinum-resistant relapse. Methods: We did a retrospective analysis of medical records from 194 patients with EOC treated with IDS at a single institution from 2007 to 2018. We calculated the median TNS and TSA and evaluated its relation to progression free survival (PFS), overall survival (OS) and time to platinum-resistant relapse (TTPR) through Kaplan-Meier and Cox regression analysis. Results: After a median follow-up of 62 months, OS was 58 months and PFS was 18 months. Most patients received at least 3 cycles of NACT (21.1% 3 cycles, 16.0% 4 cycles and 39.7% 6 cycles); and the rate of optimal cytoreduction was 75,8%. Optimal surgery was associated with survival (p < 0.001). TNS over 8 weeks and TSA over 7 weeks were associated with worse PFS (HR 1.57, 95%CI 1.07-2.31; HR 1.52, 95%CI 1.00-2.32, respectively) and OS (HR 1.83, 95%CI 1.13-2.96; HR 1.57, 95%CI 0.93-2.65, respectively) in univariate analysis but not in a multivariate analysis including residual disease as a covariate. In the subgroup of patients with residual disease < 10mm a multivariate analysis showed shorter PFS (HR 2.06, CI95% 1.16-3.66, p = 0.014) and OS (HR 2.20, CI95% 1.05-4.59, p = 0.035) for patients with TSA longer than 7 weeks. Longer TNS was associated with PFS (HR 1.66, 95%CI 1.06-2.59, p = 0.026) in univariate analysis but not in multivariate analysis. Interestingly, longer TNS was associated with shorter TTPR (65.6 vs. 35.0 months, p = 0.049) and a higher frequency of platinum resistant relapse at first relapse (48.8% versus 26.5%, p = 0.012). Conclusions: Our study provides evidence that delayed TSA is an independent prognostic factor for worse PFS and OS only in the subgroup of patients with residual disease ≤ 10mm. Longer TNS was associated with higher risk of platinum resistant relapse. One possible explanation is that NACT may select chemoresistant clones, which would have more time to grow and spread with longer intervals until surgery. Further studies are necessary to corroborate this hypothesis.

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