Low PTEN expression in patients treated with cetuximab plus chemotherapy emerged as a prognostic biomarker and should be evaluated for its predictive role for cetuximab efficacy.

BackgroundBRCA1/2 pathogenic (P) and likely pathogenic (LP) germline variants are frequent among patients with ovarian carcinoma. However, these variants have not been extensively characterized in patients with ovarian cancer in Brazil.MethodsIn this retrospective study we evaluated clinical characteristics and BRCA1/2 genetic test results from patients with ovarian carcinoma who underwent genetic counseling at A.C.Camargo Cancer Center (Brazil) between 2015 and 2017 and had performed germline genetic testing of BRCA1/2 genes.ResultsAmong 158 patients, 33 P and LP variants and were found (20.8%), 27 in BRCA1 and six in BRCA2, and six variants of unknown clinical significance (VUS). Thirteen percent of the patients did not have Multiplex Ligation-dependent Probe Amplification (MLPA) results. Three P variants in BRCA1 were found in more than one patient: c.5266dupC (p.Gln1756Profs*74), c.3331_3334delCAAG (p.Gln1111Asnfs5*), and c.211A > G (p.Arg71Gly). One LP variant in BRCA1 had not been previously described, c.4153_4154delCT (p.Leu1385Ilefs*5). Patients with previous diagnosis of breast cancer were carriers of P or LP variant in 8 of 12 cases (66.7%), and patients with a family history of ovarian or breast cancer in first- or second-degree relatives were carriers of P or LP variant in 26.7% of cases compared to 16.9% for patients without family history (p = 0.166).ConclusionPrevalence of BRCA1/2 germline P and LP variants is slightly higher than previously described by the largest occidental studies, with a high prevalence of variant c.5266dupC (p.Gln1756Profs*74) in BRCA1 observed. Moreover, we identified a new LP variant.

Background Ovarian carcinomas presenting homologous recombination deficiency (HRD), which is observed in about 50% of cases, are more sensitive to platinum and PARP inhibitor therapies. Although platinum resistant disease has a low chance to be responsive to platinum-based chemotherapy, a set of patients is retreated with platinum and some of them are responsive. In this study, we evaluated copy number alterations, HR gene mutations and HR deficiency scores in ovarian cancer patients with prolonged platinum sensitivity. Methods In this retrospective study (2005 to 2014), we selected 31 patients with platinum resistant ovarian cancer retreated with platinum therapy. Copy number alterations and HR scores were evaluated using the OncoScan® FFPE platform in 15 cases. The mutational profile of 24 genes was investigated by targeted-NGS. Results The median values of the four HRD scores were higher in responders (LOH = 15, LST = 28, tAI = 33, CS = 84) compared with non-responders (LOH = 7.5, LST = 17.5, tAI = 23, CS = 47). Patients with high LOH, LST, tAI and CS scores had better response rates, although these differences were not statistically significant. Response rate to platinum retreatment was 22% in patients with CCNE1 gains and 83.5% in patients with no CCNE1 gains ( p = 0.041). Furthermore, response rate was 54.5% in patients with RB1 loss and 25% in patients without RB1 loss ( p = 0.569). Patients with CCNE1 gains showed a worse progression free survival (PFS = 11.1 months vs 3.7 months; p = 0.008) and a shorter overall survival (OS = 39.3 months vs 7.1 months; p = 0.007) in comparison with patients with no CCNE1 gains. Patients with RB1 loss had better PFS (9.0 months vs 2.6 months; p = 0.093) and OS (27.4 months vs 3.6 months; p = 0.025) compared with cases with no RB1 loss. Four tumor samples were BRCA mutated and tumor mutations were not associated with response to treatment. Conclusions HR deficiency was found in 60% of our cases and HRD medium values were higher in responders than in non-responders. Despite the small number of patients tested, CCNE1 gain and RB1 loss discriminate patients with tumors extremely sensitive to platinum retreatment. Electronic supplementary material The online version of this article (10.1186/s12885-019-5622-4) contains supplementary material, which is available to authorized users.

Background. Treatment of advanced uterine cervical cancer has advanced little in the last 15 years. Although two phase III trials showed survival benefit with the addition of consolidation chemotherapy (CT) after cisplatin-based chemoradiotherapy (RTCT), it is not considered standard of care. We aimed to evaluate the benefit of consolidation CT compared to no additional treatment in patients treated with RTCT. Methods. This is a retrospective study including 186 patients with FIGO stage IB2, IIA2, or IIB to IVB (paraaortic lymph nodes only) uterine cervical cancer who were treated with standard RTCT alone or RTCT followed by consolidation CT. Overall survival (OS), progression free survival (PFS), and the risk of distant and local relapses were compared between the two treatment groups. Results. At 3 years OS was 91% versus 82.3% (p=0.027), PFS 84.3% versus 54.4% (p=0.047), and distant metastasis free survival (DMFS) 80.4% versus 62.5% (p=0.027) in favor of the consolidation CT group. Multivariate analysis confirmed the benefit of consolidation CT. There was no difference in locoregional free survival (LRFS). Positive lymph node was related to a higher risk of distant relapse. In the lymph node positive subgroup consolidation CT resulted in longer OS (p=0.050), PFS (p=0.014), and DMFS (p=0.022); in the lymph node negative subgroup there was no benefit from consolidation CT. Conclusions. Use of consolidation CT resulted in longer OS and PFS, mostly due to control of distant relapses. Patients at higher risk of distant relapse showed the greatest benefit. This data generates a hypothesis that could help to better select patients to consolidation CT.

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