ANA CAROLINA RIBEIRO CHAVES DE GOUVEA
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LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
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- Frequency of CDH1 germline variants and contribution of dietary habits in early age onset gastric cancer patients in Brazil(2019) GUINDALINI, Rodrigo Santa Cruz; CORMEDI, Marina Candido Visontai; MAISTRO, Simone; PASINI, Fatima Solange; BRANAS, Priscila Cristina Abduch Adas; SANTOS, Liliane dos; PEREIRA, Glaucia Fernanda de Lima; BOCK, Geertruida Hendrika de; SACCARO, Daniela Marques; KATAYAMA, Maria Lucia Hirata; FARAJ, Sheila Friedrich; SAFATLE-RIBEIRO, Adriana; RIBEIRO JUNIOR, Ulysses; DIZ, Maria Del Pilar Estevez; GOUVEA, Ana Carolina Ribeiro Chaves de; CHAMMAS, Roger; FOLGUEIRA, Maria Aparecida Azevedo KoikeIntroduction The contribution of CDH1 germline variants to gastric cancer burden among young adults is unknown in Brazil. We aimed to evaluate the frequency of CDH1 germline variants and the diet/lifestyle habits in early age onset gastric cancer (EOGC, <= 55 years old) patients. Methodology From 2013 to 2015, a total of 88 unrelated and consecutive patients diagnosed with EOGC were enrolled. All CDH1 exons and intronic boundaries were sequenced, and large genomic rearrangements were screened by MLPA. CDH1 transcription analysis was performed for variants that could potentially induce an effect on splicing. The diet and lifestyle habits of EOGC patients were compared to Brazilian population diet and lifestyle, obtained from governmental databases. Results Of 88 patients, the mean age at EOGC diagnosis was 39 years and 55% fulfilled the criteria for hereditary diffuse gastric cancer. The majority of the tumors were diffuse (74%) and poorly differentiated (80%). In total, 4 novel missense variants of uncertain significance (VUS) were identified: c.313T>A, c.387G>T, c.1676G>A, and c.1806C>A. The MLPA results revealed no rearrangements and CDH1 transcription analysis for variants of interest were inconclusive. EOGC patients had a higher red (OR:2.6, 95%CI:1.4-4.9) and processed (OR:3.1, 95%CI:1.6-6.0) meat intake and higher fruit consumption (OR:0.4, 95%IC:0.3-0.7) compared to eating habits of the Brazilian population. Conclusions No unequivocal pathogenic germline CDH1 variants were identified in Brazilian EOGC patients. Dietary habits may be associated with the EOGC development.
bookPart Terapia antissenso(2013) LEAL, Alessandro Igor Cavalcanti; ANJOS, Carlos Henrique dos; CHAVES, Ana Carolina Ribeiro- Somatic mutations in early onset luminal breast cancer(2018) ENCINAS, G.; SABELNYKOVA, V. Y.; LYRA, E. C. de; KATAYAMA, M. L. H.; MAISTRO, S.; VALLE, P. W. M. V.; PEREIRA, G. F. L.; RODRIGUES, L. M.; SERIO, P. A. M. P.; GOUVêA, A. C. R. C. de; GEYER, F. C.; BASSO, R. A.; PASINI, F. S.; DIZ, M. P. E.; BRENTANI, M. M.; GóES, J. C. G. S.; CHAMMAS, R.; BOUTROS, P. C.; FOLGUEIRA, M. A. A. K.Breast cancer arising in very young patients may be biologically distinct; however, these tumors have been less well studied. We characterized a group of very young patients (≤ 35 years) for BRCA germline mutation and for somatic mutations in luminal (HER2 negative) breast cancer. Thirteen of 79 unselected very young patients were BRCA1/2 germline mutation carriers. Of the non-BRCA tumors, eight with luminal subtype (HER2 negative) were submitted for whole exome sequencing and integrated with 29 luminal samples from the COSMIC database or previous literature for analysis. We identified C to T single nucleotide variants (SNVs) as the most common base-change. A median of six candidate driver genes was mutated by SNVs in each sample and the most frequently mutated genes were PIK3CA, GATA3, TP53 and MAP2K4. Potential cancer drivers affected in the present non-BRCA tumors include GRHL2, PIK3AP1, CACNA1E, SEMA6D, SMURF2, RSBN1 and MTHFD2. Sixteen out of 37 luminal tumors (43%) harbored SNVs in DNA repair genes, such as ATR, BAP1, ERCC6, FANCD2, FANCL, MLH1, MUTYH, PALB2, POLD1, POLE, RAD9A, RAD51 and TP53, and 54% presented pathogenic mutations (frameshift or nonsense) in at least one gene involved in gene transcription. The differential biology of luminal early-age onset breast cancer needs a deeper genomic investigation. © Encinas et al.
- Metronomic oral cyclophosphamide plus prednisone in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer(2015) BARROSO-SOUSA, Romualdo; FONSECA, Leonardo Gomes da; SOUZA, Karla Teixeira; CHAVES, Ana Carolina Ribeiro; KANN, Ariel Galapo; CASTRO JR., Gilberto de; DZIK, CarlosWe evaluated the efficacy and safety of metronomic oral cyclophosphamide (CTX) and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients. We analyzed retrospectively patients with mCRPC previously treated with docetaxel, and who received metronomic CTX (from 50 mg PO daily to 150 mg PO, 14 days/7 days off) and prednisone 10 mg PO daily between September 2009 and April 2014 were analyzed. The primary endpoint was prostate-specific antigen (PSA) decrease >= 50 %. Secondary analysis included PSA decrease >= 30 %, time-to-treatment failure (TTF) and toxicity. Demographics and baseline characteristics were summarized using descriptive statistics. PSA response and adverse events were reported as relative rates. Kaplan-Meier estimates were calculated and plotted for time-to-event endpoints. Forty patients were evaluated. The median age was 69 years old (52-86), 12 (30.0 %) patients presented a Karnofsky performance status (KPS) of <80 %, and 34 (85 %) presented with bone with or without nodal metastases. Median pretreatment PSA was 192 ng/dL (7-2696 ng/dL). All patients were previously exposed to docetaxel, including 33 (82.5 %) with docetaxel-refractory disease. PSA response rate was achieved in eight (20.0 %) out of 40 patients. Additionally, PSA declines of >= 30 % occurred in 14 (35.0 %) patients. The median TTF was 3 months (95 % confidence interval 2.5-3.5). The treatment was well tolerated. Grade 3/4 lymphopenia was reported in 11 (27.5 %) patients and was the only grade 3-4 toxicity reported. Metronomic oral CTX showed activity and safety in docetaxel-pretreated mCRPC patients. This regimen deserves further investigation in this setting.
conferenceObject Frequency of CDH1 germline mutations in diffuse gastric cancer in Brazil.(2015) GUINDALINI, Rodrigo Santa Cruz; PASINI, Fatima Solange; GOUVEA, Ana Carolina Ribeiro Chaves De; BRANAS, Priscila Abduch; CORMEDI, Marina Candido Visontai; MAISTRO, Simone; KATAYAMA, Maria Lucia Hirata; ENCINAS, Giselly; NAGY, Tauana; ESTEVEZ-DIZ, Maria Del Pilar; SAFATLE-RIBEIRO, Adriana Vaz; RIBEIRO, Ulysses; FOLGUEIRA, Maria A. A. KoikeconferenceObject Germline BRCA1 and BRCA2 mutations in Brazilian ovarian and breast cancer patients.(2018) MAISTRO, Simone; ENCINAS, Giselly; NAGY, Tauana; TEIXEIRA, Natalia; KATAYAMA, Maria Lucia H.; GOUVEA, Ana Carolina R. C.; DIZ, Maria del Pilar E.; CHAMMAS, Roger; BOCH, Geertruida H. de; FOLGUEIRA, Maria Aparecida A. K.- Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil(2016) MAISTRO, Simone; TEIXEIRA, Natalia; ENCINAS, Giselly; KATAYAMA, Maria Lucia Hirata; NIEWIADONSKI, Vivian Dionisio Tavares; CABRAL, Larissa Garcia; RIBEIRO, Roberto Marques; GABURO JUNIOR, Nelson; GOUVEA, Ana Carolina Ribeiro Chaves de; CARRARO, Dirce Maria; SABINO, Ester Cerdeira; DIZ, Maria del Pilar Estevez; CHAMMAS, Roger; BOCK, Geertruida Hendrika de; FOLGUEIRA, Maria Aparecida Azevedo KoikeBackground: Approximately 8-15% epithelial ovarian cancer patients are BRCA1 or BRCA2 germline mutation carriers. Brazilian inhabitants may have peculiar genetic characteristics associated with ethnic diversity, and studies focusing on the entire BRCA1/BRCA2 gene sequencing in Brazilian ovarian cancer patients are still lacking. The aim of this study was to evaluate BRCA1/2 mutations, through entire gene sequencing, in a Brazilian population of women with epithelial ovarian cancer. Methods: In a cross sectional study performed in one reference centre for cancer treatment in Sao Paulo, Brazil, 100 patients diagnosed with epithelial ovarian cancer unselected for family history of breast and/or ovarian cancer were included. The complete coding sequence of BRCA1/2 genes was evaluated through Next-Generation or capillary sequencing. Large deletions were investigated through Multiplex Ligation-dependent Probe Amplification (MLPA). Results: Nineteen pathogenic mutations (BRCA1: n = 17 and BRCA2: n = 2) featuring 14 different mutations, including two large deletions in BRCA1 (exon 1-2 deleted and exon 5-7 deleted) were identified. Three mutations were detected more than once (c.3331_3334delCAAG, c.5266dupC and c.4484G > T). Two novel frameshift mutations were identified, one in BRCA1 (c.961_962delTG) and one in BRCA2 (c.1963_1963delC). BRCA1/2 mutations were seen in 35.5% of the patients with first and/or second-degree relatives with breast and/or ovarian cancer. Nineteen variants of uncertain significance (VUS) were detected (BRCA1: n = 2 and BRCA2: n = 17), including five distinct missense variants (BRCA1: c. 5348 T > C; BRCA2: c.2350A > G, c.3515C > T, c.7534C > T, and c.8351G > A). Conclusions: Among epithelial ovarian cancer patients unselected for family history of cancer, 19% were BRCA1/2 germline mutation carriers. Almost 3/4 of the BRCA mutations, including two large deletions, were detected only once. Our work emphasizes the need of entire gene sequencing and MLPA screening in Brazil.
conferenceObject Somatic mutations in Luminal HER2 negative tumors from young breast cancer patients.(2015) ENCINAS, Giselly; ESTEVEZ-DIZ, Maria Del Pilar; LYRA, Eduardo C.; KATAYAMA, Maria Lucia Hirata; PASINI, Fatima Solange; MAISTRO, Simone; SABELNYKOVA, Veronica; BOUTROS, Paul; BRENTANI, Maria Mitzi; BASSO, Ricardo; GOUVEA, Ana Carolina Ribeiro Chaves De; CHAMMAS, Roger; GOES, Joao Carlos Guedes Sampaio; FOLGUEIRA, Maria A. A. KoikebookPart Aconselhamento genético em gastroenterologia(2017) DIZ, Maria Del Pilar Estevez; GOMY, Israel; COTTI, Guilherme Cutait de Castro; GOUVêA, Ana Carolina Ribeiro Chaves deconferenceObject ORAL METRONOMIC CYCLOPHOSPHAMIDE IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER STRATIFIED BY PRIOR DOCETAXEL THERAPY(2012) BARROSO-SOUSA, R.; CHAVES, A. C. R.; FONSECA, L. G.; CASTRO JR., G. De; DZIK, C.; HOFF, P. M.Background: Treatment options remain limited for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Here we aimed to investigate the efficacy and safety of low-dose oral cyclophosphamide (CTX), an intermittent metronomic chemotherapy regimen, in pts with mCRPC, previously treated or not with docetaxel. Methods: All pts previously diagnosed with mCRPC and treated with CTX 100mg/ day (3 weeks on and 1 week off, every 28 days) plus prednisone 10mg/day between Oct/2006 and Feb/2012 at our institution were included in this retrospective analysis. The primary efficacy endpoint was prostate-specific antigen (PSA) decrease ≥ 50%. Secondary endpoints were PSA decrease ≥ 30% and toxicity. Kaplan-Meier estimates were calculated and plotted for time to treatment failure (TTF). Single and multivariate Cox proportional hazards modeling was used to estimate hazard ratios with 95% confidence intervals (95% CI). Results: 51 pts with mCRPC were identified, of which 30 (59%) had been already treated with docetaxel. The median age was 72 y.o. (56-86) and 27 pts (53%) were ECOG PS0-1 and 24 pts (47%) PS2-3. Five pts presented with visceral metastasis (10%) and median PSA 525 ng/dL (12-4099) before treatment. Median number of previous cytotoxic lines was 1 (0-2). After a median number of cycles CTX of 3, PSA decrease of ≥ 50% was achieved in 28.6% and 16.7% of docetaxel-naive and docetaxel-pretreated pts, respectively (p= 0.30). Besides, PSA declines of ≥ 30% occurred in 38.1% and 30.0% of docetaxel-naive and docetaxel-pretreated patients, respectively (p= 0.54). Overall, the median TTF was estimated to be 2.4 mo. (95% CI 1.87 – 3.73). Previously treatment with docetaxel was not statistically significant to TTF, and the median TTF was 2.1 mo. (95% CI 1.6 – 3.2) for docetaxel-pretreated and 3.4 mo. (95% CI 1.7 – 5.4) for docetaxel-naïve patients (HR 1.47; 95% CI 0.78 – 2.74; p = 0.22). In general, oral CTX was safe and well tolerated and the most commonly observed G3-4 AE was lymphopenia (29%). Conclusions: Oral metronomic CTX plus prednisone seems to be active and safe in mCRPC, even in pts previously treated with docetaxel. Its convenient oral administration, low cost, and acceptable toxicity profile may justify future investigations of this classic alkylating agent in mCRPC. Disclosure: All authors have declared no conflicts of interest.