Risk of metastasis in BRCA2 carriers diagnosed with triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the neoplasia most associated with BRCA1 germline pathogenic variants (PV) and is more likely to develop metastases than the other breast cancer (BC) subtypes, mainly in the lungs and the central nervous system (CNS). Recently, BRCA2 carriers were shown to have a higher risk for developing CNS metastases. However, the patterns of recurrence and metastases of BRCA2 carriers with TNBC are unknown. METHODS: TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p < 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death. RESULTS: A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2. A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers (p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82-20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12-2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33-9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23-2.23; p = 0.574). CONCLUSIONS: Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers.

Cost-effectiveness analysis of Oncotype DX from a Brazilian private medicine perspective: a GBECAM multicenter retrospective study.

Background: Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1-3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a dataset of patients from Brazilian institutions. Methods: Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! Algorithm. The ODX score was correlated with the indication of CT according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included while in the second, only high clinical risk patients were included. The cost for ODX and CT was based on the Brazilian private medicine perspective. Results: In all, 645 patients were analyzed; 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (<11), intermediate (11-25), and high (>25) risk in 119 (18.4%), 415 (64.3%), and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, ODX was effective (5.6% reduction in CT indication) though with an incremental cost of United States Dollar (US$) 2288.87 per patient. Among 234 patients analyzed in the second model (high clinical risk only), ODX led to a 57.7% reduction in CT indication and reduced costs by US$ 4350.66 per patient. Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC and cost-attractive for the overall population in the Brazilian private medicine perspective. Its incorporation into routine practice should be strongly considered by healthcare providers.

Benefits of a standardized protocol for axillary management after neoadjuvant chemotherapy in a single center

Introduction: The axillary lymph node status is one of the most important prognostic factors in breast cancer. For locally advanced tumors, neoadjuvant chemotherapy favors higher rates of breast lumpectomy and downstaging tumor burden of axilla. The aim of this study was to evaluate the use of a standardized image-guided protocol after neoadjuvant chemotherapy to enable sentinel node dissection in patients with axillary downstaging, avoiding axillary dissection. Methods: Retrospective cohort study of data collected from medical records of patients who underwent neoadjuvant chemotherapy in a single center, from January 2014 to December 2018. The protocol comprises the placement of a metal clip in positive axillary lymph node, in patients with up to two clinically abnormal lymph nodes presented on imaging. After neoadjuvant chemotherapy, and once a radiologic complete response was achieved, sentinel node dissection was performed using blue dye and radiotracer. Axillary dissection were avoided in patients whose clipped sentinel node were negative for metastasis and in patients with three identified and negative sentinel node dissection. Results: A total of 471 patients were analyzed for this study: 303 before and 165 after the implementation of the protocol; 3 cases were excluded. The rate of sentinel node dissection in clinical nodes positive patients was statistically higher in this group when compared to patients treated before the protocol implementation (22.8% vs. 40.8%; p=0.001). Patients with triple negative and HER2-positive tumors underwent sentinel node dissection more frequently when compared to luminal tumors (p=0.03). After multivariate analysis, the variables that were associated with a greater chance of performing sentinel node dissection were clinical staging, type of surgery performed and implementation of the axillary assessment protocol. Conclusions: The results showed that the use of an easily and accessible image-guided protocol can improve sentinel node dissection in selected patients, even if the lymph node was positive previously to neoadjuvant treatment.

Comparison of hormonal receptor expression and HER2 status between circulating tumor cells and breast cancer metastases.

OBJECTIVES: Breast cancer (BC) is the most common neoplasm in women. Biopsy of metastatic lesions is recommended to confirm estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status as there are discrepancies in these patterns between primary tumors and metastases in up to 40% of the cases. Circulating tumor cells (CTCs) are related to BC outcomes and could potentially be an alternative to the invasive procedures of metastasis rebiopsy. ISET® technology is not currently employed to detect CTCs in patients with BC. Emerging data support that the characterization of CTC protein expression can refine its prognostic value. Transforming growth factor (TGF)-ß plays a role in BC progression and invasiveness. Thus, in this study, we aimed to compare ER, PR, and HER2 expression in primary tumors, CTCs, and metastases and evaluate TGF-ß type 1 receptor (TGF-ß RI) expression in CTCs as prognostic factor for progression free survival (PFS) and overall survival (OS). METHODS: This prospective study was conducted at the A.C. Camargo Cancer Center, Brazil. Blood samples were processed in ISET® (Isolation by SizE of Tumors, Rarecells, France) before computed tomography-guided biopsy of suspected metastatic lesions. Protein expression levels in CTCs were compared to those in primary tumors/metastases (medical records). RESULTS: Of the 39 patients initially included, 27 underwent both biopsies of metastases and blood collection and were considered for analysis. The concordance rates for ER, PR, and HER2 expression between primary tumors and metastases were high. No loss of HER2 expression at any metastasis site and retention of the same pattern of protein expression in all triple-negative (TN) tumors (92.5%, 81.5% and 96.2% respectively) (p<0.0001) was observed. When metastases/CTCs were classified as TN/non-TN, CTCs showed high specificity (93%), accuracy (84.2%), and negative predictive value (88%). The median OS of patients without TGF-ß RI expression in CTCs was 42.6 versus 20.8 months for TGF-ß RI expression-positive ones (p>0.05). CONCLUSION: The role of CTCs detected by ISET has not yet been established in BC. Here, we suggest that this methodology may be useful to evaluate metastasis in non-TN cases as well as TGF-ß RI expression in CTCs, which may impact patient survival. Due to sample limitations, future studies must focus on specific BC subtypes and an expansion of the cohort.

Retrospective analysis of the role of cyclin E1 overexpression as a predictive marker for the efficacy of bevacizumab in platinum-sensitive recurrent ovarian cancer.

The relative benefit of bevacizumab in ovarian cancer (OC) patients is greater the more the disease becomes platinum-resistant. Among other mechanisms of action, antiangiogenic agents may induce homologous recombination deficiency. Cyclin E1 (CCNE1) overexpression is a proposed marker of platinum resistance and is mutually exclusive with deficiency in homologous recombination. In this study, we evaluated the predictive value of CCNE1 expression with regard to the efficacy of bevacizumab. We retrospectively evaluated data from patients with platinum-sensitive recurrent OC who were treated with chemotherapy (CT) plus bevacizumab (Bev group) or CT alone (CT group) at a tertiary cancer centre from 2005 to 2017. The two groups were paired according to histology, platinum-free interval (PFI) and number of previous treatment lines. Progression-free survival (PFS) was compared between groups by log rank test and Cox regression. A total of 124 patients were included, with 62 in each group. The groups were well balanced regarding histology, PFI and number of previous treatment lines. Median PFS (mPFS) was 19.5 months for the Bev group versus 16.0 months for CT group (p = 0.150). By multivariate analysis, the HR for PFS was 2.25 (95% CI: 1.10-4.60) for CCNE1 overexpression. The benefit of bevacizumab was larger in the subgroups of patients with PFI 6-12 months (mPFS 18.6 versus 10.4 months, p = 0.002) and CCNE1 overexpression (mPFS 16.3 versus 7.0 months, p = 0.010). In conclusion, CCNE1 overexpression and PFI may suggest which patients will receive the greatest benefit from bevacizumab. These data, if confirmed by other studies, could help better select patients for antiangiogenic therapy.

HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer.

PURPOSE: Knowledge on whether low expressions of HER2 have prognostic impact in early-stage breast cancer (BC) and on its response to current chemotherapy protocols can contribute to medical practice and development of new drugs for this subset of patients, changing treatment paradigms. This study aims to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy (NACT) and survival outcomes in early-stage HER2-negative BC. METHODS: Records from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients were included. HER2-low was defined by IHC + 1 or + 2 ISH non-amplified and HER2-0 by IHC 0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) between luminal/HER2-low versus luminal/HER2-0 populations and between triple negative (TNBC)/HER2-low versus TNBC/HER2-0. RESULTS: In total, 855 HER2-negative patients were identified. The median follow-up was 59 months. 542 patients had luminal subtype (63.4%) and 313 had TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal patients, 145 had HER2 IHC + 1 (26.8%) and 91 had IHC + 2/ISH non-amplified (16.8%). In TNBC, 36 had HER2 IHC + 1 (11.5%) and 13 had IHC + 2/ISH non-amplified (4.2%). Most patients had locally advanced tumors, regardless of subtype or HER2-low status. For luminal disease, pCR was achieved in 13% of HER2-low tumors versus 9.5% of HER2-0 (p = 0.27). Similarly, there was no difference in pCR rates among TNBC: 51% versus 47% in HER2-low versus HER2-0, respectively (p = 0.64). HER2-low was also not prognostic for RFS, with 5-year RFS rates of 72.1% versus 71.7% (p = 0.47) for luminal HER2-low/HER2-0, respectively, and 75.6% versus 70.8% (p = 0.23) for TNBC HER2-low/HER2-0. CONCLUSION: Our data does not support HER2-low as a biologically distinct BC subtype, with no prognostic value on survival outcomes and no predictive effect for pCR after conventional NACT.

Comparison of hormonal receptor expression and HER2 status between circulating tumor cells and breast cancer metastases

OBJECTIVES: Breast cancer (BC) is the most common neoplasm in women. Biopsy of metastatic lesions is recommended to confirm estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status as there are discrepancies in these patterns between primary tumors and metastases in up to 40% of the cases. Circulating tumor cells (CTCs) are related to BC outcomes and could potentially be an alternative to the invasive procedures of metastasis rebiopsy. ISET® technology is not currently employed to detect CTCs in patients with BC. Emerging data support that the characterization of CTC protein expression can refine its prognostic value. Transforming growth factor (TGF)-β plays a role in BC progression and invasiveness. Thus, in this study, we aimed to compare ER, PR, and HER2 expression in primary tumors, CTCs, and metastases and evaluate TGF-β type 1 receptor (TGF-β RI) expression in CTCs as prognostic factor for progression free survival (PFS) and overall survival (OS). METHODS: This prospective study was conducted at the A.C. Camargo Cancer Center, Brazil. Blood samples were processed in ISET® (Isolation by SizE of Tumors, Rarecells, France) before computed tomography-guided biopsy of suspected metastatic lesions. Protein expression levels in CTCs were compared to those in primary tumors/metastases (medical records). RESULTS: Of the 39 patients initially included, 27 underwent both biopsies of metastases and blood collection and were considered for analysis. The concordance rates for ER, PR, and HER2 expression between primary tumors and metastases were high. No loss of HER2 expression at any metastasis site and retention of the same pattern of protein expression in all triple-negative (TN) tumors (92.5%, 81.5% and 96.2% respectively) (p<0.0001) was observed. When metastases/CTCs were classified as TN/non-TN, CTCs showed high specificity (93%), accuracy (84.2%), and negative predictive value (88%). The median OS of patients without TGF-β RI expression in CTCs was 42.6 versus 20.8 months for TGF-β RI expression-positive ones (p>0.05). CONCLUSION: The role of CTCs detected by ISET has not yet been established in BC. Here, we suggest that this methodology may be useful to evaluate metastasis in non-TN cases as well as TGF-β RI expression in CTCs, which may impact patient survival. Due to sample limitations, future studies must focus on specific BC subtypes and an expansion of the cohort.

Comparação entre expressão de receptores hormonais e de HER-2 entre células tumorais circulantes e metástases de câncer de mama / Comparison of hormonal receptor expression and HER2 status in circulating tumor cells and breast cancer metastases

Introdução: O câncer de mama é a neoplasia mais comum em mulheres. A maioria deles é diagnosticada em estágios iniciais, quando o tratamento visa a cura. Mas apesar dos avanços no tratamento, metástases à distância podem ocorrer. A biópsia das lesões metastáticas é recomendada para confirmar o status do receptor de estrogênio (RE), receptor de progesterona (RP) e receptor do fator de crescimento epidérmico humano 2 (HER2), por ocorrerem discrepâncias nesses padrões entre tumores primários e metástases em até 40% dos casos. As células tumorais circulantes (CTCs) estão relacionadas às evoluções clínicas do câncer de mama e podem potencialmente desempenhar um papel substituto aos procedimentos invasivos de rebiópsia de metástase. A tecnologia ISET® (Isolation by SizE of Tumor Cells, Rarecells-Diagnostics, Paris, França) não é usualmente empregada para detectar CTCs em pacientes com câncer de mama, embora seja reconhecida como uma ferramenta útil em alguns outros tumores. Existem dados emergentes de que a caracterização da expressão proteica das CTC pode refinar seu valor prognóstico. Sabe-se que o fator de transformação de crescimento (TGF-ß) desempenha um papel na progressão e invasividade do câncer de mama. Objetivos: Comparar a expressão de RE, RP e HER2 em tumores primários, CTCs, metástases e avaliar a expressão do receptor TGF-ß tipo 1 (TGF-ß RI) em CTCs como fator prognóstico para sobrevida global. Metodologia: Estudo realizado no A.C.Camargo Cancer Center, Brasil. As amostras de sangue foram coletadas antes da biópsia guiada por tomografia computadorizada de lesões metastáticas suspeitas e processadas pela metodologia ISET®. Os níveis de expressão proteica das CTCs foram comparados aos de tumores primários e metástases e correlacionados aos resultados clínicos. Todos os dados clínicopatológicos foram obtidos dos prontuários médicos. Resultados: Dos 39 pacientes inicialmente incluídos, 27 tiveram tanto a biópsia de metástases quanto a coleta de sangue e foram considerados para análise. As taxas de concordância para a expressão de RE, RP e HER2 entre tumores primários e metástases foram altas. Não foi observada nenhuma perda de expressão de HER2 nas metástases e os tumores triplo negativos mantiveram o mesmo padrão em todas as metástases (p <0,0001). Quando as metástases e CTCs foram classificadas como triplo negativo (TN) ou não ­ TN, as CTCs determinaram alta especificidade (93%), acurácia (84,2%) e valor preditivo negativo (88%). A sobrevida global mediana de pacientes sem expressão de TGF-ß RI em CTCs foi de 42,6 x 20,8 meses para os positivos, clinicamente relevante, porém sem significância estatística (p> 0,05). Conclusões: No câncer de mama, o papel das CTCs detectadas pelo ISET® ainda não está estabelecido. Com este estudo, sugerimos que esta metodologia possa ser útil para avaliar metástases em casos de tumores não TN, assim como a expressão de TGF-ß RI em CTCs, o que pode impactar a sobrevida. Devido à limitação da amostra, estudos futuros devem se concentrar em subtipos específicos de câncer de mama, ampliando a coorte.

Introduction: Breast cancer (BC) is the most common neoplasm in women. Most of BC are diagnosed in early stages, when treatment aims cure. Despite advances in BC treatment, distant metastases may develop. Biopsy of metastatic lesions is recommended to confirm estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, due to discrepancies in these patterns between primary tumors/metastasis in up to 40% of cases. Circulating Tumor Cells (CTCs) are related to breast cancer outcomes and could potentially play a role surrogating invasive procedures of metastasis rebiopsy. ISET® (Isolation by SizE of Tumor Cells, Rarecells-Diagnostics, Paris, France) technology is not currently employed to detect CTCs in breast cancer patients, although recognized as a useful tool in some other tumors. There are emerging data that characterization of CTC protein expression can refine its prognostic value. Transforming growth factor (TGF)-ß play a role in progression/invasiveness of BC. Objectives: To compare ER, PR and HER2 expression in primary tumors, CTCs, metastases and to evaluate TGF-ß type 1 receptor (TGF- ß RI) expression in CTCs as prognostic factor for overall survival. Methods: Study conducted at the A.C.Camargo Cancer Center, Brazil. Blood samples were processed in ISET® before computed tomography­guided biopsy of suspected metastatic lesions. Protein expression levels in CTCs were compared to those in primary tumors/metastases and correlated to clinical outcomes. All clinicopathological data were obtained from medical records. Results: From the 39 patients initially included, 27 had both biopsy of metastases and blood collection and were considered for analysis. Concordance rates for ER, PR and HER2 expression between primary tumors/metastases were high. No loss of HER2 expression at any metastasis site and retention of the same pattern in all triplenegative (TN) tumors (p <0.0001) were observed. When metastases/CTCs were classified as TN/non­TN, CTCs showed high specificity (93%), accuracy (84.2%) and negative predictive value (88%). The median overall survival of patients with no TGF-ß RI expression in CTCs was 42.6 x 20.8 months for positive ones, clinically relevant but not statistically significant (p>0.05). Conclusions: In BC, the role of CTCs detected by ISET® is not yet established. Here, we could suggest that this methodology may be useful to evaluate metastasis in non-TN cases as also TGF-ß RI expression in CTCs, which may impact survival. Due to sample limitation, future studies must focus on specific subtypes of BC, expanding the cohort.

Prognostic impact of platinum sensitivity in ovarian carcinoma patients with brain metastasis.

BACKGROUND: Brain metastasis (BM) is a rare event in ovarian cancer patients. The current prognostic scores that have been used for other tumors do not account for specific characteristics of ovarian cancer, such as platinum sensitivity. METHODS: This retrospective cohort study examined patients with ovarian carcinoma and BM who were treated at a single institution from January 2007 to December 2017. Clinical data on the diagnosis of BM and follow-up were collected. Cox regression was used to evaluate prognostic factors for overall survival (OS). RESULTS: Of 560 patients, 26 presented with BM. Eight patients were treated with surgery, 15 with whole-brain radiotherapy (RT), and 5 with stereotactic RT, and 4 patients received systemic treatment at the diagnosis of BM. The median OS was 10.8 months. The following factors were associated with OS: platinum-sensitive recurrence (HR 0.34, 95% CI 0.12-0.99; p = 0.049), higher number of previous treatment lines (HR 1.57, 95% CI 1.12-2.19; p = 0.008), ECOG performance status (HR 2.52, 95% CI 1.24-5.09; p = 0.010), and longer interval from initial diagnosis to BM (p = 0.025). Notably, the number of brain metastasis, the largest tumor size, and progression outside of the CNS were not related to survival. Platinum sensitivity was not associated with any of the classic prognostic factors in brain metastasis patients such as number or size of brain metastasis or disease progression outside the CNS strengthening the hypothesis of the importance of platinum sensitivity to the prognosis of ovarian cancer patients with BM. CONCLUSIONS: The factors related to the biological behavior of the ovarian cancer such as platinum sensitivity at the time of BM diagnosis, fewer number of previous treatment lines and interval from initial diagnosis were associated with survival in ovarian cancer patients with BM, while factors that are usually related to survival in BM in other cancers were not associated with survival in this cohort of ovarian cancer patients. The small number of patients did not allow us to exclude the prognostic role of these former factors that were not associated with survival in the present cohort.

BREAST CANCER SURVIVAL IN A BRAZILIAN CANCER CENTER: A COHORT STUDY OF 5, 095 PATIENTS / Sobrevida do câncer de mama em um centro de câncer brasileiro: um estudo de coorte de 5. 095 pacientes

Objectives: To describe the age group, clinical stage at diagnosis, treatment, and survival rates of breast cancer patients treated in a Brazilian specialized Cancer Center. Method: A hospital-based retrospective cohort study is presented herein, on women with breast cancer diagnosed between January 1, 2000 and December 31, 2012. Data were extracted from the Hospital Cancer Registry of the A.C.Camargo Cancer Center. Data on age group, histology of the tumor, TNM classification, clinical stage and treatments were described in absolute and relative frequencies for three periods. Survival curves were estimated with the Kaplan-Meier estimator. Hazard ratio (HR) and 95% confidence interval (95%CI) were calculated for all variables. Results: A total of 5,095 female breast cancer patients were identified, with most stages classified as I and II (60%). The overall survival was 82.7% for the period of 2000­2004, and 89.9% for 2010­2012 (p<0.001). Patients with invasive ductal carcinoma, who were treated with surgery and hormonal therapy, showed a reduction in the risk of death in the most recent period HRadj=0.42 (95%CI 0.34­0.53) (2010­2012). Conclusions: Early stage diagnosis and combined treatment (including HT) are predictive prognostic factors for high survival rates in patients with invasive breast cancer. Specialized cancer centers can provide valuable indications regarding cancer control policies, evaluating overall survival for breast cancer and its associated prognosis.

Objetivos: Descrever as faixas etárias, estadiamento clínico ao diagnóstico, tratamento e sobrevida global das pacientes com câncer de mama tratadas em um centro de câncer brasileiro. Método: Estudo de uma coorte retrospectiva de base hospitalar, com mulheres diagnosticadas de câncer de mama entre 1º de janeiro de 2000 e 31 de dezembro de 2012. Os dados foram extraídos do Registro Hospitalar de Câncer do A. C. Camargo Cancer Center. Faixa etária, tipo histológico, classificação TNM, estadiamento clínico e tratamento foram descritos em frequência absoluta e relativa estratificados em três períodos. As curvas de sobrevida global foram estimadas pelo método de Kaplan-Meier. A Hazard ratio (HR) com intervalo de confiança de 95% foram calculados para todas as variáveis. Resultados: O total de 5.095 pacientes mulheres com câncer de mama foi identificado, a maioria era estágio inicial 60% (I e II). A sobrevida global foi de 82,7% para o período de 2000­2004 e 89,9% para 2010­2012 (p<0,001). Pacientes com carcinoma ductal invasivo que foram tratadas com cirurgia e hormonioterapia, mostraram redução do risco de morte no período mais recente HRaj=0,42 (0,34­0,53 em 2010­2012). Conclusões: Diagnóstico precoce e tratamento combinado (incluindo hormonioterapia) são fatores prognósticos preditivos para altas taxas de sobrevida em pacientes com câncer de mama invasivo. Centros especializados em câncer podem prover informações valiosas sobre as políticas de controle do câncer, avaliando a sobrevida global do câncer de mama e fatores associados ao prognóstico.

Risk factors for pelvic and distant recurrence in locally advanced cervical cancer.

OBJECTIVE: Despite the benefits of concomitant radiotherapy and cisplatin for locally advanced cervical cancer, recurrence rates remain high. New treatment strategies such as consolidation chemotherapy and different concomitant chemotherapy combinations have been tested in recent years. Identification of the best candidates for each treatment strategy could optimize results. STUDY DESIGN: A retrospective review of data from 127 patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics Stages IIB-IVA), treated at a single institution from 2005 to 2014. Risk factors for loco-regional and systemic recurrence, and prognostic factors for overall survival (OS) were analysed using Cox regression. Survival of patients treated with consolidation chemotherapy was compared with survival of patients not treated with consolidation chemotherapy in the role cohort and in a propensity-score-matched cohort. RESULTS: With a median follow-up time of 48.7 months, loco-regional-recurrence-free survival (LRFS), distant-metastasis-free survival (DMFS) and OS at 5 years were 76.6%, 54.0% and 63.0%, respectively. On multivariate analysis, tumour size ≥6 cm was associated with shorter LRFS [hazard ratio (HR) 5.18; 95% confidence interval (CI) 1.45-18.45; p = 0.011], and adenocarcinoma (HR 2.48; 95% CI 1.10-5.57; p = 0.028) and positive lymph nodes (HR 2.21; 95% CI 1.303-4.72; p = 0.041) were associated with shorter DMFS. Tumour size ≥6 cm was associated with shorter OS (HR 2.64; 95% CI 1.09-6.35; p = 0.031). Twenty-two patients were treated with consolidation chemotherapy; on univariate analysis, these patients had longer OS compared with patients who were not treated with consolidation chemotherapy (p = 0.043). In a propensity-score-matched cohort, patients treated with consolidation chemotherapy had longer DMFS and OS compared with patients who were not treated with consolidation chemotherapy, although the difference was not significant. CONCLUSIONS: Different risk factors are associated with loco-regional and distant metastases in patients with locally advanced cervical cancer, and could potentially lead to particular therapeutic strategies. Although the number of patients treated with consolidation chemotherapy in the study cohort was small, they seemed to live longer and to have better control of distant relapse then patients who were not treated with consolidation chemotherapy.

Circulating Tumor Cells as Cancer Biomarkers in the Clinic.

It is believed that the development of metastatic cancer requires the presence of circulating tumor cells (CTCs) , which are found in a patient's circulation as rare abnormal cells comingled with billions of the normal red and white blood cells. The systems developed for detection of CTCs have brought progress to cancer treatment. The molecular characterization of CTCs can aid in the development of new drugs, and their presence during treatment can help clinicians determine the prognosis of the patient. Studies have been carried out in patients early in the disease course, with only primary tumors, and the role of CTCs in prognosis seems to be as important as it is in patients with metastatic disease. The published studies on CTCs have focused on their prognostic significance, their utility in real-time monitoring of therapies, the identification of therapeutic and resistance targets, and understanding the process of metastasis . The analysis of CTCs during the early stages, as a "liquid biopsy," helps to monitor patients at different points in the disease course, including minimal residual disease, providing valuable information about the very early assessment of treatment effectiveness. Finally, CTCs can be used to screen patients with family histories of cancer or with diseases that can lead to the development of cancer. With standard protocols, this easily obtained and practical tool can be used to prevent the growth and spread of cancer. In this chapter, we review some important aspects of CTCs , surveying the disease aspects where these cells have been investigated.

Oral Rivaroxaban for the Treatment of Symptomatic Venous Thromboembolism in 400 Patients With Active Cancer: A Single-Center Experience.

PURPOSE: To study the safety and efficacy of rivaroxaban-a direct oral anticoagulant-use in patients with active cancer and venous thromboembolism (VTE). PATIENTS AND METHODS: Retrospective cohort study of 400 patients with active cancer and associated VTE, defined as deep venous thrombosis and/or pulmonary embolism. This single-center study was carried out from January 2012 to June 2015. The aim of this study was to determine the efficacy and safety, using the incidence of recurrent symptomatic VTE and major bleeding, respectively, throughout the treatment with rivaroxaban. RESULTS: Of the 400 patients enrolled, 223 (55.8%) were female. A total of 362 (90.5%) patients had solid tumors and 244 (61%) had metastatic disease. A total of 302 (75.5%) received initial parenteral therapy with enoxaparin (median: 3, mean: 5.6, standard deviation [SD]: 6.4 days) followed by rivaroxaban. Ninety-eight patients (24.5%) were treated with on label rivaroxaban treatment. Recurrence rates were 3.25% with major bleeding occurring in 5.5% during the anticoagulant therapy (median: 118, mean: 163.9, SD: 159.9 days). CONCLUSION: Rivaroxaban can be an attractive alternative for the treatment of cancer-associated thrombosis.

Circulating tumor cells as a new and additional approach to follow-up patients with serous low-grade ovarian adenocarcinoma: a case report and review of the literature

Background: Current methods for follow-up of Ovarian Cancer (OC) are widespread, especially with CA125, which, however, is not a perfect biomarker and thus further investigation for new methods of evaluation are warranted. The feasibility of Circulating Tumor Cells (CTCs) in advanced OC was investigated in this case report. Case presentation: A 19-year-old woman with advanced low-grade serous papillary adenocarcinoma and relapsed disease did not have a CA125 correspondent with disease relapse. CTCs were evaluated, compared with CA125 and with image exams. Relapses were not correspondent to elevations of CA125. CTCs demonstrated usefulness, being proportional to major disease relapse, especially in the peritoneum. CTCs may be used as a complementary diagnosis tool when marginal/small increases in CA-125 levels are observed. Conclusions: In OC, CTCs can be an important tool to predict recurrence, response to treatment and improve the quality of decision-making, in order to offer the best treatment to a determined group of patients (AU)

The Value of Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer and Application of a Prognostic Score.

OBJECTIVES: Secondary cytoreductive surgery (SCS) is an option for treating patients with recurrent ovarian cancer. Three ongoing randomized trials are comparing SCS plus chemotherapy with chemotherapy alone, and few comparative studies have been published. MATERIALS AND METHODS: We performed a retrospective review of data on 209 patients with recurrent ovarian carcinoma who were treated at a single institution from 2000 to 2013. We analyzed prognostic factors in the recurrence setting to determine the value of SCS in a multivariate model, including propensity score, by prognostic group. RESULTS: In the univariate analysis, younger than 65 years, personal or family history of breast or ovarian cancer, stage I-II at diagnosis, residual disease 10 mm or less after primary debulking surgery, performance status 1 or less, CA125 less than 100, only 1 metastatic site of recurrence, platinum-free interval of more than 12 months, and SCS correlated with better overall survival. In the multivariate model, including propensity score, SCS remained associated with a 66% decrease in the risk of death (hazard ratio, 0.34; 95% CI, 0.15-0.76, P = 0.008). Secondary cytoreductive surgery was also linked to longer progression-free survival (hazard ratio, 0.50; 95% CI, 0.30-0.84, P = 0.008). There was no evidence of a benefit of SCS in patients with unfavorable prognosis (P for interaction = 0.654). CONCLUSIONS: Our results confirm the benefit of SCS in progression-free survival and overall survival in the recurrent setting and suggest that it exists not only for patients with a good prognosis.

[Interaction between specialties: dilated cardiomyopathy and HER2-positive breast Cancer]. / Interação entre especialidades: miocardiopatia dilatada e neoplasia de mama HER2 positiva.

Basic research may result in unexpected benefit in terms of progress in the understanding of mechanisms responsible for different diseases and their potential treatment alternatives. This is seen, for instance, when a specific situation, defined in clinical practice, may be translated into laboratory findings which suggest a new therapy for an unrelated disease, representing the inverse of the more usual bench-to-bedside path. During the past few years, the use of the monoclonal antibody trastuzumab, in the adjuvant and therapeutic context, has become of fundamental importance in the treatment of breast cancer with amplification/overexpression of HER2, resulting in significant increase in survival rates. The observation that trastuzumab also induces cardiotoxicity, and the identification of mechanisms involved in this side effect, have allowed the investigation of these factors as a therapeutic alternative for dilated cardiomyopathy, in a highly interesting fashion.

Interação entre especialidades: miocardiopatia dilatada e neoplasia de mama HER2 positiva / Interaction between specialties: dilated cardiomyopathy and HER2-positive breast Cancer / Interacción entre especialidades: miocardiopatía dilatada y neoplasia de mama HER2 positiva

O progresso no conhecimento dos mecanismos da doença e suas potenciais possibilidades de tratamento, têm com o incremento da pesquisa básica, trazido a algumas situações inusitadas. Como quando algo observado em uma situação específica, definida na prática clínica, pode ser transportado para o laboratório, instigando a investigação de uma provável terapêutica em uma doença não relacionada e fazendo o caminho inverso da "bench-to-bedside". Nos últimos anos, o uso de um anticorpo monoclonal, o trastuzumabe, mostrou-se imprescindível no tratamento das neoplasias de mama com amplificação/superexpressão de HER2, com ganho de sobrevida significativo nos contextos adjuvante e terapêutico. A observação da ocorrência de cardiotoxicidade induzida pelo trastuzumabe, assim como a identificação dos mecanismos relacionados a esse efeito colateral, possibilitaram a pesquisa desses mesmos fatores na miocardiopatia dilatada, de uma forma muito interessante.

Basic research may result in unexpected benefit in terms of progress in the understanding of mechanisms responsible for different diseases and their potential treatment alternatives. This is seen, for instance, when a specific situation, defined in clinical practice, may be translated into laboratory findings which suggest a new therapy for an unrelated disease, representing the inverse of the more usual bench-to-bedside path. During the past few years, the use of the monoclonal antibody trastuzumab, in the adjuvant and therapeutic context, has become of fundamental importance in the treatment of breast cancer with amplification/overexpression of HER2, resulting in significant increase in survival rates. The observation that trastuzumab also induces cardiotoxicity, and the identification of mechanisms involved in this side effect, have allowed the investigation of these factors as a therapeutic alternative for dilated cardiomyopathy, in a highly interesting fashion.

El progreso en el conocimiento de los mecanismos de la enfermedad y sus potenciales posibilidades de tratamiento ocurre mediante el incremento de la investigación básica que se añade a algunas situaciones inusitadas. Así como cuando algo observado en una situación específica, definida en la práctica clínica, se puede trasladar al laboratorio, fomentando la investigación de una probable terapéutica en una enfermedad no relacionada, y haciendo el camino inverso de la "bench-to-bedside". En los últimos años, el uso de un anticuerpo monoclonal, el trastuzumabe, se halló imprescindible en el tratamiento de las neoplasias de mama con amplificación/superexpresión de HER2, con ganancia de sobrevida significativa en los contextos adyuvante y terapéutico. La observación de la ocurrencia de cardiotoxicidad inducida por el trastuzumabe, así como la identificación de los mecanismos relacionados a este efecto colateral, posibilitaran la investigación de estos mismos factores en la miocardiopatía dilatada, de una forma muy interesante.