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Background: Metastatic triple-negative breast cancer (mTNBC) is an aggressive subtype of breast cancer with poor survival. Currently, the literature lacks comprehensive real-world evidence on locally recurrent and mTNBC patients. To validate the optimal treatment for patients with mTNBC, real-world evidence in combination with data from clinical trials must be evaluated as complementary. Objectives: The objective of the study is to examine outcomes and treatment patterns of patients with advanced triple-negative breast cancer (TNBC) utilizing real-world data of patients from all oncology sites across Denmark. Design: This is a retrospective, non-interventional, multi-site, population-based observational study conducted across all oncology departments in Denmark. Methods: We included all women diagnosed with metastatic or locally recurrent TNBC from January 1, 2017, to December 31, 2019, using the national Danish Breast Cancer Group database. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in the first to third treatment line. Results: The study included 243 women diagnosed with metastatic or recurrent TNBC. The median OS (mOS) was 11.6 months after the first line of treatment, 6.5 months after the second line, and 6.5 months after the third line. De novo mTNBC was associated with shorter OS (mOS: 8.3 vs 14.2 months), and those with a relapse within 18 months of primary diagnosis had shorter OS than those with a relapse after 18 months (mOS: 10.0 vs 18.2). In the first line, taxane was the preferred choice of treatment for patients with de novo mTNBC, whereas capecitabine was preferred for patients with recurrent TNBC. Conclusions: This real-world, nationwide study demonstrated poor OS among patients with metastatic or recurrent TNBC, with a mOS of 11.6 months (95% CI, 9.9-17.3). Patients who presented with de novo mTNBC or who had a relapse of their breast cancer within 18 months of primary diagnosis had shorter OS. Registration: The study was registered and approved by the Danish Capital Regions research overview (P-2021-605).
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The study aimed to compare the metastatic pattern of breast cancer and the intermodality proportion of agreement between [18F]FDG-PET/CT and CE-CT. Women with metastatic breast cancer (MBC) were enrolled prospectively and underwent a combined [18F]FDG-PET/CT and CE-CT scan to diagnose MBC. Experienced nuclear medicine and radiology physicians evaluated the scans blinded to the opposite scan results. Descriptive statistics were applied, and the intermodality proportion of agreement was used to compare [18F]FDG-PET/CT and CE-CT. In total, 76 women with verified MBC were enrolled in the study. The reported number of site-specific metastases for [18F]FDG-PET/CT vs. CE-CT was 53 (69.7%) vs. 44 (57.9%) for bone lesions, 31 (40.8%) vs. 43 (56.6%) for lung lesions, and 16 (21.1%) vs. 23 (30.3%) for liver lesions, respectively. The proportion of agreement between imaging modalities was 76.3% (95% CI 65.2-85.3) for bone lesions; 82.9% (95% CI 72.5-90.6) for liver lesions; 57.9% (95% CI 46.0-69.1) for lung lesions; and 59.2% (95% CI 47.3-70.4) for lymph nodes. In conclusion, bone and distant lymph node metastases were reported more often by [18F]FDG-PET/CT than CE-CT, while liver and lung metastases were reported more often by CE-CT than [18F]FDG-PET/CT. Agreement between scans was highest for bone and liver lesions and lowest for lymph node metastases.
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This study aimed to compare CE-CT and 2-[18F]FDG-PET/CT for response monitoring metastatic breast cancer (MBC). The primary objective was to predict progression-free and disease-specific survival for responders vs. non-responders on CE-CT and 2-[18F]FDG-PET/CT. The secondary objective was to assess agreement between response categorization for the two modalities. Treatment response in women with MBC was monitored prospectively by simultaneous CE-CT and 2-[18F]FDG-PET/CT, allowing participants to serve as their own controls. The standardized response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST) were used for response categorization. For prediction of progression-free and disease-specific survival, treatment response was dichotomized into responders (partial and complete response) and non-responders (stable and progressive disease) at the first follow-up scan. Progression-free survival was defined as the time from baseline until disease progression or death from any cause. Disease-specific survival was defined as the time from baseline until breast cancer-specific death. Agreement between response categorization for both modalities was analyzed for all response categories and responders vs. non-responders. At the first follow-up, tumor response was reported more often by 2-[18F]FDG-PET/CT than CE-CT, with only fair agreement on response categorization between the two modalities (weighted Kappa 0.28). Two-year progression-free survival for responders vs. non-responders by CE-CT was 54.2% vs. 46.0%, compared with 59.1% vs. 14.3% by 2-[18F]FDG-PET/CT. Correspondingly, 2-year disease-specific survival were 83.3% vs. 77.8% for CE-CT and 84.6% vs. 61.9% for 2-[18F]FDG-PET/CT. Tumor response on 2-[18F]FDG-PET/CT was significantly associated with progression-free (HR: 3.49, P < 0.001) and disease-specific survival (HR 2.35, P = 0.008), while no association was found for tumor response on CE-CT. In conclusion, 2-[18F]FDG-PET/CT appears a better predictor of progression-free and disease-specific survival than CE-CT when used to monitor metastatic breast cancer. In addition, we found low concordance between response categorization between the two modalities. TRIAL REGISTRATION: Clinical. TRIALS: gov. NCT03358589. Registered 30/11/2017-Retrospectively registered, http://www. CLINICALTRIALS: gov.
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Neoplasias de la Mama , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Femenino , Fluorodesoxiglucosa F18 , Estudios Prospectivos , Resultado del Tratamiento , Neoplasias de la Mama/patologíaRESUMEN
Tumor infiltrating lymphocytes (TILs) have predictive and prognostic potential in HER2-positive breast cancer (HER2 + BC). Due to tumor heterogeneity, guidelines recommend evaluation on full tumor-sections over biopsies, but aren't clear regarding tissue microarrays (TMAs). Herein, we investigate the inter-observer agreement of TILs assessment in HER2 + BC on full-sections and TMAs using a standardized method. Two pathologists assessed TILs using HE full-sections and TMAs from 244 patients with HER2 + BC. TILs were assessed in 10% intervals; values <10% evaluated as 0%, 1% or 5%. Levels of agreement were evaluated using intraclass-coefficient (ICC), Kappa statistics and concordance analysis. For inter-observer agreement for full-sections, ICC was 0.93 (95% CI 0.89-0.95) and Kappa was 0.75, corresponding to acceptable and moderate agreement respectively. For TMAs, ICC was 0.73 (95% CI: 0.62-0.81) and Kappa 0.33, corresponding to unacceptable agreement. For association in matched TMA and full-sections, ICC was 0.64 (95% CI 0.55-0.71) and Lin's concordance correlation coefficient was 0.63 (95% CI 0.55-0.71), corresponding to unacceptable agreement. There is acceptable inter-observer agreement of TILs assessment on full-sections but not TMAs and discrepancy between full-sections and TMAs. TMA preparation must include consideration for representation of both entire tumor area and tumor-microenvironment to correctly define prognostic and predictive values of potential immuno-related biomarkers.
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Neoplasias de la Mama , Linfocitos Infiltrantes de Tumor , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/patología , Variaciones Dependientes del Observador , Patólogos , Pronóstico , Receptor ErbB-2/análisis , Microambiente TumoralRESUMEN
BACKGROUND: [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy. METHODS: Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. RESULTS: [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93-1.0), 0.88 (0.82-0.92), and 0.98 (95% CI 0.97-0.99), respectively. CONCLUSION: [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017-Retrospectively registered, http://www.ClinicalTrials.gov.
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PURPOSE: To investigate the clinical impact of FDG-PET/CT for staging and treatment planning in high-risk primary breast cancer. METHODS: Women with high-risk primary breast cancer were enrolled between September 2017 and August 2019 at Odense University Hospital, Denmark. Conventional mammography with/without MRI was performed before staging by FDG-PET/CT. We studied the accuracy of FDG-PET/CT for the detection of distant metastases, the effect on the change of treatment, and the prevalence of incidental findings. Biopsy and follow-up were used as a reference standard for the accuracy analysis. RESULTS: Of 103 women, 24 (23%) were diagnosed with distant metastases by FDG-PET/CT. Among these, breast surgery was omitted in 18 and could have been spared in six. Another sixteen (16%) patients were upstaged to more advanced loco-regional disease, leading to more extensive radiotherapy. Sensitivity and specificity for diagnosing distant metastases were 1.00 (95% confidence interval: 0.86-1.00) and 0.95 (0.88-0.99), respectively. Twenty-nine incidental findings were detected in 24 women (23%), leading to further examinations in 22 and diagnosis of eight (8/22, 36%) synchronous diseases: cancer (n = 4), thyroiditis (n = 2), aorta aneurysm (n = 1), and meningioma (n = 1). CONCLUSIONS: FDG-PET/CT had a substantial impact on staging and change of treatment in women with high-risk primary breast cancer, and further examination of incidental findings was considered clinically relevant. Our findings suggest that FDG-PET/CT should be considered for primary staging in high-risk primary breast cancer to improve treatment planning.
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Neoplasias de la Mama , Fluorodesoxiglucosa F18 , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia , Femenino , Humanos , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Estudios Prospectivos , Radiofármacos , Sensibilidad y EspecificidadRESUMEN
Aim: To investigate outpatients with breast cancer perception of information before and after changed informational practice. Design: The design was a comparative study. Method: Information about breast cancer treatment and chemotherapy toxicity changed from individual to nurse-led group information. Women with early-stage breast cancer were eligible. To evaluate individual versus group information, the patients completed a questionnaire at their third cycle of chemotherapy, including Knowledge of treatment, Support from healthcare professionals or peers and general self-efficacy Ability to act in everyday life. The study is registered in OSF https://osf.io/bh7wg. Results: In total, 90 participants in two groups were included: (a) individual information (N = 44) and (b) group information (N = 46). Groups were comparable in age and educational level. Both groups found the information satisfactory, with no significant differences regarding perceived knowledge or support. Five of ten questions in self-efficacy showed significantly better outcomes in patients receiving group information but with no difference in overall self-efficacy. Group information was non-inferior compared with individual information. Patients were satisfied in both groups.
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Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Rol de la Enfermera , Calidad de Vida , Autoeficacia , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Neoadjuvant chemotherapy (NACT) has been found useful in downstaging tumours in women with primary operable breast cancer without increasing mortality. As a result of several studies supporting this, the Danish Breast Cancer Cooperative Group implemented new guidelines for the treatment of primary operable T2 N0/N1 M0 ductal carcinomas in late 2016, treating patients with six cycles of NACT. This study aimed to conduct a quality assessment of the efficacy of the NACT regime based on real-time data from a single Danish hospital. METHODS: A retrospective observational study was conducted at Odense University Hospital, Denmark, from the introduction of the NACT regime to December 2018. Patients were identified using the surgical department's registry. Through medical chart review, predefined outcomes were collected on tumour characteristics, surgical outcomes, treatment response and type of NACT treatment. Descriptive statistics and Fisher's exact test were used on relevant data. RESULTS: Among the 64 patients, 67% completed a recommended NACT regime. A 55% majority underwent lumpectomy and 64% were spared axillary dissection. Complete pathological response was found in 28% of patients. After treatment, 38% of the pre-NACT N1 patients were downstaged to N0. CONCLUSIONS: This study indicated that the NACT regime was a favourable treatment strategy for these patients. Two-thirds of patients were able to undergo a recommended NACT regime. The majority of patients were both spared axillary dissection and mastectomy. FUNDING: none. TRIAL REGISTRATION: not relevant.
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Neoplasias de la Mama , Terapia Neoadyuvante , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Mastectomía , Mastectomía SegmentariaRESUMEN
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of paclitaxel. Though no pharmacological agents have been identified to prevent CIPN, cryotherapy with frozen gloves and socks may reduce the risk of developing CIPN and thereby increase the likelihood of patients completing the planned dose of paclitaxel. PATIENTS AND METHODS: Among women with early-stage breast cancer who received at least one cycle of paclitaxel, 119 were included in the 2016 cohort who received cryotherapy when they developed symptoms of CIPN, and 96 patients in the 2017 cohort who received prophylactic cryotherapy. From electronic patient records, data were abstracted on dates and doses of adjuvant paclitaxel, dose reductions, cycle delays, symptoms of CIPN, and whether and when frozen gloves and socks were used. The outcome was the proportion of patients completing the planned 720 mg/m2 of paclitaxel cumulated over nine cycles. The hazard ratio (HR) of a dose-limiting event due to CIPN was estimated in a Cox proportional hazards model. RESULTS: In the 2016 cohort, cryotherapy was needed due to symptoms of CIPN in 54 (45%) patients. Significantly, more patients, 77% in the 2017 cohort, completed the planned dose of 720 mg/m² compared with 64% in the 2016 cohort, p = 0.017. The HR of a dose reduction or cessation due to CIPN, adjusted for age and HER-2 status, was 0.50 (95% confidence interval 0.30-0.84), p = 0.009, for the 2017 cohort compared with the 2016 cohort. CONCLUSIONS: The results of this study suggest that prophylactic cryotherapy may reduce the risk of a dose-limiting event due to CIPN and increase the proportion of patients completing the planned dose of paclitaxel in adjuvant treatment of early-stage breast cancer. Despite this, CIPN remains to be an important dose-limiting toxicity of paclitaxel.
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Neoplasias de la Mama/tratamiento farmacológico , Crioterapia/efectos adversos , Paclitaxel/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/farmacología , Medición de Resultados Informados por el PacienteRESUMEN
Chemotherapy for metastatic breast cancer (MBC) is in general given in cycles of maximum tolerated doses to potentially maximize the therapeutic outcome. However, when compared with targeted therapies for MBC, conventional and dose intensified chemotherapy has caused only modest survival benefits during the recent decades, often compromising the quality of life considerably. Navelbine is an antineoplastic agent that has shown efficacy in the treatment of a variety of cancer types, including breast cancer. Early clinical trials involving both breast cancer and lung cancer patients suggest that metronomic dosing of Navelbine might be at least as effective as classical administration (once weekly, etc.). The NAME trial compares these two strategies of Navelbine administration in MBC patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Vinblastina/administración & dosificación , Vinorelbina/administración & dosificación , Administración Intravenosa , Administración Metronómica , Adulto , Anciano , Neoplasias de la Mama/patología , Vías de Administración de Medicamentos , Femenino , Humanos , Dosis Máxima Tolerada , Persona de Mediana Edad , Metástasis de la Neoplasia , Calidad de Vida , Vinorelbina/efectos adversosRESUMEN
BACKGROUND: Hypothyroidism may occur as a late effect of breast cancer-directed treatment, particularly after radiotherapy, but little is known whether hypothyroidism affects the prognosis after breast cancer. We investigated the association between hypothyroidism and breast cancer recurrence, and all-cause mortality. METHODS: In this population-based cohort study, we used national medical registries to identify all Danish women 35 years or older diagnosed with stage I-III, operable breast cancer between 1996 and 2009. Hypothyroidism was defined as hospital diagnoses ascertained via diagnostic codes, or as prescriptions for levothyroxine. Two analytic models were used: (i) hypothyroidism present at the time of the breast cancer diagnosis (prevalent) and (ii) hypothyroidism diagnosed during follow-up as a time-varying exposure lagged by 1 year (incident). Breast cancer recurrence was defined as any local, regional, or distant recurrence or contralateral breast cancer. All-cause mortality included death from any cause in any setting. We used Cox regression models accounting for competing risks to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer recurrence and all-cause mortality. RESULTS: The study cohort included 35,463 women with breast cancer with 212,641 person-years of follow-up. At diagnosis, 1272 women had hypothyroidism and 859 women developed hypothyroidism during follow-up. In total, 5810 patients developed recurrent breast cancer. Neither prevalent nor incident hypothyroidism was associated with breast cancer recurrence (adjusted HRprevalent 1.01, 95% CI 0.87-1.19; adjusted HRincident 0.93, 95% CI 0.75-1.16, respectively). Furthermore, no differences were seen for all-cause mortality for prevalent or incident hypothyroidism (adjusted HRprevalent 1.02, 95% CI 0.92-1.14, and HRincident 1.08, 95% CI 0.95-1.23, respectively). Stratification by menopausal status, oestrogen receptor status, chemotherapy, or radiotherapy did not alter the estimates. CONCLUSIONS: Hypothyroidism present at diagnosis or during follow-up was not associated with breast cancer recurrence or all-cause mortality in women with breast cancer. Our findings provide reassurance to patients and their physicians that hypothyroidism is unlikely to impact on the clinical course of breast cancer or survival.
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Neoplasias de la Mama/epidemiología , Hipotiroidismo/epidemiología , Adulto , Anciano , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Causas de Muerte , Dinamarca/epidemiología , Femenino , Humanos , Hipotiroidismo/etiología , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Vigilancia de la Población , Medición de Riesgo , Factores de RiesgoRESUMEN
Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data. Patients and Methods Associations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes. Results Data from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P < .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P < .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); > 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS ( P = .043), but not for the DDFS and OS end points. Conclusion In this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors.
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Neoplasias de la Mama/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Supervivencia sin Enfermedad , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Tasa de Supervivencia , Adulto JovenRESUMEN
Cancer results from alterations at essential genomic sites and is characterized by uncontrolled cell proliferation, invasion and metastasis. Identification of driver genes of metastatic progression is essential, as metastases, not primary tumors, are fatal. To gain insight into the mutational concordance between different steps of malignant progression we performed exome sequencing and validation with targeted deep sequencing of successive steps of malignant progression from pre-invasive stages to asynchronous distant metastases in six breast cancer patients. Using the ratio of non-synonymous to synonymous mutations, a surprisingly large number of cancer driver genes, ranging between 3 and 145, were estimated to confer a selective advantage in the studied primary tumors. We report a substantial amount of metastasis specific mutations and a number of novel putative metastasis driver genes. Most notable are the DCC, ABCA13, TIAM2, CREBBP, BCL6B and ZNF185 genes, mainly mutated exclusively in metastases and highly likely driver genes of metastatic progression. We find different genes and pathways to be affected at different steps of malignant progression. The Adherens junction pathway is affected in four of the six studied patients and this pathway most likely plays a vital role in the metastatic process.
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Neoplasias de la Mama/patología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metástasis de la Neoplasia/genética , Neoplasias de la Mama/genética , Femenino , HumanosRESUMEN
A main controversy in cancer research is whether metastatic abilities are present in the most advanced clone of the primary tumor or result from independently acquired aberrations in early disseminated cancer cells as suggested by the linear and the parallel progression models, respectively. The genetic concordance between different steps of malignant progression is mostly unexplored as very few studies have included cancer samples separated by both space and time. We applied whole exome sequencing and targeted deep sequencing to 26 successive samples from six patients with metastatic estrogen receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis.
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Neoplasias Óseas/genética , Neoplasias de la Mama/genética , Neoplasias Hepáticas/genética , Mutación , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Proteínas del Citoesqueleto/genética , Progresión de la Enfermedad , Femenino , Genómica , Humanos , Proteínas con Dominio LIM/genética , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Proteínas Represoras/genética , Secuenciación del Exoma/métodosRESUMEN
At recurrence of breast cancer, the therapeutic target is the metastases. However, it is current practice to base the choice of systemic treatment on the biomarker profile of the primary tumor. In the present study, confirmatory biopsies were obtained from suspected metastatic lesions and compared with the primary tumors with respect to ER, HER2, and TOP2A. In the prospective tissue-collection study, 81 patients had biopsy from a suspected relapse. Additional archived paired material was included, leaving a total of 119 patients with paired primary tumor, synchronous axillary nodes (available in 52 patients) and asyncronous metastases available for analysis. ER, HER2, and TOP2A expression of primary tumors, axillary nodes and metastases were re-analysed and determined centrally by immunohistochemistry, chromogenic in situ hybridization, and fluorescence in situ hybridization. Of the 81 patients with a biopsy from a suspected relapse, 65 (80%) were diagnosed with recurrent breast carcinoma, 3 (4%) were diagnosed with other malignancies, 6 (7%) had benign conditions, and in 7 (9%) patients the biopsy was non-representative. Discordance in ER, HER2, and TOP2A (aberration vs. normal) status between primary tumor and corresponding asynchronous metastasis was 12% (14/118), 9% (10/114), and 23% (17/75), respectively. There were no significant associations with biomarker discordance and prior adjuvant therapy, or location of biopsy. Expression of ER, HER2, and TOP2A displayed discordance with a sufficient frequency to emphasize the role of confirmatory biopsies from metastatic lesions in future management of recurrent breast cancer.
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Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Carcinoma/química , ADN-Topoisomerasas de Tipo II/análisis , Proteínas de Unión al ADN/análisis , Ganglios Linfáticos/química , Recurrencia Local de Neoplasia/química , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Antígenos de Neoplasias/genética , Biomarcadores de Tumor/genética , Biopsia , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma/genética , Carcinoma/mortalidad , Carcinoma/secundario , Carcinoma/terapia , ADN-Topoisomerasas de Tipo II/genética , Proteínas de Unión al ADN/genética , Dinamarca , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación in Situ , Hibridación Fluorescente in Situ , Ganglios Linfáticos/patología , Metástasis Linfática , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Fenotipo , Proteínas de Unión a Poli-ADP-Ribosa , Pronóstico , Estudios Prospectivos , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Análisis de Supervivencia , Factores de TiempoRESUMEN
INTRODUCTION: Only 10-20% of patients with pancreatic cancer are offered operation with curative intent. If this is not possible, treatment with pre-operative radiotherapy in combination with chemotherapy offers the opportunity to reduce tumor size in patients with locally advanced disease, and possibly resection with curative intent afterwards. This treatment has been offered for the last three years at the Department of Oncology, Odense University Hospital. In the following we present our results. MATERIALS AND METHODS: A total of 26 patients with locally advanced unresectable pancreatic cancer were offered a combination of radiotherapy and chemotherapy. 4-6 weeks after treatment the patients were evaluated for resection. RESULTS: Of the 26 patients 24 completed planned treatment. Eight patients were subsequently assessed resectable. One patient refused surgery; the other 7 patients had a R0-resection. Median survival for the whole group is 12 months. Six of the patients who went through surgery are without signs of recurrent disease after median 16 months, one patient died with recurrent disease after 37 months. CONCLUSION: These results are similar to results from other countries. Therefore patients with locally advanced unresectable pancreatic cancer should be offered radiotherapy in combination with chemotherapy. Evaluation for surgery should be carried out 4-6 weeks after end of treatment. This strategy offers the opportunity for R0-recection and consequently cure.