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BACKGROUND: The phenotypes of tumor cells change during disease progression, but invasive rebiopsies of metastatic lesions are not always feasible. Here we aimed to determine whether initially HER2-negative metastatic breast cancer (MBC) patients with HER2-positive circulating tumor cells (CTCs) benefit from a HER2-targeted therapy. METHODS: The open-label, interventional randomized phase III clinical trial (EudraCT Number 2010-024238-46, CliniclTrials.gov Identifier: NCT01619111) recruited from March 2012 until September 2019 with a follow-up duration of 19.5 months. It was a multicenter clinical trial with 94 participating German study centers. A total of 2137 patients with HER2-negative MBC were screened for HER2-positive CTCs with a final modified intention-to-treat population of 101 patients. Eligible patients were randomized to standard therapy with or without lapatinib. Primary study endpoints included CTC clearance (no CTCs at the end of treatment) and secondary endpoints were progression-free survival, overall survival (OS), and safety. RESULTS: In both treatment arms CTC clearance at first follow-up visit-although not being significantly different for both arms at any time point-was significantly associated with improved OS (42.4 vs 14.1 months; P = 0.002). Patients treated additionally with lapatinib had a significantly improved OS over patients receiving standard treatment (20.5 vs 9.1 months, P = 0.009). CONCLUSIONS: DETECT III is the first clinical study indicating that phenotyping of CTCs might have clinical utility for stratification of MBC cancer patients to HER2-targeting therapies. The OS benefit could be related to lapatinib, but further studies are required to prove this clinical observation. ClinicalTrials.gov Registration Number: NCT01619111.
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Neoplasias de la Mama , Células Neoplásicas Circulantes , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Progresión de la Enfermedad , CinéticaRESUMEN
PURPOSE: In breast cancer, a pathological complete response (pCR) has been described as generally resulting in a favorable prognosis. However, there are subgroups, such as patients with a mutation in BRCA1 or BRCA2, in which the effect of pCR on the prognosis is suspected to be weaker. Patients with a family history of breast and/or ovarian cancer may therefore react differently in relation to pCR and prognosis, and this is investigated in this study. PATIENTS AND METHODS: Breast cancer patients were identified from a clinical breast cancer registry. The study subjects had been treated with neoadjuvant chemotherapy from 2001 to 2018 and their pathological and clinical information as well as medical family history were available. They were considered to have a positive family history if they had at least 1 first-degree relative with breast and/or ovarian cancer. Multivariate logistic regression analyses were performed to study the association between family history, pCR (ypT0; ypN0), and disease-free survival (DFS). RESULTS: Of 1,480 patients, 228 (15.4%) had a positive family history. The pCR rates were 24.9% in all patients, and 24.4% and 27.6% in those without/with a family history, respectively. Family history was not associated with a higher pCR rate (adjusted odds ratio [OR] 1.23; 95% confidence interval [CI] 0.85-1.76; p = 0.27) or a different disease-free survival (DFS; adjusted hazard ratio [HR] 1.15; 95% CI 0.88-1.52; p = 0.30). pCR did not affect the prognosis differently in relation to family history. CONCLUSIONS: In this retrospective analysis, family history was not associated with pCR and DFS. pCR improved survival, independently of family history.
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INTRODUCTION: Oncological second opinions are becoming increasingly important in the era of complex treatments and established certified cancer centers. Oncological guidelines with the highest levels of evidence are available, but these can only be effective to the extent that they are implemented. Therefore, we analyzed the effects of second opinions with regard to their agreement with first opinions and conformity with guidelines. METHODS: In 164 patients with a diagnosis of breast cancer or gynecological malignancy who requested a second opinion, the first and second opinions, established at the interdisciplinary tumor conference, and conformity with the guidelines were evaluated. RESULTS: The first opinion was not in agreement with the guidelines in 34.8% (15.2% diagnosis, 12.8% surgical therapy, 13.4% systemic therapy, and 5.5% radiotherapy), and the recommendations were optimized in the second opinion in 56.7% (28.7% diagnosis, 15.9% surgical therapy, 30.5% systemic therapy, and 8.5% radiotherapy). CONCLUSIONS: Oncological second opinions showed significant effects and one-third of first opinions were not in conformity with the guidelines. In a significant proportion of cases, the existing treatment plan was changed or supplemented to allow modern and individualized treatment approaches.
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INTRODUCTION: Oncological second opinions are becoming increasingly important given more complex treatment strategies, simultaneously more patients use complementary and alternative medicine (CAM), and many comprehensive cancer centers initiate integrative medicine programs. The present study focuses on analyzing the effects of a second opinion in relation to attitudes toward CAM. METHODS: In this prospective study patients (n = 97) with a diagnosis of breast cancer or gynecological malignancies who had requested a second opinion received a questionnaire before and after the second opinion concerning their attitudes toward CAM. RESULTS: The majority of patients had breast cancer (72.2%, n = 70). Only 6.2% (n = 6) stated that they had been informed about CAM by the doctors who treated them first, 21.6% (n = 21) had received information about it when seeking the second opinion. After the first opinion, 42.3% (n = 41) wanted to try CAM, the same proportion trusted orthodox medicine alone. After the second opinion, 24 patients (24.7%) wanted to try CAM, while 38.1% (n = 37) relied exclusively on orthodox medicine. There was a significant correlation between an increased patients' need for information and interest in CAM (p = 0.02). CONCLUSIONS: Today, aspects of CAM still are very often no part of oncological first and second opinions. This might hence lead to discouraging patients to try out CAM and therefore integrative medicine programs in comprehensive cancer centers might be problem-solving.
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Terapias Complementarias , Medicina Integrativa , Neoplasias , Derivación y Consulta , Centros Médicos Académicos , Neoplasias de la Mama , Femenino , Neoplasias de los Genitales Femeninos , Humanos , Estudios Prospectivos , UniversidadesRESUMEN
PURPOSE: Second opinions in oncology are becoming increasingly important in an era of more complex treatments and a growing demand for information by patients. Therefore, we analyzed their effects and influencing factors like patients' motives, subjective extent of information and satisfaction with communications. METHODS: This prospective study evaluated second opinions for patients with breast cancer or gynecological malignancy. The patients received a questionnaire before and two months after, which inquired expectations, reasons, and satisfaction with the second opinion and the attending physicians. RESULTS: A total of 164 patients were included and the majority had breast cancer (75.0%). Receiving the second opinion made 89.7% feel better informed, their need for information decreased (from 75.3% to 39.2%, P < 0.0001), and satisfaction with doctor-patient communications increased (from 61.9 to 91.8%, P = 0.0002). There were various reasons for requesting a second opinion, e.g., the extremely stressful situation of a cancer diagnosis, hope for change in the treatment recommendation or dissatisfaction with the initial physicians. CONCLUSIONS: Second opinions can lead to significantly greater patient satisfaction, meeting the need for information and leading to better management of patients in the extremely stressful situation of a cancer diagnosis. Doctor-patient communications play a key role.
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Neoplasias de la Mama/epidemiología , Neoplasias de los Genitales Femeninos/epidemiología , Derivación y Consulta , Femenino , Humanos , Persona de Mediana Edad , Motivación , Satisfacción del Paciente , Estudios Prospectivos , UniversidadesRESUMEN
One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.
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Neoplasias de la Mama/tratamiento farmacológico , Letrozol/uso terapéutico , Dolor Musculoesquelético/fisiopatología , Posmenopausia/efectos de los fármacos , Anciano , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Artralgia/inducido químicamente , Artralgia/fisiopatología , Neoplasias de la Mama/fisiopatología , Femenino , Humanos , Letrozol/efectos adversos , Persona de Mediana Edad , Dolor Musculoesquelético/inducido químicamente , Dimensión del Dolor/métodos , Posmenopausia/fisiología , Factores de TiempoRESUMEN
PURPOSE: Evidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients. METHODS: The prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients' diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test. RESULTS: In a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively). CONCLUSIONS: This analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.
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Neoplasias de la Mama/patología , Terapia de Reemplazo de Hormonas/métodos , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Edad de Inicio , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Femenino , Estudios de Asociación Genética , Humanos , Persona de Mediana Edad , Posmenopausia , Estudios Prospectivos , Análisis de Regresión , Factores de RiesgoRESUMEN
INTRODUCTION: For decades, conventional galactography was the only imaging technique capable of showing the mammary ducts. Today, diagnosis is based on a multimodal concept which combines high-resolution ultrasound with magnetic resonance (MR) mammography and ductoscopy/galactoscopy and has a sensitivity and specificity of up to 95%. This study used tomosynthesis in galactography for the first time and compared the synthetic digital 2D full-field mammograms generated with this technique with the images created using the established method of ductal sonography. Both methods should be able to detect invasive breast cancers and their precursors such as ductal carcinoma in situ (DCIS) as well as being able to identify benign findings. MATERIAL AND METHODS: Five patients with pathological nipple discharge were examined using ductal sonography, contrast-enhanced 3D galactography with tomosynthesis and the synthetic digital 2D full-field mammograms generated with the latter method. Evaluation of the images created with the different imaging modalities was done by three investigators with varying levels of experience with complementary breast diagnostics (1, 5 and 15 years), and their evaluations were compared with the histological findings. RESULTS: All 3 investigators independently evaluated the images created with ductal sonography, contrast-enhanced 3D galactography with tomosynthesis, and generated synthetic digital 2D full-field mammograms. Their evaluations were compared with the histopathological assessment of the surgical specimens resected from the 5 patients. There was 1 case of invasive breast cancer, 2 cases with ductal carcinoma in situ and 2 cases with benign findings. All 3 investigators made more mistakes when they used the standard imaging technique of ductal sonography to diagnose suspicious lesions than when they used contrast-enhanced galactography with tomosynthesis and the generated synthetic digital 2D full-field mammograms. CONCLUSION: This is the first time breast tomosynthesis was used in galactography (galactomosynthesis) to create digital 3-dimensional images of suspicious findings. When used together with the generated synthetic digital 2D full-field mammograms, it could be a useful complementary procedure for the diagnosis of breast anomalies and could herald a renaissance of this method. Compared with high-resolution ductal ultrasound, the investigators achieved better results with contrast-enhanced galactography using tomosynthesis and the generated synthetic digital 2D full-field mammograms, as confirmed by histopathological findings.
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Although mammography screening programs do not include ultrasound examinations, some diagnostic units do provide women with both mammography and ultrasonography. This article is concerned with estimating the risk of a breast cancer patient diagnosed in a hospital-based mammography unit having a tumor that is visible on ultrasound but not on mammography. A total of 1,399 women with invasive breast cancer from a hospital-based diagnostic mammography unit were included in this retrospective study. For inclusion, mammograms from the time of the primary diagnosis had to be available for computer-assisted assessment of percentage mammographic density (PMD), as well as Breast Imaging Reporting and Data System (BIRADS) assessment of mammography. In addition, ultrasound findings were available for the complete cohort as part of routine diagnostic procedures, regardless of any patient or imaging characteristics. Logistic regression analyses were conducted to identify predictors of mammography failure, defined as BIRADS assessment 1 or 2. The probability that the visibility of a tumor might be masked at diagnosis was estimated using a regression model with the identified predictors. Tumors were only visible on ultrasound in 107 cases (7.6%). PMD was the strongest predictor for mammography failure, but age, body mass index and previous breast surgery also influenced the risk, independently of the PMD. Risk probabilities ranged from 1% for a defined low-risk group up to 40% for a high-risk group. These findings might help identify women who should be offered ultrasound examinations in addition to mammography.
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Densidad de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Mamografía/métodos , Ultrasonografía Mamaria/métodos , Adulto , Factores de Edad , Anciano , Índice de Masa Corporal , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Modelos Logísticos , Persona de Mediana Edad , Imagen Multimodal , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
In breast cancer, constitutive activation of NF-κB has been reported, however, the impact of genetic variation of the pathway on patient prognosis has been little studied. Furthermore, a combination of genetic variants, rather than single polymorphisms, may affect disease prognosis. Here, in an extensive dataset (n = 30,431) from the Breast Cancer Association Consortium, we investigated the association of 917 SNPs in 75 genes in the NF-κB pathway with breast cancer prognosis. We explored SNP-SNP interactions on survival using the likelihood-ratio test comparing multivariate Cox' regression models of SNP pairs without and with an interaction term. We found two interacting pairs associating with prognosis: patients simultaneously homozygous for the rare alleles of rs5996080 and rs7973914 had worse survival (HRinteraction 6.98, 95% CI=3.3-14.4, P=1.42E-07), and patients carrying at least one rare allele for rs17243893 and rs57890595 had better survival (HRinteraction 0.51, 95% CI=0.3-0.6, P = 2.19E-05). Based on in silico functional analyses and literature, we speculate that the rs5996080 and rs7973914 loci may affect the BAFFR and TNFR1/TNFR3 receptors and breast cancer survival, possibly by disturbing both the canonical and non-canonical NF-κB pathways or their dynamics, whereas, rs17243893-rs57890595 interaction on survival may be mediated through TRAF2-TRAIL-R4 interplay. These results warrant further validation and functional analyses.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , FN-kappa B/genética , Polimorfismo de Nucleótido Simple/fisiología , Transducción de Señal , Neoplasias de la Mama/patología , Femenino , Humanos , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/administración & dosificación , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo de Nucleótido Simple , Pronóstico , Sitios de Carácter Cuantitativo , Análisis de Supervivencia , Taxoides/administración & dosificación , Adulto Joven , GemcitabinaRESUMEN
As breast cancer (BC) screening identifies many BCs with a good prognosis, which might be overdiagnosed and therefore overtreated, the identification of subgroups with a high risk for aggressive subtypes might be helpful. The aim of this case-case analysis was to investigate the association between epidemiological risk factors and molecular subtypes in a cohort of BC patients. Epidemiological risk factors for 2587 BC patients were obtained using a structured questionnaire and from the patients' charts. The histopathological information (estrogen and progesterone receptor, HER2 and Ki-67) used in the analysis was retrieved from the original pathology reports. Analyses using conditional inference regression trees were carried out on these data. The strongest influence factor on the distribution of the molecular subtypes was age at first diagnosis of BC. An influence of BMI was also identified in patients aged either more than 42 years or 49.6 years or less. Older patients aged more than 49.6 years and perimenopausal women with a BMI of 32.4 kg/m or less were most likely to develop luminal A-like BC. Young patients aged 42 years or less and perimenopausal patients with a BMI more than 32.4 kg/m more often developed triple-negative BC. The study confirmed that age at diagnosis is an important factor influencing the distribution of molecular subtypes. In the perimenopausal group, it may be postulated that BMI plays a critical role in the pathogenesis of BC, defining a subgroup that is more likely to develop triple-negative BC or luminal B-like disease and another group in which there is a more postmenopausal distribution pattern.
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Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Adulto , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
The progesterone receptor (PR) has been increasingly well described as an important mediator of the pathogenesis and progression of breast cancer. The aim of this study was to assess the role of PR status as a prognostic factor in addition to other well-established prognostic factors. Data from five independent German breast cancer centers were pooled. A total of 7,965 breast cancer patients were included for whom information about their PR status was known, as well as other patient and tumor characteristics commonly used as prognostic factors. Cox proportional hazards models were built to compare the predictive value of PR status in addition to age at diagnosis, tumor size, nodal status, grading, and estrogen receptor (ER) status. PR status significantly increased the accuracy of prognostic predictions with regard to overall survival, distant disease-free survival, and local recurrence-free survival. There were differences with regard to its prognostic value relative to subgroups such as nodal status, ER status, and grading. The prognostic value of PR status was greatest in patients with a positive nodal status, negative ER status, and low grading. The PR-status adds prognostic value in addition to ER status and should not be omitted from clinical routine testing. The significantly greater prognostic value in node-positive and high-grade tumors suggests a greater role in the progression of advanced and aggressive tumors.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Receptores de Progesterona/biosíntesis , Adulto , Anciano , Estudios de Cohortes , Femenino , Alemania , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Receptores de Progesterona/análisis , Análisis de SupervivenciaRESUMEN
PURPOSE: As breast cancer survivors are benefiting increasingly from advanced forms of therapy, the side effects of locoregional treatment in the adjuvant setting are becoming more and more important. This article presents a new method of assessing the spatial distribution of paresthesia in breast cancer survivors after different locoregional treatments. METHODS: A structured questionnaire assessing paresthesia, with body pictograms for marking paresthesia areas, was completed by 343 breast cancer survivors. The image information was digitized, generating gray-scale summation images with numbers from 0, indicating black (100 % of the patients had paresthesia), to 255, indicating white (none had paresthesia). The resulting map visualization showed the locations of paresthesia on body pictograms. The group included patients who had undergone breast-conserving surgery (BCS) and mastectomy, and also patients who had received percutaneous and interstitial radiation. RESULTS: A total of 56.5 % of the patients stated that they had paresthesia. The paresthesia areas were distributed within the range suggested by clinical experience. Most patients stated that they had paresthesia in the upper outer quadrant and axilla. Patients who had undergone mastectomy or percutaneous radiotherapy appeared to have more paresthesia on some areas of the body surface. Patients who had undergone mastectomy indicated larger areas of paresthesia than those with BCS-4,066 pixels (px) vs. 2,275 px. Radiotherapy did not appear to influence the spatial distribution of paresthesia. CONCLUSIONS: Paresthesia is a common symptom after breast cancer treatment. This paper describes a new method of assessing this side effect to improve and individualize treatment for it in the future.
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Axila , Neoplasias de la Mama/cirugía , Mastectomía/efectos adversos , Parestesia , Adulto , Anciano , Estudios Transversales , Femenino , Alemania , Humanos , Persona de Mediana Edad , Percepción , Periodo Posoperatorio , Estudios Retrospectivos , Programas Informáticos , Encuestas y Cuestionarios , Sobrevivientes/estadística & datos numéricosRESUMEN
BACKGROUND AND AIMS: Cost increases in the healthcare system are leading to a need to distribute financial resources in accordance with the value of each service performed. Health-economic decision-making models can support these decisions. Due to the previous unavailability of health utilities in Germany (scored states of health as a basis for calculating quality-adjusted life-years, QALYs) for women undergoing treatment, international data are often used for such models. However, these may widely deviate from the values for a woman actually living in Germany. It is, therefore, necessary to collect and analyze health utilities in Germany. MATERIALS AND METHODS: In a questionnaire survey, health utilities were collected, along with data for a healthy control group, for 580 female patients receiving treatment in the fields of mastology and gynecological oncology using a German version of the EuroQol questionnaire (EQ-5D) and a visual analogue scale (VAS). Data were also collected for the patients' medical history, tumor disease, and treatment. RESULTS: Significant differences with regard to quality of life were measured in relation to the individual tumor entities and in comparison to the controls. Apart from the healthy control group, patients with breast or cervical carcinoma had the best quality of life. In patients with recurrent and metastatic disease, those with breast carcinoma experienced the greatest impairment of their quality of life. According to current treatment, the most important impairment of life quality occurred in patients under radiotherapy and after surgical treatment. There are significant differences from the health utilities recorded for other countries - for example, the state of health declines much more markedly in patients with metastatic disease among American women with breast carcinoma than among German women, in whom recurrent disease and a first diagnosis of metastasis were comparable. Overall, the VAS was able to distinguish more adequately than the EQ-5D questionnaire between the different situations and impairments resulting from diagnosis and therapy. CONCLUSION: Health utilities are now, for the first time, available for further health-economics analyses in the field of gynecological oncology and mastology for women living in Germany. Important differences in these utilities from those of other countries are evident.
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Neoplasias de los Genitales Femeninos/terapia , Ginecología/estadística & datos numéricos , Indicadores de Salud , Oncología Médica/estadística & datos numéricos , Estudios de Casos y Controles , Análisis Costo-Beneficio , Femenino , Neoplasias de los Genitales Femeninos/economía , Neoplasias de los Genitales Femeninos/psicología , Alemania , Ginecología/economía , Costos de la Atención en Salud , Humanos , Masculino , Oncología Médica/economía , Calidad de VidaRESUMEN
Treatment decisions in oncology are based on a balance between the efficacy of therapy and its side effects. Patients with metastases and patients with a limited prognosis are a particular challenge, since communication about the disease situation and the expected therapeutic benefit is difficult not only for patients, but also for physicians. The aim of this study was therefore to compare the benefits expected of therapy by patients and physicians. Questionnaires were sent to 9,000 breast cancer patients and to 6,938 physicians. The questionnaires described 10 cases of breast cancer in the metastatic setting. The patients and physicians were asked to state the treatment benefit they would require to decide for the therapy options chemotherapy, endocrine therapy, antibody therapy, radiotherapy, and bisphosphonates. Additionally, the participants provided data on patient and physician characteristics. Expected treatment benefits were compared between patients and physicians, and influencing factors that modified the expected benefit were identified. Patients expected much greater benefits from the therapies offered than the physicians. For all treatment modalities, about 50 % or more of patients expected more than a 12-month increase in overall survival from all therapies. Among the doctors, this proportion ranged from 7 to 30 %. Among patients, previous experience of side effects and having young children in the family were the strongest influencing factors. Among the doctors, age and level of education had a strong influence on the expected prognostic improvement to indicate a therapy option. As expectations of treatment differ greatly between patients and doctors, a structured approach to solving this conflict is required. There appear to be some indicators that might help address the problem, such as the physicians' level of training and experience and the patients' specific social circumstances.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/psicología , Toma de Decisiones , Adulto , Anciano , Neoplasias de la Mama/terapia , Comunicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Percepción , Médicos , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del Tratamiento , Revelación de la VerdadRESUMEN
Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.
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Neoplasias de la Mama/genética , Cromosomas Humanos Par 11/genética , Ciclina D1/genética , Elementos de Facilitación Genéticos/genética , Polimorfismo de Nucleótido Simple/genética , Sitios de Unión , Estudios de Casos y Controles , Línea Celular Tumoral , Cromatina/química , Cromatina/genética , Inmunoprecipitación de Cromatina , Ciclina D1/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Femenino , Factor de Transcripción GATA3/antagonistas & inhibidores , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Luciferasas/metabolismo , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Elementos Silenciadores Transcripcionales/genética , Proteína Elk-4 del Dominio ets/antagonistas & inhibidores , Proteína Elk-4 del Dominio ets/genética , Proteína Elk-4 del Dominio ets/metabolismoRESUMEN
Prediction of the prognosis for metastatic breast cancer patients depends on molecular subtypes similar to those found in patients with primary breast cancer. Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) status determine the course of the disease and the prognosis. As Ki-67 helps to differentiate molecular subtypes in patients with primary breast cancer, the aim of this study was to assess the prognostic relevance of Ki-67 in the primary tumor in relation to its prognostic relevance for patients with metastatic breast cancer. A total of 467 patients with invasive breast cancer were identified in the database of a single breast cancer center, in whom Ki-67 had been assessed in tumor material from the breast at the time of the primary diagnosis and who had developed a metastasis at any time during the subsequent course. For these patients, tumor and patient characteristics were used to determine prognostic factors relative to overall survival after the diagnosis of distant metastases. Ki-67 was added to this model to investigate whether this might improve the prediction of overall survival. In the multivariate Cox model, age at diagnosis, body mass index, nodal status, tumor size, ER and PR status, and time from diagnosis to metastasis were identified as relevant prognostic factors. Adding Ki-67 to the model improved the prediction of overall survival. There was also a significant and relevant interaction with the PR status. In patients with a low-proliferation primary tumor, a high level of PR expression would indicate an extraordinarily good prognosis (HR 0.39; 95 % CI, 0.23-0.66). In patients with higher-proliferation primary tumors, PR status was not capable of differentiating prognostic groups. Ki-67 is useful in addition to known prognostic factors for breast cancer. It is able to indicate a group of women with a poorer prognosis, specifically in the group of patients with PR-positive breast cancer.
Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Antígeno Ki-67/análisis , Anciano , Índice de Masa Corporal , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Metástasis Linfática/patología , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Estudios RetrospectivosRESUMEN
Pregnancy and breastfeeding are major factors reducing breast cancer (BC) risk. A potential mechanism for this effect might be changes in mammographic density, but other factors might be involved. The aim of this study was to investigate factors influencing changes in breast size and breast stiffness after pregnancy. Of a consecutive cohort of 5991 women who gave birth between 1996 and 1999, 559 replied to a questionnaire including questions about breast changes. The women completed their own assessments of changes in breast size and stiffness since their last pregnancy. Factors being investigated regarding their predictive value for these changes were: BMI before pregnancy, weight gain, age at first full-term pregnancy (FFTP), number of pregnancies, breastfeeding, and BMI of the children's fathers. A decrease in breast size was reported in 21.8% of the participants and an increase in 35.1%. With regard to the breast stiffness, 66.4% reported a decrease and only 5% reported an increase. Independent predictors for increased breast size were age at FFTP, increase in BMI since last pregnancy, BMI before pregnancy, and time since FFTP. Factors predictive of greater breast stiffness included age at FFTP, BMI before FFTP, time since FFTP, breastfeeding status, and number of pregnancies. Breast changes after pregnancy depend on several variables, which are described as BC-risk factors. Individual reaction of the female breast to a pregnancy leads to different outcomes with regard to breast size and stiffness. Further studies are needed to clarify whether these individual responses interact with the effect of pregnancy on the BC risk.
Asunto(s)
Índice de Masa Corporal , Lactancia Materna/tendencias , Mama/anomalías , Mama/fisiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Hipertrofia/epidemiología , Hipertrofia/prevención & control , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Aumento de Peso/fisiologíaRESUMEN
INTRODUCTION: Although care in certified breast centers is now established throughout Germany, numerous services are still not being reimbursed. This also affects other centers involved in the specialty of gynecology such as gynecological cancer centers, perinatal centers, and endometriosis centers. Although a certified center is entitled to charge additional fees, these are in most cases not reimbursed. Calculation of additional costs is limited by the fact that data from the Institute for the Hospital Reimbursement System (Institut für das Entgeltsystem im Krankenhaus, InEK) do not reflect interdisciplinary services and procedures. For decision-makers, society's willingness to pay is an important factor in guiding decisions on the basis of social priorities. A hypothetical maximum willingness to pay can be calculated using a willingness-to-pay analysis, making it possible to identify deficiencies in the arbitrary setting of health budgets at the macro-level. MATERIALS AND METHODS: In a multicenter study conducted between November 2009 and December 2010, 2,469 patients at a university hospital and at a non-university hospital were asked about the extent of their awareness of certified centers, the influence of centers on hospital presentation, and about personal attitudes toward quality-oriented reimbursement. A subjective assessment of possible additional charges was calculated using a willingness-to-pay analysis. RESULTS: In the overall group, 53.4 % of the patients were aware of what a certified center is and 27.4 % had specific information (obstetrics 40.0/32.3 %; mastology 66.8/23.2 %; gynecological oncology 54.7/27.3 %; P < 0.001). For 43.8 %, a certified center was one reason or the major reason for presentation (obstetrics 26.2 %; mastology 66.8 %; gynecological oncology 46.6 %; P < 0.001). A total of 72.6 % were in favor of quality-oriented reimbursement and 69.7 % were in favor of an additional charge for a certified center amounting to 538.56 (mastology 643.65, obstetrics 474.67, gynecological oncology 532.47). In all, 33.9 % would accept an increase in health-insurance fees (averaging 0.3865 %), and 28.3 % were in favor of reduced remuneration for non-certified centers. CONCLUSIONS: The existence of certified centers is being increasingly recognized by patients. Additional charges for certified centers are generally supported. There is therefore a clear demand for them-from patients as well. This may be useful when negotiations are being conducted.