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1.
Eur J Med Res ; 24(1): 32, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521205

RESUMO

BACKGROUND: Growing demand for risk-reducing surgery in individuals with inherited susceptibility to cancer leads to the question whether these procedures are cost effective for the executing hospitals. This study compared the clinical costs for bilateral risk-reducing mastectomy (BRRM) with and without different types of reconstruction, risk-reducing salpingo-oophorectomy (RRSO), and their combinations with corresponding reimbursements in the statutory health-care system in Germany. PATIENTS AND METHODS: Real total costs of care for BRRM with and without reconstruction, RRSO, and their combinations were calculated as the sum of all personnel and technical costs. These costs calculated in a German University hospital were compared with the sum of all reimbursements in the German DRG-based health-care system. RESULTS: While sole RRSO, BRRM without reconstruction, and BRRM with secondary DIEP (deep inferior epigastric perforator)-reconstruction still result in a small benefit, we even found shortfalls for the hospital with all other prophylactic operations under consideration. The calculated deficits were especially high for BRRM with implant-based breast reconstruction and for combined operations when the risk reduction is achieved with a minimum of separate operations. CONCLUSIONS: Risk-reducing surgery in BRCA-mutation carriers is frequently not cost-covering for the executing hospitals in the German health-care system. Thus, appropriate concepts are required to ensure a nationwide care.

2.
Fertil Steril ; 112(4): 731-739.e1, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31371054

RESUMO

OBJECTIVE: To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. DESIGN: Genome-wide association study. SETTING: Not applicable. PATIENT(S): Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status. RESULT(S): The median age of the 1,168 women was 41 years (range 19-45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5' upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation. CONCLUSION(S): Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer.

3.
Geburtshilfe Frauenheilkd ; 79(5): 487-497, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31148849

RESUMO

Endometriosis is one of the most common benign gynecological diseases. The extremely heterogeneous complex of symptoms complicates the diagnosis and treatment of this disease. In most patients, there is a latency period of several years between the first occurrence of symptoms and the definitive diagnosis. This paper aims (1) to evaluate standards for the diagnosis and treatment of patients with (symptoms suspicious for) endometriosis in terms of feasibility, and (2) to assess the potential use of data collected by a certified clinical and scientific endometriosis center to answer scientific questions. Standards for outpatient consultations were developed for a special endometriosis outpatient clinic. Between January 2014 and December 2017, a total of 1715 outpatients with a suspicion of endometriosis presented to this special endometriosis outpatient clinic; the diagnosis and treatment of patients was carried out in accordance with the developed standards. Data of this patient cohort obtained from patient records created during outpatient consultations and from a questionnaire recorded in an Oracle-based database was analyzed. The patient cohort was also compared with another patient cohort who had attended different outpatient clinics and had been diagnosed intraoperatively with endometriosis. 41.8% of patients examined during special outpatient consultations had surgery for suspicion or recurrence of endometriosis. Endometriosis was confirmed in 81.5% of cases. Pain symptoms were the main indication for surgery in 70.1% of cases compared to 45.1% of cases in the comparison group. The structured approach used in the special endometriosis outpatient clinic is a key aspect of the care provided by the certified clinical and scientific endometriosis center. It ensures that patients are diagnosed and treated in accordance with guideline recommendations, that diagnosis and treatment comply with certification requirements, and that the collected data can be used to answer scientific questions.

4.
Int J Cancer ; 145(8): 2114-2121, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30901076

RESUMO

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.

5.
Breast Cancer Res Treat ; 175(3): 617-625, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30868391

RESUMO

PURPOSE: Several clinical trials have investigated the prognostic and predictive usefulness of molecular markers. With limited predictive value, molecular markers have mainly been used to identify prognostic subgroups in which the indication for chemotherapy is doubtful and the prognosis is favorable enough for chemotherapy to be avoided. However, limited information is available about which groups of patients may benefit from additional therapy. This study aimed to describe the prognostic effects of Ki-67 in several common subgroups of patients with early breast cancer. METHODS: This retrospective study analyzed a single-center cohort of 3140 patients with HER2-, hormone receptor-positive breast cancer. Five-year disease-free survival (DFS) rates were calculated for low (< 10%), intermediate (10-19%), and high (≥ 20%) Ki-67 expression levels, as assessed by immunohistochemistry, and for subgroups relative to age, body mass index, disease stage, tumor grade, and (neo-)adjuvant chemotherapy. It was also investigated whether Ki-67 had different effects on DFS in these subgroups. RESULTS: The 5-year DFS rates for patients with low, intermediate, and high levels of Ki-67 expression were 0.90, 0.89, and 0.77, respectively. Ki-67 was able to further differentiate patients with an intermediate prognosis into different prognostic groups relative to common clinical parameters. Patients with stage II breast cancer had 5-year DFS rates of 0.84, 0.88, and 0.79 for low, intermediate, and high levels of Ki-67 expression. Ki-67 had different prognostic effects in subgroups defined by age and tumor grade. CONCLUSIONS: Ki-67 may help identify patients in intermediate prognostic groups with an unfavorable prognosis who may benefit from further therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Antígeno Ki-67/metabolismo , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Análise de Sobrevida
6.
Breast Cancer Res Treat ; 174(2): 453-461, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30603996

RESUMO

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.


Assuntos
Neoplasias da Mama/patologia , Terapia de Reposição Hormonal/métodos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Idade de Início , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Estudos de Associação Genética , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Análise de Regressão , Fatores de Risco
7.
Breast ; 44: 81-89, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30690254

RESUMO

OBJECTIVES: In breast cancer, large tumor size, positive nodal stage and a triple-negative tumor subtype are associated with reduced survival, but the interactions between these prognostic factors are not well understood. MATERIAL AND METHODS: Here we re-evaluated the impact of tumor size, nodal stage and tumor subtype on disease-free survival (DFS), overall survival (OS), distant disease-free survival (DDFS) and breast cancer specific survival (BCSS) in a retrospective analysis using data from the adjuvant SUCCESS A trial. Subgroup analyses were conducted to assess whether the effect of tumor size and nodal stage on survival depended on tumor subtype. RESULTS: Increasing tumor size, higher nodal stage and triple negative breast cancer (TNBC) were associated with unfavorable prognosis (all p < 0.001). There was no significant interaction between tumor subtype and tumor size (p > 0.5 for all four survival endpoints), but we found significant interactions between tumor subtype and nodal stage (p < 0.05 for all four survival endpoints), with no differences in survival among tumor subtypes for patients with pN0 tumors (all p > 0.05) and pronounced differences in survival among tumor subtypes for patients with positive nodal stage (all p < 0.001). CONCLUSIONS: This analysis confirms tumor size, nodal stage and tumor subtype as independent prognostic factors in high-risk early breast cancer. Nodal-positive patients with TNBC had a considerably worse outcome compared to nodal-positive patients with another tumor subtype. This underlines the importance for early detection particularly for patients with TNBC. TRIAL REGISTRATION: EudraCT 2005-000490-21; ClinicalTrials.gov Identifier: NCT02181101.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Sobreviventes de Câncer/estatística & dados numéricos , Idoso , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
8.
Breast Cancer Res Treat ; 173(2): 319-328, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30324275

RESUMO

PURPOSE: Neoadjuvant combination treatment with chemotherapy (CTX), trastuzumab (TZM), and pertuzumab (PTZ) has been shown to result in higher pathological complete response rates (pCR) in comparison with treatment with chemotherapy and trastuzumab (CTX/TZM). This analysis was aimed at real-world validation of these results from prospective randomized trials. METHODS: In a retrospective analysis conducted in the PRAEGNANT network, patients were eligible for inclusion if they had either received neoadjuvant therapy with CTX/TZM or chemotherapy, trastuzumab, and pertuzumab (CTX/TZM/PTZ) and subsequently underwent surgery for their primary breast cancer. The effect of the two neoadjuvant regimens on pCR in addition to commonly applicable predictors of pCR was analyzed in 300 patients from three study sites, using logistic regression analyses with treatment arm, age, clinical tumor stage, grading, and hormone receptor status as predictors. RESULTS: pCR with complete disappearance of all tumor cells was seen in 30.2% (n = 58) of patients treated with CTX/TZM and in 52.8% (n = 57) of those treated with CTX/TZM/PTZ. CTX/TZM/PTZ was positively associated with pCR (adjusted odds ratio 2.44; 95% CI 1.49-4.02). Mastectomy rates were not influenced by the therapy. CONCLUSIONS: The results of clinical trials were confirmed in this dataset of patients who were treated outside of clinical trials in everyday routine work. pCR rates can be improved by 20% with pertuzumab in routine clinical use.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Trastuzumab/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Estudos Retrospectivos
9.
Cancers (Basel) ; 11(1)2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30577662

RESUMO

This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH → T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.

10.
BMC Cancer ; 18(1): 1051, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30373556

RESUMO

BACKGROUND: It has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer. This study investigates predictors of the response to neoadjuvant platinum-based or anthracycline-based treatment, and of the prognosis, in patients with triple-negative breast cancer. METHODS: A total of 121 patients with triple-negative breast cancer received neoadjuvant treatment with either platinum or anthracycline between 2008 and 2013. Pathological complete response was assessed relative to different treatments using logistic regression models with age, clinical tumor stage, grading, and Ki-67 as predictors and interaction terms, to obtain adjusted and subgroup-specific results. The impact of the pathological complete response rate on disease-free survival and overall survival was also analyzed. RESULTS: The pathological complete response rate was higher after platinum/taxane treatment compared with anthracycline/taxane (50.0% vs. 41.8%), but this was not significant in the adjusted analysis (OR 1.44; 95% CI, 0.68 to 3.09). A high histological grade (G3) was a predictor for higher pathological complete response in platinum-based therapy (OR 2.27; 95% CI, 1.00 to 5.30). The effect of neoadjuvant chemotherapy on pathological complete response was significantly different for G1-2 vs. G3 (Pinteraction = 0.013), and additional subgroup-specific differences were noted. Pathological complete response was a predictor for improved disease-free survival and overall survival in both treatment groups, with and without platinum chemotherapy. CONCLUSIONS: This retrospective study of patients with triple-negative breast cancer adds to the evidence that the treatment effect of platinum may be greatest particularly in G3 tumors. In addition, the effect of pathological complete response on the prognosis does not depend on the treatment used.


Assuntos
Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/terapia
11.
Arch Gynecol Obstet ; 298(5): 889-895, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30196359

RESUMO

PURPOSE: The aim of this study was to evaluate maternal, prenatal, perinatal, and postpartum parameters as risk factors for the later development of an attention deficit hyperactivity disorder (ADHD) in the child. METHODS: Women who had given birth at Erlangen University Hospital between 1996 and 1999 were sent a questionnaire in 2009. The results of the questionnaire were correlated with the prospectively collected data for the births in 1996-1999. RESULTS: A total of 573 mother and child pairs were analyzed. Forty-four of the mothers reported that their child had ADHD (7.7%). No significant associations were found for the following parameters: mother's age; mother's educational level; number of the pregnancy; maternal weight before and at the end of pregnancy; mother's height; alcohol consumption during pregnancy; mode of delivery; gestational week; birthweight; umbilical artery blood values; Apgar score at 5 and 10 min; or breastfeeding. The parameters of smoking in pregnancy and an Apgar score lower than 7 after 1 min were significantly associated with a risk for later development of ADHD. CONCLUSIONS: This analysis of maternal, prenatal, perinatal, and postnatal parameters found that smoking in pregnancy and a low Apgar score 1 min after birth are associated with a significantly greater risk for the development of ADHD. Beyond the question of the causal mechanism involved, this is a relevant finding, since smoking during pregnancy is a preventable risk factor.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Peso ao Nascer/genética , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Adulto , Índice de Apgar , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Feminino , Humanos , Recém-Nascido , Masculino , Parto , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Fatores de Risco , Inquéritos e Questionários
12.
Geburtshilfe Frauenheilkd ; 78(7): 707-714, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30057427

RESUMO

Background: In women with early breast cancer, a pathological complete response (pCR) after neoadjuvant chemotherapy is reported to be associated with an improvement of the survival. The aim of this survey among physicians was to investigate whether the probability of achieving pCR in patients with a hormone receptor-positive, HER2-negative disease encourages physicians to recommend neoadjuvant chemotherapy. Methods: The study was conducted via an online survey that was sent to 493 physicians, who were either known as members of national guideline committees, heads of breast cancer centers, being high recruiters in clinical trials or leading a private practice. Participants were asked about a specific case that should resemble patients for whom it is unclear, whether they should be treated with chemotherapy. Results: 113 (24.5%) physicians participated at the survey, out of which 96.5% had a work experience of more than 10 years and 94.7% were board certified in their specialty. A total of 84.1% would consider pCR for a decision concerning neoadjuvant chemotherapy. With regard to the pCR probability, 2.7 and 10.6% of the participants demanded at least a pCR rate of 5 and 10%, respectively, while 25.7% were satisfied with 20% probability, and another 25.7% with a pCR rate of 30%. Conclusions: The vast majority of the long-term experienced physicians would embrace the implementation of a further method such as the prediction of pCR probability in clinical routine to support decision making regarding the necessity of neoadjuvant chemotherapy. The cut-off of around 30% pCR probability seems to be a realizable rate to distinguish patient groups.

13.
Geburtshilfe Frauenheilkd ; 78(5): 481-492, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29880983

RESUMO

Over the last two decades genetic testing for mutations in BRCA1 and BRCA2 has become standard of care for women and men who are at familial risk for breast or ovarian cancer. Currently, genetic testing more often also includes so-called panel genes, which are assumed to be moderate-risk genes for breast cancer. Recently, new large-scale studies provided more information about the risk estimation of those genes. The utilization of information on panel genes with regard to their association with the individual breast cancer risk might become part of future clinical practice. Furthermore, large efforts have been made to understand the influence of common genetic variants with a low impact on breast cancer risk. For this purpose, almost 450 000 individuals have been genotyped for almost 500 000 genetic variants in the OncoArray project. Based on first results it can be assumed that - together with previously identified common variants - more than 170 breast cancer risk single nucleotide polymorphisms can explain up to 18% of familial breast cancer risk. The knowledge about genetic and non-genetic risk factors and its implementation in clinical practice could especially be of use for individualized prevention. This includes an individualized risk prediction as well as the individualized selection of screening methods regarding imaging and possible lifestyle interventions. The aim of this review is to summarize the most recent developments in this area and to provide an overview on breast cancer risk genes, risk prediction models and their utilization for the individual patient.

14.
Breast Care (Basel) ; 13(1): 8-14, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29950961

RESUMO

Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype 'lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach.

15.
Breast Cancer Res Treat ; 171(3): 747-758, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29951969

RESUMO

BACKGROUND: Clinical trials can offer novel and more advanced and/or novel treatments to cancer patients in advance of them being approved and available for all patients. While several studies have examined the effect of clinical trial participation on prognosis, there has been no clear conclusion from these studies. Therefore, we chose to test the influence of trial participation on pathological complete response (pCR) and mastectomy rates after neoadjuvant chemotherapy. METHODS: In this retrospective study, all patients treated with neoadjuvant chemotherapy from 2001 to 2014 were selected. A total of 1038 patients with complete treatment, patient, and tumor characteristics were included. A total of 260 of those were treated in clinical trials. We examined whether study participation status in addition to commonly known predictors for pCR improves prediction of pCR. Similar analyses were conducted for the mastectomy rate outcome measure. Finally, survival analyses were also conducted as part of an exploratory analysis. RESULTS: Study participation was an independent predictor of pCR in addition to commonly known predictors. Adjusted odds ratio (OR) for trial participants versus non-participants was 1.53 (95% CI 1.03-2.28). Additionally, study participation improved the prediction of mastectomy risk. The adjusted OR for trial participants versus non-participants was 0.62 (95% CI 0.42-0.90). Subgroup-specific differences concerning the impact of study participation could not be shown for either pCR or mastectomy rate. Survival comparisons could not be conducted due to large differences in follow-up data in patients participating in clinical trials versus those who did not participate; however, pCR was a predictor of prognosis in both groups. CONCLUSION: Patients taking part in neoadjuvant chemotherapy clinical trials have a higher pCR rate and a lower mastectomy risk than patients not participating in clinical trials for their cancer care. This finding is a supporting factor for trial participation in neoadjuvant chemotherapy trials.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Terapia Neoadjuvante , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
16.
Breast Cancer Res Treat ; 171(1): 85-94, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29725888

RESUMO

PURPOSE: BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. METHODS: Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. RESULTS: Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. CONCLUSIONS: BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Genes BRCA1 , Genes BRCA2 , Mutação , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Análise Mutacional de DNA , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
17.
BMC Cancer ; 18(1): 204, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29463222

RESUMO

BACKGROUND: The assessment of circulating tumor cells (CTCs) has been shown to enable monitoring of treatment response and early detection of metastatic breast cancer (MBC) recurrence. The aim of this study was to compare a well-established CTC detection method based on immunomagnetic isolation with a new, filtration-based platform. METHODS: In this prospective study, two 7.5 ml blood draws were obtained from 60 MBC patients and CTC enumeration was assessed using both the CellSearch® and the newly developed filtration-based platform. We analyzed the correlation of CTC-positivity between both methods and their ability to predict prognosis. Overall survival (OS) was calculated and Kaplan-Meier curves were estimated with thresholds of ≥1 and ≥5 detected CTCs. RESULTS: The CTC positivity rate of the CellSearch® system was 56.7% and of the filtration-based platform 66.7%. There was a high correlation of CTC enumeration obtained with both methods. The OS for patients without detected CTCs, regardless of the method used, was significantly higher compared to patients with one or more CTCs (p < 0.001). The median OS of patients with no CTCs vs. ≥ 1 CTC assessed by CellSearch® was 1.83 years (95% CI: 1.63-2.02) vs. 0.74 years (95% CI: 0.51-1.52). If CTCs were detected by the filtration-based method the median OS times were 1.88 years (95% CI: 1.74-2.03) vs. 0.59 years (95% CI: 0.38-0.80). CONCLUSIONS: The newly established EpCAM independently filtration-based system is a suitable method to determine CTC counts for MBC patients. Our study confirms CTCs as being strong predictors of prognosis in our population of MBC patients.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Filtração/métodos , Citometria de Fluxo , Células Neoplásicas Circulantes/patologia , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Feminino , Imunofluorescência , Humanos , Separação Imunomagnética , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/metabolismo , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reprodutibilidade dos Testes
18.
Breast ; 37: 42-51, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29100043

RESUMO

PURPOSE: This study describes comprehensive data from a breast cancer registry concerning the use of endocrine treatment (ET) and chemotherapy in the first, second and higher therapy lines in hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC). METHODS: The PRAEGNANT study is a real-time registry for patients with MBC. Therapies were categorized into the following categories: chemotherapy, aromatase inhibitor (AI), tamoxifen, fulvestrant, or everolimus plus ET and reported for first, second and third line or higher therapy use. Also treatment sequences for the first, second and third therapy line were analyzed. RESULTS: This analysis includes 958 patients with HR positive, HER2 negative MBC. 42.7% were treated with a chemotherapy in the first therapy line compared to 45.9% receiving an ET. A total of 25.9% were treated with everolimus plus anti-hormone therapy in any therapy line. 34.1% were treated with fulvestrant as single agent therapy. Analyzing therapy sequences, the administration of three different chemotherapies in a row was the most frequently used pattern. CONCLUSIONS: This analysis shows that across all three first therapy lines chemotherapy is a dominant therapy for HR positive, HER2 negative MBC patients. Education about the efficacy of ET might help to increase its use and decrease the possible burden of chemotherapy related toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Idoso , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/patologia , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Everolimo/administração & dosagem , Feminino , Fulvestranto , Alemanha , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Sistema de Registros , Tamoxifeno/administração & dosagem
19.
Breast ; 37: 154-160, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29237546

RESUMO

OBJECTIVES: Improved progression-free survival is considered as treatment goal for patients with metastatic breast cancer (MBC) since it is assumed to delay or prevent deterioration of quality of life. Aim of our analysis was to examine the influence of disease progression on health-related quality of life (HRQoL). MATERIALS AND METHODS: The PRAEGNANT study comprises a real-life registry for patients with MBC. HRQoL was assessed with the EORTC-QLQ-C30 Version 3.0 questionnaire at study entry and every 3 months thereafter. The primary endpoint was minimally important deterioration (MID) in global HRQoL score by ≥ five points between baseline and any follow-up assessment. A logistic regression model was built with MID (yes/no) at a follow-up timepoint as outcome variable and several covariates as predictors. RESULTS: In total, 329 patients were included in this analysis, with disease progression in 63 patients. Concerning the primary study aim, progression status predicted MID of global HRQoL status in addition to the other covariates. The adjusted odds ratio for the effect of progression status on MID was 2.22 (95% CI: 1.04 - 4.73). Comparisons of mean differences of QoL domains/scales yielded no differences. CONCLUSIONS: We provide evidence that disease progression in patients with metastatic breast cancer in a real-world registry has a significant negative impact on HRQoL as measured by MID of HRQoL. This study emphasizes the relevance of avoiding progression and prolonging PFS to maintain QoL.


Assuntos
Neoplasias da Mama/patologia , Progressão da Doença , Qualidade de Vida , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Sistema de Registros , Inquéritos e Questionários
20.
Oncotarget ; 8(44): 78133-78143, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-29100455

RESUMO

Hematotoxicity is one of the major side effects of chemotherapy. The aim of this study was to examine the association between single nucleotide polymorphisms (SNPs) and hematotoxicity in breast cancer patients in a subset of patients of the SUCCESS prospective phase III chemotherapy study. All patients (n = 1678) received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by three cycles of docetaxel or docetaxel/gemcitabine, depending on randomization. Germline DNA was genotyped for 246 SNPs selected from a previous genome-wide association study (GWAS) in a panel of lymphoblastoid cell lines, with gemcitabine toxicity as the phenotype. All SNPs were tested for their value in predicting grade 3 or 4 neutropenic or leukopenic events (NLEs). Their prognostic value in relation to overall survival and disease-free survival was also tested. None of the SNPs was found to be predictive for NLEs during treatment with docetaxel/gemcitabine. Two SNPs in and close to the PIGB gene significantly improved the prediction of NLEs after FEC, in addition to the factors of age and body surface area. The top SNP (rs12050587) had an odds ratio of 1.38 per minor allele (95% confidence interval, 1.17 to 1.62). No associations were identified for predicting disease-free or overall survival. Genetic variance in the PIGB gene may play a role in determining interindividual differences in relation to hematotoxicity after FEC chemotherapy.

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