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1.
ESMO Open ; 6(6): 100299, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34839105

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) have been reported to predict clinical outcome in metastatic breast cancer (MBC). Biology of CTCs may differ from that of the primary tumor and HER2-positive CTCs are found in some patients with HER2-negative tumors. PATIENTS AND METHODS: Patients with HER2-negative MBC were screened for participation in DETECT III and IV trials before the initiation of a new line of therapy. Blood samples were analyzed using CELLSEARCH. CTCs were labeled with an anti-HER2 antibody and classified according to staining intensity (negative, weak, moderate, or strong staining). RESULTS: Screening blood samples were analyzed in 1933 patients with HER2-negative MBC. As many as 1217 out of the 1933 screened patients (63.0%) had ≥1 CTC per 7.5 ml blood; ≥5 CTCs were detected in 735 patients (38.0%; range 1-35 078 CTCs, median 8 CTCs). HER2 status of CTCs was assessed in 1159 CTC-positive patients; ≥1 CTC with strong HER2 staining was found in 174 (15.0%) patients. The proportion of CTCs with strong HER2 staining among all CTCs of an individual patient ranged between 0.06% and 100% (mean 15.8%). Patients with estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors were more likely to harbor ≥1 CTC with strong HER2 staining. CTC status was significantly associated with overall survival (OS). Detection of ≥1 CTC with strong HER2 staining was associated with shorter OS [9.7 (7.1-12.3) versus 16.5 (14.9-18.1) months in patients with CTCs with negative-to-moderate HER2 staining only, P = 0.013]. In multivariate analysis, age, ER status, PR status, Eastern Cooperative Oncology Group performance status, therapy line, and CTC status independently predicted OS. CONCLUSION: CTC detection in patients with HER2-negative disease is a strong prognostic factor. Presence of ≥1 CTC with strong HER2 staining was associated with shorter OS, supporting a biological role of HER2 expression on CTCs.


Assuntos
Neoplasias da Mama , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Prognóstico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/uso terapêutico
2.
Breast ; 50: 11-18, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958661

RESUMO

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.


Assuntos
Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Terapias Complementares , Letrozol/efeitos adversos , Dor Musculoesquelética/induzido quimicamente , Idoso , Artralgia/induzido quimicamente , Feminino , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Mialgia/induzido quimicamente , Pós-Menopausa
3.
Ann Oncol ; 29(8): 1777-1783, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29893791

RESUMO

Background: Trastuzumab improves the outcome of women with HER2 positive breast cancer. We aimed to assess whether trastuzumab decreases the detection rate of circulating tumor cells (CTCs) in women with high risk, HER2 nonamplified, early breast cancer. Patients and methods: The EORTC 90091-10093 BIG 1-12 Treat CTC is a phase II trial, conducted in 70 hospitals and 6 CTC laboratories across 5 European countries. Patients with centrally confirmed HER2 nonamplified breast cancer and ≥1 centrally confirmed CTC per 15 ml of blood by CellSearch® following surgery and (neo)adjuvant chemotherapy were randomized (1 : 1) to 6 cycles of trastuzumab intravenously versus 18 weeks of observation. Randomization was stratified for center, locally confirmed estrogen receptor status and adjuvant versus neoadjuvant chemotherapy. The primary end point was rate of detection of ≥1 CTC per 15 ml of blood at week 18. Secondary end points were invasive disease-free survival (iDFS) and cardiac safety. Results: Between 30 April 2013 and 17 October 2016, 1317 patients were screened; 95 (7.2%) had detectable CTC(s), and 63 (4.8%) were randomized to trastuzumab (n = 31) or observation (n = 32). Fifty-eight patients were assessable for the primary end point, 29 in each arm. In 9 of the 58 patients, CTC(s) were still detected at week 18 : 5 in the trastuzumab and 4 in the observation arm (one-sided Fisher's exact test, P = 0.765). An Independent Data Monitoring Committee recommended stopping further accrual for futility for the primary end point. Median follow-up at database lock was 13 months (IQR 4-16.5). The 1-year iDFS was 93.8% (95% CI 77.3-98.4) in the observation versus 84.8% (95% CI 63.4-94.2) in the trastuzumab arm. No grade 2-4 cardiac events were observed in the trastuzumab arm. Conclusion: Trastuzumab does not decrease the detection rate of CTCs in HER2 nonamplified, nonmetastatic breast cancer.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/terapia , Células Neoplásicas Circulantes/efeitos dos fármacos , Trastuzumab/administração & dosagem , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Trastuzumab/efeitos adversos
4.
Geburtshilfe Frauenheilkd ; 77(6): 651-659, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28757652

RESUMO

Large-scale genotyping studies have identified over 70 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. However, knowledge regarding genetic risk factors associated with the prognosis is limited. The aim of this study was therefore to investigate the prognostic effect of nine known breast cancer risk SNPs. BC patients (n = 1687) randomly sampled in an adjuvant, randomized phase III trial (SUCCESS A study) were genotyped for nine BC risk SNPs: rs17468277 (CASP8) , rs2981582 (FGFR2) , rs13281615(8q24), rs3817198 (LSP1) , rs889312 (MAP3K1) , rs3803662 (TOX3) , rs13387042(2q35), rs4973768 (SLC4A7) , rs6504950 (COX11) . Cox proportional hazards models were used to test the SNPs' association with overall survival (OS) and progression-free survival (PFS). Additional analyses were carried out for molecular subgroups. rs3817198 in LSP1 (lymphocyte-specific protein 1) was the only SNP that significantly influenced OS (p = 0.01) and PFS (p < 0.01) in the likelihood ratio test comparing the genetic survival model with the clinical survival model. In the molecular subgroups, triple-negative patients with two minor alleles in rs3817198 had a much better prognosis relative to OS (adjusted HR 0.03; 95% CI 0.002 - 0.279) and PFS (HR 0.09; 95% CI 0.02 - 0.36) than patients with the common alleles. The same effect on PFS was shown for patients with luminal A tumors (HR 0.19; 95% CI 0.05 - 0.84), whereas patients with luminal B tumors had a poorer PFS with two minor alleles (HR 2.13; 95% CI 1.02 - 4.40). The variant in rs3817198 has a prognostic effect particularly in the subgroup of patients with triple-negative BC, suggesting a possible link with immunomodulation and BC.

5.
Breast ; 35: 130-135, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28732324

RESUMO

BACKGROUND: Premenopausal women undergoing chemotherapy are at high risk for premature ovarian failure and its long-term consequences. Data on potential markers to evaluate ovarian reserve pre- and posttreatment are limited. Anti-Müllerian hormone (AMH) known for ovarian reserve in reproductive medicine could be a surrogate marker and was assessed in premenopausal breast cancer patients of the SUCCESS A study (EUDRA-CT no. 2005-000490-21). METHODS: We identified 170 premenopausal patients, age ≤ 40 years at trial entry, who received FEC-Doc as taxane-anthracylince based chemotherapy. Blood samples were taken at three time points: Before, four weeks after and two years after adjuvant chemotherapy. Serum AMH-levels were evaluated in a central laboratory by a quantitative immunoassay AMH Gen II ELISA (Beckman Coulter, Brea, USA). RESULTS: Median age was 36 years (21-40 years). Median serum AMH-level before chemotherapy was 1.37 ng/ml (range < 0.1-11.3 ng/ml). Four weeks after chemotherapy AMH-levels dropped in 98.6% of the patients to <0.1 ng/ml (range < 0.1-0.21 ng/ml). After two years, 73.3% (n = 101) showed no evidence of ovarian function recovery (AMH <0.1 ng/ml, range < 0.1-3.9 ng/ml). Permanent chemotherapy induced amenorrhea occurred only in 50.6% of the patients. CONCLUSIONS: In this analysis, premenopausal patients showed a high rate of ovarian impairment reflected by low AMH-levels after chemotherapy.


Assuntos
Hormônio Antimülleriano/sangue , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Taxoides/administração & dosagem , Adulto , Amenorreia/induzido quimicamente , Quimioterapia Adjuvante/efeitos adversos , Feminino , Humanos , Terapia Neoadjuvante/efeitos adversos , Fatores de Tempo
6.
PLoS One ; 12(6): e0173593, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28586395

RESUMO

BACKGROUND: HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy. METHODS: The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining. RESULTS: 258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC. CONCLUSION: This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Células Neoplásicas Circulantes/patologia , Receptor ErbB-2/genética , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/sangue , Pesquisa Translacional Biomédica , Trastuzumab/administração & dosagem
7.
Geburtshilfe Frauenheilkd ; 76(5): 542-550, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27239063

RESUMO

Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients. Methods: Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3-4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support. Results: No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm. Conclusion: The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.

8.
Br J Cancer ; 114(8): 863-71, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-27031854

RESUMO

BACKGROUND: Taxane-containing adjuvant chemotherapy has been established as standard treatment in node-positive breast cancer. This study compared efficacy and tolerability of epirubicin (E)/cyclophosphamide (C) followed by docetaxel (Doc) with a dose-dense 5-fluorouracil (F)+E+ C regimen. METHODS: The ADEBAR study was a randomised phase III trial for women with primary invasive breast cancer and ⩾4 metastatic axillary lymph nodes (n=1364). Treatment consisted of four 21-day cycles of E plus C, followed by four 21-day cycles of Doc (EC-Doc), or six 28-day cycles of E plus F plus C (FEC120). RESULTS: Disease-free survival (DFS) was similar in the two treatment arms as shown by multivariate Cox regression adjusted for other prognostic factors (EC-Doc vs FEC120, hazard ratio (HR): 1.087; 95% confidence interval (CI): 0.878-1.346, P=0.444). In addition, there was no significant difference in overall survival (OS) between the two groups (HR: 0.974; 95% CI: 0.750-1.264, P=0.841). Haematologic toxicity was more common in FEC120 recipients; non-haematologic toxicities occurred more frequently in the EC-Doc arm. The serious adverse event rate was significantly higher in the FEC120 group (29.7% vs 22.5%). CONCLUSIONS: EC-Doc provides a feasible and effective alternative therapy option to FEC120 with a different safety profile in this high-risk breast cancer cohort.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Taxoides/uso terapêutico , Adulto , Idoso , Axila/patologia , Quimioterapia Adjuvante/métodos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Epirubicina/administração & dosagem , Epirubicina/uso terapêutico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Análise de Sobrevida
9.
J Cancer Res Clin Oncol ; 142(9): 1883-95, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26825607

RESUMO

INTRODUCTION: From the early days of pathology back in the nineteenth century until now, there has been an ongoing search for the missing link between solid tumors such as breast cancer and distant metastases, which sometimes occur many years after removal of the primary tumor. The "seed and soil" theory hypothesizes the early dissemination of occult tumor cells into blood or bone marrow, which can persist in a dormant state for a long time and then become precursors of metastases in distant organs which offer appropriate conditions. METHOD: Advances in immunocytochemical methods have enabled the enrichment and visualization of those disseminated tumor cells in bone marrow (DTC-BM) or circulating tumor cells (CTC) in blood. Many studies could demonstrate prognostic significance of the detection of DTC-BM or CTC in different stages of breast cancer. CONCLUSION: Further characterization of those cells by immunocytochemical stainings, fluorescence in situ hybridizations, or PCR-based molecular methods will help to understand the biology of tumor cell dissemination and metastasis formation, as well as to define potential drug targets.


Assuntos
Medula Óssea/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Células Neoplásicas Circulantes/patologia , Proliferação de Células , Feminino , Humanos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências
10.
Geburtshilfe Frauenheilkd ; 75(6): 588-596, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26166840

RESUMO

Introduction: Use of hormone therapy (HT) has declined dramatically in recent years. Some studies have reported that HT use before a diagnosis of breast cancer (BC) may be a prognostic factor in postmenopausal patients. This study aimed to examine the prognostic relevance of HT use before BC diagnosis. Methods: Four BC cohort studies in Germany were pooled, and 4492 postmenopausal patients with HT use data were identified. Patient data and tumor characteristics were compared between users and nonusers, along with overall survival (OS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Cox proportional hazards models were stratified by study center and adjusted for age at diagnosis, tumor stage, grading, nodal status, and hormone receptors. Results: Women with HT use before the diagnosis of BC were more likely to have a lower tumor stage, to be estrogen receptor-negative, and to have a lower grading. With regard to prognosis there were effects seen for OS, DMFS and LRFS, specifically in the subgroup of women with a positive hormone receptor. In these subgroups, BC patients had a better prognosis with previous HT use. Conclusions: HT use before a diagnosis of BC is associated with a more favorable prognosis in women with a positive hormone receptor status. It may be recommended that the prognostic factor HT should be documented and analyzed as a confounder for prognosis in studies of postmenopausal hormone-responsive breast cancers.

11.
Breast Cancer Res Treat ; 151(3): 569-76, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25962694

RESUMO

Obese breast cancer patients have a higher risk of lymph node metastasis and a poorer prognosis compared to patients with normal weight. For obese women with node-positive breast cancer, an association between body weight and prognosis remains unclear. In this retrospective study, we analyzed patient data from the Phase-III ADEBAR trial, in which high-risk breast cancer patients (pT1-4, pN2-3, pM0) were randomized into a docetaxel-based versus epirubicin-based chemotherapy regimen. Patients were grouped according to their BMI value as underweight/normal weight (BMI < 25 kg/m(2); n = 543), overweight (BMI 25-29.9 kg/m(2); n = 482) or obese (BMI ≥ 30 kg/m(2); n = 285). Overweight and obese patients were older, had larger tumors and were more likely to be postmenopausal at the time of diagnosis compared to underweight/normal-weight patients (all p < 0.001). Multivariate Cox regression analyses adjusting for age and histopathological tumor features showed that obese patients had a significantly shorter disease-free survival (DFS; HR 1.43; 95 % CI 1.11-1.86; p = 0.006) and overall survival (OS; HR 1.56; 95 % CI 1.14-2.14; p = 0.006) than non-obese patients. Subgroup analyses revealed that the differences in DFS and OS were significant for postmenopausal but not for premenopausal patients, and that the survival benefit of non-obese patients was more pronounced in women with hormone-receptor-positive disease. Obesity constitutes an independent, adverse prognostic factor in high-risk node-positive breast cancer patients, in particular for postmenopausal women and women with hormone-receptor-positive disease.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Obesidade/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Índice de Massa Corporal , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco
12.
J Cancer Res Clin Oncol ; 141(8): 1457-64, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25708944

RESUMO

PURPOSE: Circulating tumor cell (CTC) counts might display a superior prognostic value for overall survival (OS) compared to objective response criteria (OR) in metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: CTCs were detected using the CellSearch™ System out of 122 samples during docetaxel chemotherapy (75 mg/m(2)) at baseline (q0) and after 1 (q1), 4 (q4) and 10 (q10) cycles, in mCRPC patients (n = 33). OR was evaluated by morphologic RECIST and clinical criteria after 4 (q4) and 10 (q10) cycles. RESULTS: For OS, analyses revealed a significant prognostic value for categorical (<5 vs. ≥5) CTC counts (q0, p = 0.005; q1, p = 0.001; q4, p < 0.001; q10, p = 0.002), RECIST (q4, p < 0.001; q10, p = 0.02) and clinical criteria (q4, p < 0.001; q10, p = 0.02). Concordance of CTC counts with OR revealed a sensitivity of 83.3-87.5 % and a specificity of 68.0-76.5 % with complementary discriminatory power for OS. Comparing CTC counts with concomitant OR at q4 in multivariate analyses, an independent prognostic value for OS was found for CTC counts (HR 3.3; p = 0.02) similar to clinical (HR 4.9; p = 0.02) and radiologic response (HR 3.4; p = 0.051). Comparing the predictive value for death, early post-treatment CTC counts at q1 demonstrated significant accuracy with an area under the curve of 79.5 % (p = 0.004) similar to CTC counts at q4 (76.7 %; p = 0.009). Radiologic and clinical response at q4 displayed accuracy similar to early CTC counts at q1 (72.2 %; p = 0.03 and 75.0 %; p = 0.02) despite low sensitivities. CONCLUSIONS: CTC counts appear to be an earlier and more sensitive predictor for survival and treatment response than current OR approaches and may provide complementary information toward individualized treatment strategies.


Assuntos
Antineoplásicos/uso terapêutico , Células Neoplásicas Circulantes/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Farmacológicos/sangue , Biomarcadores Tumorais/sangue , Contagem de Células , Docetaxel , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Prognóstico , Neoplasias de Próstata Resistentes à Castração/sangue , Análise de Sobrevida
13.
Ann Oncol ; 26(1): 95-100, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25355716

RESUMO

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) has been suggested as a new biomarker and therapeutic target in breast cancer, as well as other tumor types. PATIENTS AND METHODS: We evaluated the frequency of SPARC expression among different molecular breast cancer subtypes and its role for therapy response after neoadjuvant chemotherapy. In this study, pretherapeutic core biopsies of 667 patients from the neoadjuvant GeparTrio trial were evaluated for SPARC expression by immunohistochemistry using a standardized immunoreactive score (IRS). RESULTS: An increased SPARC expression (IRS ≥6) was observed in 26% of all tumors. In triple-negative tumors, SPARC expression was increased in 37% of tumors, compared with other molecular subtypes (23% HR+/HER2-, 29% HR+/HER2+ and 22% HR-/HER2+; P = 0.038). Increased SPARC expression was associated with an increased pathological complete response (pCR) rate of 27%, compared with 15% in tumors with low SPARC expression (P < 0.001). In the triple-negative subgroup, pCR rates were 47% in tumors with high SPARC expression, compared with 26% in tumors with low SPARC expression (P = 0.032). In multivariable analysis, SPARC was independently predictive in the overall population (P = 0.010) as well as the triple-negative subgroup (P = 0.036). CONCLUSIONS: SPARC is frequently expressed in breast cancer with triple-negative breast cancer revealing the highest expression rate. High SPARC expression of the primary tumor is associated with a higher chance of achieving a pathological complete remission after TAC or TAC-NX chemotherapy. As SPARC is an albumin-binding protein and might mediate intratumoral accumulation of albumin bound drugs, SPARC should be further evaluated as a predictive marker especially for response to albumin-bound drugs like nab-paclitaxel. CLINICAL TRIAL NUMBER: NCT00544765.


Assuntos
Biomarcadores Tumorais/biossíntese , Terapia Neoadjuvante , Osteonectina/biossíntese , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxoides/uso terapêutico , Resultado do Tratamento
14.
Biomed Res Int ; 2014: 491459, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24800234

RESUMO

BACKGROUND: Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. MATERIAL AND METHODS: We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. RESULTS: The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). CONCLUSION: Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.


Assuntos
Neoplasias da Mama/patologia , Contagem de Células/métodos , Citodiagnóstico/métodos , Imuno-Histoquímica/métodos , Separação Imunomagnética/métodos , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Geburtshilfe Frauenheilkd ; 73(1): 63-69, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24771886

RESUMO

The SUCCESS-A trial is a prospective, multicenter, phase III clinical trial for high-risk primary breast cancer. It compares disease-free survival after randomization in patients treated with fluorouracil, epirubicin and cyclophosphamide followed by 3 cycles of docetaxel (FEC-D) with that of patients treated with 3 cycles of FEC followed by 3 cycles of gemcitabine and docetaxel (FEC-DG). After a second randomization patients were treated with zoledronate for 2 or 5 years. A total of 251 centers took part in the trial and 3754 patients were recruited over a period of 18 months which ended in March 2007. In a questionnaire-based survey we investigated the impact of enrollment in the trial on patient care, the choice of chemotherapy protocol and access to current oncologic information as well as overall satisfaction in the respective centers. Analysis of the 78 questionnaires returned showed that 40 % of the centers had never previously enrolled patients with these indications in clinical studies. Prior to participating in the study, 4 % of the centers prescribed CMF or other protocols in patients with high-primary breast cancer risk, 46 % administered anthracycline-based chemotherapy and 50 % gave taxane-based chemotherapy. Around half of the participating centers noted that intensity of care and overall quality of care became even better and that access to breast cancer-specific information improved through participation in the trial. After their experience with the SUCCESS-A trial, all of the centers stated that they were prepared to enroll patients in clinical phase III trials again in the future. These data indicate that both patients and physicians benefit from clinical trials, as enrollment improves treatment strategies and individual patient care, irrespective of study endpoints.

16.
Br J Cancer ; 107(6): 956-60, 2012 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-22892393

RESUMO

BACKGROUND: We were able to demonstrate a predictive value of serum HER2 (sHER2) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial. However, the role of sHER2 in patients receiving neoadjuvant therapy (NT) with lapatinib is still unclear. METHODS: The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients. The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients, of whom 109 (52%) patients received trastuzumab and 101 (48%) lapatinib at three different time points. RESULTS: Twenty-two percent of patients had elevated baseline sHER2 levels (>15 ng ml⁻¹). A decrease of sHER2 levels (>20%) in the trastuzumab and lapatinib-treated group during NT was seen in 44% and 24% of the patients, an increase of sHER2 levels (>20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02-3.2, P=0.043). A decline of sHER2 levels (>20%) during NT was a predictor for pCR in the lapatinib-treated patient group (OR: 11.7, 95% CI 1.3-110, P=0.031). CONCLUSION: Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy. Elevated baseline sHER2 levels (>15 ng ml⁻¹) and a decrease of sHER2 levels (>20%) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Quinazolinas/uso terapêutico , Receptor ErbB-2/sangue , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Esquema de Medicação , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lapatinib , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante/métodos , Valor Preditivo dos Testes , Quinazolinas/administração & dosagem , Receptores de Estrogênio/sangue , Pesquisa Translacional Biomédica , Trastuzumab , Resultado do Tratamento
17.
J Perinatol ; 32(3): 218-26, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21681177

RESUMO

OBJECTIVE: As 80% of intrauterine bone mineralization takes place during the last trimester of pregnancy, preterm infants should be supplemented postnatally with optimal doses of calcium, phosphate and vitamin D. Calcium and phosphate excretion in the urine may be used to monitor individual mineral requirements, but are sometimes difficult to interpret. The objective of this study was to assess the value of quantitative ultrasound (QUS) for the analysis of bone status in neonates. STUDY DESIGN: All admissions to three independent tertiary neonatal intensive care units were studied. In 172 preterm and term infants with a gestational age between 23 and 42 weeks (mean 33.8±5.0) and a birth weight from 405 to 5130 g (mean 2132±1091 g) bone status was evaluated prospectively by quantitative ultrasound velocity using a standardized protocol. Infants were followed in regular intervals up to their first discharge home. While measurements were conducted in weekly intervals initially (n=55), 2-week intervals were regarded as sufficient thereafter due to limited changes in QUS values within the shorter period. Infants with a birth weight below 1500 g were followed during outpatient visits until up to 17 months of age. RESULT: The intra-individual day-to-day reproducibility was 0.62%. QUS-values from the first week of life correlated significantly with gestational age and birth weight (r=0.5 and r=0.6; P<0.001). Small-for-gestational-age infants showed lower values for QUS than appropriate-for-gestational-age infants allowing for their gestational age. Follow-up measurements correlated positively with age and weight during the week of measurement (r=0.2 and r=0.4; P=0.001). Comparing bone quality at 40 weeks of age in infants born at term versus infants born at 24 to 28 weeks, preterm infants showed significantly lower QUS than term infants (P<.0001).There was a significant correlation of QUS with serum alkaline phosphatase (P=0.003), the supplementation with calcium, phosphate and vitamin D (P< 0.001 each), as well as risk factors for a reduced bone mineralization. No correlation was found between QUS and calcium or phosphate concentration in serum or urine. CONCLUSION: QUS is a highly reproducible, easily applicable and radiation-free technique that can be used to monitor bone quality in individual newborns. Further prospective randomized-trials are necessary to evaluate, if therapeutic interventions based on QUS are able to prevent osteopenia of prematurity.


Assuntos
Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Cálcio , Recém-Nascido , Recém-Nascido Prematuro , Fósforo , Peso ao Nascer , Desenvolvimento Ósseo , Cálcio/sangue , Cálcio/urina , Suplementos Nutricionais , Feminino , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Terapia Intensiva Neonatal , Análise Multivariada , Fósforo/sangue , Fósforo/urina , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , Ultrassonografia
18.
Geburtshilfe Frauenheilkd ; 72(3): 215-224, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26640286

RESUMO

Advances in research have a highly influential role to play in the strategy of early detection, treatment and aftercare of breast cancer and therefore everyday clinical practice. Newly-defined prognosis factors and a new form of molecular subtype classification, for example, are intended to help identify patients who will actually benefit from chemotherapy. In the field of neoadjuvant chemotherapy, the inclusion of the angiogenesis inhibitor Bevacizumab and dual antiHER2 therapy is being discussed. What's more, where defined criteria are met, even with positive sentinel lymph nodes, axillary dissection is not performed; besides bisphosphonates RANKL antibody Denosumab is now an option in the treatment of bone metastases.

19.
Anticancer Res ; 31(9): 2749-55, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21868516

RESUMO

BACKGROUND: The prognostic significance of disseminated tumor cells from bone marrow (BM-DTCs) of breast cancer patients has been demonstrated previously. In this study, data of a standardized long term follow-up of 829 patients with examination of BM-DTCs at primary diagnosis are presented. PATIENTS AND METHODS: BM aspiration and immunocytochemical examination of DTCs was performed according to a standardized protocol. Follow-up data of all patients were adjusted with the cancer registries of southern Bavaria. RESULTS: A total of 268 patients (32%) had BM-DTCs with a median of 2 (1-1223)/2 x 106 cells. Positive BM findings correlated with tumor size (p=0.032), but not with other histopathological parameters. After a median follow-up of 73 months, BM-DTCs were highly relevant for the development of distant metastases (p=0.006) and, beneath standard histological parameters, reduced overall survival (p=0.038). CONCLUSION: These results confirm the prognostic relevance of the detection of BM-DTCs. Newer methods, such as detection of circulating tumor cells in blood, will have to demonstrate comparable prognostic information in the future.


Assuntos
Medula Óssea/patologia , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Prognóstico
20.
Anticancer Res ; 30(11): 4563-6, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21115906

RESUMO

BACKGROUND: Inhibins are dimeric glycoproteins, composed of an alpha-subunit (INH-α) and one of two possible beta-subunits (ßA or ßB), with substantial roles in human reproduction and in endocrine-responsive tumours. Aims of this study were to determine the serological measurement of inhibin A (α-ßA) in breast cancer patients during chemotherapy. PATIENTS AND METHODS: A series of 30 breast cancer patients who underwent standardised chemotherapy were prospectively evaluated before chemotherapeutic treatment as well as four weeks after chemotherapy and two years after chemotherapy for the serological expression of inhibin A. For statistical analysis the Wilcoxon rank sum test was used for paired samples. Statistical significance was assumed at p<0.05. RESULTS: The concentration of inhibin A showed a significant decrease between data obtained before chemotherapy and after chemotherapy (p<0.005) and two-year follow-up (p<0.001). Interestingly, there were no differences in inhibin A concentrations between the four-week and two-year follow-up (p=0.744). DISCUSSION: Chemotherapy significantly decreases inhibin A concentration during chemotherapy. This might reflect a suppression of ovarian function, being also a marker for chemotherapy-induced amenorrhoea. Moreover, it has been suggested that inhibin A might be a tumour marker for breast cancer, and therefore a sudden increase in its concentration might be indicative of breast cancer recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Inibinas/sangue , Quimioterapia Adjuvante , Ciclofosfamida/uso terapêutico , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Estudos Prospectivos
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