Stem Cell Dose and Tumorbiologic Parameters as Prognostic Markers for Patients with Metastatic Breast Cancer Undergoing High-Dose Chemotherapy with Autologous Blood Stem Cell Support

Purpose: The purpose of this study was to evaluate the prognostic effect of early posttransplant lymphocyte recovery in patients with advanced breast cancer receiving highdose chemotherapy with autologous hematopoietic progenitor cell transplantation.Experimental Design: We analyzed the effect of the absolute lymphocyte count on day ؉15 posttransplant on freedom from relapse and overall survival in patients with high-risk primary breast cancer or metastatic breast cancer, enrolled between 1990 and 2001 in prospective high-dose chemotherapy trials, using a uniform regimen of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea.Results: Four hundred and seventy-six patients (264 high-risk primary breast cancer and 212 metastatic breast cancer patients) were evaluated at median follow-up of 8 years (range, 1.5-11 years). The disease-free survival and overall survival rates in the high-risk primary breast cancer group were 67% and 70%, respectively. Patients with metastatic breast cancer patients had 21.8% disease-free survival and 31.5% overall survival rates. Day ؉15 absolute lymphocyte count correlated with freedom from relapse (P ‫؍‬ 0.007) and overall survival (P ‫؍‬ 0.04) in the metastatic breast cancer group, but not in the high-risk primary breast cancer group (P ‫؍‬ 0.5 and 0.8, respectively). The prognostic effect of absolute lymphocyte count in metastatic breast cancer was restricted to those patients receiving unmanipulated peripheral blood progenitor cells (P ‫؍‬ 0.04). In contrast, absolute lymphocyte count had no significant effect in those metastatic breast cancer patients receiving bone marrow or a CD34-selected product. In multivariate analyses, the prognostic effect of day ؉15 absolute lymphocyte count in metastatic breast cancer was independent of other predictors, such as disease status, pre-high-dose chemotherapy treatment, number of tumor sites, or HER2.Conclusions: Early lymphocyte recovery is an independent outcome predictor in metastatic breast cancer patients receiving high-dose chemotherapy and an autologous peripheral blood progenitor cell transplant. These observations suggest that immune strategies targeting minimal posttransplant residual disease may prove worthwhile.

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“…Our observations contrast with previous reports (49,50). This discrepancy may be due to differences in the flow cytometric techniques.…”

Section: Discussioncontrasting

confidence: 99%

Prognostic Analysis of Early Lymphocyte Recovery in Patients with Advanced Breast Cancer Receiving High-Dose Chemotherapy with an Autologous Hematopoietic Progenitor Cell Transplant

Nieto¹,

Shpall²,

McNiece³

et al. 2004

Clinical Cancer Research

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“…Other series do not maintain the concept that the hormone receptor immunoreactivity may change after the administration of preoperative chemotherapy. In their article, Arens et al 14 compared a group of 25 patients who received neoadjuvant treatment with a control group of 30 patients who received no preoperative therapy. There were no significant differences between the biopsy specimens and the resection ones with respect to estrogen receptor expression.…”

Section: Discussion Discussion Discussion Discussionmentioning

confidence: 99%

Avaliação imunoistoquímica dos receptores de estrogênio e progesterona no câncer de mama, pré e pós-quimioterapia neoadjuvante

Pachnicki

Czeczko

Tuon

et al. 2012

Rev. Col. Bras. Cir.

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OBJETIVO: Avaliar a imunoexpressão dos receptores de estrogênio e progesterona em biópsias e peças cirúrgicas de pacientes com câncer de mama pré e pós-quimioterapia neoadjuvante e correlacionar suas alterações com o padrão de resposta à quimioterapia e diagnóstico de menopausa. MÉTODOS: Selecionaram-se 47 pacientes com diagnóstico histopatológico de carcinoma primário de mama localmente avançado. Para cada paciente existiam dois blocos: o espécime da biópsia e o da ressecção cirúrgica. A partir destes blocos foi avaliada a expressão dos receptores hormonais por imunoistoquímica com a técnica da streptoavidina-biotina-imunoperoxidase e anticorpos primários anti-RE e anti-RP. A análise estatística utilizou o teste paramétrico t de Student e o não-paramétrico exato de Fisher, com nível de significância de 5%. RESULTADOS: Das 47 pacientes, 30 apresentavam imunoexpressão positiva dos receptores hormonais. Observou-se redução significativa tanto nos níveis de receptor de estrogênio e progesterona quanto em sua imunoexpressão. Em 53,3% observaram-se mudanças nos níveis expressos de receptor de estrogênio, 56,6% em receptor de progesterona, 26,6% na imunoexpressão do receptor de estrogênio e 33,3% na imunoexpressão do receptor de progesterona. Não foi encontrada significância estatística ao correlacionar-se a influência da resposta à quimioterapia e do diagnóstico de menopausa nas pacientes com a variação na expressão dos receptores hormonais. CONCLUSÃO: A quimioterapia neoadjuvante alterou significativamente a imunoexpressão dos receptores hormonais nas pacientes da amostra, reduzindo sua positividade nas células tumorais.

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“…It can only be speculated that gains of certain DNA sequence(s) or whole chromosome(s) may lead to a tumor phenotype that is less aggressive, and the reasons for this remain unknown. The finding of Hensel et al (11), that DNA hyperdiploidy is a feature of breast cancer with superior prognosis when treated with high‐dose chemotherapy and autologous blood stem cell support, may point in the same direction. Explanations for a superior prognosis in breast cancer with gain of chromosome 11 could be a gain of tumor suppressor function or higher susceptibility of tumor cells toward apoptosis, whether spontaneous or induced by therapy.…”

Section: Discussionmentioning

confidence: 94%

FISH cytogenetics and prognosis in breast and non–small cell lung cancers

Massoner

Augustin

Duba

et al. 2004

Cytometry Part B Clinical

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Background: Interphase cytogenetics by fluorescence in situ hybridization (FISH) has been demonstrated to be a valuable diagnostic tool in effusions from patients with solid tumors. As the next step, we investigated whether certain patterns of numeric aberrations in malignant effusion cells supply prognostic information.Methods: From a large series of effusions from patients with solid tumors, 55 effusions from breast cancer and 39 effusions from non-small cell lung cancer (NSCLC) were classified as malignant by cytology or FISH. Tumor cells were classified as FISH aneuploid for chromosome 11 and/or 17 or as not aneuploid. Predominant cytogenetic anomalies and patterns of intratumor cytogenetic heterogeneity were brought in relation to overall survival rate.Results: There was no difference with respect to overall survival rate when effusions with or without aneuploidy for chromosomes 11 and 17 were compared. Likewise, in effusions with aneuploidy, there was no difference in overall survival rate among patients with different modal chromosome copy numbers (e.g., trisomy vs. tetrasomy 11) or among patients with a low or high grade of intratumor complexity (defined by the intratumor heterogeneity of FISH aneuploidy). In breast cancer, aneuploidy with gain of chromosome 11 was associated with a significantly superior survival rate, suggesting that amplification of chromosome 11 DNA is associated with a less aggressive phenotype.Conclusions: Simple chromosomal changes as determined by FISH, such as gain of chromosome 11 copy numbers in breast cancer, may be prognostic. Prospective studies in primary tumors that classify distinct prognostic groups by FISH cytogenetics are warranted.

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Stem Cell Dose and Tumorbiologic Parameters as Prognostic Markers for Patients with Metastatic Breast Cancer Undergoing High-Dose Chemotherapy with Autologous Blood Stem Cell Support

Cited by 8 publications

References 38 publications

Prognostic Analysis of Early Lymphocyte Recovery in Patients with Advanced Breast Cancer Receiving High-Dose Chemotherapy with an Autologous Hematopoietic Progenitor Cell Transplant

Prognostic Analysis of Early Lymphocyte Recovery in Patients with Advanced Breast Cancer Receiving High-Dose Chemotherapy with an Autologous Hematopoietic Progenitor Cell Transplant

Avaliação imunoistoquímica dos receptores de estrogênio e progesterona no câncer de mama, pré e pós-quimioterapia neoadjuvante

FISH cytogenetics and prognosis in breast and non–small cell lung cancers

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