Prognostic and Predictive Factors for Patients With Metastatic Breast Cancer Undergoing Aggressive Induction Therapy Followed by High-Dose Chemotherapy With Autologous Stem-Cell Support

Rizzieri, David A.; Vredenburgh, James J.; Jones, Roy B.; Ross, Maureen; Shpall, Elizabeth J.; Hussein, Atif M.; Broadwater, Gloria; Berry, Donald A.; Petros, William P.; Gilbert, Colleen; Affronti, Mary Lou; Coniglio, David; Rubin, Peter; Elkordy, M.; Long, Gwynn D.; Chao, Nelson J.; Peters, William P.

doi:10.1200/jco.1999.17.10.3064

Cited by 60 publications

(26 citation statements)

References 11 publications

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“…The significance of HMGI-C mRNA detection in peripheral blood, even allowing for the relatively small number of patients with metastatic breast cancer studied here, implies that this is a particularly strong prognostic factor. The multivariate analysis also showed that the presence of lung and liver metastases was significantly associated with worse outcome, which is consistent with previous studies, as is the fact that patients who were oestrogen receptor positive had significantly better overall survival (Rizzieri et al, 1999).…”

Section: Discussionsupporting

confidence: 90%

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Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

et al. 2003

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HMGI-C belongs to the high-mobility-group-protein (HMG) family of architectural transcription factors and considerable interest has recently been shown in its expression in neoplastic tissues and apparent involvement in tumorigenesis. We could previously demonstrate an expression of HMGI-C mRNA in the peripheral blood of breast cancer patients for the first time. In this prospective study, we evaluated the independent prognostic power of HMGI-C mRNA expression in the peripheral blood of an unselected cohort of 69 patients with metastatic breast cancer using a hemi-nested reverse transcriptase polymerase chain reaction (RT -PCR) followed by sequence analysis of the resulting PCR products. Multivariate analysis was performed using the Cox regression model. HMGI-C mRNA was detected in peripheral blood from 21 out of 69 (30%) patients with metastatic breast cancer. Median survival was 15.9 months in patients expressing HMGI-C, while in the group of patients without HMGI-C expression the median survival had not been reached yet after a median follow-up of 24.7 months and 85.4% were still alive in this group. Disease-specific survival was significantly worse for patients positive for HMGI-C in comparison to those not expressing HMGI-C (P ¼ 0.0001). In a multivariate regression analysis, HMGI-C remained an independent prognostic factor for overall survival (P ¼ 0.001) besides oestrogen receptor status (P ¼ 0.024) and presence of metastases in liver and lungs (P ¼ 0.029). HMGI-C expression in the peripheral blood of patients with metastatic breast cancer is a powerful independent indicator for poor overall survival and this is the first study to demonstrate its prognostic relevance in univariate and multivariate analysis.

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Section: Discussionsupporting

confidence: 90%

“…One area of intense breast cancer research has been in assessing prognostic factors of patient outcomes, and several molecular markers have been evaluated in association with established histologic and clinical prognostic parameters of breast cancer (Honkoop et al, 1998;Rizzieri et al, 1999;Sabbatini et al, 2000;Silva et al, 2001).…”

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confidence: 99%

Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

et al. 2003

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“…Other trials of a single cycle of HDC have reported much higher conversion rates, ranging between 20 and 60%. [30][31][32] The low conversion rate observed following the first cycle of HDC in our trial may be explained in part by the chemotherapy agents used (CEP) and the relatively short interval (3 weeks) between treatment and the response assessment. 33 The value of HDC in the setting of metastatic breast cancer remains controversial and may in fact be limited, as noted in the ABMTR analysis, to specific patient subsets.…”

Section: Discussionmentioning

confidence: 95%

Effect of induction chemotherapy and tandem cycles of high-dose chemotherapy on outcomes in autologous stem cell transplant for metastatic breast cancer

Pecora

Lazarus

Stadtmauer

et al. 2001

Bone Marrow Transplant

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Summary:We assessed the effect standard-dose induction chemotherapy and tandem cycles of high-dose chemotherapy (HDC) have on outcomes in metastatic breast cancer. One hundred and one women with metastatic breast cancer were enrolled in two non-randomized phase II studies. The first group of 64 patients (induction group) received four cycles of docetaxel 75 mg/m 2 and doxorubicin 50 mg/m 2 . The next 37 patients did not receive induction (no induction group). Both groups received two (tandem) cycles of HDC. Blood-derived stem cells were collected after the first HDC cycle, processed using CD34 + cell selection and then reinfused after the second HDC cycle. Outcomes were compared between the two groups and also to patients participating in the Philadelphia (inter-group) randomized metastatic breast cancer transplant trial (PBT-01). Intent-to-treat analysis revealed no significant differences in complete response rates (37.5% vs 27%; P = 0.20), overall response (75% vs 71%), median progression free survival (PFS) (11.9 vs 8 months; P = 0.24) and overall survival (OS) (Ͼ36 vs 25 months; P = 0.16), in the induction vs no induction groups, respectively. Adjusting for differences in known baseline characteristics, induction group patients were found to have significantly longer PFS (P = 0.002), OS (P = 0.01) and more frequent conversion from a partial to complete response (58% vs р13%, P р 0.0002) when compared with PBT-01 patients. Induction chemotherapy administered prior to tandem cycles of HDC does not appear to adversely affect outcomes in metastatic breast cancer patients. Outcomes in our induction group also compare favorably with those observed in PBT-01 and warrant further clinical investigation. Chemotherapy agents administered to patients with metastatic breast cancer in standard doses, alone or in combination, result in a low complete response rate (CR) (8-20%), short response duration (median 5-14 months) and limited overall survival (median 14-24 months). 1-3 Several pilot phase II trials using high-dose chemotherapy (HDC) supported by autologous hematopoietic stem cell transplantation appeared to result in superior outcomes, including a greater than expected percentage of patients who were disease-free (7-18%) after 5 years of follow-up. 4,5 However, results from the Philadelphia bone marrow transplant group (inter-group) phase III randomized trial (PBT-01) support the contention that patient selection bias, and not the efficacy of HDC, results in the apparent outcome advantage observed in patients with advanced breast cancer enrolled in HDC trials. [6][7][8][9] In PBT-01, a single cycle of HDC with unpurged stem cell rescue failed to improve survival over standard-dose therapy. This outcome, however, may have been a consequence of several factors. Reports of 2-year disease-free survival rates approaching 60% in two phase II trials of multiple cycles of HDC administered in rapid succession to patients with metastatic breast cancer indicate that one cycle of HDC may not be optimal. 10,11 The superiority ...

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“…It is of note that extent of disease (number of metastatic site and visceral involvement) did not differ between HDC candidates and non-candidates, and was not included in the prognostic analyses. Adverse prognostic factors for patients entering HDC trials include previous adjuvant chemotherapy, liver metastases, extensive metastatic disease and chemoresistant disease (Ayash et al, 1995;Rizzieri et al, 1999;Rowlings et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study

Cottu

Espié

et al. 2001

Br J Cancer

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SummaryThe aim of this study was to evaluate the feasibility of a high-dose intensity and high-dose density multicycle epirubicin and cyclophosphamide regimen with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to September 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) received 205 courses of cyclophosphamide 3 g m -2 and epirubicin 100 mg m -2 every 14 days. G-CSF 5 µg kg -1 day -1 was administered from day 3 to neutrophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, with ≥ 2 × 10 6 CD34+ PBSC kg -1 required for each reinfusion. 48 patients (86%) received all 4 planned courses. Early withdrawal was consecutive to infectious complications (n = 4), severe asthenia (n = 3), haemorrhagic cystitis (n = 1). A median number of 10.8 × 10 6 CD34+ PBSC kg -1 (range, 3-80) was harvested with 1 or 2 apheresis in 48 patients (94%). Median relative dose intensity was 91.3% (range, 72-102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (median duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Objective response rate was 69% in stage IV patients (31/45 evaluable pts), with a 16% complete response rate. Their median progression-free and overall survivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-related progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate its real benefit.

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Prognostic and Predictive Factors for Patients With Metastatic Breast Cancer Undergoing Aggressive Induction Therapy Followed by High-Dose Chemotherapy With Autologous Stem-Cell Support

Abstract: The chance for long-term remission with induction therapy with AFM and high-dose chemotherapy is increased for hormone receptor positive-patients with nonvisceral metastases who have not received prior adjuvant chemotherapy and have long disease-free intervals.

Cited by 60 publications

References 11 publications

Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

Effect of induction chemotherapy and tandem cycles of high-dose chemotherapy on outcomes in autologous stem cell transplant for metastatic breast cancer

High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study

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