Evaluation of the Predictive Value of Her-2/neu Overexpression and p53 Mutations in High-Risk Primary Breast Cancer Patients Treated With High-Dose Chemotherapy and Autologous Stem-Cell Transplantation

Nieto, Yago; Cagnoni, Pablo J.; Nawaz, Samia; Shpall, Elizabeth J.; Yerushalmi, Ronit; Cook, Bret; Russell, Peggy; McDermit, Janet; Murphy, James R.; Bearman, Scott I.; Jones, Roy B.

doi:10.1200/jco.2000.18.10.2070

Cited by 61 publications

(54 citation statements)

References 36 publications

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“…Nieto et al (1999) generated a predictive model based on tumour size, receptor status, and axillary nodal ratio; later they found HER2/neu overexpression (using monoclonal CB11 antibody-staining) as an additional independent predictor of RFS and OS primarily in an otherwise 'favourable' group of patients (Nieto et al, 2000). Using a polyclonal antibody-directed immunohistochemical stain the incidence of HER2/neu positive staining in our HRBC population was very similar to that reported in patients with stage II breast cancer (Thor et al, 1998) and to the selected, high risk population reported by Bitran et al (1996), although slightly lower then in the series by Nieto et al (1999). Since there is wide variation in the type and specificity of available antibodies and retrieving techniques, and the clinical significance of utilizing one antibody vs another is unclear (Ravdin et al, 1998), the predictive value of HER-2/neu amplification for choosing the optimal adjuvant therapy needs further validation.…”

Section: Discussionmentioning

confidence: 99%

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Predictors of long-term outcome following high-dose chemotherapy in high-risk primary breast cancer

et al. 2002

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We report on a predictive model of long-term outcome in 114 high-risk breast cancer patients treated with high-dose chemotherapy between 1989 and 1994. Paraffin-blocks from 90 of the 114 primaries were assessed for the presence of five risk factors: grade, mitotic index, protein expression of p53, HER2/neu, and oestrogen/progesterone receptor status; we could analyse the effect of risk factors in 84 of these 90 tumours. Seven-year relapse-free and overall survival was 58% (95% confidence interval 44 -74%) and 82% (95% confidence interval 71 -94%) vs 33% (95% confidence interval 21 -52%) and 41% (95% confidence interval 28 -60%) for patients whose primary tumours displayed 53 risk factors vs patients with 42 risk factors. For the entire group of 168 high-risk breast cancer patients, inflammatory stage IIIB disease and involved postmastectomy margins were associated with decreased relapse-free survival and overall survival; patients treated with nondoxorubicin containing standard adjuvant therapy experienced worse overall survival (RR, 2.08; 95% confidence interval 1.04 to 4.16; P=0.04), while adjuvant tamoxifen improved overall survival (RR, 0.65; 95% confidence interval 0.41 -1.01; P=0.054). Future trial designs and patient selection for studies specific for high-risk breast cancer patients should include appropriate prognostic models. Validation of such models could come from recently completed randomised, prospective trials.

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Section: Discussionmentioning

confidence: 99%

“…Better selection of patients for studies of future HDCT programmes, as well as other investigational approaches for women with HRBC, may be possible after validation of this and other (Nieto et al, 1999) prognostic models.…”

Section: Discussionmentioning

confidence: 99%

Predictors of long-term outcome following high-dose chemotherapy in high-risk primary breast cancer

et al. 2002

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“…A recent report has suggested that the axillary node ratio, defined as the number of axillary nodes involved with breast cancer divided by the absolute number of axillary nodes sampled, is an independent prognostic feature concerning transplantation outcome for this patient population. 13 We report a retrospective review of 111 women with high-risk stage II/III breast cancer with at least four positive axillary nodes undergoing autologous PBPC transplantation from 1991 to June 1999.…”

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confidence: 99%

Prognostic importance of the axillary lymph node ratio in autologous transplantation for high-risk stage II/III breast cancer

Bolwell

Andrèsen

Pohlman

et al. 2001

Bone Marrow Transplant

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Summary:The role of autologous peripheral blood progenitor cell (PBPC) transplantation for high-risk stage II/III breast cancer remains controversial. New prognostic indicators defining subsets of patients who may benefit from autologous PBPC transplantation would be clinically useful. The axillary lymph node ratio, defined by the total number of axillary nodes involved with cancer divided by the number of axillary nodes surgically sampled, has been reported to be of potential prognostic importance in transplantation for high-risk, stage II/III breast cancer. We therefore retrospectively reviewed 111 women with high-risk, stage II/III breast cancer with at least four positive axillary lymph nodes undergoing autologous PBPC transplantation from 1991 to June 1999. None of the patients had received prior radiotherapy and all had completed one, and only one, course of at least three cycles of adjuvant chemotherapy. The median number of axillary nodes sampled was 20 (range 6-40) and the median number of positive axillary nodes was 12 (range 4-35). The median node ratio, dividing the number of positive nodes by the number of sampled nodes, was 0.68. Event-free survival was strongly influenced by node ratio. Patients having a node ratio of Ͻ0.7 had a 5-year event-free survival of 68%, vs those with a node ratio of у0.7 with a 5-year event-free survival of 46% (P = 0.03). Forty percent of patients with a high node ratio have relapsed vs 20% with a low node ratio (P = 0.02). Multivariate analysis revealed that positive estrogen receptor status and a node ratio of Ͻ0.7 were independent factors related to better event-free survival (P = 0.0001 and P = 0.004, respectively). We conclude that patients having a node ratio of Ͻ0.7 have a significantly better prognosis following autologous PBPC transplantation than do patients with a ratio у0.7. Bone Marrow Transplantation (2001) 27, 843-846.

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“…Some studies have addressed prognostic factors for relapse after HDC and PBPCT. 3,20,[32][33][34][35][36][37][38][39] In the analysis by Somlo et al 37 of HRBC patients treated with two different HDC, PR negativity was the only independent prognostic factor of relapse. Nieto et al 39 described a predictive model using a scoring system that include the nodal ratio, tumor size and the ER/PR status.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of the immunocytochemical detection of contaminating tumor cells (CTC) in apheresis products of patients with high-risk breast cancer treated with high-dose chemotherapy and stem cell transplantation

Solano

Badia

Lluch

et al. 2001

Bone Marrow Transplant

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Summary:The aim of this study was to determine whether the detection of CTC in the apheresis product contribute significantly to treatment failure of patients with highrisk breast carcinoma treated with high-dose chemotherapy (HDC) and stem cell transplantation (SCT). Patients were with stage II and III adenocarcinoma of the breast with у10 axillary lymph nodes affected after primary surgery (у10 N+) who had received HDC with SCT. We analyzed retrospectively the presence of CTC as assessed by immunocytochemistry (ICC) in the apheresis products obtained after standard adjuvant chemotherapy. We compared the clinical outcome of patients who received HDC and SCT with or without CTC-positive apheresis. One hundred and twenty-seven apheresis products samples were obtained from 51 patients. Fourteen (27.4%) of these samples were CTC positive. After a median follow-up of 4.6 years, 20 patients have relapsed, 14 died from progression of their disease and 30 patients remain alive and free of progression. For the whole group of patients the 5 year probabilities of DFS and OS were 60% (IC 95%, 47-75%) and 71% (IC 95%, 55-83%), respectively. However, the 5 year probabilities of DFS were 23% (IC 95%, 0-46) and 75% (IC 95%, 60-89) for patients with CTC positive and negative, respectively. The 5 year probabilities of OS were 42% (IC 95%, 15-68) and 83% (IC 95%, 70-95) for patients with CTC positive and negative, respectively. Both univariate and multivariate analysis showed that the presence of CTC in the apheresis product was the only prognostic factor associated with a higher incidence of clinically overt disease relapse (P = 0.002) and shorter survival (P = 0.003). The presence of cytokeratin-positive metastatic cells in the apheresis product increases the risk of relapse after HDC and SCT in patients with stage II and III adeno- High-dose chemotherapy (HDC) with stem cell transplantation (STC) has been extensively used to treat women with breast cancer based on phase II studies suggesting a clinical benefit in some groups of patients with metastatic, 1-6 and high-risk breast cancer (HRBC). 7-11 However, preliminary results from most 12,13 but not all 14 phase III trials in HRBC patients, suggest no benefit for HDC over conventional treatment. Until the results from currently ongoing phase III trials determine the role of this therapy in patients with breast cancer, identification of new prognostic factors associated with an increased risk of relapse after HDC and SCT may help to define better which patients may benefit from this approach. A number of recent studies have implicated the presence of micrometastatic breast cancer cells in the bone marrow (BM) as an important and independent prognostic factor for relapse after standard chemotherapy. [15][16][17][18][19] Some studies have suggested a relation between the presence of CTC in the apheresis and relapse after HDC and SCT while other studies, mainly in patients with metastatic disease, have not been able to demonstrate such a relationship. [20][21][22] The aim of our s...

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Evaluation of the Predictive Value of Her-2/neu Overexpression and p53 Mutations in High-Risk Primary Breast Cancer Patients Treated With High-Dose Chemotherapy and Autologous Stem-Cell Transplantation

Cited by 61 publications

References 36 publications

Predictors of long-term outcome following high-dose chemotherapy in high-risk primary breast cancer

Predictors of long-term outcome following high-dose chemotherapy in high-risk primary breast cancer

Prognostic importance of the axillary lymph node ratio in autologous transplantation for high-risk stage II/III breast cancer

Prognostic significance of the immunocytochemical detection of contaminating tumor cells (CTC) in apheresis products of patients with high-risk breast cancer treated with high-dose chemotherapy and stem cell transplantation

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