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

Somlo, George; Simpson, Jean F.; Frankel, Paul; Chow, Warren; Leong, Lucille; Margolin, Kim; Morgan, Robert J.; Raschko, James; Shibata, Stephen; Forman, Stephen J.; Kogut, Neil; McNamara, M.; Molina, Arturo; Somlo, Elek; Doroshow, James H.

doi:10.1038/sj.bjc.6600450

Cited by 28 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The result of the prognostic effect of p53 seems to be in contradiction to results in the literature, where usually either no prognostic effect of p53 is reported (8) or patients with p53-positive tumors show a worse prognosis than patients with p53-negative tumors (16,28). An explanation for this result may be the scoring of p53 positivity in our study.…”

Section: Resultscontrasting

confidence: 93%

Prognostic and Predictive Effects of Immunohistochemical Factors in High-Risk Primary Breast Cancer Patients

Kröger

Milde‐Langosch²,

Riethdorf

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: To analyze prognostic and predictive effects of immunohistochemical factors within a randomized study of high-dose versus standard-dose chemotherapy in high-risk breast cancer with >10 involved lymph nodes.Experimental Design: Histopathologic specimens in 188 of 302 patients were analyzed for Ki-67, p16, maspin, Bcl-2, Her2/neu, and p53. Results: In a univariate analysis after adjustment for therapy, tumor size, and estrogen receptor, Her2/neu positivity (P = 0.001) was a negative and Bcl2 positivity (P = 0.003) was a positive prognostic factor for event-free survival. In a multivariate analysis, Her2/neu positivity (hazard ratio, 3.68; 95% confidence interval, 2.01-6.73; P = 0.0001) had a negative influence on eventfree survival, whereas p53 positivity (hazard ratio, 0.57; 95% confidence interval, 0.34-0.95; P = 0.03) and Bcl2 positivity (hazard ratio, 0.35; 95 % confidence interval, 0.19-0.64; P = 0.0006) were associated with a better event-free survival. Analyzing the predictive effect of the immunohistochemical factors, an interaction between p53 and treatment could be shown (P = 0.005). The hazard ratio for high-dose chemotherapy versus standard chemotherapy is estimated as 2.3 (95% confidence interval, 0.67-7.92) in p53-negative patients and as 0.46 (95% confidence interval, 0.2-1.07) in p53-positive patients, which indicates a superiority of high-dose chemotherapy in p53-positive patients and an inferiority in p53-negative patients. No interactive effect could be shown for the other factors. Conclusions: Her2/neu and Bcl-2 are prognostic but not predictive factors in patients with high-risk primary breast cancer; p53-positive patients might benefit more from high-dose chemotherapy than from standard chemotherapy, and p53-negative patients might benefit more from standard chemotherapy than from high-dose therapy.

show abstract

Section: Resultscontrasting

confidence: 93%

Prognostic and Predictive Effects of Immunohistochemical Factors in High-Risk Primary Breast Cancer Patients

Kröger

Milde‐Langosch²,

Riethdorf

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Our data are consistent with previous long- term reports (13)(14)(15) and suggest that the activity of HDC in HRPBC is sustained over time.…”

Section: Discussionsupporting

confidence: 93%

“…Damon et al (14) reported 53% RFS and 65% OS rates at median FU of 6.9 years in 80 patients with Ն10 ϩ nodes treated with high-dose cyclophosphamide/ thiotepa/mitoxantrone. The actuarial 7-year RFS and OS rates of 114 HRPBC patients treated at City of Hope (Duarte, CA) with two different HDC regimens were 43% and 57%, respectively (15).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Analysis and Prospective Validation of a Prognostic Model for Patients with High-Risk Primary Breast Cancer Receiving High-Dose Chemotherapy

Nieto¹,

Nawaz²,

Shpall

et al. 2004

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: We described previously a prognostic model for high-risk primary breast cancer patients receiving highdose chemotherapy (HDC). Such model included nodal ratio (no. involved nodes:no. dissected nodes), tumor size, hormone receptors, and HER2. In the present study we intended to test this model prospectively in a second patient cohort. In addition, we analyzed the long-term overall outcome of our HDC trials.Experimental Design: We analyzed all 264 patients enrolled since 1990 in our prospective trials for 4 -9؉, >10؉ nodes, or inflammatory disease. Patients of the second cohort (treated since 1997) had their prognostic score estimated prospectively before receiving HDC.Results: Fourteen patients (5.3%) died from HDCrelated complications. At median follow-up of 7.1 years, relapse-free survival and overall survival of the whole group were 69.8% and 73%, respectively. Median time to relapse was 14 months (63.5% relapses within the first 2 years, 6.7% after year 5). The model was validated in the second cohort, establishing the following pretransplant risk categories: low risk (low score, HER2؊), 44% patients, 87% freedom from relapse (FFR); intermediate risk (low score, HER2؉), 29% patients, 68% FFR; and high risk (high score, any HER2), 27% patients, 49% FFR.Conclusions: Few relapses are seen after year 5 of follow-up, which indicates the need for mature results of the randomized trials before their final interpretation or metaanalysis. Our prospectively validated prognostic model, if additionally confirmed in the randomized trial populations, may provide an insight into the relative benefit of HDC in different risk patient subsets.

show abstract

“…Factors that are present in ER -cells that enhance proliferation or inhibit apoptosis may favor replication competent viral vectors. Because ER -negativity may be associated with a poor prognosis following other forms of adjuvant therapy (30), oncolytic viral therapy holds promise in such a clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer

et al. 2006

View full text Add to dashboard Cite

Abstract. Oncolytic herpes simplex virus-1 (HSV-1) mutants selectively replicate in and lyse tumor cells. Viral replication is dependent on the cellular proliferative mechanism. Estrogen increases cellular proliferation and decreases apoptosis in estrogen receptor-positive (ER + ) human breast cancer cells. We hypothesize that the cellular changes produced by estrogen may enhance oncolytic viral replication and improve the treatment of ER + breast cancer cells. Estrogen increased proliferation and replication of the HSV-1 mutant, NV1066, in ER + breast cancer cells. Additionally, cells grown with estrogen had lower rates of apoptosis and higher bcl-2 levels at baseline and after infection. Estrogen enhanced the oncolytic effect of NV1066, with cell kills of 95% and 97% at MOIs of 0.1 and 0.5, compared to 53 and 87% respectively without estrogen (p<0.001). Therapy of ER + human breast cancer cells with a replication-competent HSV-1 mutant is improved in the presence of estrogen, in contrast to more standard therapies, such as chemotherapy and radiation, which demonstrate decreased efficacy in similar conditions. These data provide the mechanistic basis for the use of oncolytic HSV-1 in patients with hormone receptor-positive breast cancer, particularly if the disease progresses with conventional therapies.

show abstract

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

Cited by 28 publications

References 30 publications

Prognostic and Predictive Effects of Immunohistochemical Factors in High-Risk Primary Breast Cancer Patients

Prognostic and Predictive Effects of Immunohistochemical Factors in High-Risk Primary Breast Cancer Patients

Long-Term Analysis and Prospective Validation of a Prognostic Model for Patients with High-Risk Primary Breast Cancer Receiving High-Dose Chemotherapy

Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer

Contact Info

Product

Resources

About