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C-myc, not HER-2/neu, can predict recurrence and mortality of patients with node-negative breast cancer.

Schlotter CM, Vogt U, Bosse U, Mersch B, Wassmann K - Breast Cancer Res. (2003)

Bottom Line: On univariate analysis, c-myc-amplified NNBCs were associated with significantly shorter DFS at 36 months after the initial diagnosis (85.3% versus 97.3%).As compared with nonamplified cancers, HER-2/neu-amplified NNBCs did not exhibit any significant differences after 36 months and 95 months.However, those c-myc-amplified NNBC patients who did not receive adjuvant systemic therapy exhibited significantly shorter DFS and overall survival as compared with c-myc-nonamplified patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Frauenklinik Klinikum Ibbenbueren, Ibbenbueren, Germany. C.Schlotter@Klinikum-Ibbenbueren.de

ABSTRACT

Background: At present, node-negative, high-risk breast cancer patients cannot be identified with sufficient accuracy. Consequently, further strong prognostic factors are needed.

Methods: Among 181 node-negative breast cancer (NNBC) patients, c-myc and HER-2/neu oncogenes were identified prospectively using double differential PCR. The possible impact of amplification of those oncogenes on disease-free survival (DFS) and overall survival was examined. Furthermore, the possible effects of adjuvant therapies on rate of recurrence and mortality in oncogene-amplified NNBC patients were investigated.

Results: The prevalence rates for amplification of c-myc and HER-2/neu were 21.5% and 30.4%, respectively. On univariate analysis, c-myc-amplified NNBCs were associated with significantly shorter DFS at 36 months after the initial diagnosis (85.3% versus 97.3%). As compared with nonamplified cancers, HER-2/neu-amplified NNBCs did not exhibit any significant differences after 36 months and 95 months. Multivariate analysis indicated that c-myc amplification and tumour size, in contrast to HER-2/neu amplification, oestrogen receptor status, grading and age, were the only independent parameters for DFS. During the period of observation, we found no evidence for an impact of amplification of the oncogenes on overall survival in all cases. With respect to various adjuvant systemic therapies such as chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil; fluorouracil, epirubicin, cyclophosphamide) and endocrine therapy (tamoxifen), no significant differences were identified in oncogene-amplified NNBC patients in terms of DFS and overall survival. However, those c-myc-amplified NNBC patients who did not receive adjuvant systemic therapy exhibited significantly shorter DFS and overall survival as compared with c-myc-nonamplified patients.

Conclusion: C-myc amplification appears to be a strong prognostic marker with which to predict early recurrence in NNBC patients. C-myc-amplified NNBC patients without adjuvant systemic therapy experienced shorter DFS and overall survival.

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Related in: MedlinePlus

Classification and Regression Trees (CART) analysis of c-myc among 181 node-negative breast cancer patients. dd, double differential.
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Figure 1: Classification and Regression Trees (CART) analysis of c-myc among 181 node-negative breast cancer patients. dd, double differential.

Mentions: After tissue preparation, malignant and normal tissues were kept fresh and transported to the pathologist (U.B.). The pathologist dissected samples for assessment of oncogenes and hormone receptors. A positive receptor status was defined as the presence of more than 10 fmol/mg cytosol protein. The histopathological grading was performed according to the method of Bloom and Richardson [39]. Lymph node sections were stained with haemotoxylin and eosin; immunohistochemical investigations were not performed. The tumour tissues were stored at -70°C and the DNA was isolated using the Fast Prep System (Bio 101 Savant, Savant Instruments, Inc., Holbrook, NY, USA). Less than 200 mg (10–200 mg) tissue was homogenized using FastDNA Kit in the Fast Prep Machine. After preparing the DNA, the content was measured and the isolated DNA was stored at -20°C. General details for the double differential PCR technique, reproducibility and clinical significance were described previously [17,18,28,40]. A cutoff point of more than 2.0 average gene copy number (AGCN) was considered to be positive for HER-2/neu amplification [40]. To calculate the cutoff point for c-myc amplification, all NNBC patients were subjected to Classification and Regression Trees (CART) analysis. A cutoff value of 2.1 AGCN for c-myc oncogene led to the best distinction between patients. Fig. 1 shows the CART analysis for all c-myc values [41].


C-myc, not HER-2/neu, can predict recurrence and mortality of patients with node-negative breast cancer.

Schlotter CM, Vogt U, Bosse U, Mersch B, Wassmann K - Breast Cancer Res. (2003)

Classification and Regression Trees (CART) analysis of c-myc among 181 node-negative breast cancer patients. dd, double differential.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC154146&req=5

Figure 1: Classification and Regression Trees (CART) analysis of c-myc among 181 node-negative breast cancer patients. dd, double differential.
Mentions: After tissue preparation, malignant and normal tissues were kept fresh and transported to the pathologist (U.B.). The pathologist dissected samples for assessment of oncogenes and hormone receptors. A positive receptor status was defined as the presence of more than 10 fmol/mg cytosol protein. The histopathological grading was performed according to the method of Bloom and Richardson [39]. Lymph node sections were stained with haemotoxylin and eosin; immunohistochemical investigations were not performed. The tumour tissues were stored at -70°C and the DNA was isolated using the Fast Prep System (Bio 101 Savant, Savant Instruments, Inc., Holbrook, NY, USA). Less than 200 mg (10–200 mg) tissue was homogenized using FastDNA Kit in the Fast Prep Machine. After preparing the DNA, the content was measured and the isolated DNA was stored at -20°C. General details for the double differential PCR technique, reproducibility and clinical significance were described previously [17,18,28,40]. A cutoff point of more than 2.0 average gene copy number (AGCN) was considered to be positive for HER-2/neu amplification [40]. To calculate the cutoff point for c-myc amplification, all NNBC patients were subjected to Classification and Regression Trees (CART) analysis. A cutoff value of 2.1 AGCN for c-myc oncogene led to the best distinction between patients. Fig. 1 shows the CART analysis for all c-myc values [41].

Bottom Line: On univariate analysis, c-myc-amplified NNBCs were associated with significantly shorter DFS at 36 months after the initial diagnosis (85.3% versus 97.3%).As compared with nonamplified cancers, HER-2/neu-amplified NNBCs did not exhibit any significant differences after 36 months and 95 months.However, those c-myc-amplified NNBC patients who did not receive adjuvant systemic therapy exhibited significantly shorter DFS and overall survival as compared with c-myc-nonamplified patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Frauenklinik Klinikum Ibbenbueren, Ibbenbueren, Germany. C.Schlotter@Klinikum-Ibbenbueren.de

ABSTRACT

Background: At present, node-negative, high-risk breast cancer patients cannot be identified with sufficient accuracy. Consequently, further strong prognostic factors are needed.

Methods: Among 181 node-negative breast cancer (NNBC) patients, c-myc and HER-2/neu oncogenes were identified prospectively using double differential PCR. The possible impact of amplification of those oncogenes on disease-free survival (DFS) and overall survival was examined. Furthermore, the possible effects of adjuvant therapies on rate of recurrence and mortality in oncogene-amplified NNBC patients were investigated.

Results: The prevalence rates for amplification of c-myc and HER-2/neu were 21.5% and 30.4%, respectively. On univariate analysis, c-myc-amplified NNBCs were associated with significantly shorter DFS at 36 months after the initial diagnosis (85.3% versus 97.3%). As compared with nonamplified cancers, HER-2/neu-amplified NNBCs did not exhibit any significant differences after 36 months and 95 months. Multivariate analysis indicated that c-myc amplification and tumour size, in contrast to HER-2/neu amplification, oestrogen receptor status, grading and age, were the only independent parameters for DFS. During the period of observation, we found no evidence for an impact of amplification of the oncogenes on overall survival in all cases. With respect to various adjuvant systemic therapies such as chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil; fluorouracil, epirubicin, cyclophosphamide) and endocrine therapy (tamoxifen), no significant differences were identified in oncogene-amplified NNBC patients in terms of DFS and overall survival. However, those c-myc-amplified NNBC patients who did not receive adjuvant systemic therapy exhibited significantly shorter DFS and overall survival as compared with c-myc-nonamplified patients.

Conclusion: C-myc amplification appears to be a strong prognostic marker with which to predict early recurrence in NNBC patients. C-myc-amplified NNBC patients without adjuvant systemic therapy experienced shorter DFS and overall survival.

Show MeSH
Related in: MedlinePlus