C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance

Abstract

Data from basic research suggests that amplification of the proto-oncogene c-myc is important in breast cancer pathogenesis, but its frequency of amplification and prognostic relevance in human studies have been inconsistent. In an effort to clarify the clinical significance of c-myc amplification in breast cancer, we conducted a comprehensive literature search and a meta-analysis in which 29 studies were evaluated. The weighted average frequency of c-myc amplification in breast tumours was 15.7% (95% CI = 12.5–18.8%), although estimates in individual studies exhibited significant heterogeneity, P < 0.0001. C-myc amplification exhibited significant but weak associations with tumour grade (RR = 1.61), lymph-node metastasis (RR = 1.24), negative progesterone receptor status (RR = 1.27), and postmenopausal status (RR = 0.82). Amplification was significantly associated with risk of relapse and death, with pooled estimates RR = 2.05 (95% CI = 1.51–2.78) and RR = 1.74 (95% CI = 1.27–2.39), respectively. This effect did not appear to be merely a surrogate for other prognostic factors. These results suggest that c-myc amplification is relatively common in breast cancer and may provide independent prognostic information. More rigorous studies with consistent methodology are required to validate this association, and to investigate its potential as a molecular predictor of specific therapy response. © 2000 Cancer Research Campaign http://www.bjcancer.com

C‐myc gene expression alone is sufficient to confer resistance to antiestrogen in human breast cancer cells

“…19 The regulator plasmid, pUHD17-1neo (GenBank accession number U89930; pTet-On), expresses the reverse tetracycline transactivator (rtTA), a fusion protein of the mutated form of the tetracycline repressor ligated to the VP16 activation domain of the herpes simplex virus. Plasmid pUHD10-3 (GenBank accession number U89931; pTRE), contains seven copies of tetracycline operator sequences (tetO 7 ) upstream of a minimal human CMV promoter. The plasmid pUHD10-3 was modified by inserting an EcoRI c-myc cDNA fragment from pBS0/ 1myc 20 in the EcoRI site of pUHD10-3 resulting in pUHD10-3myc.…”

“…20 In addition, plasmid pUHD10-3myc contains additional SV40 poly(A) sequences 3Ј to the c-myc cDNA. Plasmid pUHC13-3 contains the luciferase gene under the control of the same tetracycline-controlled promoter (tetO 7 ) as in pUHD10-3. 19 Plasmid pCEP4 (Invitrogen Corp., Carlsbad, CA) provided resistance against hygromycin B. Plasmids pVZ1/ p21Max and pGL2M4, were gifts of Dr. R. Eisenman; the latter consists of 4 repeats of the E-box sequence (CACGTG) located proximal to a minimal SV40 promoter driving the expression of the luciferase gene.…”

“…5,6 A meta-analysis of 29 studies has revealed that, on average, 15.5% of breast cancer biopsies demonstrate c-myc gene amplification of 3-fold or greater. 6,7 Many, but not all, studies have found that c-myc amplification is significantly associated with tumour grade, lymph-node metastasis, negative estrogen and progesterone receptor status, risk of relapse, high S-phase fraction and amplification of c-erbB-2. 6 Using real-time RT-PCR, Bieche et al 8 reported that c-myc is over expressed in 22% of breast tumors (n ϭ 134), with levels 3.2-to 19-times that of normal breast tissue.…”

Frequent amplification and overexpression of CCND1 in male breast cancer

“…6,8,9 Moreover, the ERBB2 oncogene has recently received attention as a target for antibody-based therapy. 7 MBC is a rare disease representing only 1% of all breast cancer cases, but does have clinical importance especially in families with BRCA2 mutations where 11% of breast carcinomas occur in men.…”

“…MYC is amplified in 15% of FBC and the amplification has been associated with poor prognosis and development of lymph node metastases. 8 CCND1, a critical factor involved in cell cycle progression, is amplified in 5-23% of FBC and associates with increased risk of relapse and decreased survival. 9 Besides these known oncogene loci, genome-wide screening by comparative genomic hybridization has revealed several chromosomal regions that frequently show increased copy number in FBC.…”