Relationship of c-myc Amplification to Progression of Breast Cancer From In Situ to Invasive Tumor and Lymph Node Metastasis

Watson, Peter H.; Safneck, Janice R.; Le, Khuong; Dubik, Don; Shiu, Robert P. C.

doi:10.1093/jnci/85.11.902

Cited by 72 publications

(43 citation statements)

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“…Our data suggest that the three regions of amplification are not involved in the process by which cells acquire metastatic capacity. Our findings are in agreement with those of Watson et al (1993), who suggested that MYC gene amplification can occur at an early stage of tumour progression and does not always persist in nodal metastases. Taken together, the results of this latter study and of our own study suggest that MYC (and also ERBB2) amplification plays a major role in the development of primary breast cancer but not in the distant spread of tumour cells.…”

Section: Discussionsupporting

confidence: 93%

Classical gene amplifications in human breast cancer are not associated with distant solid metastases

Driouch

Mh²,

Beuzelin³

et al. 1997

Br J Cancer

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Summary To determine the relationship between breast cancer progression and gene amplification, we screened 62 distant metastases and 122 primary breast tumours for the amplification of the proto-oncogenes MYC and ERBB2 and the 11 ql 3 chromosomal region. Surprisingly, solid metastases showed an absence of gene amplification. These results suggest that the amplification of the proto-oncogenes MYC and ERBB2 and the 11 ql 3 chromosomal region seem to be involved mainly in the genesis of the primary breast tumour rather than its progression.Keywords: breast cancer; relapse; MYC; ERBB2, 11q13 region Breast cancer is the most common malignancy in women; one in nine Caucasian women are likely to develop breast cancer in their lifetime. Cancer progression can be divided into two major processes: primary site tumorigenesis and metastasis. Metastases are the main cause of death from cancer. Both genetic and epigenetic events may be involved in the process by which individual cells acquire the characteristics required for invasion, dissemination, survival and growth at the metastatic site. Cells have a genetically determined metastatic potential (Liotta et al, 1991). While tumorigenesis is known to involve multiple genetic alterations (Bishop, 1991), the situation is probably far more complex in the case of metastases.Breast cancer results from early and/or late mutational events. Constitutional mutations in susceptibility genes (BRCAI, BRCA2, TP53, etc.) confer a predisposition to familial breast cancer. Sporadic breast cancer occurs through an accumulation of somatic mutations, i.e. amplifications of proto-oncogenes (MYC and ERBB2) and chromosomal band 1 q13, mutations of TP53 and loss of heterozygosity (LOH) of chromosomes and chromosome arms 1, 3p, 6q, 7q, 8p, 11, 13q, 16q, 17, 18q and 22q (Bieche and Lidereau, 1995).If alterations of specific genes are associated with the invasive process, they would probably be more frequently altered in metastases than in primary tumours. Brison (1993) reviewed several studies on different primary human tumours at different stages and suggested that proto-oncogene amplifications are probably late events in tumour progression. However, it is not yet known whether specific chromosomal regions are involved in invasive breast carcinoma because of a lack of screening studies for genetic alterations in secondary events, in particular distant metastases. MATERIALS AND METHODSHere we investigated the role of genetic amplifications in the acquisition of metastatic potential by means of restriction Torloni, 1981). The tumours were mostly invasive (85%); 40% of them were grade II and 40% were grade III. A third of the tumours did not show any lymph node metastases (N-). Primary tumours and matching pleural effusions were available from 12 patients. None of the 122 patients had undergone radiation therapy or chemotherapy before primary surgery. Patients whose metastases were sampled had undergone different adjuvant therapies. The median time to diagnosis of the distant metastases after prima...

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Section: Discussionsupporting

confidence: 93%

Classical gene amplifications in human breast cancer are not associated with distant solid metastases

Driouch

Mh²,

Beuzelin³

et al. 1997

Br J Cancer

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“…Amplification data in Champeme et al (1994), Scorilas et al (1995) and Berns et al (1992) were excluded from estimation of the overall proportion, since they were originally reported in Bieche et al (1994), Scorilas et al (1993) and Berns et al (1992b), respectively. Of the 29 reports, 26 determined c-myc amplification by Southern blot, three by slot blot (Tsuda et al, 1989;Zhou et al, 1989;Borg et al, 1992), and two by polymerase chain reaction (Watson et al, 1993;Lonn et al, 1995). Two studies utilized more than one method (Zhou et al, 1989;Lonn et al, 1995).…”

Section: Results Of Citation Searchmentioning

confidence: 99%

“…However, subsequent reports containing new data on prognostic factors or survival were also incorporated into pooled analyses of the specific clinical end-points. Data from studies that used more than one method to determine the overall frequency of amplification were included separately in subgroup analyses of the individual methods (Zhou et al, 1989;Watson et al, 1993). Consideration of methodologic aspects included the sources of tissue and amplification controls, specification of the positive threshold for gene amplification, and a description of the characteristics of the study population (Trock et al, 1997).…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 99%

“…Slot blotting and PCR methods demonstrated a lower level of amplification with frequencies of 6.7% (95% CI = 0.1-14.3%) and (11.4% (95% CI = 0.4-22.4%), respectively. The two studies that employed two methods (Tsuda et al, 1989;Watson et al, 1993), Southern blotting and either slot blotting or PCR, for determining gene amplification indicated that both methods produced frequencies consistent with one another, although the individual values were not provided.…”

Section: Proportion Of C-myc-amplified Tumoursmentioning

confidence: 99%

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

et al. 2000

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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

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“…Expression of Myc proteins is deregulated in approximately one-third of human cancers through a variety of mechanisms (Cole, 1986;Kelly and Siebenlist, 1986;Spencer and Groudine, 1991). Overexpression of Myc is especially common in certain advanced cancers, such as hormone-independent adenocarcinomas of the breast and prostate, where it is associated with poor prognosis (Berns et al, 1992;Borg et al, 1992;Hehir et al, 1993;Kreipe et al, 1993;Shiu et al, 1993;Watson et al, 1993;Strohmeyer and Slamon, 1994;Bova and Isaacs, 1996;Cher et al, 1996;Jenkins et al, 1997). However, since deregulation is su cient for oncogenic activation, the involvement of Myc in late stage cancers may be even broader than suggested by these studies.…”

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confidence: 99%

Mechanisms of apoptosis by c-Myc

1999

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Relationship of c-myc Amplification to Progression of Breast Cancer From In Situ to Invasive Tumor and Lymph Node Metastasis

Abstract: These results suggest that c-myc amplification can occur at an early stage in tumor progression and that amplification does not always persist in the nodal metastasis.

Cited by 72 publications

References 0 publications

Classical gene amplifications in human breast cancer are not associated with distant solid metastases

Classical gene amplifications in human breast cancer are not associated with distant solid metastases

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

Mechanisms of apoptosis by c-Myc

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