Skip to main content
SpringerLink
Log in

Correlation of allelic loss with poor postoperative survival in breast cancer

  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Background

Allelic losses of tumor suppressor genes or the chromosomal regions harboring them in the DNA of tumor cells may become useful postoperative prognostic indicators.

Methods

To examine whether specific allelic losses correlate with postoperative survival in a five-year prospective follow-up, we tested tumors from a cohort of 504 breast cancer patients for allelic loss of 18 microsatellite markers representing either known tumor suppressor genes or regions where genetic alterations are frequent in breast tumors.

Results

Patients with allelic loss at 1 p34, 3p25, 8p22, 13q12, 17pl3.3, or 17q21.1 had a significantly higher risks of postoperative mortality compared with those whose tumors retained both alleles at those loci (at lp34, the 5-year mortality rate was 23% among patients with loss vs 10% with retention, p=0.0100; at 3p25, 22% vs 9%, p=0.0014; at 8p22, 24% vs 7%, p=0.0177; at 13ql2, 19% vs 8%, p=0.0093; at 17pl3.3, 19% vs 9%, p=0.0078; and at 1 Zq21.1, 17% vs 10%, p= 0.0475).

Conclusion

Allelic losses at these loci can serve as negative prognostic indicators to guide postoperative management, especially in the selection of those who will benefit from intensive adjuvant therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

LOH:

Loss of heterozygosity

References

  1. Callahan R, Campbell G: Mutations in human breast cancer; An overview.J Natl Cancer Inst 81:1780–1786, 1989.

    Article  PubMed  CAS  Google Scholar 

  2. Knudson AG: Anti-oncogenes and human cancer.Proc Natl Acad Sci USA 90:10914–10921, 1993.

    Article  PubMed  CAS  Google Scholar 

  3. Harris JR, Henderson IC: Staging and prognostic factors. In: Harris JR ed, Breast Diseases, pp327-346, Philadelphia, 1987.

  4. McGuire W, Clark G: Prognostic factors and treatment decision in axillary node-negative breast cancers.N Engl J Med 326:1756–1761, 1992.

    PubMed  CAS  Google Scholar 

  5. Sato T, Tanigami A, Yamakawa K,et al: Allelotype of breast cancer; Cumulative allele losses promote tumor progression in primary breast cancer.Cancer Res 50:7184–7189, 1990.

    PubMed  CAS  Google Scholar 

  6. Sato T, Akiyama F, Sakamoto G,et al: Accumulation of genetic alterations and progression of primary breast cancer.Cancer Res 51:5794–5799, 1991.

    PubMed  CAS  Google Scholar 

  7. Takita K, Sato T, Miyagi M,et al: Correlation of loss of alleles on the short Arms of chromosomes 11 and 17 with metastasis of primary breast cancer to lymph nodes.Cancer Res 52:3914–3917, 1992.

    PubMed  CAS  Google Scholar 

  8. Saito H, Inazawa J, Saito S,et al: Detailed deletion mapping of chromosome 17q in ovarian and breast cancers; 2-cM region on 17q21.3 often and commonly deleted in tumors.Cancer Res 53:3382–3385, 1993.

    PubMed  CAS  Google Scholar 

  9. Harada Y, Katagiri T, Ito I,et al: Genetic studies of 457 breast cancers; Clinicopathologic parameters compared with genetic alterations.Cancer 74:2281–2286, 1994.

    Article  PubMed  CAS  Google Scholar 

  10. Ito I, Yoshimoto M, Iwase T,et al: Association of genetic alterations on chromosome 17 and loss of hormone receptors in breast cancer.Br J Cancer 71:438441, 1995.

    Google Scholar 

  11. Tsukamoto K, Ito N, Yoshimoto M,et al: Two distinct commonly deleted regions on chromosome 13q suggest involvement of BRCA2 and retinoblastoma genes in sporadic breast carcinomas.Cancer 78:1929–1934, 1996.

    Article  PubMed  CAS  Google Scholar 

  12. Tsukamoto K, Ito N, Yoshimoto M,et al: Allelic loss on chromosome lp is associated with progression and lymph node metastasis of primary breast carcinoma.Cancer 82:317–322, 1998.

    Article  PubMed  CAS  Google Scholar 

  13. Iida A, Isobe R, Yoshimoto M,et al: Localization of a breast cancer tumor-suppressor gene to a 3-cM interval within chromosomal region 16p22.Br J Cancer 75:264–267, 1997.

    PubMed  CAS  Google Scholar 

  14. Iida A, Kurose K, Isobe R,et al: Mapping of a new target region of allelic loss to a 2-cM interval at 22ql3.1 in primary breast cancer.Genes Chrom Cancer 21:108–112, 1998.

    Article  PubMed  CAS  Google Scholar 

  15. Matsumoto S, Kasumi F, Sakamoto G,et al: Detailed deletion mapping of chromosome arm 3p in breast cancer; A 2-cM region on 3pl4.3-21.1 and a 5-cM region on 3p24.3-25.1 commonly deleted in tumors.Genes Chrom Cancer 20:1–7, 1997.

    Article  Google Scholar 

  16. Yokota T, Matsumoto S, Yoshimoto M,et al: Mapping of a breast cancer tumor suppressor gene locus to a 4-cM interval on chromosome 18q21.Jpn J Cancer Res 88:959–964, 1997.

    PubMed  CAS  Google Scholar 

  17. Nakata T, Yoshimoto M, Kasumi F,et al: Identification of a new commonly deleted region within a 2-cM interval of l1pll in breast cancers.Eur J Cancer 34:417–421, 1998.

    Article  PubMed  CAS  Google Scholar 

  18. Japanese Breast Cancer Society: The general rules for clinical and pathological recording of breast cancer.Jpn J Surg 19:612–632, 1989.

    Article  Google Scholar 

  19. Dib C, Faure S, Fizames C: A comprehensive gene-tic map of the human genome based on 5,264 microsatellites.Nature 380:152–154, 1996.

    Article  PubMed  CAS  Google Scholar 

  20. Slamon DJ, Clark GM, Wong SG,et al: Human breast cancer; Correlation of relapse and survival with amplification of the HER-2/neu oncogene.Science 235:177–182, 1987.

    Article  PubMed  CAS  Google Scholar 

  21. Varley JM, Swallow JE, Brammar WJ,et al: Alterations to either c-erbB2 or c-myc proto-oncogenes in breast carcinoma correlate with poor short-term prognosis.Oncogene 1:423–430, 1987.

    PubMed  CAS  Google Scholar 

  22. Borg A, Tandon AK, Sigurdsson H,et al: HER-2/new amplification predicts poor survival in node-positive breast cancer.Cancer Res 50:4332–4337, 1990.

    PubMed  CAS  Google Scholar 

  23. Berns EM, Klijn JGM, Van Staveren IL,et al: Prevalence of amplification of the oncogenes c-myc, HER2/neu, and int-2 in one thousand human breast tumours; Correlation with steroid receptors.Eur J Cancer 213:697–700, 1992.

    Article  Google Scholar 

  24. Tompson AM, Steel CM, Chetty U,et al: p53 gene mRNA expression and chromosome 17p allele loss in breast cancer.Br J Cancer 61:74–78, 1990.

    Google Scholar 

  25. Deng G, Chen LC, Schott DR,et al: Loss of heterozygosity and p53 gene mutations in breast cancer.Cancer Res 54:499–505, 1994.

    PubMed  CAS  Google Scholar 

  26. Bieche I, Champene MH, Matifas F,et al: Loss of heterozygosity on chromosome 7q and aggressive primary breast cancer.Lancet 339:139–143, 1992.

    Article  PubMed  CAS  Google Scholar 

  27. Catzavelos C, Bhattacharya N, Ung Y,et al: Decreased levels of the cell-cycle inhibitor p27-Kipl protein; Prognostic implications in primary breast cancer.Nat Med 3:227–230, 1997.

    Article  PubMed  CAS  Google Scholar 

  28. Porter P, Malone KE, Heagerty PJ,et al: Expression of cell-cycle regulators p27-kipl and cyclin E, alone and in combination, correlate with survival in young breast cancer patients.Nat Med 3:222–225, 1997.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Nippon

    Mitsuru Emi, Yoshihito Utada, Kaori Minobe & Satoshi Matsumoto

  2. Department of Surgery & Pathology, Nippon

    Masataka Yoshimoto, Futoshi Akiyama, Takuji Iwase, Goi Sakamoto & Fujio Kasumi

  3. Department of Human Genome Analysis, Cancer Institute & Hospital, Japanese Foundation for Cancer Research, Nippon

    Mitsuru Emi, Takaaki Sato & Yusuke Nakamura

  4. Department of Surgery, Daini Hospital, Tokyo Women’s Medical University, Tokyo

    Yoshihito Utada, Shunsuke Haga & Tetsuro Kajiwara

  5. Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo, Tokyo

    Yusuke Nakamura

Authors
  1. Mitsuru Emi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshihito Utada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masataka Yoshimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takaaki Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kaori Minobe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Satoshi Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Futoshi Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takuji Iwase
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shunsuke Haga
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tetsuro Kajiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Goi Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Fujio Kasumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yusuke Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Emi, M., Utada, Y., Yoshimoto, M. et al. Correlation of allelic loss with poor postoperative survival in breast cancer. Breast Cancer 6, 351–356 (1999). https://doi.org/10.1007/BF02966452

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02966452

Key words

Search

Navigation