Skip to main content
SpringerLink
Log in

MMP-2 positivity and age less than 40 years increases the risk for recurrence in premenopausal patients with node-positive breast carcinoma

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Node-positive breast carcinoma is associated with a poor prognosis. Some patients benefit from adjuvant chemotherapy but new treatment modalities should still be developed in order to further increase the cure rate in this patient group. Prognostic factors are needed to define patients for such studies. Here, the prognostic value of matrix metalloproteinase-2 (MMP-2) and age was evaluated in 108 premenopausal, node-positive breast carcinoma patients treated with an adjuvant chemotherapy. Expression of MMP-2 protein was studied in paraffin-embedded tissue sections from primary tumors by using specific MMP-2 monoclonal antibody in an immunohistochemical staining. Age less than 40 years predicted 5-year recurrence free survival (RFS) as unfavorable, being 74% in patients 41–49 years of age and 54% in those under age 40 (p=0.02). The 5-year RFS rate was 85% in patients with an MMP-2 negative primary tumor while it was 65% in the MMP-2 positive patient group. This difference was not, however, statistically significant (p=0.07). Correlation between hematogenous metastasis and MMP-2 positivity in breast carcinoma was demonstrated for the first time (p=0.03). A risk group for a relapse was identified using MMP-2 immunohistochemistry and age. The RFS rate in patients less than 40 years with an MMP-2 positive primary tumor was only 50% while it was 74% in other premenopausal patients (p=0.007). Young age and MMP-2 positivity may, thus, associate with early relapse in node-positive breast carcinoma.

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

References

  1. Cody HS: The impact of mammography in 1096 consecutive patients with breast cancer, 1979- 1993. Equal value for patients younger and older than 50 years. Cancer 76: 1579–1584, 1995

    Google Scholar 

  2. Valero V, Buzdar A, Hortobagyi G: Locally advanced breast cancer. Oncologist 1: 8–17, 1996

    Google Scholar 

  3. Mouridsen HT, Rose C, Brincker H: Adjuvant systemic therapy in high-risk breast cancer. The Danish Breast Cancer Cooperative Group's trials of cyclophosphamide or CMF in premenopausal and tamoxifen in postmenopausal patients. In: Senn HJ, (ed) Recent Results in Cancer Research, Adjuvant Chemotherapy of Breast Cancer. Heidelberg, Springer, 1984

  4. Stetler-Stevenson WG, Liotta LA, Kleiner DE Jr: Extracellular matrix; Role of matrix metalloproteinase in tumour invasion and metastasis. FASEB J 7: 1434–1441, 1993

    Google Scholar 

  5. Höyhtyä M, Fridman R, Komareck D, Porter-Jordan K, StetlerStevenson WG, Liotta LA, Liang C-M: Immunohistochemical localization of matrix metailoproteinase 2 and its specific inhibitor TIMP-2 in neoplastic tissue with monoclonal antibodies. Int J Cancer 54: 500–505, 1994

    Google Scholar 

  6. Tryggvason K, Höyhtyä M, Pyke C: Type IV collagenases in invasive tumours. Breast Cancer Res Treat 24: 209–218, 1993

    Google Scholar 

  7. Monteagudo C, Merino MJ, San-Juan J, Liotta LA, Stetler-Stevenson WG: Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol 136: 585–592, 1990

    Google Scholar 

  8. Davies B, Miles DW, Happerfield LC, Naylor MS, Bobrow LG, Rubens RD, Balkwill FR: Activity of type IV collagenases in benign and malignant breast disease. Br J Cancer 67: 1126–1131, 1993

    Google Scholar 

  9. Visscher DW, Höyhtyä M, Ottosen SK, Liang C-M, Sarka FH, Crissman JD: Enhanced expression of tissue inhibitor of metalloproteinase-2 ( TIMP-2 ) in stroma of breast carcinomas correlates with tumour recurrence. Int J Cancer 59: 339–344, 1994

    Google Scholar 

  10. Daidone MG, Silvestrini R, D'Errico A, Di Fronzo C, Benini E, Mancini AM, Garbisa S, Liotta LA, Grigioni WF: Laminin receptors, collagenase IV and prognosis in node-negative breast cancers. Int J Cancer 48: 529–532, 1991

    Google Scholar 

  11. Talvensaari-Mattila A, Pääkkö P, Höyhtyä M, Blanco-Sequeiros G, Turpeenniemi-Hujanen T: Matrix metalloproteinase-2 immunoreactive protein, a marker of aggressiveness in breast carcinoma. Cancer 83: 1153–1162, 1998

    Google Scholar 

  12. Hermanek P, Sobin LH, eds: UICC TNM Classification of malignant tumours. 4th ed. 2nd rev. Berlin: Springer-Verlag, 1992

    Google Scholar 

  13. Scarff RW, Torloni H: Histological typing of breast tumours. WHO: Geneva, 1986

    Google Scholar 

  14. Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer. Br J Cancer 11: 359–377, 1957

    Google Scholar 

  15. Hsu SM, Raine L, Fanger H: The use of avidin- biotinperoxidase complex (ABC) in immunoperoxidase technique: A comparison between ABC and unlabeled antiboby (PAP) procedures. J Histochem Cytochem 29: 577–580, 1981

    Google Scholar 

  16. Marqulies IMK, Höyhtyä M, Evans C, Stracke ML, Liotta LA, Stetler-Stevenson WG: Urinary type IV collagenase elevated levels are associated with bladder transitional cell carcinoma. Cancer Epidemiol Biomarkers & Prevention 467–474, 1992

  17. Autio-Harmainen H, Hurskainen T, Niskasaari K, Höyhtyä M, Tryggvason K: Simultaneous expression of 72 kilodalton type IV collagenase and type IV collagen a1(IV) chain genes by cells of early human placenta and gestational endometrium. Lab Invest 67: 191–200, 1992

    Google Scholar 

  18. Autlo-Harmainen H, Karttunen T, Hurskainen T, Höyhtyä M, Kauppila A, Tryggvason K: Expression of 72 kDa type IV collagenase in benign and malignant ovarian tumors. Lab Invest 69: 312–321, 1993

    Google Scholar 

  19. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481, 1958

    Google Scholar 

  20. Mantel N: Evaluation of survival data and two new rank order statistics arising in this consideration. Cancer Chemother Rep 50: 163–170, 1966

    Google Scholar 

  21. Nixon AJ, Neuberg D, Hayes DF, Gelman R, Connolly JL, Schitt S, Abner A, Recht A, Vicini F, Harris JR: Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer. J Clin Oncol 12: 888–894, 1994

    Google Scholar 

  22. Rochefordiere A, Asselain B, Campana F, Scholl S, Fenton J, Vilcoq JR, Durand J-C, Pouillart P, Magdelenat H, Fourquet A: Age as prognostic factor in premenopausal breast carcinoma. Lancet 341: 1039–1043, 1993

    Google Scholar 

  23. Boyages J, Recht A, Connolly JL, Schnitt SJ, Gelman R, Kooy H, Love S, Osteen RT, Cady B, Silver B, Harris JR: Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy. Radiotherapy Oncol 19: 29–41, 1990

    Google Scholar 

  24. Solin LJ, Fowble B, Schultz DJ, Goodman RL: Age as a prognostic factor for patients treated with definitive irradiation for early stage breast cancer. Int J Radiat Oncol Biol Phys 16: 373–381, 1989

    Google Scholar 

  25. Bartelink H, Borger JH, van Dongen JA, Peterse JL: The impact of tumor size and histology on local control after breast-conserving therapy. Radiotherapy Oncol 11: 297–303, 1988

    Google Scholar 

  26. Crowe JP, Gordon NH, Shenk RR, Zollinger RM, Brumberg DJ, Shuck JM: Age does not predict breast cancer outcome. Arch Surg 129: 483–488, 1994

    Google Scholar 

  27. Kini VR, White JR, Horwitz EM, Dmuchowski CF, Martinez AA, Vicini FA: Long term results with breast-conserving therapy for patients with early stage breast carcinoma in a community hospital setting. Cancer 82: 127–133, 1988

    Google Scholar 

  28. Kim SH, Simkovich-Heerdt A, Tran KN, Maclean B, Borgen PI: Women 35 years of age or younger have higher locoregional relapse rates after undergoing breast conservation therapy. J Am Coll Surg 187: 1–8, 1998

    Google Scholar 

  29. Väisänen A, Kallioinen M, Taskinen P, Turpeenniemi-Hujanen T: Prognostic value of MMP-2 immunoreactive protein (72 kD type IV collagenase) in primary skin melanoma. J Pathol 186: 51–58, 1998

    Google Scholar 

  30. Väisänen A, Tuominen H, Kallioinen M, Turpeenniemi-Hujanen T: Matrix metalloproteinase-2 (72 kD type IV collagenase) expression occurs in the early stage of human melanocytic tumour progression and may have prognostic value. J Pathol 180: 283–289, 1996

    Google Scholar 

  31. Väisänen A, Kallioinen M, von Dickhoff K, Laatikainen L, Höyhtyä M, Turpeenniemi-Hujanen T: Matrix metalloproteinase-2 (MMP-2) immunoreactive protein - a new prognostic marker in uveal melanoma? J Pathol 188: 56–62, 1999

    Google Scholar 

  32. Foidart JM: Stromal proteases in the progression of breast cancer. Bulletin et Memoires de I Academie Royale de Medecine de Belgique 152: 229–235, 1997

    Google Scholar 

  33. Polette M, Gilbert N, Stas I, Nawrocki B, Noel A, Remace A, Stetler-Stevenson WG, Birembaut P, Foidart M: Gelatinase A expression and localization in human breast cancers. An in situ hybridization study and immunohistochemical detection using confocal microscopy. Virchows Archiv 424: 641–645, 1994

    Google Scholar 

  34. Clavel C, Polette M, Doco M, Binninger I, Birembaut P: Immunolocalization of matrix metallo-proteinases and their tissue inhibitor in human mammary pathology. Bull Cancer 79: 261–270, 1992

    Google Scholar 

  35. Levy AT, Cioce V, Sobel ME, Garbisa S, Grigioni WF, Liotta LA, Stetler-Stevenson W: Increased expression of the Mr 70,000 type IV collagenase in human colonic adenocarcinoma. Cancer Res 51: 439–444, 1991

    Google Scholar 

  36. Pyke C, Ralfkiaer E, Tryggvason K, Dano K: Messenger RNA for two type IV collagenases is located in nonmalignant stromal cells in human colon cancer. Am J Pathol 142: 359–365, 1993

    Google Scholar 

  37. Poulsom R, Pignatelli M, Stetler-Stevenson WG, Liotta LA, Wright PA, Jeffery RE, Longcroft JM, Rogers L, Stamp GW: Stromal expression of 72 kda type IV collagenase (MMP-2) and TIMP-2 mRNAs in colorectal neoplasia. Am J Pathol 141: 389–396,1992

    Google Scholar 

  38. Poulsom R, Hanby AM, Pignatelli M, Jeffery RE, Longcroft JM, Rogers L, Stamp GW: Expression of gelatinase A and TIMP-2 mRNAs in desmoplastic fibroblasts in both mammary carcinomas and basal cell carcinomas of the skin. J Clin Pathol 46: 429–436, 1993

    Google Scholar 

  39. Okada A, Bellocq JP, Rouyer N, Chenard MP, Rio MC, Chambon P, Basset P: Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci 92: 2730–2734, 1995

    Google Scholar 

  40. Wolf C, Rouyer N, Lutz Y, Adida C, Loriot M, Bellocq JP, Chambon P, Basset P: Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression. Proc Natl Acad Sci 90: 1843–1847 1993

    Google Scholar 

  41. Ueno H, Nakamura H, lnoue M, Imai K, Noguchi M, Sato H, Seiki M, Okada Y: Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas. Cancer Res 57: 2055–2060, 1997

    Google Scholar 

Download references

Authors
  1. Anne Talvensaari-Mattila
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paavo Pääkkö
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taina Turpeenniemi-Hujanen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Talvensaari-Mattila, A., Pääkkö, P. & Turpeenniemi-Hujanen, T. MMP-2 positivity and age less than 40 years increases the risk for recurrence in premenopausal patients with node-positive breast carcinoma. Breast Cancer Res Treat 58, 285–291 (1999). https://doi.org/10.1023/A:1006326513176

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006326513176

Search

Navigation