Prognostic Value of Proliferation in Invasive Breast Cancer: a Review

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2004 Jun 29

PMID 15220356

Citations 122

Authors

P J van Diest

E van der Wall

J P A Baak

Affiliations

Soon will be listed here.

Abstract

Breast cancer is the leading cause of death among solid tumours in women, and its incidence is increasing in the West. Adjuvant chemotherapy and hormonal treatment improve survival but have potentially serious side effects, and are costly. Because adjuvant treatment should be given to high risk patients only, and traditional prognostic factors (lymph node status, tumour size) are insufficiently accurate, better predictors of high risk and treatment response are needed. Invasive breast cancer metastasises haematogenously very early on, so many breast cancer prognosticators are directly or indirectly related to proliferation. Although studies evaluating the role of individual proliferation regulating genes have greatly increased our knowledge of this complex process, the functional end result-cells dividing-has remained the most important prognostic factor. This article reviews the prognostic value of different proliferation assays in invasive breast cancer, and concludes that increased proliferation correlates strongly with poor prognosis, irrespective of the methodology used. Mitosis counting provides the most reproducible and independent prognostic value, and Ki67/MIB1 labelling and cyclin A index are promising alternatives that need methodological fine tuning.

Citing Articles

Identification of CKAP2 as a Potential Target for Prevention of Gastric Cancer Progression: A Multi-Omics Study.

Liu X, Zhang W, Wang H, Yang W Int J Mol Sci. 2025; 26(4).

PMID: 40004022 PMC: 11855583. DOI: 10.3390/ijms26041557.

Characterizing the evolutionary dynamics of cancer proliferation in single-cell clones with SPRINTER.

Lucas O, Ward S, Zaidi R, Bunkum A, Frankell A, Moore D Nat Genet. 2024; 57(1):103-114.

PMID: 39614124 PMC: 11735394. DOI: 10.1038/s41588-024-01989-z.

Breast cancer survival prediction using an automated mitosis detection pipeline.

Stathonikos N, Aubreville M, de Vries S, Wilm F, Bertram C, Veta M J Pathol Clin Res. 2024; 10(6):e70008.

PMID: 39466133 PMC: 11514500. DOI: 10.1002/2056-4538.70008.

Recovering single-cell expression profiles from spatial transcriptomics with scResolve.

Chen H, Lee Y, Ovando-Ricardez J, Rosas L, Rojas M, Mora A Cell Rep Methods. 2024; 4(10):100864.

PMID: 39326411 PMC: 11574286. DOI: 10.1016/j.crmeth.2024.100864.

Emerin deficiency drives MCF7 cells to an invasive phenotype.

Hansen E, Rolling C, Wang M, Holaska J Sci Rep. 2024; 14(1):19998.

PMID: 39198511 PMC: 11358522. DOI: 10.1038/s41598-024-70752-5.

References

Pietilainen T, Lipponen P, Aaltomaa S, Eskelinen M, Kosma V, Syrjanen K . The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer. J Cancer Res Clin Oncol. 1996; 122(11):687-92. DOI: 10.1007/BF01209033. View

Kato T, Kameoka S, Kimura T, Tanaka S, Nishikawa T, Kobayashi M . p53, mitosis, apoptosis and necrosis as prognostic indicators of long-term survival in breast cancer. Anticancer Res. 2002; 22(2B):1105-12. View

Harris G, Denley H, Pinder S, Lee A, Ellis I, Elston C . Correlation of histologic prognostic factors in core biopsies and therapeutic excisions of invasive breast carcinoma. Am J Surg Pathol. 2002; 27(1):11-5. DOI: 10.1097/00000478-200301000-00002. View

Courdi A, Hery M, Dahan E, Gioanni J, Abbes M, Monticelli J . Factors affecting relapse in node-negative breast cancer. A multivariate analysis including the labeling index. Eur J Cancer Clin Oncol. 1989; 25(2):351-6. DOI: 10.1016/0277-5379(89)90029-1. View

Meyer J, MCDIVITT R . Reliability and stability of the thymidine labeling index of breast carcinoma. Lab Invest. 1986; 54(2):160-4. View

Silvestrini R, Daidone M, Mastore M, Di Fronzo G, Coradini D, Boracchi P . Cell kinetics as a predictive factor in node-positive breast cancer treated with adjuvant hormone therapy. J Clin Oncol. 1993; 11(6):1150-5. DOI: 10.1200/JCO.1993.11.6.1150. View

Thor A, Moore DH I, Edgerton S, Kawasaki E, Reihsaus E, Lynch H . Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst. 1992; 84(11):845-55. DOI: 10.1093/jnci/84.11.845. View

Clahsen P, van de Velde C, Duval C, Pallud C, Mandard A, van den Broek L . The utility of mitotic index, oestrogen receptor and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol. 1999; 25(4):356-63. DOI: 10.1053/ejso.1999.0657. View

Bergers E, Jannink I, van Diest P, Cuesta M, Meyer S, van Mourik J . The influence of fixation delay on mitotic activity and flow cytometric cell cycle variables. Hum Pathol. 1997; 28(1):95-100. DOI: 10.1016/s0046-8177(97)90286-0. View

10.

Biesterfeld S, Noll I, Noll E, Wohltmann D, Bocking A . Mitotic frequency as a prognostic factor in breast cancer. Hum Pathol. 1995; 26(1):47-52. DOI: 10.1016/0046-8177(95)90113-2. View

11.

Aaltomaa S, Lipponen P, Papinaho S, Syrjanen K . Proliferating-cell nuclear antigen (PC10) immunolabelling and other proliferation indices as prognostic factors in breast cancer. J Cancer Res Clin Oncol. 1993; 119(5):288-94. DOI: 10.1007/BF01212727. View

12.

Weidner N, Moore 2nd D, Ljung B, Waldman F, Goodson 3rd W, Mayall B . Correlation of bromodeoxyuridine (BRDU) labeling of breast carcinoma cells with mitotic figure content and tumor grade. Am J Surg Pathol. 1993; 17(10):987-94. DOI: 10.1097/00000478-199310000-00003. View

13.

Pinder S, Wencyk P, Sibbering D, Bell J, Elston C, Nicholson R . Assessment of the new proliferation marker MIB1 in breast carcinoma using image analysis: associations with other prognostic factors and survival. Br J Cancer. 1995; 71(1):146-9. PMC: 2033442. DOI: 10.1038/bjc.1995.30. View

14.

Dowsett M, Archer C, Assersohn L, Gregory R, Ellis P, Salter J . Clinical studies of apoptosis and proliferation in breast cancer. Endocr Relat Cancer. 2000; 6(1):25-8. DOI: 10.1677/erc.0.0060025. View

15.

Aaltomaa S, Lipponen P, Eskelinen M, Kosma V, Marin S, Alhava E . Mitotic indexes as prognostic predictors in female breast cancer. J Cancer Res Clin Oncol. 1992; 118(1):75-81. DOI: 10.1007/BF01192316. View

16.

Baak J, van Diest P, ARIENS A, van Beek M, BELLOT S, Fijnheer J . The Multicenter Morphometric Mammary Carcinoma Project (MMMCP). A nationwide prospective study on reproducibility and prognostic power of routine quantitative assessments in The Netherlands. Pathol Res Pract. 1989; 185(5):664-70. DOI: 10.1016/S0344-0338(89)80213-4. View

17.

Bevilacqua P, Verderio P, Barbareschi M, Bonoldi E, Boracchi P, Dalla Palma P . Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity, in node-negative breast carcinoma. Breast Cancer Res Treat. 1996; 37(2):123-33. DOI: 10.1007/BF01806494. View

18.

Fitzgibbons P, Page D, Weaver D, Thor A, Allred D, Clark G . Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000; 124(7):966-78. DOI: 10.5858/2000-124-0966-PFIBC. View

19.

Laroye G, Minkin S . The impact of mitotic index on predicting outcome in breast carcinoma: a comparison of different counting methods in patients with different lymph node status. Mod Pathol. 1991; 4(4):456-60. View

20.

van der Linden J, Lindeman J, Baak J, Meijer C, Herman C . The Multivariate Prognostic Index and nuclear DNA content are independent prognostic factors in primary breast cancer patients. Cytometry. 1989; 10(1):56-61. DOI: 10.1002/cyto.990100110. View