Skip to main content
SpringerLink
Log in
Book cover

Breast Cancer 2nd edition pp 323–343Cite as

Histopathologic and Molecular Markers of Prognosis and Response to Therapy

  • Chapter

Part of the book series: M.D. Anderson Cancer Care Series ((MDCCS))

The routine pathologic evaluation of breast cancer must yield the histopathologic subtype, precise measurements of tumor size, and information regarding surgical margin status and lymph node status. Accurate determination of histopathologic or nuclear grade provides valuable additional prognostic information. Three molecular markers are routinely assessed to assist with treatment selection: estrogen and progesterone receptors are measured to determine eligibility for endocrine therapy, and HER-2 amplification is assessed to determine eligibility for trastuzumab therapy. Additional commercially available prognostic and predictive tests may be ordered if clinically indicated. Oncotype DX, a multigene assay, could help identify women with estrogen receptor-positive, lymph node-negative breast cancer who have a good prognosis with adjuvant endocrine therapy alone and therefore may receive little or no benefit from additional adjuvant chemotherapy. MammaPrint is a recently approved multigene assay that can assist in predicting the prognosis of women with stage I or II, lymph node-negative breast cancer. The most appropriate treatment decisions often require integration of prognostic and predictive information from multiple sources. Free and clinically validated online decision-making tools, the most widely used of which is available at www. adjuvantonline.com, are available to assist physicians in making personalized treatment recommendations based on the clinical, pathologic, and molecular features of the cancer.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adjuvant therapy for breast cancer. NIH Consensus Statement Online 2000;17: 1–23. http://consensus.nih.gov/cons/114/114_statement.htm.

  • Altman DG, Lyman GH. Methodological challenges in the evaluation of prognostic factors in breast cancer. Breast Cancer Res Treat 1998;52:289–303.

    Article  PubMed  CAS  Google Scholar 

  • Bast Jr RC, Ravdin P, Hayes DF, et al. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001;19:1865–1878.

    PubMed  Google Scholar 

  • Benson JR, Weaver DL, Mittra I, et al. The TNM staging system and breast cancer. Lancet Oncol 2003;4:56–60.

    Article  PubMed  Google Scholar 

  • Bonneterre J, Thürlimann B, Robertson JFR, et al. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability Study. J Clin Oncol 2000;18:3748–3757.

    PubMed  CAS  Google Scholar 

  • Brogi E. Benign and malignant spindle cell lesions of the breast. Semin Diagn Pathol 2004;21:57–64.

    Article  PubMed  Google Scholar 

  • Buyse M, Loi S, van’t Veer L, et al. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 2006;98:1183–1192.

    Article  PubMed  CAS  Google Scholar 

  • Cocquyt VF, Blondeel PN, Pepypere HT, et al. Different responses to preoperative chemotherapy for invasive lobular and invasive ductal breast carcinoma. Eur J Surg Oncol 2003;29:361–367.

    Article  PubMed  CAS  Google Scholar 

  • D’Eredita’ G, Giardina C, Martellotta M, et al. Prognostic factors in breast cancer: the predictive value of the Nottingham Prognostic Index in patients with a long-term follow-up that were treated in a single institution. Eur J Cancer 2001;37:591–596.

    Article  PubMed  Google Scholar 

  • Di Leo A, Isola J. Topoisomerase II alpha as a marker predicting the efficacy of anthracyclines in breast cancer: are we at the end of the beginning? Clin Breast Cancer 2003;4:179–186.

    Article  PubMed  CAS  Google Scholar 

  • Droufakou S, Deshmane V, Roylance R, et al. Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the breast. Int J Cancer 2001;92:404–408.

    Article  PubMed  CAS  Google Scholar 

  • Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 1998;16: 2672–2685.

    PubMed  CAS  Google Scholar 

  • Foekens JA, Atkins D, Zhang Y, et al. Multicenter validation of a gene expression-based prognostic signature in lymph node-negative primary breast cancer. J Clin Oncol 2006;24:1665–1671.

    Article  PubMed  CAS  Google Scholar 

  • Fuchs IB, Lichtenegger W, Buehler H, et al. The prognostic significance of epithelial-mesenchymal transition in breast cancer. Anticancer Res 2002;22:3415–3419.

    PubMed  Google Scholar 

  • Gobbi H, Simpson JF, Borowsky A, et al. Metaplastic breast tumors with a dominant fibromatosis-like phenotype have a high risk of local recurrence. Cancer 1999;85:2170–2182.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein NS, Ferkowicz M, Odish E, et al. Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol 2003;120:86–92.

    Article  PubMed  Google Scholar 

  • Goldstein NS. Does the level of E-cadherin expression correlate with the primary breast carcinoma infiltration pattern and type of systemic metastases? Am J Clin Pathol 2002;118:425–434.

    Article  PubMed  CAS  Google Scholar 

  • Gong Y, Yan K, Lin F, et al. Determination of oestrogen-receptor status and ERBB2 status of breast carcinoma: a gene-expression profiling study. Lancet Oncol 2007;8:203–211.

    Article  PubMed  CAS  Google Scholar 

  • Habel LA, Quesenberry CP, Jacobs M, et al. Gene expression and breast cancer mortality in Northern California Kaiser Permanente patients: a large population-based case control study [abstract]. Proc Am Soc Clin Oncol 2005;24:603a.

    Google Scholar 

  • Harvey JM, Clark GM, Osborne CK, et al. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999;17:1474–1781.

    PubMed  CAS  Google Scholar 

  • Hess KR, Anderson K, Symmans WF, et al. Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol 2006;24:4236–4244.

    Article  PubMed  CAS  Google Scholar 

  • Hu Z, Fan C, Oh DS, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006;7:96.

    Article  PubMed  CAS  Google Scholar 

  • Janicke F, Prechtl A, Thomssen C, et al. Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J Natl Cancer Inst 2001;93:913–920.

    Article  PubMed  CAS  Google Scholar 

  • Katz A, Saad ED, Porter P, et al. Primary systemic chemotherapy of invasive lobular carcinoma of the breast. Lancet Oncol 2007;8:55–62.

    Article  PubMed  CAS  Google Scholar 

  • Korkola JE, DeVries S, Fridlyand J, et al. Differentiation of lobular versus ductal breast carcinomas by expression microarray analysis. Cancer Res 2003;63: 7167–7175.

    PubMed  CAS  Google Scholar 

  • Look MP, van Putten WL, Duffy MJ, et al. Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. J Natl Cancer Inst 2002;94:116–128.

    PubMed  CAS  Google Scholar 

  • Mouridsen H, Gershanovich M, Sun Y, et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001;19:2596–2606.

    PubMed  CAS  Google Scholar 

  • Nichols DW, Wolff DJ, Self S, et al. A testing algorithm for determination of HER2 status in patients with breast cancer. Ann Clin Lab Sci 2002;32:3–11.

    PubMed  CAS  Google Scholar 

  • Olivotto IA, Bajdik CD, Ravdin PM, et al. Population-based validation of the prognostic model ADJUVANT! for early breast cancer. J Clin Oncol 2005;23:2716–2725.

    Article  PubMed  Google Scholar 

  • Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:2817–2826.

    Article  PubMed  CAS  Google Scholar 

  • Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24:3726–3734.

    Article  PubMed  CAS  Google Scholar 

  • Pedersen L, Zedeler K, Holck S, et al. Medullary carcinoma of the breast. Prevalence and prognostic importance of classical risk factors in breast cancer. Eur J Cancer 1995;31A(13–14): 2289–2295.

    Article  PubMed  CAS  Google Scholar 

  • Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000;406:747–752.

    Article  PubMed  CAS  Google Scholar 

  • Pusztai L, Ayers M, Stec J, et al. Gene expression profiles obtained from fine-needle aspirations of breast cancer reliably identify routine prognostic markers and reveal large-scale molecular differences between estrogen-negative and estrogen-positive tumors. Clin Cancer Res 2003;9:2406–2415.

    PubMed  CAS  Google Scholar 

  • Pusztai L, Mazouni C, Anderson K, et al. Molecular classification of breast cancer: limitations and potential. Oncologist 2006;11:868–877.

    Article  PubMed  CAS  Google Scholar 

  • Ravdin PM, Siminoff IA, Harvey JA. Survey of breast cancer patients concerning their knowledge and expectations of adjuvant therapy. J Clin Oncol 1998;16:515–521.

    PubMed  CAS  Google Scholar 

  • Ravdin PM, Siminoff LA, Davis GJ, et al. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 2001;19:980–991.

    PubMed  CAS  Google Scholar 

  • Reis-Filho JS, Cancela-Paredes J, Milanezi F, et al. Clinicopathologic implications of E-cadherin reactivity in patients with lobular carcinoma in situ of the breast. Cancer 2002;94:2114–2115; author reply 2115–2116.

    Article  PubMed  Google Scholar 

  • Renton SC, Gazet JC, Ford HT, et al. The importance of the resection margin in conservative surgery for breast cancer. Eur J Surg Oncol 1996;22:17–22.

    Article  PubMed  CAS  Google Scholar 

  • Rhodes A, Jasani B, Barnes DM, et al. Reliability of immunohistochemical demonstration of estrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems. J Clin Pathol 2000;53:125–130.

    Article  PubMed  CAS  Google Scholar 

  • Rhodes A. Quality assurance in immunohistochemistry. Am J Surg Pathol 2003;27:1284–1285.

    PubMed  Google Scholar 

  • Roche PC, Suman VJ, Jenkins RB, et al. Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831. J Natl Cancer Inst 2002;94:855–857.

    PubMed  Google Scholar 

  • Ross JS, Linette GP, Stec J, et al. Breast cancer biomarkers and molecular medicine. Expert Rev Mol Diagn 2003;3:573–585.

    Article  PubMed  CAS  Google Scholar 

  • Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 2005a;11: 5678–5685.

    Article  PubMed  CAS  Google Scholar 

  • Rouzier R, Pusztai L, Delaloge S, et al. Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer. J Clin Oncol 2005b;23:8331–8339.

    Article  PubMed  Google Scholar 

  • Rüdiger T, Höfler H, Kreipe H, et al. Quality assurance in immunohistochemistry: results of an interlaboratory trial involving 172 pathologists. Am J Surg Pathol 2002;26:873–882.

    Article  PubMed  Google Scholar 

  • Santini D, Ceccarelli C, Taffurelli M, et al. Differentiation pathways in primary invasive breast carcinoma as suggested by intermediate filament and biopathological marker expression. J Pathol 1996;179:386–391.

    Article  PubMed  CAS  Google Scholar 

  • Sastre-Garau X, Jouve M, Asselain B, et al. Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns. Cancer 1996;77:113–120.

    Article  PubMed  CAS  Google Scholar 

  • Simon R, Altman DG. Statistical aspects of prognostic factor studies in oncology. Br J Cancer 1994;69:979–985.

    PubMed  CAS  Google Scholar 

  • Simpson JF, Gray R, Dressler LG, et al. Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189. J Clin Oncol 2000;18:2059–2069.

    PubMed  CAS  Google Scholar 

  • Singletary SE, Allred C, Ashley P, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 2002;20:3628–3636.

    Article  PubMed  Google Scholar 

  • Sneige N, Yaziji H, Mandavilli SR, et al. Low-grade (fibromatosis-like) spindle cell carcinoma of the breast. Am J Surg Pathol 2001;25:1009–1016.

    Article  PubMed  CAS  Google Scholar 

  • Solin LJ, Fowble BL, Schultz DJ, et al. The significance of the pathology margins of the tumor excision on the outcome of patients treated with definitive irradiation for early stage breast cancer. Int J Radiat Oncol Biol Phys 1991;21:279–287.

    PubMed  CAS  Google Scholar 

  • Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor sub-classes with clinical implications. Proc Natl Acad Sci U S A 2001;98:10869–10874.

    Article  PubMed  CAS  Google Scholar 

  • Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003;100:8418–8423.

    Article  PubMed  CAS  Google Scholar 

  • Symmans WF, Weg N, Gross J, et al. A prospective comparison of stereotaxic fine-needle aspiration versus stereotaxic core needle biopsy for the diagnosis of mammographic abnormalities. Cancer 1999;85:1119–1132.

    Article  PubMed  CAS  Google Scholar 

  • Thomson TA, Hayes MM, Spinelli JJ, et al. HER-2/neu in breast cancer: interobserver variability and performance of immunohistochemistry with 4 antibodies compared with fluorescent in situ hybridization. Mod Pathol 2001;14:1079–1086.

    Article  PubMed  CAS  Google Scholar 

  • Tsuda H, Takarabe T, Hasegawa T, et al. Myoepithelial differentiation in high-grade invasive ductal carcinomas with large central acellular zones. Hum Pathol 1999;30:1134–1139.

    Article  PubMed  CAS  Google Scholar 

  • van de Vijver M. Emerging technologies for HER2 testing. Oncology 2002;63 (suppl 1): 33–38.

    Article  PubMed  CAS  Google Scholar 

  • van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002;347:1999–2009.

    Article  PubMed  Google Scholar 

  • Van’t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002;415:530–536.

    Article  Google Scholar 

  • Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 2005;365:671–679.

    PubMed  CAS  Google Scholar 

  • Weidner N, Moore DH 2nd, Vartanian R. Correlation of Ki-67 antigen expression with mitotic figure index and tumor grade in breast carcinomas using the novel "paraffin"-reactive MIB1 antibody. Hum Pathol 1994;25:337–342.

    Article  PubMed  CAS  Google Scholar 

  • Wolff AC, Hammond EH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007;25:118–145.

    Article  PubMed  CAS  Google Scholar 

  • Zhao J, Wu R, Au A, et al. Determination of HER2 gene amplification by chromogenic in situ hybridization (CISH) in archival breast carcinoma. Mod Pathol 2002;15:657–665.

    Article  PubMed  Google Scholar 

Download references

Authors
  1. Lajos Pusztai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Fraser Symmans
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Surgical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA

    Kelly K. Hunt MD

  2. Department of Plastic Surgery, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA

    Geoffrey L. Robb MD

  3. Department of Radiation Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA

    Eric A. Strom MD

  4. Department of Stem Cell Transplantation and Cellular Therapy Department of Breast Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA

    Naoto T. Ueno MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science + Business Media, LLC

About this chapter

Cite this chapter

Pusztai, L., Symmans, W.F. (2008). Histopathologic and Molecular Markers of Prognosis and Response to Therapy. In: Hunt, K.K., Robb, G.L., Strom, E.A., Ueno, N.T. (eds) Breast Cancer 2nd edition. M.D. Anderson Cancer Care Series. Springer, New York, NY. https://doi.org/10.1007/978-0-387-34952-7_11

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-34952-7_11

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-34950-3

  • Online ISBN: 978-0-387-34952-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation