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Erschienen in: World Journal of Surgery 7/2010

01.07.2010

Does Analysis of Biomarkers in Tumor Cells in Lymph Node Metastases Give Additional Prognostic Information in Primary Breast Cancer?

verfasst von: Anna-Karin Falck, Mårten Fernö, Pär-Ola Bendahl, Lisa Rydén

Erschienen in: World Journal of Surgery | Ausgabe 7/2010

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Abstract

Background

Prognostic and treatment-predictive biomarkers in primary breast cancer are routinely analyzed in the primary tumor, whereas metastatic tumor cells in lymph node metastases are not characterized. The present study aimed to define the concordance between biomarkers in matched pairs of breast cancers and lymph node metastases and to relate their expression to clinical outcome.

Methods

Patients with primary breast cancer treated with adjuvant tamoxifen for 2 years were included. A tissue microarray of primary tumors and lymph node metastases was constructed, and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed immunohistochemically in 262, 257, 104, and 101 patients, respectively. Five years’ distant disease-free survival (DDFS) was used as the primary end point.

Results

The concordance for biomarker expression in primary tumors and corresponding lymph node metastases was 93% for ER, 84% for PR, 97% for HER2, and 85% for Ki67. The discordant cases for HER2 status were all negative in the tumor but positive in the node. ER positivity was a significant independent predictor of improved 5-year DDFS when analyzed in the primary tumor as well as in the lymph node metastases. Ki67 positivity analyzed in both locations correlated with shortened DDFS. HER2 positivity at both locations was an indicator of early relapse.

Conclusions

The concordance for the biomarkers analyzed in matched pairs of primary tumors and lymph node metastases was high. Moreover, survival analyses showed that the expression of biomarkers in lymph node metastases can provide prognostic information when no analyses of the primary tumor can be done. Treatment selection based on biomarkers in the lymph node is a topic for further studies.
Literatur
1.
Zurück zum Zitat Cinieri S, Orlando L, Fedele P et al (2007) Adjuvant strategies in breast cancer: new prospectives, questions and reflections at the end of 2007. St. Gallen international expert consensus conference. Ann Oncol 18(Suppl 6):vi63–vi65CrossRefPubMed Cinieri S, Orlando L, Fedele P et al (2007) Adjuvant strategies in breast cancer: new prospectives, questions and reflections at the end of 2007. St. Gallen international expert consensus conference. Ann Oncol 18(Suppl 6):vi63–vi65CrossRefPubMed
2.
Zurück zum Zitat Carter CL, Allen C, Henson DE (1989) Relation of tumor size, lymph node status, and survival in 24, 740 breast cancer cases. Cancer 63:181–187CrossRefPubMed Carter CL, Allen C, Henson DE (1989) Relation of tumor size, lymph node status, and survival in 24, 740 breast cancer cases. Cancer 63:181–187CrossRefPubMed
3.
Zurück zum Zitat Jatoi I, Hilsenbeck SG, Clark GM et al (1999) Significance of axillary lymph node metastasis in primary breast cancer. J Clin Oncol 17:2334–2340PubMed Jatoi I, Hilsenbeck SG, Clark GM et al (1999) Significance of axillary lymph node metastasis in primary breast cancer. J Clin Oncol 17:2334–2340PubMed
4.
Zurück zum Zitat Early Breast Cancer Trialists Group (1998) Tamoxifen for early breast cancer: an overview of the randomized trials. Lancet 351:1451–1467CrossRef Early Breast Cancer Trialists Group (1998) Tamoxifen for early breast cancer: an overview of the randomized trials. Lancet 351:1451–1467CrossRef
5.
Zurück zum Zitat Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672CrossRefPubMed Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672CrossRefPubMed
6.
Zurück zum Zitat Breast International Group (BIG) 1-98 Collaborative Group, Thurlimann B et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757CrossRefPubMed Breast International Group (BIG) 1-98 Collaborative Group, Thurlimann B et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757CrossRefPubMed
7.
Zurück zum Zitat Hurvitz SA, Pietras RJ (2008) Rational management of endocrine resistance in breast cancer: a comprehensive review of estrogen receptor biology, treatment options, and future directions. Cancer 113:2385–2397CrossRefPubMed Hurvitz SA, Pietras RJ (2008) Rational management of endocrine resistance in breast cancer: a comprehensive review of estrogen receptor biology, treatment options, and future directions. Cancer 113:2385–2397CrossRefPubMed
8.
Zurück zum Zitat Klein CA (2009) Parallel progression of primary tumors and metastases. Nat Rev Cancer 9(4):302–312CrossRefPubMed Klein CA (2009) Parallel progression of primary tumors and metastases. Nat Rev Cancer 9(4):302–312CrossRefPubMed
9.
Zurück zum Zitat De la Haba-Rodriguez JR, Ruiz Borrego M, Gómez España A et al (2004) Comparative study of the immunohistochemical phenotype in breast cancer and its lymph node metastatic location. Cancer Investig 22(2):219–224CrossRef De la Haba-Rodriguez JR, Ruiz Borrego M, Gómez España A et al (2004) Comparative study of the immunohistochemical phenotype in breast cancer and its lymph node metastatic location. Cancer Investig 22(2):219–224CrossRef
10.
Zurück zum Zitat Dikicioglu E, Barutca S, Meydan N et al (2005) Biological characteristics of breast cancer at the primary tumor and the involved lymph nodes. Int J Clin Pract 59(9):1039–1044CrossRefPubMed Dikicioglu E, Barutca S, Meydan N et al (2005) Biological characteristics of breast cancer at the primary tumor and the involved lymph nodes. Int J Clin Pract 59(9):1039–1044CrossRefPubMed
11.
Zurück zum Zitat Cardoso F, Di Leo A, Larsimont D et al (2001) Evaluation of HER2, p53, bcl-2, topoisomerase II-alpha, heat-shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes. Ann Oncol 42(7):615–620CrossRef Cardoso F, Di Leo A, Larsimont D et al (2001) Evaluation of HER2, p53, bcl-2, topoisomerase II-alpha, heat-shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes. Ann Oncol 42(7):615–620CrossRef
12.
Zurück zum Zitat Chebil G, Bendahl PO, Idvall I et al (2003) Comparison of immunohistochemical and biochemical assay of steroid receptors in primary breast cancer—clinical associations and reasons for discrepancies. Acta Oncol 42:719–725CrossRefPubMed Chebil G, Bendahl PO, Idvall I et al (2003) Comparison of immunohistochemical and biochemical assay of steroid receptors in primary breast cancer—clinical associations and reasons for discrepancies. Acta Oncol 42:719–725CrossRefPubMed
13.
Zurück zum Zitat Honeth G, Bendahl PO, Ringner M et al (2008) The CD44+/CD24− phenotype is enriched in basal-like breast tumors. Breast Cancer Res 10:R53CrossRefPubMed Honeth G, Bendahl PO, Ringner M et al (2008) The CD44+/CD24− phenotype is enriched in basal-like breast tumors. Breast Cancer Res 10:R53CrossRefPubMed
14.
Zurück zum Zitat Ahlin C, Aaltonen K, Amini RM et al (2007) Ki67 and cyclin A as prognostic factors in early breast cancer. What are the optimal cut-off values? Histopathology 51:491–498CrossRefPubMed Ahlin C, Aaltonen K, Amini RM et al (2007) Ki67 and cyclin A as prognostic factors in early breast cancer. What are the optimal cut-off values? Histopathology 51:491–498CrossRefPubMed
15.
Zurück zum Zitat Becker TE, Ellsworth RE, Deyarmin B et al (2008) The genomic heritage of lymph node metastases: implications for clinical management of patients with breast cancer. Ann Surg Oncol 15:1056–1063CrossRefPubMed Becker TE, Ellsworth RE, Deyarmin B et al (2008) The genomic heritage of lymph node metastases: implications for clinical management of patients with breast cancer. Ann Surg Oncol 15:1056–1063CrossRefPubMed
16.
Zurück zum Zitat Weigelt B, Glas AM, Wessels LF et al (2003) Gene expression profiles of primary breast tumors maintained in distant metastases. Proc Natl Acad Sci U S A 100:15901–15905CrossRefPubMed Weigelt B, Glas AM, Wessels LF et al (2003) Gene expression profiles of primary breast tumors maintained in distant metastases. Proc Natl Acad Sci U S A 100:15901–15905CrossRefPubMed
17.
Zurück zum Zitat Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874CrossRefPubMed Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874CrossRefPubMed
18.
Zurück zum Zitat Santinelli A, Pisa E, Stramazzotti E et al (2008) HER2 status discrepancy between primary lesions and metastatic sites. Impact on targeted therapy. Int J Cancer 122(5):999–1004CrossRefPubMed Santinelli A, Pisa E, Stramazzotti E et al (2008) HER2 status discrepancy between primary lesions and metastatic sites. Impact on targeted therapy. Int J Cancer 122(5):999–1004CrossRefPubMed
19.
Zurück zum Zitat Ryden L, Haglund M, Bendahl PO et al (2009) Reproducibility of human epidermal growth factor receptor 2 analysis in primary breast cancer—a national survey performed at pathology departments in Sweden. Acta Oncol 48:860–866PubMed Ryden L, Haglund M, Bendahl PO et al (2009) Reproducibility of human epidermal growth factor receptor 2 analysis in primary breast cancer—a national survey performed at pathology departments in Sweden. Acta Oncol 48:860–866PubMed
Metadaten
Titel
Does Analysis of Biomarkers in Tumor Cells in Lymph Node Metastases Give Additional Prognostic Information in Primary Breast Cancer?
verfasst von
Anna-Karin Falck
Mårten Fernö
Pär-Ola Bendahl
Lisa Rydén
Publikationsdatum
01.07.2010
Verlag
Springer-Verlag
Erschienen in
World Journal of Surgery / Ausgabe 7/2010
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-010-0499-z

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