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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options

Authors: Peter F. McAnena, Andrew McGuire, A. Ramli, C. Curran, C. Malone, R. McLaughlin, K. Barry, James A.L. Brown, M. J. Kerin

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Recent studies have shown that breast cancer subtype can change from the primary tumour to the recurrence. Discordance between primary and recurrent breast cancer has implications for further treatment and ultimately prognosis. The aim of the study was to determine the rate of change between primary and recurrence of breast cancer and to assess the impact of these changes on survival and potential treatment options.

Methods

Patient demographics were collected on those who underwent surgery for breast cancer between 2001 and 2014 and had a recurrence with biopsy results and pathology scoring of both the primary and recurrence.

Results

One hundred thirty two consecutive patients were included. There were 31 (23.5%) changes in subtype. Discordance occurred most frequently in luminal A breast cancer (n = 20), followed by triple negative (n = 4), luminal B (n = 3) and HER2 (n = 3). Patients who changed from luminal A to triple negative (n = 18) had a significantly worse post-recurrence survival (p < 0.05) with overall survival approaching significance (p = 0.064) compared to concordant luminal A cases (n = 46). Overall receptor discordance rates were: estrogen receptor 20.4% (n = 27), progesterone receptor 37.7% (n = 50) and HER2 3% (n = 4). Loss of estrogen receptor and progesterone receptor was more common than gain (21 vs. 6 (p = 0.04) and 44 vs. 6 (p = 0.01) respectively). Nine patients (6.8%) gained receptor status potentially impacting treatment options.

Conclusion

Discordance in subtype and receptor status occurs between primary and recurrent breast cancer, ultimately affecting survival and potentially impacting treatment options.
Appendix
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Literature
1.
go back to reference Ferlay J,SI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon: International Agency for Research on Cancer; 2013. Ferlay J,SI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon: International Agency for Research on Cancer; 2013.
2.
go back to reference Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRefPubMed Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRefPubMed
3.
go back to reference Network CGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.CrossRef Network CGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.CrossRef
4.
go back to reference Sorlie T, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–74.CrossRefPubMedPubMedCentral Sorlie T, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–74.CrossRefPubMedPubMedCentral
5.
go back to reference Early Breast Cancer Trialists' Collaborative, G. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.CrossRef Early Breast Cancer Trialists' Collaborative, G. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.CrossRef
6.
go back to reference Aurilio G, et al. A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur J Cancer. 2014;50(2):277–89.CrossRefPubMed Aurilio G, et al. A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur J Cancer. 2014;50(2):277–89.CrossRefPubMed
7.
go back to reference Lindstrom LS, et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol. 2012;30(21):2601–8.CrossRefPubMed Lindstrom LS, et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol. 2012;30(21):2601–8.CrossRefPubMed
8.
go back to reference Liedtke C, et al. Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann Oncol. 2009;20(12):1953–8.CrossRefPubMedPubMedCentral Liedtke C, et al. Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann Oncol. 2009;20(12):1953–8.CrossRefPubMedPubMedCentral
9.
go back to reference Santinelli A, et al. HER-2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy. Int J Cancer. 2008;122(5):999–1004.CrossRefPubMed Santinelli A, et al. HER-2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy. Int J Cancer. 2008;122(5):999–1004.CrossRefPubMed
10.
go back to reference Amir E, et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012;30(6):587–92.CrossRefPubMed Amir E, et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012;30(6):587–92.CrossRefPubMed
11.
go back to reference Allred DC, et al. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod pathol off j U S Canadian Acad Pathol, Inc. 1998;11(2):155–68. Allred DC, et al. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod pathol off j U S Canadian Acad Pathol, Inc. 1998;11(2):155–68.
12.
go back to reference Jacobs TW, et al. Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration–approved scoring system. J Clin Oncol. 1999;17(7):1983.CrossRefPubMed Jacobs TW, et al. Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration–approved scoring system. J Clin Oncol. 1999;17(7):1983.CrossRefPubMed
13.
go back to reference Owens MA, Horten BC, Da Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004;5(1):63–9.CrossRefPubMed Owens MA, Horten BC, Da Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004;5(1):63–9.CrossRefPubMed
14.
go back to reference Wolff AC. CDK4 and CDK6 inhibition in breast cancer - a new standard. N Engl J Med. 2016;375(20):1993–4.CrossRefPubMed Wolff AC. CDK4 and CDK6 inhibition in breast cancer - a new standard. N Engl J Med. 2016;375(20):1993–4.CrossRefPubMed
15.
go back to reference St Romain P, et al. Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis. Hum Pathol. 2012;43(3):398–404.CrossRefPubMed St Romain P, et al. Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis. Hum Pathol. 2012;43(3):398–404.CrossRefPubMed
16.
go back to reference Dieci MV, et al. Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: a single-institution analysis. Ann Oncol. 2013;24(1):101–8.CrossRefPubMed Dieci MV, et al. Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: a single-institution analysis. Ann Oncol. 2013;24(1):101–8.CrossRefPubMed
17.
go back to reference Shiino S, et al. Prognostic impact of discordance in hormone receptor status between primary and recurrent sites in patients with recurrent breast cancer. Clin Breast Cancer. 2016;16(4):e133–40.CrossRefPubMed Shiino S, et al. Prognostic impact of discordance in hormone receptor status between primary and recurrent sites in patients with recurrent breast cancer. Clin Breast Cancer. 2016;16(4):e133–40.CrossRefPubMed
19.
go back to reference Kimbung S, et al. Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications. Oncotarget. 2015;6(32):33306–18.CrossRefPubMedPubMedCentral Kimbung S, et al. Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications. Oncotarget. 2015;6(32):33306–18.CrossRefPubMedPubMedCentral
20.
go back to reference Hoefnagel LDC, et al. Discordance in ERα, PR and HER2 receptor status across different distant breast cancer metastases within the same patient. Ann Oncol. 2013;24(12):3017–23.CrossRefPubMed Hoefnagel LDC, et al. Discordance in ERα, PR and HER2 receptor status across different distant breast cancer metastases within the same patient. Ann Oncol. 2013;24(12):3017–23.CrossRefPubMed
21.
go back to reference Chan A, et al. A retrospective study investigating the rate of HER2 discordance between primary breast carcinoma and locoregional or metastatic disease. BMC Cancer. 2012;12(1):555.CrossRefPubMedPubMedCentral Chan A, et al. A retrospective study investigating the rate of HER2 discordance between primary breast carcinoma and locoregional or metastatic disease. BMC Cancer. 2012;12(1):555.CrossRefPubMedPubMedCentral
22.
go back to reference Yeung C, et al. Estrogen, progesterone, and HER2/neu receptor discordance between primary and metastatic breast tumours-a review. Cancer Metastasis Rev. 2016;35(3):427–37.CrossRefPubMed Yeung C, et al. Estrogen, progesterone, and HER2/neu receptor discordance between primary and metastatic breast tumours-a review. Cancer Metastasis Rev. 2016;35(3):427–37.CrossRefPubMed
23.
go back to reference Allred DC. Commentary: hormone receptor testing in breast cancer: a distress signal from Canada. Oncologist. 2008;13(11):1134–6.CrossRefPubMed Allred DC. Commentary: hormone receptor testing in breast cancer: a distress signal from Canada. Oncologist. 2008;13(11):1134–6.CrossRefPubMed
24.
go back to reference Shipitsin M, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007;11(3):259–73.CrossRefPubMed Shipitsin M, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007;11(3):259–73.CrossRefPubMed
26.
go back to reference Pertschuk LP, et al. Marked Intratumoral heterogeneity of the proto-oncogene her-2/neu determined by three different detection systems. Breast J. 1999;5(6):369–74.CrossRefPubMed Pertschuk LP, et al. Marked Intratumoral heterogeneity of the proto-oncogene her-2/neu determined by three different detection systems. Breast J. 1999;5(6):369–74.CrossRefPubMed
27.
go back to reference Kurbel S. Selective reduction of estrogen receptor (ER) positive breast cancer occurrence by estrogen receptor modulators supports etiological distinction between ER positive and ER negative breast cancers. Med Hypotheses. 2005;64(6):1182–7.CrossRefPubMed Kurbel S. Selective reduction of estrogen receptor (ER) positive breast cancer occurrence by estrogen receptor modulators supports etiological distinction between ER positive and ER negative breast cancers. Med Hypotheses. 2005;64(6):1182–7.CrossRefPubMed
28.
go back to reference Lacroix M, Toillon RA, Leclercq G. Stable 'portrait' of breast tumors during progression: data from biology, pathology and genetics. Endocr Relat Cancer. 2004;11(3):497–522.CrossRefPubMed Lacroix M, Toillon RA, Leclercq G. Stable 'portrait' of breast tumors during progression: data from biology, pathology and genetics. Endocr Relat Cancer. 2004;11(3):497–522.CrossRefPubMed
30.
go back to reference Shah SP, et al. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature. 2009;461(7265):809–13.CrossRefPubMed Shah SP, et al. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature. 2009;461(7265):809–13.CrossRefPubMed
31.
go back to reference Chambers AF, et al. Molecular biology of breast cancer metastasis. Clinical implications of experimental studies on metastatic inefficiency. Breast Cancer Res. 2000;2(6):400–7.CrossRefPubMedPubMedCentral Chambers AF, et al. Molecular biology of breast cancer metastasis. Clinical implications of experimental studies on metastatic inefficiency. Breast Cancer Res. 2000;2(6):400–7.CrossRefPubMedPubMedCentral
32.
34.
go back to reference Gong Y, et al. Stability of estrogen receptor status in breast carcinoma: a comparison between primary and metastatic tumors with regard to disease course and intervening systemic therapy. Cancer. 2011;117(4):705–13.CrossRefPubMed Gong Y, et al. Stability of estrogen receptor status in breast carcinoma: a comparison between primary and metastatic tumors with regard to disease course and intervening systemic therapy. Cancer. 2011;117(4):705–13.CrossRefPubMed
35.
go back to reference Zidan J, et al. Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer. 2005;93(5):552–6.CrossRefPubMedPubMedCentral Zidan J, et al. Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer. 2005;93(5):552–6.CrossRefPubMedPubMedCentral
36.
go back to reference Thompson AM, et al. Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the breast recurrence in tissues study (BRITS). Breast Cancer Res. 2010;12(6):R92.CrossRefPubMedPubMedCentral Thompson AM, et al. Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the breast recurrence in tissues study (BRITS). Breast Cancer Res. 2010;12(6):R92.CrossRefPubMedPubMedCentral
37.
go back to reference Amir E, et al. Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies. Cancer Treat Rev. 2012;38(6):708–14.CrossRefPubMed Amir E, et al. Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies. Cancer Treat Rev. 2012;38(6):708–14.CrossRefPubMed
38.
go back to reference Simmons C, et al. Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases? Ann Oncol. 2009;20(9):1499–504.CrossRefPubMedPubMedCentral Simmons C, et al. Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases? Ann Oncol. 2009;20(9):1499–504.CrossRefPubMedPubMedCentral
39.
go back to reference Van Poznak C, et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2015;33(24):2695–704.CrossRefPubMedPubMedCentral Van Poznak C, et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2015;33(24):2695–704.CrossRefPubMedPubMedCentral
40.
go back to reference Gupta S, et al. Quality improvement guidelines for percutaneous needle biopsy. J Vasc Interv Radiol. 2010;21(7):969–75.CrossRefPubMed Gupta S, et al. Quality improvement guidelines for percutaneous needle biopsy. J Vasc Interv Radiol. 2010;21(7):969–75.CrossRefPubMed
41.
42.
go back to reference Davidson NE. “Take two”? The role of second opinions for breast biopsy specimens. BMJ. 2016;353:i3256.PubMed Davidson NE. “Take two”? The role of second opinions for breast biopsy specimens. BMJ. 2016;353:i3256.PubMed
Metadata
Title
Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options
Authors
Peter F. McAnena
Andrew McGuire
A. Ramli
C. Curran
C. Malone
R. McLaughlin
K. Barry
James A.L. Brown
M. J. Kerin
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4101-7

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