- Volume 15 Issue 21
DOI QR Code
Alterations in Hormonal Receptor Expression and HER2 Status between Primary Breast Tumors and Paired Nodal Metastases: Discordance Rates and Prognosis
- Ba, Jin-Ling (Department of Breast Surgery, General Surgery, the First Hospital of China Medical University) ;
- Liu, Cai-Gang (Department of Breast Surgery, General Surgery, the First Hospital of China Medical University) ;
- Jin, Feng (Department of Breast Surgery, General Surgery, the First Hospital of China Medical University)
- Published : 2014.11.28
Background: We aimed to evaluate the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression discordance in matched pairs of primary breast cancer and lymph node metastasis specimens and determine the effect of discordance on prognosis. Materials and Methods: Among all patients diagnosed with lymph node metastases from 2004 to 2007, primary tumors and paired lymph node metastases were resected from 209 patients. The status of ER, PR, and HER2 expression was analyzed immunohistochemically in 200, 194, and 193 patients, respectively. Discordance was correlated with prognosis. Results: Biomarker discordance between primary tumors and paired lymph node metastases was 25.0% (50/200) for ER status, 28.9% (56/194) for PR status, and 14.0% (27/193) for HER2 status. ER positivity was a significant independent predictor of improved survival when analyzed in primary tumors and lymph node metastases. Patients with PR-positive primary tumors and paired lymph node metastases displayed significantly enhanced survival compared to patients with PR-positive primary tumors and PR-negative lymph node metastases. Patients with ER- and PR-positive primary tumors and paired lymph node metastases who received endocrine therapy after surgery displayed significantly better survival than those not receiving endocrine therapy. Similalry treated patients with PR-negative primary tumors and PR-positive paired lymph node metastases also displayed better survival than those not receiving endocrine therapy. Conclusions: Biomarker discordance was observed in matched pairs of primary tumors and lymph node metastases. Such cases displayed poor survival. Thus, it is important to reassess receptor biomarkers used for lymph node metastases.
- Ataseven B, Gologan D, Gunesch A, et al (2012). HER2/neu, Topoisomerase 2a, Estrogen and Progesterone Receptors: Discordance between Primary Breast Cancer and Metastatic Axillary Lymph Node in Expression and Amplification Characteristics. Breast Care (Basel), 7, 465-70. https://doi.org/10.1159/000345467
- 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, 12, 615-20. https://doi.org/10.1023/A:1011182524684
- Carlsson J, Nordgren H, Sjostrom J, et al (2004). HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review. Br J Cancer, 90, 2344-8.
- Chanbers AF, Naumov Gn, Vantyghem SA, et al (2000). Molecular biology of breast cancer Metastasis. Clinical implications of experimental studies on metastatic inefficency. Breast Cancer Res, 2, 400-7. https://doi.org/10.1186/bcr86
- Cinieri S, Orlando L, Fedele P, et al (2007). Adjuvant strategies in breast cancer: new prospective, questions and reflections at the end of. St. Gallen international expert consensus conference. Ann Oncol, 18, 63-5.
- D'Andrea MR, Limiti MR, Bari M, et al (2007). Corrlation between genetic and biological aspects in primary nonmetastatic breast cancers and corresponding synchronous axillary lymph node metastasis. Breast Cancer Res Treat, 101, 279-84. https://doi.org/10.1007/s10549-006-9300-2
- De la Haba-Rodriguguez JR, Ruiz Borrego M, Gomez Espana A, et al (2004). Comparative study of the immunohistochemical phenotype in breast cancer and its lymph node metastatic location. Cancer Invest, 22, 219-24. https://doi.org/10.1081/CNV-120030210
- Deyarmin B, Kane JL, Valente AL, van Laar R, Gallagher C, Shriver CD, Ellsworth RE et al (2013). Effect of ASCO/CAP guidelines for determining ER status on molecular subtype. Ann Surg Oncol, 20, 87-93. https://doi.org/10.1245/s10434-012-2588-8
- 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, 1039-44. https://doi.org/10.1111/j.1742-1241.2005.00546.x
- Early Breast Cancer Trialists' Collaborative Group (EBCTCG) (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet, 365, 1687-717. https://doi.org/10.1016/S0140-6736(05)66544-0
- Early Breast Cancer Trialists' Collaborative Group (EBCTCG) (2011). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patientlevel mataanalysis of randomised trials. Lancet, 378, 771-84. https://doi.org/10.1016/S0140-6736(11)60993-8
- Early Breast Cancer Trialists'Collaborative Group (EBCTCG) (2012). Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100000 women in 123 randomised trials. Lancet, 379, 432-44. https://doi.org/10.1016/S0140-6736(11)61625-5
- Gancberg D, Di Leo A, Cardoso F, et al (2002). Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol, 13, 1036-43. https://doi.org/10.1093/annonc/mdf252
- Goldhirsch A, Ingle JN, Gelber RD, Panel members et al (2009). Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol, 20, 1319-29. https://doi.org/10.1093/annonc/mdp322
- Gomez-Fernandez C, Daneshbod Y, Nassiri M, et al (2008). lmmunohistochemically determined estrogen receptor phenotype remains stable in recurrent and metastatic braest cancer. Am J Clin Pathol, 130, 879-82. https://doi.org/10.1309/AJCPD1AO3YSYQYNW
- Hammond ME, Hayes DF, Wolff AC, Mangu PB, Temin S et al (2010). American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract, 6, 195-197. https://doi.org/10.1200/JOP.777003
- Huang TH, Wu F, Loeb GB et al (2009). Upregulation of miR-21 by HER2/neu signaling promotes cell invasion. J Biol Chem, 284, 18515-24. https://doi.org/10.1074/jbc.M109.006676
- Jatoi I, Hilsenceck SG, Clark GM, et al (1999). Significance of axillary lymph node metastasis in primary breast cancer cases. J Clin Oncol, 17, 2334-40.
- Jonat W, Giurescu M, Robertson JFR (2002). The clinical efficacy of progesterone antagonists in breast cancer. In: Robertson JFR, Nicholson RI, Hayes DF, eds. Endocrine Therapy of breast cancer, 1st edn. London: Dunitz, Taylor &Francis, 117-24.
- Ling Li, Li-Zhang Chen et al (2012). Factors influencing axillary lymph node metastasis in invasive breast cancer. Asian Pac J Cancer Prev, 13, 251-4. https://doi.org/10.7314/APJCP.2012.13.1.251
- Masood S, Bui MM (2000). Assessment of Her-2/neu overexpression in primary breast cancer and their metastatic lesions:an immunohistochemical study. Ann Clin Lab Sci, 30, 259-65.
- Maynadier M, Nirde P, Ramirez JM, et al (2008). Role of estrogens and their receptors in adhesion and invasiveness of breast cancer cells. Adv Exp Med Biol, 617, 485-91. https://doi.org/10.1007/978-0-387-69080-3_48
- Nemoto T, Vana J, Bedwani R et al (1980). Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer, 45, 2917-24. https://doi.org/10.1002/1097-0142(19800615)45:12<2917::AID-CNCR2820451203>3.0.CO;2-M
- Ge Q-D, Lv N, Kong Y-N, et al (2012). Clinical characteristics and survival analysis of breast cancer molecular subtypes with hepatic metastases. Asian Pacific J Cancer Prev, 13, 5081-6. https://doi.org/10.7314/APJCP.2012.13.10.5081
- Raica M, Compean AM, Ceausu RA, et al (2014). Hormone receptors and HER2 expression in primary breast carcinoma and corresponding lymph node metastasis: do we need both? Anticancer Res, 3, 1435-40.
- Simon R, Nocito A, Hubscher T et al (2001). Patterns of HER-2/neu amplification and overexpression in primary and metastatic breast cancer. J Natl Cancer Inst, 93, 1141-6. https://doi.org/10.1093/jnci/93.15.1141
- Slamon D, Eiermann W, Robert N et al (2011). Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med, 365, 1273-83. https://doi.org/10.1056/NEJMoa0910383
- Smith I, Procter M, Gelber RD et al (2007). 2-Year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet, 369, 29-36. https://doi.org/10.1016/S0140-6736(07)60028-2
- Tanner M, jarvinen P, lsola J (2001). Amplification of HER-2/neu and topoisomerase llalpha in primary and metastatic breast cancer. Cancer Res, 61, 5345-8.
- Tsutsui S, Ohno S, Murakami S et al (2002). EGFR, c-erbB2 and p53 protein in the primary lesions and paired metastatic regonal lymph nodes in breast cancer. Eur J Surg Oncol, 28, 383-7. https://doi.org/10.1053/ejso.2002.1259
- Identifying Differentially Expressed Genes and Screening Small Molecule Drugs for Lapatinib-resistance of Breast Cancer by a Bioinformatics Strategy vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10847
- Could the Breast Prognostic Biomarker Status Change During Disease Progression? An Immunohistochemical Comparison between Primary Tumors and Synchronous Nodal Metastasis vol.16, pp.10, 2015, https://doi.org/10.7314/APJCP.2015.16.10.4317
- P-cadherin: a useful biomarker for axillary-based breast cancer decisions in the clinical practice vol.30, pp.5, 2017, https://doi.org/10.1038/modpathol.2016.232