The objective of this study is to investigate how the change of hormone receptor (HR) and human epidermal growth factor receptor-2 (Her-2) status is related to patients’ clinical features. One hundred ninety-three cases of patients treated at general hospital of PLA from 2000 to 2015 with advanced breast cancer were included. All patients developed recurrence that were re-biopsied and had complete pathological profile both at initial diagnosis and at relapse. HR status before and after relapse were available for all patients, while only 143 cases had Her-2 status at the two stages. The changes of ER, PR, and Her-2 status and their association with clincopathological factors and DFS were analyzed. The discordant rates of ER, PR, and Her-2 status between primary breast cancer and recurrent tumor were 34.2, 38.3, and 16.8 %, respectively. At relapse, the rates of gain of ER and PR positivity were 10.9 and 13.5 %, respectively; the rates of loss of ER and PR positivity were 23.3 and 24.9 %. Loss of positivity was more frequent than gain of positivity (pER < 0.000, pPR = 0.001). Among patients with Her-2 negative primary tumors, 15.4 % acquired Her-2 positivity at relapse; and among Her-2 positive patients at initial diagnosis, 1.4 % turned to Her-2 negative at relapse; gain of positivity was more frequent than loss of positivity (p < 0.000). Patients with tumor larger than 2 cm in diameter were more likely to experience change of Her-2 status (25.0 vs 5.8 %, p = 0.005). Yet, the change of ER/PR was not significantly associated with the size of primary tumor. Patients with ER positive recurrent disease and PR positive primary tumor had a DFS of more than 40 months. Compared to patients who maintained PR negative, patients who gained PR positivity at relapse had significantly longer DFS by 8.5 % (35.2 vs 26.7 months, p = 0.024). Patients losing ER positivity at relapse had shorter DFS by 7.8 months compared to those with stable ER positive tumors; patients gaining ER positivity experienced longer DFS by 8.3 months; but both differences were not statistically significant. Loss of Her-2 positivity was associated with longer DFS by 13.8 months as opposed to stable Her-2 status, without statistical significance. For patients with Her-2 negative primary tumor, the changes of Her-2 status were not associated with DFS. 34.2, 38.3, and 16.8 % of breast cancer patients had their ER, PR, and Her-2 status changed after recurrence, and these changes of receptor status were associated with DFS to some degree. Gain of PR positivity at relapse was significantly correlated with longer DFS.
Breast cancer Estrogen receptor Progesterone receptor Her-2 Disease-free survival
This is a preview of subscription content, log in to check access.
This work was supported by the Wu Jieping Medical Foundation (320.6750.14331).
Compliance with ethical standards
The study protocol was approved by the Chinese Ethics Committee of Human Resources at the General Hospital of the People’s Liberation Army. Written informed consent was obtained from the patients.
National Cancer Center & Disease prevention and Control Bureau, Ministry of Health. Chinese Cancer Registry Annual Report. Official document. Beijing: Press of Military Medical Science; 2012.Google Scholar
Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.CrossRefPubMedGoogle Scholar
Goldhirsch A, Ingle JN, Gelber RD, et al. Thresholds for therapies: highlights of the stgallen international expert consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009;20(8):1319–29.CrossRefPubMedPubMedCentralGoogle Scholar
Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the st. gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 2011;22(8):1736–47.CrossRefPubMedPubMedCentralGoogle Scholar
Early Breast Cancer Trialists’ Collaborative Group. 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.CrossRefGoogle Scholar
Broom RJ, Tang PA, Simmons C, et al. Changes in estrogen receptor, progesterone receptor and her-2/neu status with time: discordance rates between primary and metastatic breast cancer. Anticancer Res. 2009;29(5):1557–62.PubMedGoogle Scholar
Iindström LS, Karlsson E, Wilking UM. 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.CrossRefGoogle Scholar
Arnedos M, Nerurkar A, Osin P, et al. Discordance between core needle biopsy (CNB) and excisional biopsy (EB) for estrogen receptor (ER), progesterone receptor (PgR) and HER2 status in early breast cancer (EBC). Ann Oncol. 2009;20(12):1948–52.CrossRefPubMedGoogle Scholar
Nishimura R, Osako T, Okumura Y, et al. Changes in the ER, PgR, HER2, p53 and Ki-67 biological markers between primary and recurrent breast cancer: discordance rates and prognosis. World J Surg Oncol. 2011;9:131.CrossRefPubMedPubMedCentralGoogle Scholar
Gong XY, Ding H. Brest pathology. 1st ed. Beijing: People’s Medical Publishing House; 2009.Google Scholar
Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med. 2010;134(6):907–22.PubMedPubMedCentralGoogle Scholar
Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013.CrossRefPubMedGoogle Scholar
Mavrova R, Radosa J, Schmitt K, et al. Estrogen, progesterone, and Her-2/neu receptor expression discrepancy in primary tumors and in-breast relapse in patients with breast cancer. Breast J. 2014;20(3):322–4.CrossRefPubMedGoogle Scholar
Narayan M, Wilken JA, Harris LN, et al. Trastuzumab-induced HER reprogramming in “resistant” breast carcinoma cells. Cancer Res. 2009;69(6):2191–4.CrossRefPubMedGoogle Scholar
Dieci MV, Barbieri E, Piacentini F. 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.CrossRefPubMedGoogle Scholar
Dieci MV, Piacentini F, Dominci M. Quantitative expression of estrogen receptor on relapse biopsy for ER-positive breast cancer: prognostic impact. Anticancer Res. 2014;34(7):3657–62.PubMedGoogle Scholar
Braun L, Mietzsch F, Seibold P, et al. Intrinsic breast cancer subtypes defined by estrogen receptor signaling-prognostic relevance of progesterone receptor loss. Mod Pathol. 2013;26(9):1161–71.CrossRefPubMedGoogle Scholar
Knutson TP, Lange CA. Tracking progesterone receptor-mediated actions in breast cancer. Pharmacol Ther. 2014;142(1):114–25.CrossRefPubMedGoogle Scholar
Hosoda M, Yamamoto M, Nakano K, et al. Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2014;144(2):249–61.CrossRefPubMedGoogle Scholar