Only estrogen receptor “positive” is not enough to predict the prognosis of breast cancer
Beginning in 2018, biomarkers including estrogen receptor (ER) status were incorporated in the 8th AJCC staging system. ER expression levels were not considered in these changes. We hypothesized that the levels of ER expression could affect the prognosis of breast cancer.
A retrospective review was conducted to identify all female patients with invasive breast cancer between 2003 and 2012. ER negative (group I), weakly ER-positive (group II), and strongly ER-positive (group III) were defined as Allred total scores of 0–2, 3–5, and 6–8, respectively. We examined a multigene panel, designated the BCT score, which is a newly developed prognostic model for predicting the risk of a distant metastasis.
Among the 4949 patients enrolled in this study, 1310 (26.5%), 361 (7.3%), and 3277 (66.2%) were categorized as group I, II, and III, respectively. Median F/U duration was 57.8 months. Compared to group III, patients in group II were younger, had larger tumors, and were also more likely to have PR-negative tumors, HER-2 amplification, high Ki-67, and high nuclear grade. Between group II and III, there was a significant difference in OS (P = 0.0764, 0.909, and 0.010, respectively). After adjusting for additional factors that may affect OS, the HR for OS showed higher in group II than in group III. The baseline median BCT score indicated that lower ER expression was associated with significantly higher BCT score (P < 0.0001) and significantly more likely to have high risk group (P < 0.0001) relative to higher levels of ER expression group.
ER expression levels affect the prognosis of breast cancer. The risk for patients with weakly ER-positive breast cancer should not be underestimated.
KeywordsBreast neoplasm Estrogen receptor Prognosis
This research was supported by Samsung Medical Center Grant (SMO1170021) and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C1142).
Compliance with ethical standards
Conflict of interest
JK and BK are employees of Gencurix. The other authors have no competing interests to declare.
- 6.Barnes DM, Harris WH, Smith P, Millis RR, Rubens RD (1996) Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. Br J Cancer 74:1445–1451CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Weiss A, Chavez-MacGregor M, Lichtensztajn DY, Yi M, Tadros A, Hortobagyi GN, Giordano SH, Hunt KK, Mittendorf EA (2018) Validation study of the American Joint Committee on Cancer eighth edition prognostic stage compared with the anatomic stage in breast cancer. JAMA Oncol 4:203–209CrossRefPubMedGoogle Scholar
- 9.American Joint Committee on Cancer (2016) AJCC cancer staging manual, 8th edn. Springer, ChicagoGoogle Scholar
- 10.Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (2010) AJCC cancer staging manual, 7th edn. Springer, New YorkGoogle Scholar
- 13.Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF (2013) 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 31:3997–4013CrossRefGoogle Scholar
- 14.Gong G, Kwon MJ, Han J, Lee HJ, Lee SK, Lee JE, Lee SH, Park S, Choi JS, Cho SY, Ahn SH, Lee JW, Cho SR, Moon Y, Nam BH, Nam SJ, Choi YL, Shin YK (2017) A new molecular prognostic score for predicting the risk of distant metastasis in patients with HR+/HER2- early breast cancer. Sci Rep 7:45554CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Paik S, Tang G, Shak S, Kim C, Bake rJ, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP, Geyer CE Jr, Wickerham DL, Wolmark N (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24:3726–3734CrossRefPubMedGoogle Scholar
- 20.Tang P, Wang J, Hicks DG, Wang X, Schiffhauer L, McMahon L, Yang Q, Shayne M, Huston A, Skinner KA, Griggs J, Lyman G (2010) A lower Allred score for progesterone receptor is strongly associated with a higher recurrence score of 21-gene assay in breast cancer. Cancer Invest 28:978–982CrossRefPubMedGoogle Scholar
- 22.Sheffield BS, Kos Z, Asleh-Aburaya K, Wang XQ, Leung S, Gao D, Won J, Chow C, Rachamadugu R, Stijleman I, Wolber R, Gilks CB, Myles N, Thomson T, Hayes MM, Bernard PS, Nielsen TO, Chia SK (2016) Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor. Breast Cancer Res Treat 155:483–490CrossRefPubMedGoogle Scholar
- 23.Iwamoto T, Booser D, Valero V, Murray JL, Koenig K, Esteva FJ, Ueno NT, Zhang J, Shi W, Qi Y, Matsuoka J, Yang EJ, Hortobagyi GN, Hatzis C, Symmans WF, Pusztai L (2012) Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1–10% ER-positive by immunohistochemistry. J Clin Oncol 30:729–734CrossRefPubMedGoogle Scholar
- 26.Balduzzi A, Bagnardi V, Rotmensz N, Dellapasqua S, Montagna E, Cardillo A, Viale G, Veronesi P, Intra M, Luini A, Pruneri G, Mastropasqua G, Goldhirsch A, Colleoni M (2014) Survival outcomes in breast cancer patients with low estrogen/progesterone receptor expression. Clin Breast Cancer 14:258–264CrossRefPubMedGoogle Scholar
- 29.Raghav KP, Hernandez-Aya LF, Lei X, Chavez-Macgregor M, Meric-Bernstam F, Buchholz TA, Sahin A, Do KA, Hortobagyi GN, Gonzalez-Angulo AM (2012) Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers. Cancer 118:1498–1506CrossRefPubMedGoogle Scholar
- 30.Yi M, Huo L, Koenig KB, Mittendorf EA, Meric-Bernstam F, Kuerer HM, Bedrosian I, Buzdar AU, Symmans WF, Crow JR, Bender M, Shah RR, Hortobagyi GN, Hunt KK (2014) Which threshold for ER positivity? A retrospective study based on 9639 patients. Ann Oncol 25:1004–1011CrossRefPubMedPubMedCentralGoogle Scholar