Outcome Prediction for Estrogen Receptor–Positive Breast Cancer Based on Postneoadjuvant Endocrine Therapy Tumor Characteristics
By M. Ellis, Y. Tao, Jingqin R Luo, R. A’Hern, D. Evans, A. Bhatnagar, Hilary A. Chaudri Ross, Alexander von Kameke, William Miller, I. Smith and 2 more. Journal of the National Cancer Institute, 2008
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Background Understanding how tumor response is related to relapse risk would help clinicians make decisions about additional treatment options for patients who have received neoadjuvant endocrine treatment for estrogen receptor–positive (ER+) breast cancer. Methods Tumors from 228 postmenopausal women with confirmed ER+ stage 2 and 3 breast cancers in the P024 neoadjuvant endocrine therapy trial, which compared letrozole and tamoxifen for 4 months before surgery, were analyzed for posttreatment ER status, Ki67 proliferation index, histological grade, pathological tumor size, node status, and treatment response. Cox proportional hazards were used to identify factors associated with relapse-free survival (RFS) and breast cancer–specific survival (BCSS) in 158 women. A preoperative endocrine prognostic index (PEPI) for RFS was developed from these data and validated in an independent study of 203 postmenopausal women in the IMPACT trial, which compared treatment with anastrozole, tamoxifen, or the combination 3 months before surgery. Statistical tests were two-sided. Results Median follow-up in P024 was 61.2 months. Patients with confirmed baseline ER+ clinical stage 2 and 3 tumors that were downstaged to stage 1 or 0 at surgery had 100% RFS (compared with higher stages, P < .001). Multivariable testing of posttreatment tumor characteristics revealed that pathological tumor size, node status, Ki67 level, and ER status were independently associated with both RFS and BCSS. The PEPI model based on these factors predicted RFS in the IMPACT trial (P = .002). Conclusions Breast cancer patients with pathological stage 1 or 0 disease after neoadjuvant endocrine therapy and a low-risk biomarker profile in the surgical specimen (PEPI score 0) have an extremely low risk of relapse and are therefore unlikely to benefit from adjuvant chemotherapy.
Subfields: Cancer Research, Genetics, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/1037cea0baf177614abf2af4da687768256ae270
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Citations in the corpus
- Deconstructing the molecular portraits of breast cancer (2010, background): “In addition, features of the Luminal B subtype such as high Ki-67 and low ER status in postsurgical samples, were independently associated with relapse-free survival after treatment with neoadjuvant letrozole or tamoxifen (P024 trial) (Ellis et al., 2008).”
- Biological determinants of endocrine resistance in breast cancer (2009, background): “Although proliferation is reduced in almost all ER-positive breast cancers following neoadjuvant endocrine therapy, the level of proliferation following short-term therapy is a better predictor of outcome than its pretreatment level or the magnitude of the decrease in proliferation following treatme”
- Assessment of Ki67 in Breast Cancer: Updated Recommendations From the International Ki67 in Breast Cancer Working Group (2020, positive): “In the Z1031 trial, the preoperative prognostic index (PEPI) is a weighted multi-factoral algorithm consisting of residual tumor size, node status, ER status, and Ki67 (94).”