Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics

Matthew J. Ellis, Yu Tao, Jingqin Luo, Roger A'Hern, Dean B. Evans, Ajay S. Bhatnagar, Hilary A. Chaudri Ross, Alexander von Kameke, William R. Miller, Ian Smith, Wolfgang Eiermann, Mitch Dowsett

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1380-1388
Number of pages9
JournalJNCI: Journal of the National Cancer Institute
Volume100
Issue number19
DOIs
Publication statusPublished - 1 Oct 2008

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