Journal of the National Cancer Institute Advance Access published online on September 23, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn309
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Outcome Prediction for Estrogen Receptor–Positive Breast Cancer Based on Postneoadjuvant Endocrine Therapy Tumor Characteristics
Affiliations of authors: Siteman Cancer Center, Washington University, St Louis, MO (MJE, YT, JL); Clinical Trials and Statistics Unit, Institute of Cancer Research, Sutton, UK (RAH); Novartis Pharma AG, Basel, Switzerland (DBE, ASB, HACR, AvK); Edinburgh Breast Unit, Edinburgh University, Edinburgh, UK (WRM); Royal Marsden Hospital, London, UK (IS, MD); Red Cross Women’s Hospital, Munich, Germany (WE)
Correspondence to: Matthew J. Ellis, MB, BChir, PhD, Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Ave, St Louis, MO 63119 (e-mail: mellis{at}wustl.edu).
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.
| CONTEXT AND CAVEATS Prior knowledge Endocrine therapy before surgery increases the rate of breast conservation surgery for patients with hormone receptor–positive breast cancer, but factors to predict risk of relapse after treatment have not been identified. Study design Posttreatment prognostic factors from patients enrolled in clinical trials of neoadjuvant endocrine therapy were used to develop and validate a model to predict risk of relapse. Contribution A model that includes information on standard surgical staging parameters after neoadjuvant endocrine treatment, estrogen receptor status, and levels of Ki67 proliferation antigen can define broad relapse risk groups. Implications Data from this model may prove useful with respect to other decisions that must be made after a patient is treated with neoadjuvant endocrine therapy, such as the use of adjuvant chemotherapy. Limitations The studies used for developing and validating the model were small, used different treatments, and had relatively short median follow-up data available (just more than 5 years). From the Editors
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Manuscript received March 10, 2008; revised July 14, 2008; accepted July 29, 2008.
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J Natl Cancer Inst 2008 100: 1337.
J Natl Cancer Inst 2008 100: 1337.
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