Outcome Prediction for Estrogen Receptor-Positive Breast Cancer Based on Postneoadjuvant Endocrine Therapy Tumor Characteristics

Abstract

BackgroundUnderstanding 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.MethodsTumors 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.ResultsMedian 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).ConclusionsBreast 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.

Correlation of Ki-67 Proliferative Antigen Expression and Tumor Response to Induction Chemotherapy Containing Cell Cycle-Specific Agents in Head and Neck Squamous Cell Carcinoma

“…In controlled trials of endocrine therapy for estrogen receptor-positive breast cancer, dynamic changes in Ki-67 expression levels measured 2 weeks after starting therapy, as opposed to static pretreatment Ki-67 expression, were associated with recurrence-free survival [24,35]. Greater reductions in Ki-67 expression with endocrine therapy associated with more benefit.…”

“…Ki-67 protein expression is not used as prognostic or predictive factors in HNSCC because studies evaluating Ki-67 for these purposes have been inconclusive [17][18][19][20][21][22]. However, in breast cancer, Ki-67 expression is significantly associated with a robust tumor response to hormone therapy and anthracycline-based neoadjuvant chemotherapy [23,24]. Further, Ki-67 is a component of two commercial tests for breast cancer recurrence risk that predict efficacy of therapy [25,26].…”

Estrogen receptor‐positive/human epidermal growth factor receptor 2‐negative breast tumors

“…4 It is noteworthy that Future studies also should focus on neoadjuvant endocrine therapy, especially for luminal A breast cancer. If our study is replicated in this setting, then use of the preoperative endocrine prognostic index (PEPI) score, which has been correlated with patient outcomes, 35 should be preferred to the Sataloff scale. It will also be helpful in future studies to compare PET parameters with other factors, such as gene expression signatures (Oncotype DX; Genomic Health Inc., Redwood City, Calif).…”

Current status of the prognostic molecular biomarkers in breast cancer: A systematic review

“…Aromatase expression by breast cancer cells has been shown to influence the effectiveness of endocrine treatments for breast cancer (8,9). Ellis et al (10) conducted a study using a sample from a clinical trial comparing tamoxifen and letrozole as neoadjuvant endocrine therapies, and found that aromatase expression levels in tumor and somatic cells was correlated with treatment-induced changes in Ki-67, RFS, and breast cancer-specific survival (BCSS) (11)(12)(13).…”