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Avoidance and Period-Shortening of Neoadjuvant Chemotherapy Against Triple-Negative Breast Cancer in Stages I and II: Importance of Ki-67 Labeling Index and the Recognition of Apocrine-Type Lesions.

ABSTRACT: BACKGROUND:Triple-negative breast cancer encompasses heterogeneous subtypes. Neoadjuvant chemotherapy is ineffective against some triple-negative breast cancers, while others show a favorable prognosis despite chemoresistance. METHODS:A total of 51 cases with stages I and II triple-negative breast cancer were analyzed; 34 triple-negative breast cancers treated with neoadjuvant chemotherapy were divided into "good responders" (n = 22), showing therapeutic effect G2b or G3 in surgical specimens, and "poor responders" with therapeutic effect G0, G1a, G1b, and G2a (n = 12). Neoadjuvant chemotherapy was spared in 17 cases (non-neoadjuvant chemotherapy group). Apocrine-type triple-negative breast cancer was defined as triple-negative breast cancer immunoreactive for both androgen receptor and forkhead-box protein A1. Triple-negative breast cancer other than apocrine-type (n = 16) and special types (myoepithelial, medullary, adenoid cystic, and spindle cell carcinomas, n = 6) was categorized as basal-like subtype (n = 29). Prognosis was evaluated in each category. RESULTS:Neoadjuvant chemotherapy provoked significant effects against basal-like triple-negative breast cancer with high Ki-67 labeling (?50%), and tumor-infiltrating lymphocytes predicted high chemosensitivity. Neoadjuvant chemotherapy was avoidable in triple-negative breast cancer of apocrine- and special types showing low (<50%) Ki-67 labeling. Ten (59%) lesions in the non-neoadjuvant chemotherapy group belonged to the apocrine-type. When clinical complete remission shown by contrast-enhanced magnetic resonance imaging was reached in the course of neoadjuvant chemotherapy against basal-like triple-negative breast cancer, the neoadjuvant chemotherapy period was shortened in 14 (64%) of 22 good responders. Disease-free and overall survival rates were excellent in all groups. CONCLUSIONS:The following 2 hypothetical proposals should be proven by large-scale clinical trials. Immunohistochemical recognition of apocrine-type triple-negative breast cancer with low Ki-67 labeling is important for avoiding ineffective/unnecessary neoadjuvant chemotherapy. By employing appropriate clinical imaging, period-shortening is achievable in basal-like triple-negative breast cancer with high Ki-67 labeling.

SUBMITTER: Kubouchi K

PROVIDER: S-EPMC7370551 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Avoidance and Period-Shortening of Neoadjuvant Chemotherapy Against Triple-Negative Breast Cancer in Stages I and II: Importance of Ki-67 Labeling Index and the Recognition of Apocrine-Type Lesions.

Kubouchi Koichi K Shimada Kyosuke K Yokoe Takamichi T Tsutsumi Yutaka Y

Technology in cancer research & treatment 20200101

<h4>Background</h4>Triple-negative breast cancer encompasses heterogeneous subtypes. Neoadjuvant chemotherapy is ineffective against some triple-negative breast cancers, while others show a favorable prognosis despite chemoresistance.<h4>Methods</h4>A total of 51 cases with stages I and II triple-negative breast cancer were analyzed; 34 triple-negative breast cancers treated with neoadjuvant chemotherapy were divided into "good responders" (n = 22), showing therapeutic effect G2b or G3 in surgic ...[more]

PMID: 32677589

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Project description:PurposeThe recent publication of the ACOSOG Z1031 trial results demonstrated that Ki-67 proliferation marker-based neoadjuvant endocrine therapy response monitoring could be used for tailoring the use of adjuvant chemotherapy in ER+HER2-negative breast cancer patients. In this paper, we describe the development of the Ki-67 clinical trial assay used for this study.MethodsKi-67 assay assessment focused on reproducing a 2.7% Ki-67 cut-point (CP) required for calculating the Preoperative Endocrine Prognostic Index and a 10% CP for poor endocrine therapy response identification within the first month of neoadjuvant endocrine treatment. Image analysis was assessed to increase the efficiency of the scoring process. Clinical outcome concordance for two independent Ki-67 scores was the primary performance metric.ResultsDiscordant scores led to a triage approach where cases with complex histological features that software algorithms could not resolve were flagged for visual point counting (17%). The final Ki-67 scoring approach was run on T1/2 N0 cases from the P024 and POL trials (N = 58). The percent positive agreement for the 2.7% CP was 87.5% (95% CI 61.7-98.5%); percent negative agreement 88.9% (95% CI: 65.3-98.6%). Minor discordance did not affect the ability to predict similar relapse-free outcomes (Log-Rank P = 0.044 and P = 0.055). The data for the 10% early triage CP in the POL trial were similar (N = 66), the percentage positive agreement was 100%, and percent negative agreement 93.55% (95% CI: 78.58-99.21%). The independent survival predictions were concordant (Log-rank P = 0.0001 and P = 0.01).ConclusionsWe have developed an efficient and reproducible Ki-67 scoring system that was approved by the Clinical Trials Evaluation Program for NCI-supported neoadjuvant endocrine therapy trials. Using the methodology described here, investigators are able to identify a subgroup of patients with ER+HER2-negative breast cancer that can be safely managed without the need of adjuvant chemotherapy.

Dataset Information

Avoidance and Period-Shortening of Neoadjuvant Chemotherapy Against Triple-Negative Breast Cancer in Stages I and II: Importance of Ki-67 Labeling Index and the Recognition of Apocrine-Type Lesions.

Publications

Avoidance and Period-Shortening of Neoadjuvant Chemotherapy Against Triple-Negative Breast Cancer in Stages I and II: Importance of Ki-67 Labeling Index and the Recognition of Apocrine-Type Lesions.

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