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The prognostic and predictive potential of Ki-67 in triple-negative breast cancer.

ABSTRACT: As a cell proliferation biomarker, Ki-67 is principally used in ER+/HER2- breast cancer. However, the importance and the best cutoff point of Ki-67 in triple-negative breast cancer (TNBC) remains unclear and was evaluated in this study.A total of 1800 patients with early invasive TNBC between 2011 and 2016 at Fudan University Shanghai Cancer Center were consecutively recruited for this study. The optimal cutoff for Ki-67 was assessed by Cutoff Finder. Propensity score matching (PSM, ratio?=?1:2) was performed to match the Ki-67^low group with the Ki-67^high group. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups using the Kaplan-Meier method and Cox regression model. The most relevant cutoff value for Ki-67 for prognosis was 30% (p?=?0.008). At the cutoff point of 30%, worse DFS and OS were observed in the Ki-67^high group. In multivariate analyses, N-stage (p?1N₀M₀ (stage I) TNBCs. For 945 N- TNBC patients, adjuvant chemotherapy (CT) was associated with better OS in the Ki-67^high group (p?=?0.017) than in the Ki-67^low group (p?=?0.875). For stage I/Ki-67^low patients, adjuvant CT did not affect DFS (p?=?0.248). Thus, Ki-67 cutoff at 30% had early independent prognostic and predictive potential for OS and DFS in TNBCs, and Ki-67?>?30% was significantly associated with worse prognosis, especially for stage I patients. For stage I/Ki-67^low TNBC patients, the advantage of CT is unclear, providing the basis for future de-escalation therapy.

SUBMITTER: Zhu X

PROVIDER: S-EPMC6959292 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The prognostic and predictive potential of Ki-67 in triple-negative breast cancer.

Zhu Xiuzhi X Chen Li L Huang Binhao B Wang Yue Y Ji Lei L Wu Jiong J Di Genhong G Liu Guangyu G Yu Keda K Shao Zhimin Z Wang Zhonghua Z

Scientific reports 20200114 1

As a cell proliferation biomarker, Ki-67 is principally used in ER+/HER2- breast cancer. However, the importance and the best cutoff point of Ki-67 in triple-negative breast cancer (TNBC) remains unclear and was evaluated in this study.A total of 1800 patients with early invasive TNBC between 2011 and 2016 at Fudan University Shanghai Cancer Center were consecutively recruited for this study. The optimal cutoff for Ki-67 was assessed by Cutoff Finder. Propensity score matching (PSM, ratio = 1:2) ...[more]

PMID: 31937819

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Project description:IntroductionOverexpression of the androgen receptor (AR) characterizes a distinct molecular subset of triple negative breast carcinomas (TNBC). The role of AR as a prognostic/predictive biomarker in TNBC is controversial, but increasing evidence suggests that this subset may respond to therapeutic agents targeting AR. Evaluation of AR has not been standardized, and criteria for selection of patients for antiandrogen therapy remain controversial. In this study we determine the appropriate threshold of AR immunoreactivity to define AR positive (AR+) TNBC, describe the clinicopathologic features of AR+ TNBC, and discuss the utility of AR positivity as a prognostic and predictive marker in TNBC.Materials and methods135 invasive TNBC processed in accordance with ASCO/CAP guidelines, were immunostained for AR. Clinicopathologic features of AR+ TNBC were analyzed and compared to AR negative (AR-) TNBC. Patients' age, tumor size, tumor grade, lymph node status, proliferation rate, immunopositivity for EGFR, CK5/6, Ki-67, and disease free survival (DFS) were evaluated statistically.ResultsA 1% cutpoint was confirmed as the appropriate threshold for AR positivity. Using this cutpoint 41% of 135 TNBC were AR+. AR+ TNBC occurred in older women, were larger, had lower mean proliferation rate and increased incidence of axillary metastasis than AR- TNBC. 76% of TNBC with apocrine morphology were AR+. A subset of AR+TNBC expressed basal markers (EGFR and CK5/6). A prognostic model was created.SummaryAR identifies a heterogeneous group of TNBC. Additional evaluation of EGFR expression allowed us to stratify TNBCs into 3 risk groups with significant differences in DFS and therapeutic implications: low-risk (AR+ EGFR-) which represents the LAR molecular subtype with the best prognosis and may benefit the most from anti-androgen therapies; high-risk (AR- EGFR+) which represents the basal molecular subtype with the worst prognosis and may benefit the most from chemotherapy regimens; intermediate-risk (AR+EGFR+ and AR-EGFR-) TNBC with an intermediate prognosis. Prospective trials are required to further validate this prognostic and predictive grouping.

Dataset Information

The prognostic and predictive potential of Ki-67 in triple-negative breast cancer.

Publications

The prognostic and predictive potential of Ki-67 in triple-negative breast cancer.

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