Abstract P2-08-51: Residual Ki67 index and PRPTD mutational status after neoadjuvant chemotherapy containing platinum salts predicts the survival in triple negative breast cancer
Authors: Huang L 
Published: May 2019

Background: Platinum salts have demonstrated sufficient efficacy and safety to consider their use in a neoadjuvant setting for triple negative breast cancer (TNBC). In this study, we focused on the prognostic value of Ki-67 and PRPTD in TNBC patients who received neoadjuvant chemotherapy containing platinum salts.

Patients and Methods: We retrospectively analyzed 145 TNBC cases to compare the activity and tolerability of cisplatin and carboplatin. Two groups received weekly paclitaxel and platinum salts for 4 cycles. Immunohistochemistry assessment of EGFR, Ki67, CK5/6, CK14 was conducted in paraffin-embedded tumor samples after neoadjuvant treatment. Nonsense/missense mutations of PTPRD were also evaluated in these tumor samples determined by using next generation sequencing.

Results: In total, 87% of patients in the cisplatin group and 82% of patients in the carboplatin group experienced a clinical objective response after 4 cycles (P=0.570). Pathological complete response (pCR) occurred similarly in both groups (44% versus 42%, P=0.789). In survival analysis, there was no difference between two regimens. The pathological variables of univariate Cox analysis were obtained from EGRF, Ki67 index, CK5/6, CK14, PTPRD mutational status in residual tumor after NAC. Multivariate Cox analysis identified two significant prognostic factors, including Ki67 index and PRPTD mutational status. The most common grade 3/4 adverse events were neutropenia and leukopenia.

Clinical and pathological evaluationCategoryCisplatin groupCarboplatin groupOR [95% CI]P valueypT0/is,ypN0--0.911 (0.459-1.806)0.789No29 (56%)54 (58%)--Yes23 (44%)39 (42%)--ypT0/is,ypN0/+--1.031 (0.523-2.034)0.930No25 (48%)44 (47%)--Yes27 (52%)49 (53%)--MP grade for breast--NA0.448MP 527 (52%)49 (53%)--MP 48 (15%)8 (9%)--MP 314 (27%)24 (26%)--MP 23 (6%)9 (10%)--MP 10 (0%)3 (3%)--Clinical response after 2 cycles--NA0.352CR3 (6%)2 (2%)--PR43 (82%)84 (90%)--Overall (CR or PR)46 (88%)86 (92%)--SD or PD6 (12%)7 (8%)--Clinical response after 4 cycles--NA0.570CR8 (15%)11 (12%)--PR37 (72%)65 (70%)--Overall (CR or PR)45 (87%)76 (82%)--SD or PD2 (4%)7 (8%)--

Prognostic value of pathological variables in predicting disease free survival using univariate and multivariate Cox modelCategoryUnivariate Cox Analysis Odds ratio (95% CI)P-valueMultivariate Cox Analysis Odds ratio (95% CI)P-valueEGFR negative vs. positive1.353 (0.548-3.342)0.512--Ki67 ≤20% vs. &gt;20%3.951 (1.291-12.094)0.0166.239 (1.614-24.114)0.008CK5/6 negative vs. positive0.822 (0.324-2.085)0.680--CK 14 negative vs. positive1.396 (0.541-3.604)0.490--PTPRD wide type vs. mutation type3.219 (1.117-9.277)0.0307.362 (2.305-23.513)0.001Abbreviation: EGFR. epidermal growth factor receptor; PTPRD. protein tyrosine phosphatase receptor type delta

Conclusion: There was no significant difference between the groups in adverse events. Both types of platinum salts and weekly paclitaxel are feasible therapies that achieved high pCR rates and tolerability in TNBC patients. Ki67 index and PRPTD mutational status in residual tumor should be suggested as promising biomarkers to predict the prognosis.

Citation Format: Huang L. Residual Ki67 index and PRPTD mutational status after neoadjuvant chemotherapy containing platinum salts predicts the survival in triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-51.