Triple negative breast cancer (TNBC) is commonly associated with a poor prognosis. Platinum-compounds (P) and low dose oral cyclophosphamide (mCy) have showed activity in TNBC, exerting a direct cytotoxic and possibly immunomodulating activity. Neutrophil (ANC) to lymphocyte (ALC) ratio (NLR), derived NLR (ANC/[White blood cells − ANC]; dNLR), platelet to ALC ratio (PLR), and high lactate dehydrogenase (LDH) level have been proposed as measures of inflammatory/immunosuppressive status, associated with poor prognosis. The aim of this study is to evaluate these biomarkers in TNBC patients treated with P+mCy combination.
We report an exploratory retrospective analysis on cohort of advanced TNBC patients treated in a phase II trial with the combination of cisplatin (60 mg/mq Q3W) and mCy (50 mg QOD). Clinical data, complete blood count, and LDH level at baseline were collected. NLR>2.5, dLNR>3, PLR>200, and LDH>ULN were considered as significant. Survival analyses were performed using the Kaplan-Meier method and the Cox proportional-hazards model.
A total of 47 patients treated from October 2011 to September 2015 were included. Median age was 55 years (26-77). More than 40% of the patients received the combination therapy as 2nd line, while 36% was heavily pretreated (>2 lines). Objective response rate and 6-month disease control rate were 23.3% and 57.9%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 4.2 (2.9-5.4) and 12.7 (7.9-17.5) months, respectively. At univariate analysis, NLR>2.5 and PLR>200 were not associated with PFS and OS. dNLR>3 and LDH>ULN were associated with both reduced mPFS (1.8 vs 4.8 mo, HR 2.74, 95% CI 1.41-5.31, p=.003; 3.2 vs 5.8 mo, HR 2.19, 1.11-4.32, p=.023) and OS (4.2 vs 13.3 mo, HR 5.29, 2.22-12.6, p<.001; 5.7 vs 14.3 mo, HR 2.79, 1.26-6.15, p=.011). At multivariable Cox regression analysis, dNLR>3, but not LDH>ULN, was independently associated with PFS and OS.
dNLR confirmed a potential role to improve the selection of TNBC patients more likely to benefit from platinum-based and mCy regimens. Its validity, along with the implementation of new predictive biomarkers, warrants further studies for prospective validation.
Giuseppe Curigliano, MD PhD.
Has not received any funding.
All authors have declared no conflicts of interest.