Abstract
sBackgroundAlthough peripheral blood-based parameters (PBBPs) are reported as prognostic indicators in patients with breast cancers, their utility has not been studied in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC). Tumor-infiltrating lymphocytes (TILs) might be a predictive factor in patients with HER2-positive ABC treated with pertuzumab and trastuzumab (PT) plus docetaxel. We aimed to evaluate whether PBBPs could have predictive value in HER2-positive ABC treated with pertuzumab and trastuzumab (PT) combined with eribulin (ERI) or nab-paclitaxel (Nab-PTX).MethodsData from 51 patients included in two single-arm, phase II trials were included in this retrospective-prospective study; the ERI + PT (N = 30) and Nab-PTX + PT (N = 21) combinations were registered under clinical trials number UMIN000012375 and UMIN000006838, respectively. We assessed PBBPs using prospectively collected data and investigated the association with progression-free survival (PFS); we evaluated absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). The cutoff values for ALC, NLR, and PLR were set at 1000 or 1500 cells/μL, 2, and 250, respectively.ResultsPFS was significantly improved in patients with ALC ≥1500/μL compared to those with ALC 1000–, <1500/μL or ALC < 1000/μL (P = 0.0106). High baseline ALC was significantly associated with improved PFS (≥1500/μL; hazard ratio [HR]: 0.3715; 95% confidence interval [CI]: 0.1735–0.7955; P = 0.0108). In contrast, improved PFS was not significantly associated with NLR or PLR. Improved PFS in patients with ALC ≥1500/μL was observed irrespective of visceral metastasis or chemotherapy regimen.ConclusionsOur results showed that baseline ALC was a predictive factor for PFS in HER2-positive ABC treated with PT irrespective of combined chemotherapy regimen. Anti-tumor effects might be mediated not only by the tumor microenvironment, but also by systemic peripheral circulating lymphocytes. Baseline systemic parameters such as peripheral lymphocyte count might be beneficial in addition to disease extent for predicting the efficacy of PT treatment.Trial registrationUMIN000012375, registration date: 21NOV2013, and UMIN000006838, registration date: 6DEC2011.
Highlights
Peripheral blood-based parameters (PBBPs) are reported as prognostic indicators in patients with breast cancers, their utility has not been studied in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC)
High baseline absolute lymphocyte count (ALC) was significantly associated with improved progression-free survival (PFS) (≥1500/μL; hazard ratio [Hazard ratio (HR)]: 0.3715; 95% confidence interval [Confidence interval (CI)]: 0.1735–0.7955; P = 0.0108)
Our results showed that baseline ALC was a predictive factor for PFS in HER2-positive ABC treated with pertuzumab and trastuzumab (PT) irrespective of combined chemotherapy regimen
Summary
Peripheral blood-based parameters (PBBPs) are reported as prognostic indicators in patients with breast cancers, their utility has not been studied in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC). Tumor-infiltrating lymphocytes (TILs) might be a predictive factor in patients with HER2-positive ABC treated with pertuzumab and trastuzumab (PT) plus docetaxel. Pertuzumab and trastuzumab are humanized monoclonal anti-HER2 antibodies with complementary proposed mechanisms of action. Both antibodies work through the disruption of HER2 dimerization with HER3 and other epidermal growth factor receptors (EGFRs), leading to the inhibition of HER2 signaling [4]. ADCC can induce innate immune system responses via Fcγ receptors These responses are sustained by natural killer (NK) cells; concomitantly, adaptive immunity involving tumor-infiltrating lymphocytes (TILs) develops in response to a specific antigen, which is sustained by T and B lymphocytes [5]. The association of TILs with clinical outcomes suggests a significant role for antitumor immunity in HER2-positive ABC [6]
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