Predictive impact of absolute lymphocyte counts for progression-free survival in human epidermal growth factor receptor 2-positive advanced breast cancer treated with pertuzumab and trastuzumab plus eribulin or nab-paclitaxel

Abstract

AbstractsBackgroundAlthough 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.

Utility of the Absolute Lymphocyte Count and Neutrophil/Lymphocyte Ratio for Predicting Survival in Patients with Metastatic Breast Cancer on Eribulin: A Real-World Observational Study

“…Given that clinicians have been greatly concerned with predicting prognosis through easily available biomarkers, numerous studies have investigated the association between NLR and prognosis among patients with breast cancer receiving chemotherapy [16,17]. Although ALC has received less attention than NLR in this perspective [22], our study has shown that ALC was significantly and independently associated with PFS among metastatic patients with breast cancer receiving eribulin. As mentioned previously, eribulin can activate Patients with ALC ≥1,500/μL had significantly better PFS than those with ALC < 1,500/μL (a; p = 0.013), whereas those with NLR ≥5.0 had significantly worse PFS than those with NLR < 5.0 (b; p = 0.020).…”

Neutrophil to Lymphocyte Ratio as Prognostic and Predictive Factor in Breast Cancer Patients: A Systematic Review

“…We identified eight studies with data on NLR as a prognostic factor in patients with metastatic BC [54][55][56][57][58][59][60][61]. Four articles (50%) enrolled patients with all molecular subtypes [54,[56][57][58], two focused on patients with HER2-positive BC [55,61], one on patients with TNBC [60] and one on patients with hormone receptor-positive BC receiving hormone therapy as initial treatment [59] (Table 5).…”

“…In these studies, the NLR cut-off value ranged from 1.9 to 3 (always based on previous studies), and the number of enrolled patients varied between 34 and 171. Six studies (75%) reported data on Asian populations [54][55][56]58,59,61]. Table 5.…”

“…Studies including only Specific BC Molecular Subtypes: Vernieri et al [60] showed that in 57 patients with TNBC, NLR was an independent prognostic factor for PFS (HR = 2.65; 95%CI 1.36-5.18; p = 0.004). Two studies focused on patients with HER2-positive tumors [55,61], and one found that NLR was correlated with PFS in the multivariate analysis (HR = 0.27; 95%CI 0.10-0.63; p < 0.001) [61]. NLR was an independent prognostic factor for PFS in patients with hormone receptor-positive BC receiving endocrine therapy as initial treatment (HR = 3.93; 95%CI 1.4-10.84; p = 0.008) [59].…”

Roles of neutrophil/lymphocyte ratio in prognosis and in differentiation of potential beneficiaries in HER2-positive breast cancer with trastuzumab therapy

“…Moreover, two recent studies showed the different results concerning the relationship between absolute lymphocyte account and disease progression in HER2-positive BC [2,17]. In this study, we retrospectively analyzed the NLR as the predictive factor of 843 HER2-positive BC patients with or without trastuzumab treatment.…”