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BMC Cancer. 2018 Oct 16;18(1):982. doi: 10.1186/s12885-018-4888-2.

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.

Author information

1
Hyogo College of Medicine, Department of Surgery, Division of Breast and Endocrine Surgery, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan.
2
The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Breast Medical Oncology, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
3
Kansai Rosai Hospital, Department of Surgery, 3-1-69 Inabaso, Amagasaki, Hyogo, 660-8511, Japan.
4
Hyogo Prefectural Amagasaki General Medical Center, Department of Breast Surgery, 2-17-77 East Namba-machi, Amagasaki, Hyogo, 660-8550, Japan.
5
Hyogo College of Medicine, Department of Surgery, Division of Breast and Endocrine Surgery, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan. ymiyoshi@hyo-med.ac.jp.

Abstract

BACKGROUND:

Although 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).

METHODS:

Data 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.

RESULTS:

PFS 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.

CONCLUSIONS:

Our 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 REGISTRATION:

UMIN000012375 , registration date: 21NOV2013, and UMIN000006838 , registration date: 6DEC2011.

KEYWORDS:

Absolute lymphocyte counts; HER2-positive ABC; Host immunity; Pertuzumab; Predictive biomarker; Trastuzumab

PMID:
30326862
PMCID:
PMC6191898
DOI:
10.1186/s12885-018-4888-2
[Indexed for MEDLINE]
Free PMC Article

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