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A low NLR at baseline was significantly associated with improved PFS in patients treated with eribulin but not in those treated with nab-paclitaxel. Therefore, the baseline NLR might be clinically useful for selecting patients who would benefit from eribulin.

Adjuvant treatments for operable breast cancers are determined according to subtypes defined based on estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. The ER+/HER2- subtype can be divided into luminal A and luminal B usually by Ki67 expression levels. Although tumor size, lymph node metastasis and tumor grade have been widely accepted in daily clinical practice, the identification of further prognostic indicators especially in the ER+/HER2- subtype is warranted. A total of 387 operated breast cancers for which maximum standardized uptake value (SUVmax) on the F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) were available at baseline were retrospectively analyzed. The optimal cutoff value of SUVmax for relapse-free survival (RFS) was determined to be 3.585 by means of the receiver operating characteristics curve with an area under the curve of 0.6795 (95% CI: 0.5972 to 0.7618, p = 0.0006, sensitivity: 78.8%, specificity: 57.1%). The RFS of patients with SUVmax-high (n = 178) was significantly (p = 0.0003) worse compared with those with SUVmax-low (n = 209). This significant association was prominently recognized in the ER+/HER2- subtype. By multivariable analysis, SUVmax (hazard ratio: 3.83, 95% confidence interval: 1.28-11.51, p = 0.017), tumor size (4.22, 1.39-12.82, p = 0.011) and lymph node metastasis (4.44, 1.81-10.87, p = 0.0012) were significant and independent prognostic factors for RFS. The ER+/HER2- subtype demonstrated consistently worse RFS in the SUVmax-high patients both in the luminal A (p = 0.037) and luminal B (p = 0.047) subtypes. Combination of Ki67 and SUVmax appears to be useful for selecting patients who have inferior prognosis and need further adjuvant treatment of the ER+/HER2- subtype.

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.

No abstract

Although the neutrophil-to-lymphocyte ratio (NLR) is a valuable prognostic factor for early breast cancer, the patient subgroups that may benefit the most from NLR analysis remain unknown. The present study analyzed the prognostic significance of NLR according to absolute lymphocyte counts (ALCs). A total of 889 patients with operated early breast cancers were retrospectively recruited. Existing NLR and ALC baseline data from the time-period prior to operation or preoperative chemotherapy were collected. The cutoff value for NLR was set at 2.72 according to the receiver operating characteristic curve. Recurrence-free survival (RFS) of NLR-low patients at baseline (n=582) was significantly better than that of NLR-high patients (n=307, P= 0.036). Improved patient prognoses were observed in the NLR-low, ALC-high (>1,688/µl; 5-year RFS, 0.88 vs. 0.57; P<0.0001) subgroup (n=355), but not in the NLR-low, ALC-low (≤1,688/µl; 5-year RFS, 0.87 vs. 0.87; P= 0.46) subgroup (n=534). Using multivariate analysis, NLR was observed to be a significant and independent factor for RFS (hazard ratio: 3.52; 95% confidence interval: 1.61-7.32; P= 0.0023) in the ALC-high breast cancer subgroup. Prognostic significance for baseline NLR was found exclusively in the ALC-high subgroup. Since NLR is a simple marker, the results obtained here might be useful for identifying patients who have high recurrence risk, and those that are candidates for additional treatments.

The efficacy of trastuzumab emtansine (T-DM1) is prolonged for some patients; however, the predictive factors remain unknown. We focused on a peripheral blood biomarker, the neutrophil-to-lymphocyte ratio (NLR), regarding T-DM1 treatment efficacy. Fifty-three advanced or metastatic breast cancers treated with T-DM1 were retrospectively recruited from three institutes. The NLR in the peripheral blood was measured at baseline and after one cycle. The cutoff value of the NLR was set at median value 2.56. The progression-free survival (PFS) of patients with NLR-low at baseline (n = 26; median, not reached) was significantly better than that of patients with NLR-high (n = 27; median, 4.13 months; hazard ratio [HR], 0.226; 95% confidence interval [CI], 0.112–0.493; p = 0.0001). Longer overall survival was significantly associated with a low NLR (HR, 0.384; 95% CI, 0.170–0.910; p = 0.0296). In the subgroup analysis, patients with NLR-low consistently had longer PFS compared to those with NLR-high irrespective of the number of prior chemotherapy regimens, prior trastuzumab, visceral metastasis, estrogen receptor status, and human epidermal growth factor receptor 2 (HER2) score. Although detailed mechanisms remain unknown, treatment efficacy of T-DM1 may be partly mediated by activation of the immune system. Low baseline NLR appears to be beneficial for treatment with T-DM1 in HER2-positive breast cancers.

The impact of Ki67 suppression on clinical response seems to be restricted to ER-positive breast cancers. Since PgR expression levels of premenopausal ER-positive cancers were significantly reduced in clinical responders, inhibition of estrogen signaling due to chemotherapy-induced amenorrhea may be involved in this association.