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.
This study characterizes the glucomannan utilization operon (gmuBACDREFG, formerly ydhMNOPQRST) of Bacillus subtilis. Transcription of the operon is induced by konjac glucomannan and requires the last mannanase gene (gmuG). Cellobiose and mannobiose, possible degradation products of glucomannan by GmuG, are strong inducers of transcription. It is shown that an internal regulator gene (gmuR) encodes a repressor of the operon, as disruption of this gene enhances transcription of the operon in the absence of inducers. The expression of the glucomannan utilizing operon of B. subtilis is thus induced by degraded glucomannan products, and repressed by an internal repressor.
Background/Aim: This study aimed to improve the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and tumour-infiltrating lymphocytes (TILs). Patients and Methods: In this retrospective study, NLR and TIL data from 677 operated breast cancer patients were analysed. The cut-off value of NLR was set at 2.72, and TIL levels were classified as low (<10%), intermediate (≥10 to <50%), and high (≥50%). Results: Recurrence-free survival (RFS) was significantly longer in patients with low NLR (n=459) than in those with high NLR (n=218) (p=0.0383). In ERpositive/HER2-negative and TIL-low breast cancers, there were significant associations between NLR levels and RFS (p=0.0129) or overall survival (OS) (p=0.0046). On multivariate analysis, NLR was a significant and independent factor for OS (hazard ratio=3.78; 95% confidence interval=1.21-14.17; p=0.022). Conclusion: These data may be useful for predicting patient prognosis and understanding the clinical significance of immune status in breast cancers.
Background
The usefulness of
18
F-fluorodeoxyglucose-positron emission tomography/computed tomography for evaluating the treatment efficacy of breast cancers is well-established; however, the predictive values of parameters such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) remain unknown.
Methods
This study examined 199 breast cancers treated with primary systemic chemotherapy (PSC) followed by operation, and determined the values of maximum standardized uptake value (SUV
max
), peak SUV (SUV
peak
), mean SUV (SUV
mean
), MTV, and TLG at baseline. Among these cases, data on early changes in these metabolic parameters in 70 breast cancers were also assessed.
Results
A pathological complete response (pCR) was achieved in 64 breast cancers. Breast cancers with low MTV at baseline had a significantly higher pCR rate than breast cancers with high MTV (47.9% vs. 23.4%;
p
=
0.0005). High reduction rates (∆) of SUV
max
(
p
=
0.0001), SUV
peak
(
p
=
0.0001), and SUV
mean
(
p
<
0.0001) resulted in an increased pCR compared with those for low ∆. The pCR rate was highest for the combination of low MTV and high ∆SUV
mean
(86.7%), and lowest for high MTV and low ∆SUV
mean
(15.4%); the remaining combinations were intermediate (58.6%;
p
<
0.0001). The combination of low MTV at baseline and high ∆SUV
mean
was a significant and independent predictor for pCR (odds ratio 28.63; 95% confidence interval 1.94–422.42;
p
=
0.0146) in multivariable analysis.
Conclusions
Low levels of MTV at baseline and a high reduction of SUV
mean
after PSC was significantly associated with pCR. These findings suggest the usefulness of these metabolic parameters for predicting the treatment efficacy of breast cancers.
Electronic supplementary material
The online version of this article (10.1245/s10434-019-07325-8) contains supplementary material, which is available to authorized users.
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