Radiofrequency Catheter Ablation for Atrial Fibrillation Patients on Hemodialysis (From the Kansai Plus Atrial Fibrillation Registry)　- Clinical Impact of Early Recurrence.

BACKGROUND: Catheter ablation (CA) for atrial fibrillation (AF) in patients on hemodialysis (HD) is reported to have a high risk of late recurrence (LR). However, the relationship between early recurrence (ER) within a 90-day blanking period after CA in AF patients and LR in HD patients remains unclear. METHODS AND RESULTS: Of the 5,010 patients in the Kansai Plus Atrial Fibrillation Registry, 5,009 were included in the present study. Of these patients, 4,942 were not on HD (non-HD group) and 67 were on HD (HD group). HD was an independent risk factor for LR after the initial CA (adjusted hazard ratio 1.6; 95% confidence interval 1.1-2.2; P=0.01). In patients with ER, the rate of sinus rhythm maintenance at 3 years after the initial CA was significantly lower in the HD than non-HD group (11.4% vs. 35.4%, respectively; log-rank P=0.004). However, in patients without ER, there was no significant difference in the rate of sinus rhythm maintenance at 3 years between the HD and non-HD groups (67.7% vs. 74.5%, respectively; log-rank P=0.62). CONCLUSIONS: ER in HD patients was a strong risk factor for LR. However, even HD patients could expect a good outcome without ER after the initial CA.

Atrial Fibrillation Ablation Outcomes and Heart Failure (from the Kansai Plus Atrial Fibrillation Registry).

The impact of rhythm outcomes on heart failure (HF) hospitalizations remains unknown after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). We sought to elucidate whether AF recurrence was associated with HF hospitalizations after AF RFCA. We conducted a large-scale, prospective, multicenter, observational study (Kansai Plus Atrial Fibrillation Registry), enrolling 5,010 consecutive patients (age 64 ± 10 years, 27.3% female, and 35.7% nonparoxysmal AF) who underwent an initial AF RFCA at 26 centers. The median follow-up duration was 2.9 years. The cumulative 3-year incidence of HF hospitalizations after the initial RFCA was 1.84% (0.69%/year). Hospitalized patients with HF were older with a higher prevalence of nonparoxysmal AF, renal dysfunction, diabetes, and underlying heart disease pre-RFCA. HF hospitalizations occurred more often in patients with than without recurrences (3.27 vs 0.84%, log-rank p <0.0001). After adjusting for confounders using a Cox model, AF recurrence remained an independent predictor of HF hospitalizations (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.80 to 4.47, p <0.0001). AF recurrence was a distinct HF hospitalization risk in patients with a left ventricular ejection fraction ≥50% (HR 4.54, 95% CI 2.38 to 8.65, p <0.0001) but not <50% (HR 1.31, 95% CI 0.65 to 2.62, p = 0.45), with significant interactions. Furthermore, patients with AF recurrences within 1 year had a greater HF hospitalization risk after 1 year (1.61% vs 0.79%, log-rank p = 0.019). In conclusion, AF recurrence after RFCA was independently associated with HF hospitalizations.

Catheter Ablation for Paroxysmal Atrial Fibrillation With Sick Sinus Syndrome: Insights From the Kansai Plus Atrial Fibrillation Registry.

BACKGROUND: Coexisting sick sinus syndrome (SSS) is associated with both electrical and structural atrial remodelling in patients with atrial fibrillation (AF). Limited data are available concerning catheter ablation (CA) for AF in this condition. This study investigated the efficacy of CA as a curative therapy for AF and SSS in a large-scale prospective multicentre registry. METHODS: The Kansai Plus Atrial Fibrillation (KPAF) registry enrolled 5,010 consecutive patients who underwent CA for AF; this included 3,133 patients with paroxysmal AF (mean age, 66 years; male, 69.3%; mean CHA2DS2-VASc score, 2.05±1.50; SSS, n=315 [tachy-brady syndrome, n=285]). The endpoints included the recurrence of AF with a blanking period of 90 days after CA, and de novo pacemaker implantation during the follow-up period (median duration, 2.93 years). RESULTS: The AF-free survival did not significantly differ between patients with and those without SSS (n=2,818) after the initial (log-rank p=0.864) and final sessions (log-rank p=0.268). Pacemakers were implanted in 48 patients with SSS, and implantation in this group was significantly associated with AF recurrence, including early recurrence (adjusted odds ratio, 3.57; 95% confidence interval, 1.67-7.64; p=0.002). The remaining 85.3% of patients with SSS did not require pacemaker implantation at 3 years after CA. CONCLUSIONS: Coexisting SSS did not adversely affect recurrence-free survival after CA for paroxysmal AF. Pacemaker implantation was not required in most patients with SSS, with AF recurrence serving as a strong predictor for this.

Characteristics of Patients With Metastatic Breast Cancer Who Survived more than 10 Years.

BACKGROUND/AIM: Despite advances in the treatment of breast cancer, metastatic breast cancer (MBC) remains difficult to cure, and few MBC patients survive 10 years after receiving a breast cancer metastasis diagnosis. We collected the cases of patients with MBC who survived >10 years post-metastasis diagnosis and assessed the patients' characteristics. PATIENTS AND METHODS: We retrospectively analyzed the cases of 245 consecutive patients diagnosed with MBC between January 2005 and December 2012 at our institution. Among them, 167 patients with confirmed survival of >10 years (i.e., long-term survival) or confirmed death at ≤10 years post-metastasis diagnosis were enrolled. RESULTS: There were 22 patients with MBC who survived >10 years. Regarding the cancer subtypes, 11 patients (50%) with long-term survival were HER2-positive. Seven of the 11 patients with HER2-positive MBC have been without recurrence although anti-HER2 therapy was discontinued. Triple-negative breast cancer (TNBC) was most common in the patients who survived ≤5 years but was not present in the >10-year survival group. In the HER2-negative cases, more cases in the long-term survival group were treated with local therapy (34.4% in the <5-year survival group, 43.8% in the 5-10-year group, and 72.7% in the >10-year group). CONCLUSION: MBC patients who survive >10 years after being diagnosed with metastasis are more likely to be HER2-positive and treated with local therapy. This suggests the efficacy of anti-HER2 therapy, and, conversely, clarifies unmet needs in TNBC and luminal-type MBC. The usefulness of local therapy was also supported by our findings.

Identification of MicroRNAs Associated with Histological Grade in Early-Stage Invasive Breast Cancer.

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing from early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with differential expression using bioinformatics. A total of 108 microRNAs were significantly differentially expressed in normal breast and breast cancer tissues. Using clinicopathological information and microRNA sequencing data of 430 patients with breast cancer from The Cancer Genome Atlas (TCGA), the differences in candidate microRNAs between low- and high-grade tumors were identified. Comparing the expression of the 108 microRNAs between low- and high-grade cases, 25 and 18 microRNAs were significantly upregulated and downregulated, respectively, in high-grade cases. Clustering analysis of the TCGA cohort using these 43 microRNAs identified two groups strongly predictive of histological grade. miR-3677 is a microRNA upregulated in high-grade breast cancer. The outcome analysis revealed that patients with high miR-3677 expression had significantly worse prognosis than those with low miR-3677 expression. This study shows that microRNAs are associated with histological grade in early-stage invasive breast cancer. These findings contribute to the elucidation of a new mechanism of breast cancer growth regulated by specific microRNAs.

Long-term prognosis of patients undergoing radiofrequency catheter ablation for atrial fibrillation: comparison between heart failure subtypes based on left ventricular ejection fraction.

AIMS: Heart failure (HF) prognosis has been reported similar in patients with preserved vs. reduced left ventricular ejection fraction (LVEF). This study compared the long-term prognosis of HF patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). METHODS AND RESULTS: Among 5010 patients undergoing RFCA in Kansai Plus AF registry, 656 patients (13.1%) with a documented history of HF were enrolled in the study before RFCA. The primary endpoint was a composite of all-cause death, HF hospitalization, and stroke or systemic embolism. Patients with reduced (<40%), mid-range (40-49%), and preserved (≥50%) LVEF were 98 (14.9%), 107 (16.3%), and 451 (68.8%) patients, respectively. The prevalence of ischaemic heart disease and cardiomyopathies was higher among patients with reduced as compared with preserved LVEF (27.6% vs. 10.0%, P < 0.05 and 36.7% vs. 15.3%, P < 0.05, respectively). The median follow-up period was 2.9 years. The 3-year cumulative risk for the primary endpoint was higher in patients with reduced LVEF (32.7%) compared to those with mid-range (11.7%) or preserved (11.6%) LVEF (P < 0.001). Reduced LVEF was the most significant independent risk factor for primary endpoint (hazard ratio, 2.83; 95% confidence interval 1.74-4.61, P < 0.001). The 3-year arrhythmia recurrence rate was similar among the groups (48.2%, 42.8%, and 47.3%, respectively, P = 0.75). CONCLUSION: This study raises hypothesis that patients with HFrEF and AF had approximately three times higher risk for a composite of all-cause death, HF hospitalization, and stroke or systemic embolism after AF ablation compared with patients with HFmrEF or HFpEF.

Prognostic value of tumor-infiltrating lymphocytes in estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer.

Tumor-infiltrating lymphocytes (TILs) are a significant prognostic factor in triple-negative breast cancer. However, the clinicopathological significance of TILs in estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer remains unclear. The purpose of the present study was to evaluate the role of TILs in the prognosis of ER-positive and HER2-negative breast cancer. A total of 65 consecutive patients with ER-positive and HER2-negative breast cancer were examined. TILs in stromal tissue (str-TILs) were graded using the International TILs Working Group criteria. The association between several clinicopathological factors and TIL grade were investigated, and the prognostic impact of TILs was compared between luminal A-like and luminal B-like breast cancer. A total of 51 patients (78.5%) had low-grade (0-10%), 11 (16.9%) had intermediate (10-40%) and 3 (4.6%) had high-grade (40-90%) str-TIL levels. There was a significant association between high levels of Ki67 expression and a high str-TIL count. Relapse-free survival was significantly worse in patients with luminal B-like cancer compared with that in patients with luminal A-like cancer. Patients with an intermediate or high str-TIL count had a better prognosis compared with those with a low str-TIL count. All patients with luminal B-like cancer and intermediate or high str-TIL levels developed no recurrence during follow-up. In conclusion, there was a significant correlation between high-grade str-TIL levels and high tumor cell proliferation rate, as well as high levels of Ki67 expression.

The association between late-phase early recurrence within the blanking period after atrial fibrillation catheter ablation and long-term recurrence: Insights from a large-scale multicenter study.

BACKGROUND: The relationship between the timing of the first early recurrence and late recurrence after a single catheter ablation procedure for atrial fibrillation is controversial. METHODS: The Efficacy of Short-Term Use of Antiarrhythmic Drugs After Catheter Ablation for Atrial Fibrillation trial followed 2038 patients who underwent radiofrequency catheter ablation for atrial fibrillation. RESULTS: Of the patients, 907 (45%) had early recurrences within 90 days after the initial ablation. We divided these patients into two groups according to the timing of the first early recurrence episode, namely the ER1 group (early recurrence during the early phase; 0-30 days, n = 814) and ER2 group (early recurrence during the late phase; 31-90 days, n = 93). Three years after ablation, patients with early recurrences had a significantly lower event-free rate from late recurrences after a 90-day blanking period than patients without early recurrences (36.2% and 74.2%, respectively; log-rank, P < 0.0001). Three years after ablation, the event-free rate was significantly higher in the ER1 than the ER2 group (38.3% and 17.1%, respectively; log-rank, P < 0.0001). Moreover, the event-free rate at 3 years in the ER2 group was extremely low (5.6%) in patient with non-paroxysmal atrial fibrillation. CONCLUSION: Early recurrences were strongly associated with late recurrences, especially in patients with the first recurrence episode at >1 month within the blanking period after a single ablation procedure. Therefore, these patients should undergo close observation during follow-up, when they had especially with non-paroxysmal atrial fibrillation.

Phase II Study of Nab-paclitaxel Plus Cyclophosphamide Plus Trastuzumab Neoadjuvant Chemotherapy in Early HER-2-positive Breast Cancer.

BACKGROUND/AIM: This phase II trial evaluated the efficacy and safety of neoadjuvant nab-paclitaxel plus cyclophosphamide (CPA) plus trastuzumab (AbraC-HER) in patients with early HER2-positive breast cancer. PATIENTS AND METHODS: This was a single-arm, open-label, single-center prospective phase II study. The primary endpoint was pathological complete response rate (pCR rate). The secondary endpoints were clinical antitumor efficacy and the frequency and severity of adverse events. RESULTS: Fifty-nine patients were enrolled in this study. pCR (ypT0/is ypN0) was achieved in 29 patients (49%). The overall response rate was 88.1% (52/59) in all patients. Dose reductions because of adverse events occurred in 3 patients (5.1%) and relative dose intensity was 98%. Compared to Abra-HER, AbraC-HER induced fewer adverse effects. CONCLUSION: Treatment with nab-paclitaxel plus CPA plus trastuzumab was tolerable and effective with a high pCR rate. This AbraC-HER neoadjuvant therapy may be a feasible new treatment option for patients with early HER2-positive breast cancer.

Oncological safety of immediate breast reconstruction with skin- or nipple-sparing mastectomy: the value of tumor-to-dermis distance measured by preoperative ultrasonography.

BACKGROUND: Immediate breast reconstruction with skin-sparing (SSM) or nipple-sparing mastectomy (NSM) has become a common procedure. In this study, we evaluated the distance between breast tumor and skin in a series of patients undergoing IBR as it relates to oncologic safety, namely, the incidence of recurrence. METHODS: The distance of the tumor to the dermis, rather than the outer layer of skin, was the key parameter of our preoperative ultrasound measurements. Our data set comprised the cases of 171 patients and 181 breasts with breast cancer that had undergone two-stage breast reconstruction by expander. The median age of the patients was 47 years (25-75 years). The overall median follow-up period was 47.1 months (8.8-125.3 months). Eighty-five breasts underwent IBR with SSM/NSM; the others underwent conventional mastectomy. RESULTS: Among the total of 181 reconstructed breast mounds, the locoregional recurrence rate was 1.1% (2 breasts) with no cases of skin flap recurrence or skin flap necrosis. The tumor-to-dermis distance of cases with skin preservation (NSM/SSM) was significantly less than that of cases with conventional mastectomy (3.8 ± 2.7 mm vs 5.2 ± 2.4 mm). In cases with invasive carcinoma, all cases whose tumor-to-dermis distance was less than 2 mm underwent resection of the skin immediately overlying the tumor. CONCLUSIONS: Our results suggested that a 2-mm distance between the dermis and tumor on ultrasound evaluation is sufficient for the use of this tissue as a skin flap in SSM/NSM procedures. Our study indicated that immediate breast reconstruction with SSM/NSM can be an oncologically safe surgical option for breast cancer. However, we recommend that resection of the skin overlying the tumor be performed in cases with invasive breast cancer in which the tumor-to-dermis distance is less than 2 mm. TRIAL REGISTRATION: Patients in this study were retrospectively registered. This study design was approved by our Clinical Ethics Committee (No 1297) ( http://ciru.dept.showa.gunma-u.ac.jp/guidance/storage-sample/list.html ).

Prospective observational study of chemotherapy-induced alopecia after sequential FEC + taxane and the effects of age in breast cancer patients.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a common and quite distressing adverse effects of chemotherapy. There are few detailed observational studies of CIA or of the impact of age on CIA. We performed a prospective observational study to investigate the prevalence and degree of CIA, including CIA of eyebrows, eyelashes, and body, and we examined patient's recovery from CIA, focusing on age-depending effects. METHODS: We analyzed 68 female Japanese patients with breast cancer (median age 53 years, range 29-76 years) who received perioperative adjuvant chemotherapy with fluorouracil/epirubicin/cyclophosphamide (FEC) and taxane. A questionnaire was administered at the point of chemotherapy completion and 6 and 12 months after chemotherapy completion. RESULTS: CIA occurred in all patients, with severe hair loss irrespective of age. CIA occurred mainly in the scalp but also in the eyebrows, eyelashes, and body for most of the patients. There were significant associations between the patient's age and the onset of hair regrowth in the eyebrows, eyelashes, and body. The onset of eyebrows, eyelash, and body hair growth were significantly shorter in the premenopausal patients. Any hair changes (e.g., thinned diameter, softer texture, curlier structure) were reported by 85.3% of the patients. CONCLUSIONS: Severe CIA occurred in all 68 patients who received FEC and taxane chemotherapy. The present findings provide the first data demonstrating that age was not associated with the degree or incidence of hair loss, but age affected the recovery from CIA. These results contribute more accurate information provision and insights regarding the proper treatment of CIA.

Implications of Topoisomerase (TOP1 and TOP2α) Expression in Patients With Breast Cancer.

BACKGROUND/AIM: We evaluated the usefulness of topoisomerases (TOPs) expression as prognostic predictors in breast cancer. PATIENTS AND METHODS: We retrospectively investigated sixty cases with primary breast cancer. We evaluated the tumor and non-tumor mRNA levels of TOP1 and TOP2α using quantitative reverse-transcription polymerase chain reaction. TOP1/TOP2α positivity was defined as the ratio of the mRNA expression of cancer/normal tissue of >1 for both TOP1 and TOP2α. RESULTS: TOP1 and TOP2α were markedly overexpressed in breast cancer tissues compared to normal breast tissues. Of the 60 cases, 46 (76.7%) were positive for TOP1/TOP2α. The relapse-free survival was relatively shorter for patients with positive TOP1/TOP2α. There was no recurrent disease among the 14 patients who were negative for TOP1/TOP2α, whereas four of the 46 TOP1/TOP2α-positive patients had disease recurrence. CONCLUSION: Negative TOP1 or TOP2α expression may be useful for predicting better prognoses in breast cancer patients.

Phase II study of sequential S-1 and cyclophosphamide therapy in patients with metastatic breast cancer.

BACKGROUND: S-1 and cyclophosphamide (CPA) can be given orally, and their combination may have great potential for treating metastatic breast cancer (MBC). A phase I study of sequential S-1 and CPA therapy was conducted in patients with MBC; the recommended doses that were determined for this regimen were 80 mg/m2/day for S-1 and 100 mg/m2/day for CPA. We then conducted a phase II study of this oral S-1 and CPA regimen. METHODS: This was a single-arm, open-label, single-center prospective phase II study to evaluate the efficacy of a sequential S-1 and CPA regimen for MBC. S-1 was administered orally 2×/day for 14 consecutive days, and then CPA was administered orally 2×/day for 14 consecutive days in a repeating 4-week cycle (S-1 for 2 weeks, CPA for 2 weeks). The primary endpoint was the overall response rate (ORR). Secondary endpoints included the overall survival (OS), progression-free survival (PFS), clinical benefit rate (CBR) and safety. RESULTS: Thirty-six patients were enrolled in this study. The overall response was complete response in 0 (0%), partial response in 12 (33.3%), stable disease in 12 (33.3%), and progressive disease in 11 (30.1%) patients. The ORR was 33.3% (12/36). The CBR was 66.7% (24/36). The median PFS was 9.5 months (95%CI: 7.8-12.6 months). The median OS was 20.2 months (95%CI: 15.0-25.4 months) Grade 3/4 adverse events included leukopenia in seven patients (19.4%). Dose reductions because of adverse events occurred in 12 patients (33.3%). There was no treatment-related mortality. CONCLUSION: The combination of sequential therapy with S-1 and CPA was tolerable and had efficacy with good disease control. Sequential therapy with S-1 and CPA may be a feasible new treatment option for patients with MBC; however, further study is warranted to explore the efficacy of this therapy. TRIAL REGISTRATION: JRCT, JRCTs031180296 . Registered 2 December 2019 - Retrospectively registered.

VEGF-A Is Associated With the Degree of TILs and PD-L1 Expression in Primary Breast Cancer.

BACKGROUND/AIM: Vascular endothelial growth factor-A (VEGF-A), an important angiogenic factor, has been reported to effect cancer growth and development. Recent reports indicated that anti-VEGF therapy has an important effect of enhancing anti-tumor immunity in various cancers. In the current study, we investigated the relationship between VEGF-A expression and immunological factors, including programmed cell death ligand 1 (PD-L1) and the degrees of stromal tumor-infiltrating lymphocytes (TILs) in breast cancer. PATIENTS AND METHODS: This study enrolled 97 cases with invasive breast cancer who had undergone surgery without preoperative therapy. The grades of stromal-TILs were evaluated using the criteria of the International Working Group for TILs in breast cancer: low, intermediate, and high. VEGF-A and PD-L1 positivity were evaluated by immunohistochemistry. The relationship between VEGF-A expression and the expression of PD-L1 and TILs was investigated. RESULTS: Among the 97 cases, 37 (38.1%) had positive VEGF-A expression in the breast tumor. We divided the cases in two groups based on the VEGF-A expression levels. The analysis revealed that PD-L1 positivity was significantly associated with VEGF-A expression in the breast tumor (29.7% vs. 10.0%, p=0.014). Among the cases with positive PD-L1, 36.7% of VEGF-positive cases and none of VEGF-negative cases had low TILs in the breast tumor. CONCLUSION: VEGF-A expression in breast cancer may reflect PD-L1 expression in the tumor. VEGF-A may act as a negative biomarker of TILs in PD-L1-positive breast cancer. Our results suggest that VEGF-A may be predictive of immunological features and may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.

Implications of Low Serum Albumin as a Prognostic Factor of Long-term Outcomes in Patients With Breast Cancer.

BACKGROUND/AIM: We examined the relationship between preoperative serum albumin levels and long-term outcomes in patients with breast cancer. PATIENTS AND METHODS: We retrospectively analyzed the records of 157 patients who underwent breast cancer surgery at a single institution. We divided the patients into those with <4.0 g/dl and those with ≥4.0 g/dl preoperative serum albumin. RESULTS: The overall median follow-up period was 86.7 months. Among the 157 patients, 19 (12.1%) had decreased serum albumin levels preoperatively. A significant association with preoperative albumin levels was found only for patient age; however, we were unable to determine an association between preoperative albumin levels and various clinical features. The recurrence-free survival (p=0.030) and the overall survival (p=0.001) were both significantly shorter in patients with low albumin levels. CONCLUSION: Low serum albumin levels were associated with poor prognosis, but not with poor-prognostic factors. Therefore, low albumin levels may reflect the tumor microenvironment in breast cancer.

Sex differences in atrial fibrillation ablation outcomes: insights from a large-scale multicentre registry.

AIM: The impact of sex differences on the clinical outcomes of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is controversial. We investigated the sex differences regarding the efficacy and clinical outcomes of RFCA of AF. METHODS AND RESULTS: We conducted a large-scale, prospective, multicentre, observational study (Kansai Plus Atrial Fibrillation Registry). We enrolled 5010 consecutive patients who underwent an initial RFCA of AF at 26 centres (64 ± 10 years; non-paroxysmal AF, 35.7%). The median follow-up duration was 2.9 years. Female patients (n = 1369, 27.3%) were older (female vs. male, 68 ± 9 vs. 63 ± 11 years, P < 0.0001) with a lower prevalence of non-paroxysmal AF (27.1% vs. 38.9%, P < 0.0001). Fewer females experienced time-dependent pulmonary vein (PV) reconnections and more females received a non-PV foci ablation than males in the index RFCA. The 3-year cumulative incidence of AF recurrences in the multivariate analysis after single procedures was significantly higher in females than males (43.3% vs. 39.0%, log rank P = 0.0046). Females remained an independent predictor of AF recurrence (hazard ratio 1.24; 95% confidence interval 1.12-1.38, P < 0.0001). The AF recurrence rates after multiple procedures were also higher in females, but fewer females experienced PV reconnections during second sessions. More females experienced de novo pacemaker implantations during the long-term follow-up. Females were associated with a higher risk of heart failure hospitalizations and major bleeding after RFCA in the multivariate analysis. CONCLUSIONS: Females experienced more frequent AF recurrences probably due to non-PV arrhythmogenicity and de novo pacemaker implantations than males during the long-term follow-up after RFCA of AF.

Relationship Between FDG Uptake and the Platelet/lymphocyte Ratio in Patients With Breast Invasive Ductal Cancer.

BACKGROUND/AIM: We investigated the relationship between F18-fluorodeoxyglucose (FDG) uptake and the platelet/lymphocyte ratio (PLR), as both represent inflammation. PATIENTS AND METHODS: We retrospectively analyzed the cases of 143 consecutive invasive ductal carcinoma patients who had undergone preoperative FDG-PET and surgery. We divided the patients into groups based on their maximum standardized uptake value (SUVmax) values: low (<2.5) and high (≥2.5) and based on their PLRs: low (<130) and high (≥130). We determined the relationships between the SUVmax or PLR and clinicopathological features. RESULTS: Seventy-three patients (51.0%) had a high SUVmax in their primary tumor. There were significant associations between SUVmax and the PLR. A multivariate analysis revealed that high PLR, but not NLR, was independent factor associated with a high SUVmax. Seventy-four patients (51.7%) had a high PLR; The factors significantly associated with high PLR were large tumor size, presence of node metastasis, presence of vascular invasion, high NLR, and high SUVmax. CONCLUSION: In breast cancer patients, the PLR is independently associated with the SUVmax, but not with recurrent disease. In breast cancer patients with a high SUVmax and/or PLR, these values may reflect the tumor microenvironment.

FDG uptake reflects breast cancer immunological features: the PD-L1 expression and degree of TILs in primary breast cancer.

BACKGROUND: High F18-fluorodeoxyglucose (FDG) uptake has been reported to be a predictor of poor prognosis in patients with breast cancer. We investigated the relationship between FDG uptake and immunological factors, including the data of programmed cell death-ligand 1 (PD-L1), CD8, and tumor-infiltrating lymphocytes (TILs). METHODS: Breast cancer tissues of 97 patients who underwent surgery without preoperative therapy were examined. The grade of stromal TILs was immunohistochemically evaluated using the criteria of the International TILs Working Group in breast cancer. PD-L1 positivity and CD8 positivity were immunohistochemically evaluated. The FDG uptakes were evaluated based on the standardized uptake value max (SUVmax). The relationships between SUVmax and TIL grade and expression of PD-L1 and CD8 were investigated. RESULTS: Among the 97 patients, 41 (42.3%) had a high SUVmax in their primary tumor, based on the SUVmax cut-off value 3 yielded by receiver operating characteristic curves. PD-L1 was positive in 17 patients (17.5%). Our analyses revealed that large tumor size, high nuclear grade, high degree of TILs and positive expression of PD-L1 were significantly associated with high SUVmax in the primary tumor. There were significant associations between SUVmax and the degree of TILs (r = 0.428, p < 0.001) and between SUVmax and the PD-L1 positivity (r = 0.413, p < 0.001). All cases with a high degree of TILs showed high CD8 expression. CONCLUSION: Our results indicate that the FDG uptake may be predictive of immunological features including TILs and PD-L1 expression in breast cancer patients. Additional research is necessary to further evaluate FDG-PET as a biomarker of immune checkpoint therapy in breast cancer.

The pathological complete response and secreted protein acidic and rich in cysteine expression in patients with breast cancer receiving neoadjuvant nab-paclitaxel chemotherapy.

Biomarkers that can accurately predict treatment response are required for indicating optimal neoadjuvant treatments. The current study assessed the predictive value of secreted protein acidic and rich in cysteine (SPARC) mRNA expression for the response to neoadjuvant nab-paclitaxel (nab-PTX) therapy in patients with breast cancer. It was hypothesized that SPARC expression can affect the response to albumin-bound taxanes, including nab-PTX since SPARC binds albumin with a high affinity. Pre-therapeutic specimens of core needle biopsies were analyzed from 50 patients in a phase II trial of neoadjuvant nab-PTX and the factors that were associated with a pathological complete response (pCR) were assessed. The pre-therapeutic tumor mRNA levels of chemotherapy-related proteins were quantified, including SPARC, and the correlations with post-therapeutic clinicopathological factors were assessed, including with pCR. The results demonstrated that pre-therapeutic SPARC mRNA expression was significantly higher in non-pCR patients compared with patients with pCR (92.37±55.33 vs. 56.53±30.19; P=0.027). A cutoff point of 48.5 was determined using receiver operating characteristic (ROC) curve analysis (sensitivity, 83.3%; specificity, 50.0%), and patients were classified into low and high SPARC expression groups. High SPARC expression was associated with histological grade (P=0.035), estrogen receptor expression (P=0.037), and progesterone receptor expression (P=0.002) but not with HER2 (P=0.895), and Ki-67 LI (P=0.743) expression. The results of the current study indicated that a high SPARC mRNA expression was a negative predictor of pCR following neoadjuvant nab-PTX therapy regardless of breast cancer subtype. The phase II study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the National Hospital Organization Takasaki General Medical Center (Registration nos. H23-9 and H23-33).

Eribulin Suppresses New Metastases in Patients With Metastatic Breast Cancer.

BACKGROUND/AIM: This study aimed to investigate the progression type of metastatic breast cancer (MBC) in patients undergoing eribulin chemotherapy. MATERIALS AND METHODS: We retrospectively investigated the cases of 66 consecutive patients with MBC who underwent eribulin chemotherapy. RESULTS: A total of 15 patients (22.7%) received eribulin as a 3rd-line or later treatment, and 17 (25.8%) received eribulin as a 1st-line treatment. The overall response was complete response in 0 (0%), partial response in 15 (22.7%), stable disease in 27 (40.9%), and progressive disease in 24 (36.4%) patients. By the time of data cut-off, time to treatment failure (TTF) events had been observed in 60 patients (90.9%), among whom, 15 (25%) had disease progression due to NM, and 45 (75%) had disease progression due to PL. In the regimen before eribulin administration, among 49 patients, 24 (49.0%) had disease progression due to NM. Luminal-type patients and those with triple-negative breast cancer exhibited a similar tendency, i.e., the rate of NM was lower in the patients treated with eribulin. The rate of NM was lower in the patients treated with eribulin in the 1st-line setting than that in patients treated with eribulin as a later treatment. CONCLUSION: Eribulin has a potential antitumor mechanism to prevent new metastasis. Eribulin may be effective against both the epithelial-mesenchymal transition (EMT) process and new metastasis.