A case of autoimmune encephalitis in a patient with a solitary intracranial plasmacytoma.

A 65-year-old woman presented with fever and abnormal behavior. Magnetic resonance imaging showed swelling of the left medial temporal lobe and an intracranial extra-axial occipital tumor. While her neurological symptoms improved after the administration of corticosteroid therapy under the suspicion of autoimmune encephalitis, the occipital tumor unexpectedly shrank, and the diagnosis of a solitary plasmacytoma was confirmed by biopsy. Additional examinations revealed elevated anti-glutamate receptor antibodies in the cerebrospinal fluid. The patient was diagnosed with autoimmune encephalitis concurrent with an intracranial solitary plasmacytoma. Central nervous system involvement can be considered a neurological complication in patients with a solitary plasmacytoma.

Longitudinal Changes in Iron and Myelination Within Ischemic Lesions Associate With Neurological Outcomes: A Pilot Study.

BACKGROUND: Combined quantitative susceptibility mapping and R2* relaxometry can distinguish iron and myelin components in ischemic lesions. We aimed to investigate whether longitudinal changes in magnetic susceptibility and R2* values within ischemic lesions were associated with neurological outcomes. METHODS: In this single-center prospective study, we included patients, 20 to 90 years of age, who were consecutively admitted to the stroke care unit between August 2020 and March 2022 due to acute ischemic stroke. The participants underwent 2 instances of quantitative susceptibility mapping and R2* relaxometry scanning before and after stroke rehabilitation. We compared the changes in these quantitative measures across different subtypes of acute ischemic stroke. Multiple linear regression models were used to investigate the associations between the National Institutes of Health Stroke Scale scores and the mean magnetic susceptibility and R2* values in ischemic lesions. RESULTS: Among a total of 112 patients with acute ischemic stroke, 32 participants (aged 73.3±9.4 years; 20 men and 12 women) were evaluated. The median time from stroke onset to the first imaging was 5 days and that to the second imaging was 102 days. The changes in magnetic susceptibility values of branch atheromatous disease were higher than those of cardioembolism (mean difference, 0.018 [95% CI, 0.009-0.027] ppm; P<0.001) and lacunar (mean difference, 0.013 [95% CI, 0.005-0.020] ppm; P=0.004). Across all patients, the changes in National Institutes of Health Stroke Scale scores were associated with those of magnetic susceptibility values (coefficient, 0.311 [95% CI, 0.098-0.520]; P=0.017) but not with R2* values (coefficient, 0.114 [95% CI, -0.127 to 0.345]; P=0.291). CONCLUSIONS: The longitudinal changes in the magnetic susceptibility values within ischemic lesions were associated with neurological outcomes during the restorative stages poststroke in patients experiencing acute ischemic stroke. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050719.

Assessing white matter microstructural changes in idiopathic normal pressure hydrocephalus using voxel-based R2* relaxometry analysis.

Background: R2* relaxometry and quantitative susceptibility mapping can be combined to distinguish between microstructural changes and iron deposition in white matter. Here, we aimed to explore microstructural changes in the white matter associated with clinical presentations such as cognitive impairment in patients with idiopathic normal-pressure hydrocephalus (iNPH) using R2* relaxometry analysis in combination with quantitative susceptibility mapping. Methods: We evaluated 16 patients clinically diagnosed with possible or probable iNPH and 18 matched healthy controls (HC) who were chosen based on similarity in age and sex. R2* and quantitative susceptibility mapping were compared using voxel-wise and atlas-based one-way analysis of covariance (ANCOVA). Finally, partial correlation analyses were performed to assess the relationship between R2* and clinical presentations. Results: R2* was lower in some white matter regions, including the bilateral superior longitudinal fascicle and sagittal stratum, in the iNPH group compared to the HC group. The voxel-based quantitative susceptibility mapping results did not differ between the groups. The atlas-based group comparisons yielded negative mean susceptibility values in almost all brain regions, indicating no clear paramagnetic iron deposition in the white matter of any subject. R2* and cognitive performance scores between the left superior longitudinal fasciculus (SLF) and right sagittal stratum (SS) were positively correlated. In addition to that, R2* and gait disturbance scores between left SS were negatively correlated. Conclusion: Our analysis highlights the microstructural changes without iron deposition in the SLF and SS, and their association with cognitive impairment and gait disturbance in patients with iNPH.

Relationship between brain iron dynamics and blood-brain barrier function during childhood: a quantitative magnetic resonance imaging study.

BACKGROUND: Mounting evidence suggests that the blood-brain barrier (BBB) plays an important role in the regulation of brain iron homeostasis in normal brain development, but these imaging profiles remain to be elucidated. We aimed to establish a relationship between brain iron dynamics and BBB function during childhood using a combined quantitative magnetic resonance imaging (MRI) to depict both physiological systems along developmental trajectories. METHODS: In this single-center prospective study, consecutive outpatients, 2-180 months of age, who underwent brain MRI (3.0-T scanner; Ingenia; Philips) between January 2020 and January 2021, were included. Children with histories of preterm birth or birth defects, abnormalities on MRI, and diagnoses that included neurological diseases during follow-up examinations through December 2022 were excluded. In addition to clinical MRI, quantitative susceptibility mapping (QSM; iron deposition measure) and diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL; BBB function measure) were acquired. Atlas-based analyses for QSM and DP-pCASL were performed to investigate developmental trajectories of regional brain iron deposition and BBB function and their relationships. RESULTS: A total of 78 children (mean age, 73.8 months ± 61.5 [SD]; 43 boys) were evaluated. Rapid magnetic susceptibility progression in the brain (Δsusceptibility value) was observed during the first two years (globus pallidus, 1.26 ± 0.18 [× 10- 3 ppm/month]; substantia nigra, 0.68 ± 0.16; thalamus, 0.15 ± 0.04). The scattergram between the Δsusceptibility value and the water exchange rate across the BBB (kw) divided by the cerebral blood flow was well fitted to the sigmoidal curve model, whose inflection point differed among each deep gray-matter nucleus (globus pallidus, 2.96-3.03 [mL/100 g]-1; substantia nigra, 3.12-3.15; thalamus, 3.64-3.67) in accordance with the regional heterogeneity of brain iron accumulation. CONCLUSIONS: The combined quantitative MRI study of QSM and DP-pCASL for pediatric brains demonstrated the relationship between brain iron dynamics and BBB function during childhood. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000039047, registered January 6, 2020.

Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer.

PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042). Also, the disease-free survival periods were prolonged following treatment of hyperlipidemia (p = 0.047, hazard ratio: 0.399) and statin administration (p = 0.028, hazard ratio: 0.328). CONCLUSION: In cT1 breast cancer, the results suggest that oral statin therapy may contribute to favorable outcomes.

[The Long Term Result of Rhomboid Flap Reconstruction for Locally Advanced Breast Cancer].

In patients undergoing mastectomy for locally advanced breast cancer, surgical skin flap reconstruction is sometimes required in order to cover large skin defects. Generally, we reconstruct by using latissimus dorsi or rectus abdominis when the direct closure is difficult. These constructions are difficult and have various complications. Our facility started rhomboid flap reconstruction after mastectomy. We report the result of rhomboid flap reconstruction. Five patients were performed rhomboid flap reconstruction. Three of 5 patients were cutaneous invasion, 1 patient was skin metastasis after mastectomy, and the other patient was Paget's disease. Regarding post operative complications, there were 2 cases of surgical site infection, 2 cases of skin necrosis and 1 case of seroma. The median length of postoperative hospital stay was 9 days. Median follow-up period was 381 days(221-508 days). Only 1 patient progressed. The median progression-free survival was 332 days(221-508 days). Rhomboid flap reconstruction is effective way for the improvement of the QOL of the patients with advanced breast cancer because the long term result was not bad and we can repair large skin defect easily.

Clinical verification of the relationship between serum lipid metabolism and immune activity in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Lipid metabolism has been recently reported to affect the prognosis and tumor immune activity in cancer patients. However, the effect of lipid metabolism on chemosensitivity in patients with breast cancer treated with neoadjuvant chemotherapy (NAC) remains unclear. METHODS: We examined 327 patients with breast cancer who were treated with NAC followed by curative surgery. The correlations between the serum levels of total cholesterol (TC) and triglyceride (TG) and the clinicopathological features, including the efficacy of NAC, neutrophil-to-lymphocyte ratio (NLR), and absolute lymphocyte count (ALC), were evaluated retrospectively. RESULTS: Serum TG levels were increased after NAC in all the subtypes, and the rate of change was the highest, especially in triple-negative breast cancer (TNBC) (21.0% → 48.1%). In addition, only TNBC patients with an objective response (OR) had significantly higher TG levels after NAC than those without (P = 0.049). Patients with a high ALC before NAC had significantly higher TG levels after NAC than patients with all breast cancer (P = 0.001), HER2-enriched breast cancer (P = 0.021), and TNBC (P = 0.008). Patients with a low NLR before NAC had significantly higher TG levels after NAC only among patients with TNBC (P = 0.025). In patients with human epidermal growth factor receptor 2-enriched breast cancer, the group with normal TC levels before NAC had significantly better OS than those with high TC levels (P = 0.013, log-rank test), and in patients with TNBC, the group with high TC levels after NAC had significantly better OS than those with normal TC levels (P = 0.014, log-rank test). CONCLUSIONS: Good systemic immune activity and chemosensitivity may be associated with lipid metabolism regulated by NAC in TNBC patients.

Eribulin Treatment Promotes Re-expression of Estrogen Receptor in Endocrine Therapy-resistant Hormone Receptor-positive Breast Cancer Cells.

BACKGROUND/AIM: Hypoxia is significantly associated with the development of drug resistance, and endocrine therapy is ineffective against hormone receptor (HR)-positive breast cancer in hypoxic tumor environments. Eribulin has a unique anticancer effect in breast cancer cells and improves tumor hypoxia by vascular remodeling. Therefore, we investigated the effect of eribulin on HR-positive breast cancer cells that were resistant to endocrine blockade. MATERIALS AND METHODS: We established hypoxia-resistant breast cancer cell lines by continuous culture in a hypoxic environment. Parental and hypoxia-resistant cell lines were treated with eribulin and/or tamoxifen, and estrogen receptor (ER)-, epithelial-mesenchymal transition-, and hypoxia-related gene and protein expression changes in each surviving cell line were assessed. In addition, proliferation was assessed after eribulin treatment in the parental and hypoxia-resistant cell lines. We also assessed the effect of eribulin in vivo using subcutaneous xenograft models. RESULTS: Hypoxia-resistant cell lines showed significantly decreased expression of epithelial and ER-related markers and exhibited a higher level of resistance to tamoxifen. Conversely, eribulin treatment increased epithelial and ER-related gene and protein expression in hypoxia-resistant cell lines and enhanced the anticancer effect of tamoxifen. In in vivo xenograft models, eribulin treatment of hypoxia- and tamoxifen-resistant tumors slightly induced the re-expression of ER. In addition, hypoxia-resistant tumors treated with eribulin tended to respond better to tamoxifen. CONCLUSION: Eribulin ameliorated the aggressive behavior caused by hypoxia and induced the re-expression of ER in hypoxia-resistant breast cancer cells. Eribulin treatment of HR-positive breast cancer may resensitize cells to hormone blockade.

Prognostic Impact of Smoking on Bevacizumab Combination Chemotherapy for Advanced Breast Cancer.

BACKGROUND/AIM: Smoking has been a proven carcinogenic risk factor for various cancers, including breast cancer. Furthermore, smoking has been recognized as a prognostic factor of breast cancer. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) used in combination with chemotherapy to treat breast cancer. We, herein, investigated the effect of smoking on the prognosis of unresectable breast cancer patients who received bevacizumab plus weekly paclitaxel. PATIENTS AND METHODS: From April 2011 to June 2022, 131 patients received bevacizumab plus weekly paclitaxel for unresectable breast cancer. At their first visit to our hospital, smoking status (i.e., period of smoking and amount of smoking per day) was evaluated by interview, and packs-years were calculated. RESULTS: Time to treatment failure (TTF) was significantly longer in the high packs-years group than the low packs-years group (p=0.010, log-rank). The log-rank test showed that the high packs-years group had a significantly longer overall survival than the low packs-years group (p=0.049, log-rank). Multivariate analysis of TTF revealed that progesterone receptor (p=0.005, HR=0.408) and packs-years (p=0.007, HR=0.391) were independent factors. CONCLUSION: A history of smoking may impact prognosis of combination chemotherapy with bevacizumab for advanced breast cancer treatment.

Factor Analysis of Intraoperative Bleeding Loss and its Impact on Prognosis in Breast Cancer.

BACKGROUND/AIM: Intraoperative blood loss (IBL) during the surgical treatment of various cancers affects complication rates and prognosis. However, few studies have examined the importance of minimal IBL in breast cancer surgery. We used factor analysis to examine the prognostic importance of IBL in breast cancer. PATIENTS AND METHODS: One hundred ninety-seven patients who underwent mastectomy plus axillary lymph node dissection (level II) after preoperative chemotherapy between June 2007 and June 2021 were included. Pearson's Chi-square test was used to confirm the relationships between different factors. Kaplan-Meier survival curves and the log-rank test were used to examine prognosis. Logistic regression was performed using a Cox proportional hazards model. RESULTS: The median IBL was 55.0 g (range=5.0-420.0 g). IBL was <100 g in 143 patients (72.5%), 100-200 g in 39 patients (19.8%), and >200 g in 15 patients (7.6%). Logistic regression analysis showed that patients with IBL ≥200 g had a significantly worse prognosis (disease-free survival: p=0.003, log-rank test; overall survival: p<0.001, log-rank test). Factor analysis revealed that HER2-negative status (p=0.015), non-pathological complete response (p=0.031), obesity (p=0.001), heavy smoking (p=0.047), and diabetes mellitus (p=0.004) were significantly associated with increased IBL. CONCLUSION: IBL in breast cancer was correlated with various clinicopathological factors associated with a poor prognosis, suggesting that increased IBL may be associated with poor prognosis in breast cancer as well.

Clinical Verification on the Predictors for Febrile Neutropenia in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Febrile neutropenia (FN) is a potentially life-threatening complication of chemotherapy. In this study, we evaluated the predictors for FN according to neoadjuvant chemotherapy (NAC) in all breast cancer subtypes. PATIENTS AND METHODS: We examined 327 patients with breast cancer treated with NAC. The correlation between the development of FN and clinicopathological features, including systemic inflammatory markers, and prognosis was evaluated retrospectively. RESULTS: There were no significant differences between patients with and without FN in terms of disease-free survival or overall survival (p=0.562, p=0.149, log-rank, respectively). Low body mass index (BMI) (p<0.001), white blood cells (WBC) at baseline (p=0.008), and NAC regimen (p=0.026) significantly related with FN in all patients with breast cancer. Moreover, among patients with hormone receptor-positive/human epidermal growth factor receptor 2-positive breast cancer, low WBC (p=0.007) and low absolute lymphocyte counts (ALC) at baseline (p=0.039) were significantly associated with FN, and overall survival was significantly worse in patients with FN development (p=0.039, log-rank). CONCLUSION: Poor immune activity-related factors, low ALC or BMI, may be useful to predict the development of FN in patients with breast cancer.

Early-onset Alzheimer Disease Associated With Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. Although recent reports have noted that cognitive impairment is common in NMOSD, little longitudinal information is available on the trajectories of cognitive function in the disease. Here, we report a case of a 55-year-old woman with an 11-year history of NMOSD who visited our memory clinic for progressive memory loss. She was diagnosed with early-onset Alzheimer disease based on amyloid and tau positron emission tomography imaging biomarkers. This is the first report of early-onset Alzheimer disease in a patient with NMOSD. Complications of Alzheimer disease should be considered when patients with NMOSD exhibit rapid cognitive decline. More longitudinal studies of NMOSD with cognitive impairment are needed.

The Effect of Smoking on Endocrine Therapy for Stage IV Hormone Receptor Positive Breast Cancer.

BACKGROUND/AIM: Smoking worsens breast cancer prognosis. It has been reported that tobacco components directly reach the mammary gland tissue, causing smoking-related DNA damage and biological effects. We hypothesized that smoking may have characteristics that affect the therapeutic effect and clinical course in patients with stage IV hormone receptor-positive breast cancer (HRBC) who received endocrine therapy as the first-line treatment. PATIENTS AND METHODS: Fifty-six patients diagnosed with stage IV HRBC were treated with endocrine therapy as the first-line treatment. Before treatment, the period and amount of smoking were confirmed through patient interviews, and each pack-year was recorded. RESULTS: Disease progression with new metastases was more frequent in smokers than non-smokers during endocrine therapy as first-line treatment (p=0.034). Furthermore, as the pack-year increased, new metastases tended to appear [pack-year ≤15; hazard ratio (HR)=1.929, p=0.507; pack-year 15-30, HR=3.857, p=0.223; pack-year >30, HR=7.714, p=0.028]. CONCLUSION: In stage IV HRBC, smoking increases the metastatic potential of breast cancer, suggesting that changes in its biology may lead to poor prognosis.

Validation of the Optimum Timing of Assessment of Tumor Infiltrating Lymphocytes During Preoperative Chemotherapy for Breast Cancer.

BACKGROUND/AIM: Tumor microenvironment (TME) assessment is considered to play an important role in the prediction of prognosis and therapeutic response following breast cancer treatment. No consensus has been reached regarding evaluation methods despite reports on the utilization of tumor-infiltrating lymphocytes (TILs) for immune TME (iTME) monitoring. Optimum timing of iTME assessment has not yet been established. PATIENTS AND METHODS: Two hundred thirty-nine patients were treated with neoadjuvant chemotherapy (NAC). During the period from diagnostic needle biopsy to NAC initiation for breast cancer, the optimal evaluation timing was examined using a receiver operating characteristic (ROC) curve analysis. RESULTS: A significant correlation between TILs and pathological complete response (pCR) was only observed in the short-term group (≤35 days) (p=0.033). Prognostic analysis revealed that in the short-term group, patients with high TIL levels had a significantly better survival prognosis relative to those with low TIL levels (>35 days) [disease-free survival (DFS): p=0.001, overall survival (OS): p=0.021]. TILs were identified as an independent factor affecting DFS in a multivariate analysis (p=0.008, hazard ratio=0.130). CONCLUSION: TIL assessment during NAC for breast cancer is a prognostic predictor only when performed at ≤35 days before NAC initiation.

Differences in tumor-infiltrating lymphocyte density and prognostic factors for breast cancer by patient age.

BACKGROUND: Lymphocytes that surround cancer participate in tumor-related immune responses and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs index the tumor microenvironment and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TIL density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of preoperative chemotherapy (POC) in BC patients who were aged either less than 45 years or more than 60 years. METHODS: We retrospectively examined the data of 356 breast cancer patients who underwent POC, including 75 patients aged ≤ 45 years and 116 patients aged > 60 years. Using pre-treatment needle biopsy specimens, TIL density was compared for each age group by Student's t-test. After analyzing different factors that affect TIL density, prognostic factors were also examined. RESULTS: Older patients with triple-negative BC had significantly lower TIL density than younger patients, while in human epidermal growth factor receptor 2 (HER2)-enriched BC, TIL density was significantly higher in the younger age group than that in the older age group. In addition, younger patients with HER2-rich breast cancer showed significantly higher complete pathological response rates than older patients with HER2-rich BC. In addition, significant differences in overall survival were observed among these patients with triple-negative BC. CONCLUSIONS: Our study suggests that younger BC patients possess significantly higher TIL density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.

Penumbra Detection With Oxygen Extraction Fraction Using Magnetic Susceptibility in Patients With Acute Ischemic Stroke.

BACKGROUND: The oxygen extraction fraction (OEF) has been applied to identify ischemic penumbral tissue, but is difficult to use in an urgent care setting. This study aimed to investigate whether an OEF map generated via magnetic resonance quantitative susceptibility mapping (QSM) could help identify the ischemic penumbra in patients with acute ischemic stroke. MATERIALS AND METHODS: This prospective imaging study included 21 patients with large anterior circulation vessel occlusion who were admitted <24 h after stroke onset and 21 age-matched healthy controls. We identified the ischemic penumbra as the region with a Tmax of >6 s during dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) and calculated the perfusion-core mismatch ratio between the ischemic penumbra and infarct core volumes. The OEF values were measured based on magnetic susceptibility differences between the venous structures and brain tissues using rapid QSM acquisition. Volumes with increased OEF values were compared to the ischemic penumbra volumes using an anatomical template. RESULTS: Eleven patients had a perfusion-core mismatch ratio of ≥1.8, and reperfusion therapy was recommended. In these patients, the volumes with increased OEF values of >51.5%, which was defined using the anterior circulation territory OEF values from the 21 healthy controls, were positively correlated with the ischemic penumbra volumes (r = 0.636, 95% CI: 0.059 to 0.895, P = 0.035) and inversely correlated with the 30-day change in the National Institutes of Health Stroke Scale scores (r = -0.624, 95% CI: -0.891 to -0.039, P = 0.041). CONCLUSION: Tissue volumes with increased OEF values could predict ischemic penumbra volumes based on DSC-MRI, highlighting the potential of the QSM-derived OEF map as a penumbra biomarker to guide treatment selection in patients with acute ischemic stroke.

Outcome Prediction After Neoadjuvant Chemotherapy (NAC) for Breast Cancer, Using Tumor-infiltrating Lymphocytes Within Fibrotic Foci of Tumor Stroma (FF-TILs).

BACKGROUND/AIM: Tumor-infiltrating lymphocytes (TILs), which are indicators of immune response monitoring, are generally mononuclear immunocytes that aggregate with tumors and are thought to have a close relationship with cancer cells. On the other hand, a fibrotic focus (FF) within the stroma of a tumor is a histological formation that plays an important role in the cancer microenvironment with regard to proliferation and development. Here, we focused on TILs that exist within the FF and performed pathological evaluations. PATIENTS AND METHODS: Of the 320 patients treated with neoadjuvant chemotherapy (NAC), 239 subjects who were able to evaluate FF-TILs were targeted. Lymphocytes that infiltrate the FF are FF-TILs. RESULTS: The disease-free survival (DFS) period after NAC for the high-FF-TIL group was found to be significantly longer than that for the low-FF-TIL group for all cases (p<0.001) and for all subtypes of triple-negative breast cancer (TNBC) (p=0.001), human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p=0.010), and hormone receptor-positive breast cancer (HRBC) (p=0.003). In multivariable analysis as well, high-FF-TIL group classification was an independent factor for recurrence after NAC for all cases [p<0.001, hazard ratio (HR)=0.198] and all subtypes of TNBC (p=0.006, HR=0.172), HER2BC (p=0.025, HR=0.135), and HRBC (p=0.007, HR=0.228). CONCLUSION: FF-TILs are possibly a useful factor for predicting recurrence of breast cancer after NAC.

Utility of Follow-up With Absolute Lymphocyte Count in Patients Undergoing Eribulin Treatment for Early Detection of Progressive Advanced or Metastatic Breast Cancer.

BACKGROUND/AIM: Eribulin, a non-taxane microtubule inhibitor, improves the tumor immune microenvironment via vascular remodeling. Systemic peripheral immune markers such as absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) have been reported as prognostic factors of patients treated with eribulin. However, the usefulness of the longitudinal changes of these blood parameters during eribulin treatment remains unknown. PATIENTS AND METHODS: A total of 97 patients with locally advanced or metastatic breast cancer treated with eribulin were recruited. ALC and NLR values were collected at each cycle of treatment. The correlation between ALC and NLR and prognosis and antitumor effects was retrospectively evaluated. RESULTS: Progression-free and overall survival for patients with a base line ALC ≥1,500/µl was significantly better than that for those with a lower ALC (p=0.049 and p=0.004, respectively). The mean ALC in the non-progressive disease (PD) group increased, while that in the PD group slightly decreased over time. A low ALC at the last cycle was significantly correlated with PD (p=0.030). Of the 64 patients with PD, 47 were classified as having progression due to a pre-existing lesion (PPL), and 17 patients were classified as having progression due to new metastasis (PNM). The mean ALC for the PPL group slightly increased during eribulin treatment, while that for the PNM group decreased. CONCLUSION: Eribulin treatment may have improved the immune status in eribulin responders. Monitoring ALC values may be useful for early assessment of response to therapy.

Clinical Significance of Expression of Immunoadjuvant Molecules (LAG-3, TIM-3, OX-40) in Neoadjuvant Chemotherapy for Breast Cancer.

BACKGROUND/AIM: Various immunosuppressive factors that inhibit the immune response to cancer are present in cancer cells and the cancer microenvironment. Co-inhibitory and co-stimulatory receptors are dynamically expressed on T-cells as immunoadjuvant molecules that regulate the state of T-cell activity. In this report we focus on immunoadjuvant molecules such as LAG-3, TIM-3, and OX-40, for which there have been few published reports. We investigated the expression of LAG-3, TIM-3 and OX-40 in tumor-infiltrating lymphocytes (TILs), and clinically verified the significance of that expression in relation to neoadjuvant thermotherapy (NAC). PATIENTS AND METHODS: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, LAG-3, TIM-3 and OX-40 status were assessed by immunohistochemistry. RESULTS: The group with low-LAG-3 expression was significantly smaller than the group with high expression in triple-negative breast cancer (TNBC) (p=0.038) and HER2-enriched breast cancer (HER2BC) (p=0.021), while the total number of pathological complete response (pCR) patients was greater (p<0.001). In TNBC and HER2BC, the pCR rate was significantly higher in the low-LAG-3 expression group than in the high-LAG-3 expression group (p<0.001 and p=0.02, respectively). Moreover, on multivariate analysis low-LAG-3 expression status was an independent predictor of favorable prognosis (TNBC: p=0.014, HR=8.124; HER2BC: p=0.048, HR=10.400). CONCLUSION: Our findings suggest that LAG-3 may become a biomarker in highly malignant breast cancers such as TNBC and HER2BC that can predict the therapeutic efficacy of NAC.

The Effect of Smoking on Progression from Ductal Carcinoma In Situ to Invasive Ductal Breast Carcinoma: A Retrospective Study.

BACKGROUND/AIM: If ductal carcinoma in situ (DCIS) is diagnosed by needle biopsy, invasion is often found by removing the entire tumor and performing pathological examination. Smoking is a risk factor for carcinogenesis in breast cancer. We examined the correlation between the risk of invasion found by postoperative pathology and smoking history in patients diagnosed with DCIS by preoperative biopsy. PATIENTS AND METHODS: We examined 128 patients who were diagnosed with DCIS by preoperative biopsy. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. RESULTS: Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. Number of pack-years was not an independent factor (p=0.349, OR=0.329), but current-smoker status (p=0.006, OR=not calculable) was an independent factor with VAB (p=0.018, OR=0.327). CONCLUSION: Tobacco components may have an influence on the progression from DCIS to invasive ductal carcinoma.