An observational, prospective, open label, multicenter study to evaluate the safety and effectiveness of pegfilgrastim as secondary prophylaxis to decrease the incidence of febrile neutropenia in Korean female patients with breast cancer.

PURPOSE: Pegfilgrastim is a widely used long-acting granulocyte colony-stimulating factor (G-CSF) that prevents febrile neutropenia (FN) in patients with breast cancer receiving chemotherapy. This study aimed to evaluate the incidence of chemotherapy-related FN events and other adverse events (AEs) during chemotherapy in Korean patients with breast cancer treated with pegfilgrastim as secondary prophylactic support. MATERIALS AND METHODS: This was a multicenter, open-label, prospective, observational study. A total of 1255 patients were enrolled from 43 institutions. The incidence of FN was evaluated as the primary endpoint. The secondary endpoints included (1) incidence of bone pain, (2) proportion of patients with a relative dose intensity (RDI) of ≥85%, and (3) proportion of patients with AE. RESULTS: Pegfilgrastim administration reduced FN by 11.8-1.6%. The highest incidence of bone pain was observed at the time point of the 1st day after the administration and mild bone pain was the most common of all bone pain severity. The mean RDI was 98.5 ± 7.3%, and the proportion of the patients with and RDI≥85% was 96.9% (1169/1233). AEs were reported in 52.6% of the patients, and serious drug reactions occurred in only 0.7%. CONCLUSION: The use of pegfilgrastim as secondary prophylaxis was effective and safe for preventing FN in patients with breast cancer who were treated with chemotherapy.

Association of Galectin 9 Expression with Immune Cell Infiltration, Programmed Cell Death Ligand-1 Expression, and Patient's Clinical Outcome in Triple-Negative Breast Cancer.

Galectin-9 (Gal-9) is an immune checkpoint protein that facilitates T cell exhaustion and modulates the tumor-associated microenvironment, and could be a potential target for immune checkpoint inhibition. This study was conducted to assess Gal-9 expression in triple-negative breast cancer (TNBC) and evaluate its association with programmed cell death ligand 1 (PD-L1) expression and immune cell infiltration in tumors and the clinical outcome of patients. Overall, 109 patients with TNBC were included. Gal-9 expression was assessed its relationships with tumor clinicopathologic characteristics, tumor-infiltrating lymphocyte (TIL) levels, PD-L1+ immune cells, and tumor cells by tissue microarray and immunohistochemistry. Low Gal-9 expression was statistically correlated with higher tumor stage (p = 0.031) and presence of lymphovascular invasion (p = 0.008). High Gal-9 expression was associated with a high level of stromal TILs (sTIL; p = 0.011) and positive PD-L1 expression on tumor cells (p = 0.004). In survival analyses, low Gal-9 expression was associated with significantly poor OS (p = 0.013) in patients with TNBC with PD-L1 negativity in tumor cells. Our findings suggest that increased Gal-9 expression is associated with changes in the antitumor microenvironment, such as increased immune cell infiltration and antimetastatic changes. This study emphasizes the predictive value and promising clinical applications of Gal-9 in TNBC.

Silicone-induced lymphadenopathy mimicking recurrence of breast cancer on positron emission tomography-computed tomography, correctly diagnosed on ultrasound.

Silicone-induced lymphadenopathy is a rare complication associated with silicone breast implants. It is usually asymptomatic and found incidentally during imaging. We report a case of silicone lymphadenopathy in a patient who had undergone a mastectomy and breast reconstruction for breast cancer. During follow-up, a positron emission tomography-computed tomography examination revealed lymph nodes that were suspicious for cancer recurrence. However, sonography was able to correctly diagnose silicone-induced lymphadenopathy and exclude cancer metastasis.

Ultrasound surveillance on detection of nonpalpable supraclavicular recurrence after breast cancer surgery.

AIMS: To evaluate the clinical utility of supraclavicular scanning for locoregional lymph node (LN) assessment in postoperative screening surveillance using ultrasonography (US) in patients who underwent breast cancer surgery. MATERIAL AND METHODS: From July 2004 to February 2019, 280 suspicious findings for locoregional recurrence in the lymph node (LRL) on postoperative screening US were detected in 266 asymptomatic patients who underwent breast cancer surgery. Suspicious features of LRL on US included the marked hypoechogenicity, round or irregular shape, eccentric cortical thickening and replacement of the fatty hilum of the LNs. The bilateral breasts, including mastectomy sites, bilateral axillae, internal mammary areas and supraclavicular areas, were included in the scan range of postoperative US. RESULTS: Of 280 LNs with suspicious findings for LRL, LRL of supraclavicular LNs was confirmed in 24 LNs according to cytopathology results. Multivariate logistic regression analysis revealed that higher overall staging of primary breast cancer (odds ratio [OR] 2.361 [95% confidence interval (CI) 1.302-4.282]; p=0.005), higher N staging of primary breast cancer (OR 3.086 [95% CI 1.479-6.441]; p=0.003), older patient age (OR 1.060 [95% CI 1.026-1.095]; p<0.001) and breast-conserving surgery (OR 2.253 [95% CI 1.184-4.289]; p=0.013) were independently associated with LRL of supraclavicular LNs. Tumor size, nuclear grade, histological type, hormonal receptor status of the primary cancer, and bilateral cancer were not associated with LRL (p=0.216, p=0.205, p=0.789, p=0.899, and p=0.900, respectively). CONCLUSION: Routine supraclavicular scanning in postoperative screening surveillance using US in breast cancer patients with higher staging could be useful for the detection of LRL of supraclavicular LNs.

Abdominal actinomycosis misconceived as intestinal lymphoma: Report of a case.

INTRODUCTION: Abdominal actinomycosis is a rare clinical entity and it is difficult to make the correct preoperative diagnosis because of its nonspecific clinical symptoms and varied radiological findings. The diagnosis is usually made after the patient undergoes an operation and tissue is available for pathological evaluation. When the diagnosis is made, the patient should be treated with the appropriate long-term antibiotics. PRESENTATION OF CASE: A 69-year-old male patient was transferred to our hospital complaining of a palpable mass, painful abdominal discomfort, weight loss, and night sweating. After colonoscopy and radiologic studies, our presumptive diagnosis was intestinal lymphoma combined with ileocecal intussusception. He was found to have abdominal actinomycosis after surgery and successfully treated with ampicillin for six months. DISCUSSION: Pre-operative radiological imaging in abdominal actinomycosis is unlikely to allow a definitive diagnosis, but CT scanning is the single most useful imaging modality. Although we performed preoperative radiological studies, including CT, none led to a diagnosis of abdominal actinomycosis, we mistakenly considered the case as intestinal lymphoma combined with ileocecal intussusception. CONCLUSION: Physicians should include abdominal actinomycosis in the differential diagnosis when an abdominal mass presents an irregular, infiltrative growth pattern, even though ileocecal intussusception is an extremely rare presentation in abdominal actinomycosis.

Clinical subtypes and prognosis in breast cancer according to parity: a nationwide study in Korean Breast Cancer Society.

PURPOSE: We explored the association between parity and the risk of developing a specific subtype of breast cancer. We also assessed the association between parity and prognosis according to subtypes. METHODS: A total of 158,189 patients were enrolled in the Korean Breast Cancer Society Registry database between 1996 and 2015 in Korea. The database provided information on sex, age, number of parity, surgical method, stage, histological findings, presence of biologic markers, adjuvant therapy, and date and cause of death. RESULTS: The patients with higher parity showed a higher ratio of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) subtypes. In univariate analysis, women with TNBC who had more than three children had a worse prognosis compared to other groups (HR 1.83; 95% CI 1.34-2.49; P < 0.001). This association was also observed in women younger than 50 years (HR 1.63; 95% CI 1.07-2.48; P = 0.021). In multivariate analysis stratified by subtypes, women who had more than three children were associated with a worse prognosis in TNBC in the total population (HR 1.53; 95% CI 1.11-2.12; P = 0.011). This association was also observed in patients younger than 50 years of age (HR 1.53; 95% CI 1.09-2.61; P = 0.017). CONCLUSION: Women who had more than three children were more likely to develop hormone receptor-negative (HR-) subtypes. Women who had more than three children were associated with worse prognosis in patients younger than 50 years of age and in patients with TNBC.

Clinical implication of subcategorizing T2 category into T2a and T2b in TNM staging of breast cancer.

Regarding TNM staging in breast cancer, T2 category is currently not divided into subcategories even though it covers a wider range of tumor sizes than T1 category. Using Korean Breast Cancer Registry database, data of 41 071 women diagnosed as non-metastatic T2 breast cancer between 2001 and 2014 were analyzed. Cutoff value for optimal tumor size was approximated by receiver operating characteristic (ROC) curve to subcategorize T2 tumors. Overall survival (OS) was compared between two subcategories. Median follow-up period was 65 months. Of 41 071 patients, 4504 (11.0%) died. Based on ROC curve analysis, 3.0 cm was selected as the cutoff value. Five-year OS rate was 91% in patients with breast tumors ≤3.0 cm (T2a) and 86% in patients with breast tumors >3.0 cm (T2b) (log-rank P < 0.001). T2b subcategory showed worse OS than T2a subcategory regardless of node status (log-rank P < 0.001 for all node categories). Within every subgroup defined by primary OS analysis covariates, T2b subcategory consistently showed worse outcome compared to T2a subcategory. By multivariate analysis, T2b subcategory was a significant independent prognostic factor of OS (hazard ratio: 1.26, 95% CI = 1.18-1.34). T2 category of breast cancer could be subcategorized into T2a and T2b with a cutoff value of 3 cm. These subcategories definitely showed different OSs even after adjusted for known prognostic factors. Subcategorization of T2 category might be useful for predicting prognosis more accurately and tailoring adjuvant therapy.

T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer.

PURPOSE: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological para-meters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. METHODS: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. RESULTS: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). CONCLUSION: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

Eribulin Mesylate Combined with Local Treatment for Brain Metastasis from Breast Cancer: Two Case Reports.

The prognosis associated with brain metastasis arising from breast cancer is very poor. Eribulin is a microtubule dynamic inhibitor synthesized from halichondrin B, a natural marine product. In a phase III study (EMBRACE), eribulin improved overall survival in patients with heavily pretreated metastatic breast cancers. However, these studies included few patients with brain metastases. Metastatic brain tumors (MBT) were detected during first-line palliative chemotherapy in a 43-year-old woman with breast cancer metastasis to the lung and mediastinal nodes; the genetic subtype was luminal B-like human epidermal growth factor receptor 2 (HER2)-negative. Whole brain radiotherapy (WBRT) followed by eribulin treatment continuously decreased the size, and induced regression, of the MBT with systemic disease stability for 12 months. Another 48-year-old woman with metastatic breast cancer (HER2+ subtype) presented with MBT. Following surgical resection of the tumor, eribulin with concurrent WBRT showed regression of the MBT without systemic progression for 18 months.