We aimed to identify the factors affecting the successful tumor engraftment in breast cancer patient-derived xenograft (PDX) models. Further, we investigated the prognostic significance and the functional importance of the PDX engraftment-related genes in triple-negative breast cancers (TNBC). The clinico-pathologic features of 81 breast cancer patients whose tissues were used for PDX transplantation were analyzed to identify the factors affecting the PDX engraftment. A gene signature associated with the PDX engraftment was discovered and its clinical importance was tested in a publicly available dataset and in vitro assays. Nineteen out of 81 (23.4 %) transplanted tumors were successfully engrafted into the PDX models. The engraftment rate was highest in TNBC when compared to other subtypes (p = 0.001) and in recurrent or chemotherapy-resistant tumors compared to newly diagnosed primary tumors (p = 0.024). PDX tumors originated from the TNBC cases showed more rapid tumor growth in mice. Gene expression profiling showed that down-regulation of genes involved in the tumor-immune interaction was significantly associated with the successful PDX engraftment. The engraftment gene signature was associated with worse survival outcome when tested in publicly available mRNA datasets of TNBC cases. Among the engraftment-related genes, PHLDA2, TKT, and P4HA2 showed high expression in triple-negative breast cancer cell lines, and siRNA-based gene silencing resulted in reduced cell invasion and proliferation in vitro. Our results show that the PDX engraftment may reflect the aggressive phenotype in breast cancer. Genes associated with the PDX engraftment may provide a novel prognostic biomarker and therapeutic targets in TNBC.

PurposePatients with triple-negative breast cancer (TNBC) with pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) have superior survival outcomes compared to those with residual disease after NAC. This study investigated the value of three biomarkers, p53, Ki-67, and Bcl-2 for predicting pCR in NAC-treated patients with TNBC.MethodsBetween 2003 and 2012, 198 patients with pathologically confirmed primary TNBC were treated with two different taxane-based chemotherapeutic regimens prior to surgery. Before NAC, expression of p53 (cutoff 25%), Ki-67 (cutoff 10%), and Bcl-2 (cutoff 10%) was assessed immunohistochemically in core biopsy specimens. The incidence of pCR was correlated with the expression of these biomarkers.ResultsOverall, pCR occurred in 37 of the 198 patients (18.7%). A significant association was observed between the pCR rate and overexpression of the p53 and Ki-67 biomarkers. Multivariate analysis showed that only p53 expression was independently associated with pCR to NAC (odds ratio, 3.961; p=0.003). The sensitivity, specificity, positive predictive value, and negative predictive value of p53 expression for predicting pCR were 77.8%, 50.3%, 26.2%, and 90.9%, respectively. The pCR rate was the lowest (5.2%) in patients with low expression of both p53 and Ki-67, and it was the highest (25.8%) when both biomarkers showed high expression.ConclusionExpression of p53 was significantly associated with pCR after NAC in patients with TNBC, suggesting that this biomarker might be particularly valuable in identifying TNBC patients prone to have residual disease after NAC.

No abstract

PurposeThe ability to accurately predict the likelihood of achieving breast conservation surgery (BCS) after neoadjuvant chemotherapy (NCT) is important in deciding whether NCT or surgery should be the first-line treatment in patients with operable breast cancers.Materials and MethodsWe reviewed the data of 513 women, who had stage II or III breast cancer and received NCT and surgery from a single institution. The ability of various clinicopathologic factors to predict the achievement of BCS and tumor size reduction to ≤ 3 cm was assessed. Nomograms were built and validated in an independent cohort.ResultsBCS was performed in 50.1% of patients, with 42.2% of tumors reduced to ≤ 3 cm after NCT. A multivariate logistic regression analysis showed that smaller initial tumor size, longer distance between the lesion and the nipple, absence of suspicious calcifications on mammography, and a single tumor were associated with BCS rather than mastectomy (p < 0.05). Negative estrogen receptor, smaller initial tumor size, higher Ki-67 level, and absence of in situ component were associated with residual tumor size ≤ 3 cm (p < 0.05). Two nomograms were developed using these factors. The areas under the receiver operating characteristic curves for nomograms predicting BCS and residual tumor ≤ 3 cm were 0.800 and 0.777, respectively. The calibration plots showed good agreement between the predicted and actual probabilities.ConclusionWe have established a model with novel factors that predicts BCS and residual tumor size after NCT. This model can help in making treatment decisions for patients who are candidates for NCT.

Rationale:Lymphangiomas develop in the head, neck, and axilla of patients <2 years old in more than 90% of cases. They are rarely reported in adults.Patient concerns:Here, we report on a 37-year-old woman with a firm, hypoechoic 3.3 cm mass in the right upper, outer quadrant of the breast with discomfort, and swelling of the right axillary region.Diagnosis and interventions:She underwent wide excision of the right breast and axillary lesion and the lesion pathologic finding is lymphangioma of the breast.Outcomes:She was in good condition with no signs of postoperative complications and no evidence of recurrence at 6 months postsurgery.Lessons:Despite the rarity of breast cystic lymphangioma, its evaluation should be considered for prompt diagnosis and definitive treatment to prevent recurrence and complications. Furthermore, this is the first case of concomitant lymphangioma of the breast parenchyma and axillary region.

Purpose Approval of eribulin for metastatic breast cancer was based on data primarily from Western patients, and there is a paucity of data on the effectiveness and safety of eribulin for Asian patients. To determine the effectiveness and safety of eribulin in Korean women with breast cancer in a real-world setting, we conducted a nationwide, multicenter, retrospective study. Methods Patients with locally advanced or metastatic breast cancer who were treated with eribulin in 14 centers throughout Korea were included in this study. Eribulin was generally administered at a dose of 1.23 mg/m 2 (equivalent to 1.4 mg/m 2 eribulin mesylate) by intravenous infusion for 2–5 min, or as a diluted solution, on Days 1 and 8 of every 21-day cycle. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included median PFS, overall survival (OS), time-to-treatment failure (TTF), tumor response rate, and incidence of hematologic treatment-emergent adverse events (TEAEs). Results The safety and full analysis populations included 398 and 360 (38 had no efficacy data) patients, respectively. The PFS rate at 6 months was 37.8%. Median PFS, OS, and TTF were 134, 631, and 120 days, respectively. Objective response rate, clinical benefit rate, and disease control rate were 18.1%, 50.6%, and 49.4%, respectively. Hematologic TEAEs were reported in 65.1% of patients; neutropenia (56.8%) and anemia (11.3%) were most common. Conclusion Real-world effectiveness and safety of eribulin in Korean breast cancer patients were consistent with previous reports; no new safety concerns were identified.

PurposeGermline mutations in the BRCA1 and BRCA2 genes confer increased risks for breast cancers. However, the clinical presentation of breast cancer among women who are carriers of the BRCA1 or BRCA2 (BRCA1/2 carriers) mutations is heterogenous. We aimed to identify the effects of the reproductive histories of women with the BRCA1/2 mutations on the clinical presentation of breast cancer.MethodsWe retrospectively analyzed clinical data on women with proven BRCA1 and BRCA2 mutations who were recruited to the Korean Hereditary Breast Cancer study, from 2007 to 2014.ResultsAmong the 736 women who were BRCA1/2 mutation carriers, a total of 483 women had breast cancers. Breast cancer diagnosis occurred at significantly younger ages in women who experienced menarche at ≤14 years of age, compared to those who experienced menarche at >14 years of age (37.38±7.60 and 43.30±10.11, respectively, p<0.001). Additionally, the number of full-term pregnancies was significantly associated with the age of diagnosis, especially in women with the BRCA2 mutation. The prevalence of advanced stages (stage II or III vs. stage I) of disease in parous women was higher than in nulliparous women (68.5% vs. 55.2%, p=0.043). This association was more pronounced in women with the BRCA2 mutation (hazard ratio, 2.67; p=0.014).ConclusionOur results suggest that reproductive factors, such as the age of onset of menarche and the presence of parity, are associated with the clinical presentation patterns of breast cancer in BRCA1/2 mutation carriers.

Xanthomonas campestris pv. vesicatoria (Xcv) causes brown spots on the leaves, stems, and fruits of plants, called bacterial leaf scorch (BLS). For the control of pathogens, antibiotics have been used frequently, and they can develop the resistance. In this study, the bactericidal and synergistic effects of caraway oil and its main components against the pathogen (Xcv) were investigated. The tested caraway oil consisted of 58.4% of carvone and 31.1% of limonene. The minimum inhibitory concentration (MIC) of caraway oil and carvone was the same as 125 μg mL−1, and the minimum bactericidal concentration (MBC) was 1000 μg mL−1 for caraway oil and 500 μg mL−1 for carvone, while limonene showed no inhibition below 1000 μg ml−1. In the growth of Xcv, carvone treatment over 31.3 μg mL−1 inhibited dose-dependently, and the bactericidal effect showed after 18 h more than 250 μg mL−1; It was agreed with the release of intracellular components over 250 μg mL−1, especially. Furthermore, carvone damaged the plasmid DNA of Xcv, and it would be the reason for the bactericidal activity. The synergistic effect of carvone was found with β-lactams selectively; the fractional inhibitory concentration (FIC) indexes of carvone with ampicillin or amoxicillin were below 0.5, and the mixture of carvone (125 μg mL−1) and ampicillin (500 μg mL−1) showed the bactericidal activity as well.