Retroperitoneal endoscopic median arcuate ligament incision with interventional radiology: a case report and literature review.

Compression of the celiac artery (CA) associated with median arcuate ligament compression syndrome can result in aneurysms at the pancreaticoduodenal arcade. If the aneurysm ruptures, treatment with interventional radiology (IVR) is recommended. Subsequently, the median arcuate ligament (MAL) should be incised to prevent the recurrence of the aneurysm. Retroperitoneal endoscopic MAL incision reduces the risk of adhesive bowel obstruction. However, there is few surgical landmark for retroperitoneal MAL incision. We used IVR to detect CA for MAL incision. Case Presentation: A 44-year-old man presented to our hospital with complaints of abdominal pain and clouding of consciousness. Contrast-enhanced computed tomography of the abdomen showed contrast leakage from pancreaticoduodenal artery aneurysm, and the CA was compressed by MAL, leading to the diagnosis of pancreaticoduodenal artery aneurysm rupture associated with median arcuate ligament compression syndrome. IVR was performed to block the blood flow to the aneurysm. After 2 months from life-saving IVR, we performed retroperitoneal endoscopic MAL incision with IVR. The patient was discharged 8 days after surgery. Echocardiography and contrast-enhanced computed tomography 2 months after discharge confirmed that the compression and flow of the CA had improved. Clinical Discussion: In retroperitoneal endoscopic MAL incision, there has been few landmark to identify MAL and CA. Retroperitoneal procedure with IVR can identify MAL easily. This is a useful technique, and it is important to accumulate more cases to standardize the technique. Conclusion: Retroperitoneal endoscopic MAL incision with IVR has not been reported, this procedure can make it easier to detect MAL.

Emergency laparoscopic trans-abdominal pre-peritoneal repair (TAPP) for irreducible inguinal hernia in Covid-19 patient: A case report and literature review.

Introduction: With the global pandemic of COVID-19 for over two years, we might have to proceed surgical operation of patients with COVID-19 infection because of its emergency. Here we present a case who received an emergency operation for an irreducible inguinal hernia with COVID-19. We safely performed trans-abdominal pre-peritoneal repair (TAPP) in one surgery without any problems. Presentation of case: 52-year-old male with no specific past medical history came to the emergency department with complaints of right inguinal bulging and abdominal pain. On physical examination, a bulge in the right inguinal region was observed, so a right irreducible inguinal hernia was suspected. Since he had fever, we conducted a COVID-19 antigen test and it was positive. Because we could not return with manually, we decided to perform emergency surgery with appropriate infection control techniques. After laparoscopic return of the intestinal tract, a mesh was implanted using TAPP. The patient was discharged 2 days after surgery. Discussion: Even in pandemic of COVID-19, cases of irreducible inguinal hernia could be occur. COVID-19 has systemic inflammation, so we worried about mesh infection. But this patient took TAPP safely in emergency surgery with COVID-19. Conclusion: We experienced a case of TAPP proceeded patient with COVID-19. We considered that placement of a foreign material is acceptable when it is necessary in COVID-19 patient safely.

[A Case of Transcatheter Arterial Chemoembolization and Surgical Resection of Left 7th Rib Metastasis after Surgery for Hepatocellular Carcinoma].

The patient was an 81-year-old man. After a liver posterior segmentectomy for hepatocellular carcinoma, a painful bulge was observed in the left anterior thoracic region during a routine outpatient visit. Elevated tumor markers and contrast- enhanced CT scan revealed a mass with contrast effect in the left 7th rib. Ultrasound-guided biopsy revealed hepatocellular carcinoma metastatic to the left 7th rib. There were no other obvious metastases, and the diagnosis of a single bone metastasis was made. The patient did not request chemotherapy and underwent transcatheter arterial chemoembolization 4 times. The patient did not show any improvement in tumor markers or shrinkage of the tumor, and his quality of life was deteriorated due to increased pain. The patient underwent left chest wall tumor resection and chest wall reconstruction. Postoperative tumor markers were normalized and pain improved markedly. We report a case of postoperative recurrence- free survival for 2 years.

Axillary Lymph Node Swelling After COVID-19 Booster Vaccination: Japanese Case Report and Literature Review.

BACKGROUND/AIM: COVID-19 has been a global pandemic for more than 2 years, and vaccination against COVID-19 using an mRNA vaccine is widespread. The COVID-19 vaccination can cause specific side-effects, such as axillary lymph node swelling; therefore, breast oncologists should pay attention to such occurrences. Initially, only two COVID-19 vaccinations were planned; however, in some countries third or fourth vaccines have been administered. Here, we present a female case who developed axillary lymph node swelling after her third vaccination. We have also reviewed the literature regarding this side-effect after a third or fourth COVID-19 vaccination. CASE REPORT: A 64-year-old woman who came to our clinic regarding a mammography abnormality in her left breast. She had no palpable mass, but a left breast mass was shown by mammography, and ultrasonography and magnetic resonance imaging indicated a hamartoma. At 2 months after her second COVID-19 vaccination when she underwent these tests, she had no axillary lymph node swelling. We planned a follow-up after 6 months. At her next visit, by chance, she underwent ultrasonography 14 days after she received a third COVID-19 vaccination, and a swollen axillary lymph node was observed. CONCLUSION: Axillary lymph node swelling can occur after a third COVID-19 vaccination. Therefore, breast oncologists will have to consider this side-effect of COVID-19 vaccination when diagnosing breast tumors.

Timing and Duration of Axillary Lymph Node Swelling After COVID-19 Vaccination: Japanese Case Report and Literature Review.

BACKGROUND/AIM: COVID-19 vaccination is now performed in most of the world to limit the spread of the disease. The first mRNA vaccine was approved in clinical settings and has specific side effects including axillary lymph node swelling, which can be misdiagnosed as breast cancer metastasis. The timing of axillary lymph node swelling and its duration are unclear. Here, we present a Japanese case and review of the existing literature. CASE REPORT: We report the case of a 67-year-old woman with breast calcification. She had regular follow ups in our hospital for this calcification and received ultrasonography of the breast and axilla at every visit. She visited 6 months before having her COVID-19 vaccination, and 7 days and 6 months after the first COVID-19 vaccination. She had a swollen axillary lymph node 7 days after the first vaccination, which although it was improved, remained for 6 months. CONCLUSION: Axillary lymph node swelling occurred 7 days after vaccination and remained up to 6 months after it.

Axillary Lymph Node Swelling Mimicking Breast Cancer Metastasis After COVID-19 Vaccination: A Japanese Case Report and Literature Review.

BACKGROUND/AIM: COVID-19 started to spread as a pandemic in December 2019 and COVID-19 vaccination has been initiated worldwide. The efficacy of vaccination has been scientifically proven, but it might cause axillary lymph node swelling. To diagnose patients with axillary lymph node swelling caused by COVID-19 vaccination, we herein reviewed existing literature on this symptom. CASE REPORT: We report the case of a 70-year-old woman with a breast tumour. She had undergone cecum cancer surgery and regular computed tomography (CT). During breast tumour follow-up, she received scheduled CT that indicated severe axillary lymph node swelling mimicking breast cancer metastasis. We performed aspiration biopsy cytology of that lymph node, and determined this was not cancer metastasis but an effect of the COVID-19 vaccine. We confirmed this diagnosis at one month after computed tomography showed that the lymph node swelling had improved. CONCLUSION: Axillary lymph node swelling can occur after COVID-19 vaccination. Therefore, it is important to consider the effect of the COVID-19 vaccination on axillary lymph node swelling when diagnosing breast tumours.

Brief collaborative care intervention to reduce perceived unmet needs in highly distressed breast cancer patients: randomized controlled trial.

OBJECTIVES: Our newly developed brief collaborative care intervention program has been suggested to be effective in reducing breast cancer patients' unmet needs and psychological distress; however, there has been no controlled trial to investigate its effectiveness. The purpose of this study was to examine the effectiveness of the program in relation to patients' perceived needs and other relevant outcomes for patients including quality of life, psychological distress and fear of recurrence (Clinical trial register; UMIN-CTR, Clinical registration number; R5172). METHODS: Fifty-nine highly distressed breast cancer patients receiving adjuvant chemotherapy and/or hormonal therapy were randomly assigned either to a treatment as usual group or to a collaborative care intervention, consisting of four sessions that mainly included assessment of the patients' perceived needs, learning skills of problem-solving treatment for coping with unmet needs and psycho-education provided by trained nurses supervised by a psycho-oncologist. RESULTS: Although >80% of the eligible patients agreed to participate, and >90% of participants completed the intervention, there were no significant differences with regard to patients' needs, quality of life, psychological distress and fear of recurrence, both at 1 and 3 months after intervention. CONCLUSION: Newly developed brief collaborative care intervention program was found to be feasible and acceptable. The trial, however, failed to show the effectiveness of the program on patients' relevant subjective outcomes. Further intervention program having both brevity and sufficient intensity should be developed in future studies.

COVID-19 Screening of Breast Cancer Patients During Treatment: A Single Center Experience in Japan.

Background/Aim: Breast cancer treatment mainly involves interventional methods such as surgical resection and chemotherapy. How to best perform these treatments during the COVID-19 pandemic remains to be established. Patients and Methods: Patients with breast cancer who received SARS-CoV-2 PCR screening before cancer treatment from December 2020 to April 2021 were included. PCR screening was performed within 72 hours of the scheduled admission time and treatment. Results: A total of 19 tests in 15 patients were analysed. Fourteen cases displayed no symptoms, and five cases had some symptoms. COVID PCR tests were negative in all cases. Conclusion: COVID-19 screening can ensure that breast cancer patients do not miss scheduled treatments as a result of the pandemic. Diagnosis of patients with symptoms that are shared by COVID-19 infection, chemotherapy, and breast cancer recurrence must be performed carefully.

Genetic and environmental factors and serum hormones, and risk of estrogen receptor-positive breast cancer in pre- and postmenopausal Japanese women.

Breast cancer incidence in Japanese women has more than tripled over the past two decades. We have previously shown that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive, HER2-negative subtype. We conducted a case-control study; ER-positive, HER2-negative breast cancer patients who were diagnosed since 2011 and women without disease were recruited. Environmental factors, serum levels of testosterone and 25-hydroxyvitamin D, and common genetic variants reported as predictors of ER-positive breast cancer or found in Asian women were evaluated between patients and controls in pre- and postmenopausal women. To identify important risk predictors, risk prediction models were created by logistic regression models. In premenopausal women, two environmental factors (history of breastfeeding, and history of benign breast disease) and four genetic variants (TOX3-rs3803662, ESR1-rs2046210, 8q24-rs13281615, and SLC4A7-rs4973768) were considered to be risk predictors, whereas three environmental factors (body mass index, history of breastfeeding, and hyperlipidemia), serum levels of testosterone and 25-hydroxyvitamin D, and two genetic variants (TOX3-rs3803662 and ESR1-rs2046210) were identified as risk predictors. Inclusion of common genetic variants and serum hormone measurements as well as environmental factors improved risk assessment models. The decline in the birthrate according to recent changes of lifestyle might be the main cause of the recent notable increase in the incidence of ER-positive breast cancer in Japanese women.

[Three Poor Performance Status(PS)Cases of Metastatic Breast Cancer Controlled with Adjustment of Dosing Interval and Dosage of Bevacizumab and Paclitaxel].

A standard symptomatic therapy regimen of bevacizumab(BV)plus paclitaxel(PTX)was planned for use in 3 cases of metastatic breast cancer. Due to poor patient performance status(PS)because of malignant pleural effusion and ascites, the initial standard regimen was determined to be unsuitable. However, adjustment and fine-tuning of the BV plus PTX interval and dosage were found to be effective in improving symptoms, and consequently obtained good efficacy. Adverse effects were managed with drug withdrawal and symptomatic therapy. The 3 clinical cases all included females aged 62-76 years old, with a median age of 67.6. One case was classified as PS 3, and 2 were classified as PS 4. The main deciding factors for initiating the regimen of BV plus PTX were 2 cases of malignant pleural effusion and 1 case of malignant ascites, which contributed to worsening of the overall PS. With adjustment and fine-tuning of the BV plus PTX interval and dosage, we were able to safely achieve symptomatic improvement in 3 metastatic breast cancer cases, in which the overall PS grade was unsuitable for standard chemotherapy.

Collaborative care intervention for the perceived care needs of women with breast cancer undergoing adjuvant therapy after surgery: a feasibility study.

OBJECTIVE: This study aimed to investigate the feasibility of an intervention program for women with breast cancer undergoing adjuvant anticancer therapy, and determine its preliminary effectiveness in reducing their unmet needs and psychological distress. METHODS: The intervention was based on the collaborative care model, and compromised four domains: identification of unmet needs, problem-solving therapy and behavioral activation supervised by a psychiatrist, psychoeducation and referral to relevant departments. Eligible women with breast cancer were provided the collaborative care intervention over four sessions. The feasibility of the program was evaluated by the percentage of women who entered the intervention and by the percentage of adherence to the program. Self-reported outcomes were measured by the Supportive Care Needs Survey-Short Form 34 (SCNS-SF34), the Profile of Mood States (POMS), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Concern about Recurrence Scale, and pre- and post-intervention satisfaction with medical care. RESULTS: In total, 40 patients participated in this study. The rate of participation in the intervention was 68%, and the rate of adherence was 93%. Participants had significantly improved scores on total perceived needs, physical needs and psychological needs on the SCNS-SF34; vigor and confusion on the POMS and function (physical, emotional and cognitive), nausea and vomiting, dyspnea, appetite loss and financial difficulties on the EORTC QLQ-C30 compared with the baseline assessment. CONCLUSIONS: Our findings indicated the intervention program was feasible. Further study is needed to demonstrate the program's effectiveness in reducing unmet needs.

Diagnostic approach to breast cancer patients based on target metabolomics in saliva by liquid chromatography with tandem mass spectrometry.

BACKGROUND: Breast cancer is one of the most fearful diseases due to its increasing worldwide prevalence. A number of screening tests has been employed including clinical examinations and mammography. However, another screening method, which is a simple, not embarrassing, and low cost, is highly desired. Based on these findings, we are currently investigating the determination of polyamines including their acetylated structures for the diagnosis of breast cancer patients. We established a diagnostic approach to breast cancer patients based on the ratios of polyamines in saliva by a UPLC-MS/MS analysis. METHODS: Twelve polyamines including their acetylated form were labeled with DBD-F, separated by a reversed-phase chromatography and detected by a Xevo TQ-S tandem mass spectrometer. RESULTS: Eight polyamines (e.g., SPM, CAD, Ac-SPM, N1-Ac-SPD, N8-Ac-SPD) strongly correlated with the cancer patients. A simple 1-order equation was developed for the discrimination of the breast cancer patients and healthy persons (Y=0.5XSPM-3XAc-SPM-0.15XSPD-3.5XN8-Ac-SPD+0.5XN1-Ac-SPD+0.04XCAD). The concordance rate of the breast cancer patients and the healthy persons by the equation was 88% and 76% on the training set, respectively, whereas those on the validation set was both 88%. The score Y in the equation tended to correlate with the cancer stage of the patients and increased with the more serious conditions. The determination of polyamines in the saliva after the cancer patient operations was also performed to identify the concentration change before and after the surgical treatment. The discriminant analysis using 6 polyamines (i.e., N8-Ac-SPD, N1-Ac-SPD, CAD, DAc-SPD, PUT, and Ac-PUT), which were the most influenced molecules derived from the ROC analysis, was performed using the relative percentage. Both the sensitivity and specificity indicated nearly 80% from the ROC analysis result using the ratio of N8-Ac-SPD/(N1-Ac-SPD+N8-Ac-SPD). CONCLUSION: The discrimination equation appears to be useful for the diagnosis of breast cancer patients. Furthermore, the ratio of N8-Ac-SPD/(N1-Ac-SPD+N8-Ac-SPD) may be adopted as an index of the health status after the surgical treatment.

Digital mammography versus digital breast tomosynthesis for detection of breast cancer in the intraoperative specimen during breast-conserving surgery.

PURPOSE: To compare the diagnostic ability of specimen radiography using digital mammography (DM) and digital breast tomosynthesis (DBT) for detecting breast cancer and evaluating its extension in the intraoperative specimen. METHODS: Sixty-five specimens from 65 women (median 62 years; range 34-86) obtained during breast-conserving surgery were prospectively investigated. Specimens underwent DM (25-40 kVp, 12-322 mA s) and DBT (25-34 kVp, 13-137 mA) in two orthogonal planes, anteroposterior (AP) and latero-lateral (LL). Images were interpreted by a radiologist to detect invasive lesions and their extensive intraductal components (EIC) or ductal carcinomas in situ (DCIS); afterwards, they were compared with histopathological findings. RESULTS: In AP views, 96 % of the invasive lesions were detected by both the methods. Of the EICs, 55 and 65 % were detected by DM and DBT, respectively (P = 0.61). Of the DICSs, 31 and 38 % were detected by DM and DBT, respectively (P > 0.99). In LL views, 71 and 13 % of the invasive lesions were detected by DBT and DM, respectively (P < 0.0001). Of the EICs, 42 and 10 % were detected by DBT and DM, respectively (P = 0.0078). Of the 13 DCISs, 42 and 8 % were detected by DBT and DM, respectively (P = 0.32). The whole lesion and contour could be delineated in 45 % by DBT and in 6.2 % by DM (P < 0.0001). CONCLUSIONS: DBT could detect breast cancer more accurately than DM in LL views, indicating its potential to more precisely diagnose vertical invasion.

HER2 mutation status in Japanese HER2-positive breast cancer patients.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) gene amplification/overexpression is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-HER2 agents. HER2 somatic mutations have been reported, and these may influence the effect of HER2-targeted drugs. METHODS: Here, we sought HER2 mutations in a group of 135 Japanese breast cancer patients with HER2-positive tumors. We analyzed HER2 mutations by direct Sanger sequencing of two major areas, the extracellular domain at position 309-310 and the kinase domain between 755 and 781. RESULTS: Two patients with the HER2 somatic mutation S310F in the extracellular domain were found in this series. One patient with the S310F mutation had a node-negative invasive ductal carcinoma classified as HER2 2+ by the HercepTest and fluorescence in situ hybridization (FISH) positive, and which was estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative. Another patient with the S310F mutation had an apocrine carcinoma with seven lymph nodes positive for metastasis, classified as HER2 3+ by the HercepTest, but which was FISH-negative, as well as ER-negative and PgR-negative. Both patients had received adjuvant single-agent trastuzumab therapy, and had no local recurrence or distant metastasis for five and three years after surgery, respectively. CONCLUSIONS: Our data show that HER2 mutations are rare in HER2-positive Japanese breast cancer patients. The two mutations found in this study were identical, S310F. We suggest that in vitro experiments to determine whether the S310F mutation could be involved in resistance to anti-HER2 drugs are worthwhile in future.

Prognostic impact of a single-nucleotide polymorphism near the CTSO gene in hormone receptor-positive breast cancer patients.

BACKGROUND: Tamoxifen can reduce the occurrence of breast cancer by a half in high-risk women. Recently, a genome-wide association study identified two single-nucleotide polymorphisms (SNPs) near or in the CTSO and ZNF423 genes that were associated with breast cancer risk during tamoxifen therapy. We hypothesized that these two SNPs could be associated with increased recurrence in breast cancer patients who received adjuvant tamoxifen therapy. METHODS: A total of 586 breast carcinomas were available for SNP genotyping assays. TaqMan pre-designed SNP genotyping assays were used to identify the presence of CTSO rs10030044 and ZNF423 rs8060157. We then investigated the relationship between CTSO rs10030044 genotypes and mRNA expression levels of CTSO and BRCA1 in 290 breast cancer patients. RESULTS: We found a positive correlation between the variant GG genotype of CTSO rs10030044 and shorter disease-free survival, or overall survival in hormone receptor-positive breast cancer patients receiving adjuvant tamoxifen therapy. In contrast, this genotype was not associated with prognosis in hormone receptor-negative breast cancer patients. Multivariate Cox regression analysis revealed that this genotype was an independent factor indicating a poor prognosis in hormone receptor-positive breast cancer patients receiving adjuvant tamoxifen therapy. No association was found between CTSO genotype and mRNA expression of CTSO and BRCA1. ZNF423 rs8060157 genotype was not associated with prognosis in this study. CONCLUSION: We show that a SNP near the CTSO gene is a poor prognostic factor in breast cancer although further research might help to reveal the factors linking this genotype and prognosis.

FOXA1 expression after neoadjuvant chemotherapy is a prognostic marker in estrogen receptor-positive breast cancer.

BACKGROUND: Recent studies have indicated that the response to chemotherapy and the prognostic impact of a pathological complete response (pCR) after neoadjuvant chemotherapy differ among breast cancer subtypes. Predictors of response to chemotherapy and prognostic factors for survival might be different in estrogen receptor (ER)-positive breast cancer. METHODS: Women with Stage II to III ER-positive HER2-negative breast cancer treated with anthracycline and taxane-containing neoadjuvant chemotherapy between 2003 and 2011 were retrospectively analyzed. Expression of forkhead box A1 (FOXA1), B cell lymphoma 2 (BCL2) and microtubule-associated protein tau (MAPT) as well as ER, progesterone receptor, HER2 and Ki67 was examined by immunohistochemistry in pre- and post-treatment specimens. Factors predictive of response to neoadjuvant chemotherapy and distant disease-free survival were analyzed. RESULTS: Tumor grade was positively correlated with Ki67 expression. Expression levels of ER were positively correlated with expression levels of HER2, BCL2, FOXA1 and MAPT in pre-treatment tumors. The Ki67 labeling index was the only factor that was significantly associated with clinical response measured by the reduction of tumor volume and pCR. Lymph node status, expression of ER before neoadjuvant chemotherapy and expression of FOXA1 after neoadjuvant chemotherapy were significantly associated with distant disease-free survival, both by univariate and multivariate analyses. CONCLUSIONS: Patients with ER-positive HER2-negative breast cancer should be selected for neoadjuvant chemotherapy. FOXA1 expression could be a prognostic marker in ER-positive breast cancer.

Immunohistochemical determination of the miR-1290 target arylamine N-acetyltransferase 1 (NAT1) as a prognostic biomarker in breast cancer.

BACKGROUND: There are many molecular differences between estrogen receptor α (ERα)-positive and ER-negative breast cancers. Recent analyses have shown that the former can be divided into two subtypes, luminal A and luminal B. These differ in response to endocrine therapy and chemotherapy, and in prognosis. In a previous study, we found that microRNA (miR)-1290 that was significantly down-regulated in luminal A tumors and its potential target arylamine N-acetyltransferase 1 (NAT1). The aim of the present study was to determine whether NAT1 is a bona fide target of miR-1290, and to investigate the impact of NAT1 on breast cancer prognosis. METHODS: Luciferase reporter assays were employed to validate NAT1 as a putative miR-1290 target gene. Expression of NAT1, ERα, progesterone receptor (PgR) and HER2 was analyzed in 394 breast cancer samples by immunohistochemistry. RESULTS: NAT1 was confirmed to be a direct target of miR-1290. Levels of expression of NAT1 were positively correlated with those of ERα (P < 0.0001) and PgR (P < 0.0001), but negatively correlated with both tumor grade and size (P < 0.0001). Kaplan-Meier analysis showed that the presence of NAT1 was significantly associated with increased overall survival (OS) (P = 0.0416) in these patients. Similarly, significant associations of NAT1 with disease-free survival (DFS) (P = 0.0048) and OS (P = 0.0055) in those patients who received adjuvant endocrine therapy with tamoxifen (n = 176) were found. Moreover, NAT1 was also significantly associated with increased DFS (P = 0.0025) and OS (P = 0.0007) in the subset of lymph node-positive patients (n = 147). Univariate and multivariate analyses showed significant associations between levels of NAT1 and DFS (P = 0.0005 and 0.019, respectively). CONCLUSIONS: We report that miR-1290 directly targets the NAT1 3'-UTR and that NAT1 protein expression is correlated with improved OS of breast cancer patients. NAT1 is a possible prognostic biomarker for lymph node-positive breast cancer. Thus, miR-1290 and its target NAT1 are associated with important characteristics of breast cancer.

High expression of LMTK3 is an independent factor indicating a poor prognosis in estrogen receptor α-positive breast cancer patients.

OBJECTIVE: Over 70% of breast cancers are estrogen receptor alpha-positive, and endocrine therapy targeting estrogen action decreases mortality from breast cancer. Recently, a novel protein kinase that regulates estrogen receptor alpha activity, lemur tyrosine kinase-3, has been identified. In this study, we investigated whether messenger RNA expression and polymorphisms of the gene encoding the kinase, LMTK3, are associated with prognosis in breast cancer patients during long-term follow-up. METHODS: First, we investigated the relationship between messenger RNA expression of LMTK3 and patient outcome in 219 breast cancers. The effects of several variables on survival were tested by Cox proportional hazards regression analysis. Next, we performed LMTK3 genotyping in 471 breast cancers to clarify the prognostic role of these polymorphisms. RESULTS: Our data showed that LMTK3 expression level was not associated with prognosis in all patients. We then analyzed the impact of LMTK3 mRNA expression on the prognosis of breast cancer according to estrogen receptor alpha status. Both disease-free survival and overall survival were significantly shorter in estrogen receptor alpha-positive patients with high LMTK3 expression receiving adjuvant endocrine therapy than in those patients with low LMTK3 expression. Multivariate Cox regression analysis revealed that high LMTK3 expression was an independent poor prognostic factor in estrogen receptor alpha-positive breast cancer patients. We did not find any correlation between LMTK3 genotypes and prognosis of breast cancer patients in our series. CONCLUSIONS: Our results show that high expression of LMTK3 is an independent prognostic factor in estrogen receptor alpha-positive breast cancer patients receiving adjuvant endocrine therapy.

Highly frequent and enhanced injection site reaction induced by peripheral venous injection of fosaprepitant in anthracycline-treated patients.

BACKGROUND: Fosaprepitant-associated injection site reaction (ISR) has been reported in patients treated with cisplatin, an irritant drug. We conducted this retrospective study to clarify the incidence and symptoms of fosaprepitant-associated ISR in patients treated with anthracycline. PATIENTS AND METHODS: Fifty six patients receiving 159 injections administering doxorubicin/cyclophosphamide (AC), fluorouracil/epirubicin/cyclophosphamide (FEC), or rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-)CHOP regimen through a peripheral vein at ambulatory treatment centers reviewed for this study from patients' medical records. Incidence of ISR was compared between 24 patients with fosaprepitant injection (fosaprepitant group) and 32 patients without fosaprepitant (control group). Frequency and symptoms of ISR per injection were also compared between 61 injections with fosaprepitant and 98 injections without fosaprepitant. RESULTS: Both the ISR incidence rate per patient and per injection were significantly higher in the fosaprepitant group than in the control group (67% vs. 16%; P=0.0002, 34% vs. 8.2%; P<0.0001, respectively). By multivariate analysis, fosaprepitant injection was found to be a significant independent variable correlated with ISR risk. Symptoms observed in 61 injections of fosaprepitant were pain (n=14, 23%), erythema (n=10, 16%), swelling (n=6, 10%), and delayed drip infusion (n=6, 10%). After the observation period, no ISR occurred when the administration route was changed to central venous injection or oral aprepitant was administered despite the continuation of chemotherapy. CONCLUSION: ISR occurred more frequently and severely when fosaprepitant was injected through the peripheral vein in patients treated with anthracyclines compared to those without fosaprepitant.

HER2 mutation status in Japanese HER2-negative breast cancer patients.

OBJECTIVE: Human epidermal growth factor receptor 2 (HER2) gene amplification is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-human epidermal growth factor receptor 2 agents. Human epidermal growth factor receptor 2 somatic mutations have been reported in patients without human epidermal growth factor receptor 2 gene amplification. Since these are activating mutations, these patients may also benefit from human epidermal growth factor receptor 2-targeted drugs. METHODS: In this study, we searched for human epidermal growth factor receptor 2 mutations in a group of 286 Japanese breast cancer patients with human epidermal growth factor receptor 2-negative tumors. The activating mutations of human epidermal growth factor receptor 2 identified were analyzed by direct Sanger sequencing of two major areas: the extracellular domain at 309-310 and the kinase domain between 755 and 781. RESULTS: Two tumors were found to have a human epidermal growth factor receptor 2 somatic mutation; one with I767M mutation and another with D769Y. No mutation was observed in the extracellular domain. One of these patients with human epidermal growth factor receptor 2 mutation recurred early with liver metastasis. CONCLUSIONS: Better knowledge of human epidermal growth factor receptor 2 mutation status will help us to choose personalized molecular targeted therapy for use in human epidermal growth factor receptor 2-negative Japanese breast cancer patients.