A pilot randomized controlled study to determine the effectiveness of video educational tool in BRCA1/2 pre-test counseling for Japanese breast cancer patients.

BRCA1/2 genetic testing has become clinically important in breast cancer care, but increasing demand may put a burden on the shortage of healthcare professionals. We performed a single-center, pilot randomized controlled study to assess the effectiveness of employing a video educational tool that included standard pre-test genetic counseling elements related to BRCA1/2. Patients with operable breast cancer who met the criteria for genetic testing based on age, sex, subtype, and family history were recruited. Sixty consenting participants were randomized 1:1 and placed in groups that received either traditional face-to-face pre-test counseling or video-viewing and face-to-face decisional support. To assess decisional conflict in the participants, surveys based on the Decisional Conflict Scale (DCS) were administered two times, once immediately after intervention and again 2-4 weeks later. The time taken for counseling and confirmation of whether the participants had undergone testing were also recorded. The difference in the total DCS scores between the two groups was not significantly different for either of the survey periods, and there was no significant difference in the number of participants who underwent testing (23/30 [76.7%] vs. 26/30 [86.7%]; p = 0.51). However, the "effective decision" subscale score was significantly higher in the video group 2-4 weeks after counseling (31.01 ± 16.82 vs. 21.43 ± 16.09; p = 0.04 [mean ± SD]). The time taken for counseling was significantly shorter in the video group (8.00 ± 4.5 vs. 27.00 ± 7.61 min; p < 0.001 [median ± SD]). Our findings indicate the potential benefit of the video educational tool for providing BRCA1/2-related information. These tools may also enable healthcare professionals to spend more time supporting psychological issues. Notably, after some time, patients may question whether their decision was appropriate. Therefore, it is necessary to identify those in conflict and provide them with proper support.

[A Case of Metastatic Recurrent Breast Cancer Successfully with Olaparib in Late Line Therapy].

A 44-years-old woman who underwent bilateral mastectomy was treated with chemotherapy after axillary lymph nodes and liver metastases recurrence. She was referred to our hospital for BRCA1/2 germline test and the test revealed BRCA2 pathogenic mutation. Before the administration of olaparib as the fourth-line therapy, liver dysfunction, caused by extensive liver metastasis, was observed. The liver damage improved, and tumor markers decreased immediately as shown in the blood test and CT examination results after 2 months; indicating marked reduction of liver metastasis. In the OlympiAD trial, the patients received olaparib as either the first-, second- or third-line treatment; however, few data on the efficacy of olaparib in the patients, as a late line treatment, were reported. In this article, we report a case of a woman in whom olaparib was used as the fourth-line treatment for metastatic recurrent breast cancer. A high therapeutic effect was obtained and the quality of life has been maintained in her for the past 1 year.

Antibody-Conjugated Signaling Nanocavities Fabricated by Dynamic Molding for Detecting Cancers Using Small Extracellular Vesicle Markers from Tears.

Small extracellular vesicles (sEVs) are reliable biomarkers for early cancer detection; however, conventional detection methods such as immune-based assays and microRNA analyses are not very sensitive and require sample pretreatments and long analysis time. Here, we developed a molecular imprinting-based dynamic molding approach to fabricate antibody-conjugated signaling nanocavities capable of size recognition. This enabled the establishment of an easy-to-use, rapid, sensitive, pretreatment-free, and noninvasive sEV detection platform for efficient sEV detection-based cancer diagnosis. An apparent dissociation constant was estimated to be 2.4 × 10-16 M, which was ∼1000 times higher than that of commercial immunoassays (analysis time, 5 min/sample). We successfully used tears for the first time to detect cancer-related intact sEVs, clearly differentiating between healthy donors and breast cancer patients, as well as between samples collected before and after total mastectomy. Our nanoprocessing strategy can be easily repurposed for the specific detection of other types of cancer by changing the conjugated antibodies, thereby facilitating the establishment of liquid biopsy for early cancer diagnosis.

[A Case of Primary Lymphoma of the Breast with Hepatic Cirrhosis].

We report a case of primary lymphoma of the breast complicated by heart failure and alcoholic-decompensated hepatic cirrhosis. The patient was a woman in her 60s who noticed a right breast tumor growing 3 months previously. The size of the tumor was approximately 5 cm, and the tumor had infiltrated the skin. There was no metastasis to the axillary lymph node or other organs by CT. We performed right breast mastectomy. Pathology indicated diffuse large B cell lymphoma(DLBCL). We considered chemotherapy, but her general condition was not good because of hepatic cirrhosis, so we administered palliative care. Although chemotherapy is the first choice of treatment for DLBCL, it is necessary to individually consider each patient's circumstances.

Survival outcomes of neoadjuvant chemotherapy with zoledronic acid for HER2-negative breast cancer.

BACKGROUND: A randomized phase 2 trial in women with HER2-negative breast cancer has shown that adding zoledronic acid (ZOL) to neoadjuvant chemotherapy (CT) has potential anticancer benefits in postmenopausal and triple-negative (TN) breast cancer patients. We report the data for the secondary end point of disease-free survival (DFS). METHODS: Patients were randomly assigned to receive CT or CT + ZOL (CT-Z). All patients received four cycles of FEC100 followed by 12 cycles of paclitaxel weekly. ZOL (4 mg) was administered 3-4 times weekly for 7 wk to the CT-Z group patients. The primary end point was pathologic complete response (pCR). The secondary end points were the clinical response rates, rate of breast-conserving surgery, safety, and DFS. RESULTS: Of the 188 patients enrolled, 95 were assigned to the CT group and 93 to the CT-Z group. DFS and overall survival were analyzed in 92 and 88 patients with the mean times of 5.15 y and 5.38 y, respectively. The 3-y DFS rate was 84.6% in the CT group and 90.8% in the CT-Z group (P = 0.188). The particular benefit from ZOL for the neoadjuvant CT seen as improvement of the pCR rate was indicated in the 3-y DFS period for TN cancer cases (CT versus CT-Z: 70.6% versus 94.1%) but not for postmenopausal cases. CONCLUSIONS: ZOL did not improve DFS when combined with CT. However, the improvement of the pCR rate translated to survival outcomes in TN breast cancer. The short-term application of ZOL may not be sufficient to improve the outcome in postmenopausal patients.

Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015.

BACKGROUND: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. METHODS: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety. RESULTS: A total of 42 patients were enrolled in this study. The objective response rate and clinical benefit rate were 24 and 43%, respectively. The median progression-free survival was 4.0 months. The median overall survival was 11.1 months. Grade 3/4 neutropenia was the most common hematologic toxicity, occurring in 22 patients (54%). Nonhematologic toxicity was moderate and transient, with fatigue (48%) being the most common condition and no severe adverse event reported. CONCLUSION: The combination of gemcitabine and vinorelbine is an effective and tolerable regimen for HER2-negative, taxane-pretreated, metastatic breast cancer patients in Japan.

Phase II randomized, controlled trial of 1 day versus 3 days of dexamethasone combined with palonosetron and aprepitant to prevent nausea and vomiting in Japanese breast cancer patients receiving anthracycline-based chemotherapy.

PURPOSE: Dexamethasone, plus a 5-HT3 receptor antagonist and an NK-1 receptor antagonist are recommended for controlling the chemotherapy-induced nausea and vomiting (CINV) of highly emetogenic chemotherapy. Several days of dexamethasone are effective for CINV; however, dexamethasone also has side effects. The purpose of this trial was to investigate whether the use of a second-generation 5-HT3 receptor antagonist and an NK-1 receptor antagonist could allow a reduced dose of dexamethasone for breast cancer patients receiving highly emetogenic chemotherapy. METHODS: Eighty breast cancer patients who received an anthracycline-cyclophosphamide combination regimen were enrolled. The patients were randomized to arm A (dexamethasone days 1-3) and arm B (dexamethasone day 1). The primary endpoint was complete response (CR) (no emetic episodes and no rescue medication) during the overall phase (days 1-5). The secondary endpoints were the CR during the delayed phase (days 2-5), complete control (CC) (no emetic episodes, no rescue medication, and no more than mild nausea) during the overall phase, and the safety of this antiemetic therapy. RESULTS: There were no significant differences in the rates of CR and CC between arm A and B as follows: CR overall phase--arm A: 82.9%, 90% confidence interval [CI] 71.3-90.5% vs arm B: 82.1%, 90% CI 70.0-90.0%; p = 1.00; CR delayed phase--arm A: 87.8%, 90% CI 77.0-93.9% vs arm B: 94.9%, 90% CI 85.6-98.3%; p = 0.43; CC overall phase--arm A: 48.8%, 90% CI 36.4-61.3% vs arm B: 61.5%, 90% CI 48.4-73.2%; p = 0.27. There were very few adverse events and no severe adverse events associated with this antiemetic therapy. CONCLUSIONS: The results suggest that the antiemetic effect provided by dexamethasone administered for 3 days can be obtained by dexamethasone administered for 1 day.

[A Patient with a Pathological Complete Response to Neo-Adjuvant Chemotherapy for Triple-Negative Breast Cancer Followed by Recurrence after Six Months].

The patient was a 68-year-old woman who received neo-adjuvant chemotherapy(4 courses of weekly paclitaxel plus bevacizumab and 4 courses of 5-fluorouracil epirubicin, and cyclophosphamide)for cT1N1M0, Stage II A right-sided triplenegative breast cancer(TNBC). Right breast-conserving surgery with axillary lymph-node dissection was performed. The postoperative pathological diagnosis was a complete response. Six months after surgery, the patient developed lower and right-sided back pain. Detailed examination revealed multiple metastases to the liver, bone, lymph nodes of the mediastinum, and bile duct. The recurrence was treated with biweekly paclitaxel plus bevacizumab. The patient's pain dramatically improved. However, the duration of the response was only 3 months. The patient received eribulin as a second-line treatment, but did not respond and subsequently died. TNBC is considered to have relatively good outcomes if a pathological complete response(pCR)is obtained after preoperative chemotherapy. However, recurrence occurred after only 6months in our patient. In patients with TNBC, physical examinations and simple laboratory tests should be performed every 1 to 2 months after surgery, even if a pathological complete response is obtained. We used paclitaxel plus bevacizumab to treat recurrence of TNBC. Although this treatment did not prolong overall or disease-free survival, the patient temporarily responded, and her quality of life was maintained. Further studies are needed to elucidate the pathogenesis of TNBC and to develop more effective treatments.

The safety of concentrated trastuzumab in 100 ml of saline solution for administration to patients with HER2-positive breast cancer: a phase 1 study.

BACKGROUND: It is recommended that administration of trastuzumab should be carried out in a volume of 250 ml of saline solution over 90 min. Since 2011, recommendations have allowed a shortening of the administration time to 30 min at the second administration. However, the volume to be administered is still 250 ml. The purpose of this study was to evaluate the safety of trastuzumab administered in 100 ml of saline solution over 30 min. METHODS: This study enrolled patients with HER2-positive breast cancer. Three dose levels of trastuzumab, each in 100 ml of saline solution, were used (2, 6 and 8 mg/kg). The primary end point was the determination of safety. RESULTS: Nine patients were enrolled. Since no adverse events were observed, the 8 mg/kg/100 ml saline solution dose level was the recommended dose. CONCLUSIONS: A 30-min administration of trastuzumab in 100 ml of saline solution is safe in patients with HER2-positive breast cancer.

[Determination of treatment strategies for a 43-year-old single woman with Stage IV breast cancer].

The patient was a 43-year-old single woman. Her family history included schizophrenia in her mother and manic-depression in her father. Remicade® (infliximab) had been administered for 3 years to treat rheumatoid arthritis. The patient initially presented to our hospital with dyspnea. Computed tomography revealed left-sided breast cancer associated with multiple bone tumors and multiple pulmonary nodules. A poorly mobile mass with an ulcer was found in left breast. Core-needle biopsy and fluorescent in situ hybridization (FISH)revealed an invasive ductal carcinoma that was positive for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2, 2 +). The clinical diagnosis was Stage IV T4bN3M1 cancer (metastases to the lungs, liver, and bone). Because of the presence of bone metastasis, the patient was admitted and she received complete bed rest as supportive therapy. However, the patient decided to receive treatment on an outpatient basis after carefully discussing the following points: 1) treatment of pulmonary metastasis with dyspnea should receive priority; 2) anticancer agents not causing nausea were required; 3) the risk of bone fractures as a complication (spinal cord injury); 4) how she wanted to spend the limited time available with her family; and 5) how the patient wanted to.

Induction of the DNA-Repair Gene POLQ only in BRCA1-mutant Breast-Cancer Cells by Methionine Restriction.

BACKGROUND/AIM: BRCA1/2 mutations in breast cancer cells impair homologous recombination and promote alternative end joining (Alt-EJ) for DNA-damage repair. DNA polymerase theta, encoded by POLQ, plays a crucial role in Alt-EJ, making it a potential therapeutic target, particularly in BRCA1/2-mutant cancers. Methionine restriction is a promising approach to target cancer cells due to their addiction to this amino acid. The present study investigated the expression of POLQ in BRCA1/2 wild-type and BRCA1-mutant breast cancer cells under methionine restriction. MATERIALS AND METHODS: POLQ mRNA expression was measured using qRT-PCR in BRCA1/2 wild-type (MDA-MB-231) and BRCA1- mutant (HCC1937 and MDA-MB-436) breast-cancer cells under normal, or serum-restricted, or serum- and methionine-restricted conditions. RESULTS: Compared to BRCA1/2 wild-type cells, BRCA1-mutant cells displayed significantly higher basal POLQ expression in normal medium. Methionine restriction further increased POLQ expression in the BRCA1-mutant cells but decreased it in the BRCA1/2 wild-type cells. CONCLUSION: The present findings suggest that methionine restriction showed differential effects on POLQ expression, potentially impacting Alt-EJ activity, in BRCA1/2 wild-type and BRCA1-mutant breast-cancer cells. Further investigation is needed to explore the potential of combining methionine restriction with DNA-repair inhibitors, such as PARP inhibitors, to overcome drug resistance in BRCA1/2 mutant cancers.

High Frequency of BRCA2 c.5576_5579del Carriers in Kakogawa, Japan.

Background/Aim: Certain germline pathogenic variants (PVs), known as founder mutations, have been frequently observed in specific regions and ethnic groups. In Japan, several pathogenic variants of BRCA1/2 have been identified as founder mutations, with their distribution varying across different regions. This retrospective study aimed to further investigate the detailed distribution and correlation between genotype and clinical features among breast cancer patients. Patients and Methods: This study was conducted at Kobe University Hospital and three collaborating institutions. It included breast cancer patients who underwent BRCA1/2 genetic testing between July 1, 2018, and March 31, 2021, and were found to have germline PVs. Clinical characteristics and breast cancer subtypes were compared between carriers of BRCA2 c.5576_5579del and those with other PVs. Additionally, the detection rate of BRCA2 c.5576_5579del was compared with that observed in a previous report. Results: A total of 38 breast cancer patients were included; PVs in BRCA1 and BRCA2 were detected in 12 and 26 patients, respectively, 12 of whom were BRCA2 c.5576_5579del carriers. BRCA2 c.5576_5579del carriers were more likely to develop triple negative breast cancers among all BRCA2 PV carriers. BRCA2 c.5576_5579del accounted for 30.8% of the PVs detected, with a particularly high frequency of 72.7% at Kakogawa Central City Hospital. Conclusion: BRCA2 c.5576_5579del was detected with a particularly high frequency in Hyogo Prefecture, especially in Kakogawa city. In the future, a survey of the distribution of the BRCA2 c.5576_5579del carriers may provide more clarity regarding their localization.

[A case of facial nerve palsy induced by nab-paclitaxel].

The patient was a 60-year-old woman who underwent total mastectomy and axillary lymph node dissection for right breast cancer. She was treated with adjuvant chemotherapy( epirubicin plus cyclophosphamide[EC]and paclitaxel), hormone therapy, and radiation therapy. Multiple lung, lymph node, and bone metastases were detected after 4 years. The patient subsequently received nab-paclitaxel (nabPTX, 260 mg/m2, triweekly) and zoledronate therapy. Ptosis of her right eyebrow and the right angle of her mouth were observed after 8 courses of nabPTX, and peripheral right facial nerve palsy was diagnosed. She underwent rehabilitation, and facial nerve palsy improved after 9 months. Peripheral facial nerve palsy is a very rare adverse event of nabPTX. This is the first case report of peripheral facial nerve paralysis associated with nab- PTX.

Methionine Restriction Increases Exosome Production and Secretion in Breast Cancer Cells.

BACKGROUND/AIM: Methionine addiction is the elevated requirement for exogenous methionine for growth and survival of cancer cells, termed the Hoffman effect. Methionine-addicted cancer cells synthesize normal or excess amounts of methionine but still need an external source of methionine. Methionine restriction (MR) by either a methionine-free medium or in vivo by a low-methionine diet or by methioninase, selectively arrests cancer cells in the late S/G2 cell cycle phase, but not normal cells. The present study focuses on the comparison of production and secretion of exosomes by cancer cells under MR and normal conditions. MATERIALS AND METHODS: MDA-MB-231 cells (triple-negative breast cancer), containing exosomes labeled with CD63-GFP (CD63-GFP exosomes), were visualized by fluorescence microscopy. MDA-MB-231 cells expressing exosome-specific CD63-GFP were cultured in methionine-containing (MET+) or in methionine-free (MET-) DMEM conditions. Exosomes were isolated from conditioned medium of cultured MDA-MD-231 cells by ultracentrifugation and characterized by nanoparticle tracking analysis (NTA) and Western blotting. RESULTS: When MDA-MB-231-CD63-GFP cells were cultured under MR conditions, they arrested their growth and CD63-GFP-expressing exosomes were strongly increased in the cells. MR resulted in approximately a 2-fold increase in exosome production and secretion per cell, even though cell growth was arrested. Methionine restriction thus resulted in elevated exosome production and secretion per surviving cell. CONCLUSION: Exosome production and secretion in the cancer cells increased under MR, suggesting a relation between MR and exosome production and secretion.

Target-Oriented Classification of Triple-negative Breast Cancer.

BACKGROUND/AIM: Breast cancer that is estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor-2 (HER2)-negative is termed triple-negative breast cancer (TNBC). Cytotoxic chemotherapy remains the first choice of treatment against TNBC due to lack of specific therapeutic targets. TNBC is not classified based on therapeutic targets, but recently, the development of targeted therapies - including immune checkpoint inhibitors and poly (adenosine diphosphate-ribose) polymerase inhibitors - has gained attention. This study aimed to examine a novel target-oriented TNBC classification to further facilitate targeted therapy by classifying TNBC based on the breast cancer 1 (BRCA1)-like as well as the protein expression of HER2, programmed death ligand 1 (PD-L1), androgen receptor (AR), cytokeratin 5/6, and epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: We enrolled 17 patients with primary TNBC who did not receive preoperative chemotherapy and underwent surgery at the Kobe University Hospital, Japan, between January 1, 2018, and July 31, 2019. Immunohistochemical staining was performed on tumor specimens, while a BRCAness test was performed using multiplex ligation-dependent probe amplification (MLPA) analysis. A BRCAness score 0.5 or higher was considered BRCA1-like. RESULTS: Tumors were classified as HER2-low (immunohistochemistry score 1+ or 2+ and FISH negative), PD-L1 positive, AR positive, or BRCA1-like. HER2-low, PD-L1 positive, AR positive, and BRCA1-like were detected in 11 (64.7%), 4 (23.5%), 6 (35.3%), and 6 (35.3%) samples. The tumor of only one patient could not be classified into any of these categories. CONCLUSION: Almost all TNBC cases can be classified according to treatable targets.

[A case of liver metastasis of breast cancer responding to letrozole].

The patient was a 68-year-old woman who had a right mastectomy performed in another hospital in 1987. Her right breast tumor was histologically diagnosed IDC and ER(-), with an uncertain PgR and HER2. Tamoxifen was administered as adjuvant therapy for five years after surgery. Because she had abdominal pain in January, 2007, she consulted her family doctor. At that doctor's hospital, metastatic tumors of the liver were found, and she was therefore referred to our hospital. A liver biopsy of the tumor was conducted in our hospital, and hormone therapy was also conducted because her cancer status was ER(+), PgR(+), HER2(0), and was not life-threatening. Hormone therapy had a good effect on the tumor. ER, PgR and HER2 expression might make the difference between a primary tumor and a metastatic one, as in this case. Therefore, we should perform biopsies on metastatic tumors to determine the best treatment method. There is a possibility that hormone therapy will become an effective therapeutic procedure for breast cancer patients who are hormone receptor positive, are not in a life threatening situation, and have had a long, disease-free survival. We reported one case in which the aromatase third generation inhibitor letrozole was effective for treating liver metastases of breast cancer.

Size Dependency of Selective Cellular Uptake of Epigallocatechin Gallate-modified Gold Nanoparticles for Effective Radiosensitization.

The high incidence and mortality of cancer make it a global health issue. However, conventional cancer therapies have several disadvantages, especially serious side effects due to low selective toxicity to cancer cells. Gold nanoparticles (AuNPs) are an excellent drug carrier, enhance drug delivery efficiency, and hold promise for photothermal and radiation therapies. (-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenolic antioxidant constituent of green tea, has a potent antitumor effect, and binds specifically to the 67 kDa laminin receptor, which is overexpressed on the surface of several cancer cell lines such as HeLa and MDA-MB-231 cells. We synthesized EGCG-modified AuNPs (EGCG-AuNPs) using ratios (nEGCG/ngold) from 1:2 to 10:1 and evaluated their size, morphology, stability, antioxidant ability, cytotoxicity, cellular uptake, and uptake mechanisms in vitro in comparison with the conventional AuNPs prepared by using citrate as the reducing agent (citrate-AuNPs). In HeLa cells, EGCG-AuNPs (10:1) (135 nm diameter, sea-urchin-like shape) exhibited the highest cellular uptake. Conversely, EGCG-AuNPs (1:2) (39 nm diameter, spherical shape) were preferentially taken up by MDA-MB-231 cells. Cellular uptake of EGCG-AuNPs toward normal cells (NIH3T3 cells) was found to be in a nonspecific manner, and the amount of uptake was suppressed. X-ray irradiation after cellular uptake of EGCG-AuNPs (1:2) in MDA-MB-231 cells significantly enhanced irradiation-induced cell death. These findings suggest enhanced cellular uptake of EGCG-AuNPs with a 39 nm diameter and their potential use in combinatorial therapeutics of EGCG-AuNPs for breast cancer.

A Rare Case of Bilateral Pectoralis Major Muscle Defect and Abnormal Muscle.

A 56-year-old female patient with left breast cancer presented at our hospital. Preoperative CT scan showed an isolated bilateral pectoralis major muscle defect and abnormal muscle originating from the entire sternum and inserting in the lower ribs and rectus sheath. Total mastectomy and axillary lymph node dissection were performed. We believe that this case is unique and that others like it have never been reported. If there is a defect in the pectoralis major muscle, reconstructive surgery with a tissue expander is contraindicated. Therefore, preoperative evaluation of the chest wall musculature on imaging is recommended.

Identification of Breast Cancer Stem Cells Using a Newly Developed Long-acting Fluorescence Probe, C5S-A, Targeting ALDH1A1.

BACKGROUND/AIM: Aldehyde dehydrogenase (ALDH) 1A1 is a well-known marker for cancer stem cells (CSCs), characterized by self-renewal capacity and multidrug resistance in breast cancer. We developed a near-infrared turn-on fluorescence probe for ALDH1A1, C5S-A, which is suitable for observing and analyzing viable cells. Here, we demonstrated the utility of C5S-A in CSC research using breast cancer cell lines. MATERIALS AND METHODS: To evaluate concordance between C5S-A and conventional stem cell markers, breast cancer cells sorted for ALDEFLUOR-positive cells and for CD44+/CD24- cell populations were stained with C5S-A. Tumorigenicity of C5S-A-positive cells was examined by mammosphere formation assay and subcutaneous transplantation to immunodeficient mice. Additionally, to determine how long fluorescence from a single staining remained observable, we cultured breast cancer cells for 5 days after C5S-A staining. We then evaluated whether C5S-A-positive cells possessed resistance to cytotoxic drugs by chronological imaging. RESULTS: C5S-A staining showed good concordance with conventional breast CSC markers, and good utility for research into CSC characteristics in breast cancer cell lines, including tumorigenesis. Additionally, C5S-A was observable for more than 3 days with a single staining. Using this property, we then confirmed that C5S-A-positive cells possessed resistance to cytotoxic drugs, which is one of the characteristics of CSCs. CONCLUSION: We showed that C5S-A is suitable for CSC research using breast cancer cell lines, and confirmed its utility in observing cells over time.

Device-related Mycobacterium mageritense Infection in a Patient Treated with Nivolumab for Metastatic Breast Cancer.

Treatment with anti-programmed cell death-1 (PD-1) antibodies improves the anti-cancer immune response and can provide a meaningful clinical benefit to cancer patients. However, this treatment can result in specific autoimmune toxicities, termed immune-related adverse events (irAEs). Although irAEs are well recognized, the development of infectious diseases due to this treatment is not often observed. Some recent reports have indicated that patients who receive anti-PD-1 antibodies are at a higher risk for tuberculosis than others. However, reports on nontuberculous mycobacterial infection during anti-PD-1 antibody treatment are still rare. We herein report the first case of Mycobacterium mageritense infection during anti-PD-1 antibody treatment.