Metformin Alters Tumor Immune Microenvironment, Improving the Outcomes of Breast Cancer Patients With Type 2 Diabetes Mellitus.

This study investigated the clinical effect of metformin on breast cancer patients with preexisting type 2 diabetes mellitus (T2DM). We analyzed 177 patients with T2DM who underwent breast cancer surgery and assessed tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) in patients who underwent tumor resection with or without metformin treatment using multiplex immunohistochemistry (IHC). Patients who received metformin either pre- or postoperatively exhibited reduced distant organ recurrence and improved postoperative recurrence-free survival compared to those of patients who did not. Additionally, in a subgroup of 40 patients receiving preoperative systemic therapy, metformin treatment was associated with increased rates of pathological complete response. IHC analysis revealed significantly lower levels of cluster of differentiation (CD) 68(+) CD163(+) M2-type TAMs (p < 0.01) but higher CD3(+) and CD8(+) TIL densities in the metformin-treated group compared with the same parameters in those without metformin treatment, with a significant difference in the CD8(+)/CD3(+) TIL ratio (p < 0.01). Despite the constraints posed by our small sample size, our findings suggest a potential role for metformin in modulating the immunological microenvironment, which may contribute to improved outcomes in diabetes patients with breast cancer.

[Long-Term Survival of a Patient with Triple-Negative Breast Cancer with Hormone Receptor Status Conversion between Primary and Metastatic Tumors].

Patients with triple-negative breast cancer have poor survival after recurrence. However, previous studies have shown that receptor conversion can occur between primary breast tumor and metastatic sites. Herein, we describe the case of a 54- year-old woman with advanced breast cancer, which showed receptor conversion from primary tumor(triple-negative)to distant metastases(Luminal type). The patient had undergone left radical mastectomy and left axillary lymph node dissection at another hospital(pT3N0M0, Stage ⅡB, ER-negative, PgR-negative, and HER2-negative). She was referred to our hospital for adjuvant chemotherapy with 3 courses of 5-fluorouracil, epirubicin, and cyclophosphamide and 3 courses of docetaxel. Around 26 months after the surgery, the follow-up CT scan showed multiple lung nodules. Another 9 months later, her left axillary and mediastinal lymph nodes were enlarged. She received several courses of anticancer chemotherapy. After paclitaxel and bevacizumab were administered as seventh-line chemotherapy, a vacuum-assisted biopsy of the left axillary lymph node was performed to confirm the presence of metastasis. Furthermore, immunohistochemistry results showed that the metastatic tumor was ER-positive, PgR-positive, and HER2-negative. Fulvestrant and palbociclib were then initiated as first-line endocrine therapy. She has been stable for more than 18 months since. It is essential to perform biopsies of metastatic sites for optimal management of patients with metastatic breast cancer.

Neoadjuvant chemotherapy for primary sarcoma of the breast: a case report.

BACKGROUND: Primary sarcoma of the breast is rare. Surgery has been the only curative treatment available. Recently, neoadjuvant chemotherapy including anthracycline/ifosfamide has been reported effective for patients with high-risk sarcomas in a prospective trial. CASE PRESENTATION: A 52-year-old Japanese woman presented with a mass in her left breast. The 10 cm tumor was fixed to her chest wall on examination. A skin biopsy was performed which showed leiomyosarcoma. Neoadjuvant chemotherapy was given and the tumor became mobile. A mastectomy and axillary dissection were performed with surgically negative margins. After neoadjuvant chemotherapy, the amount of necrosis was profoundly influenced by chemotherapy, and the histological effect of neoadjuvant chemotherapy was assessed in reference to pre-neoadjuvant chemotherapy magnetic resonance imaging. CONCLUSION: In contrast to many other cancers, the evaluation of various treatments and of the histological effect of neoadjuvant chemotherapy for sarcoma has been difficult due to the rarity of these tumors. We report the case of a patient with a breast sarcoma, treated with neoadjuvant chemotherapy and discuss the appropriate pathological evaluation and therapeutic management.

Functional Expression of Mucin1 in Human Duodenal Adenocarcinoma.

OBJECTIVE: Mucin1 (MUC1), a member of the mucin family, is a glycoprotein which is often expressed in malignant cells. However, the expression and function of MUC1 in human duodenal adenocarcinoma (DAC) has not yet been characterized because of its low frequency. Here, we examined the functional roles of core protein (MUC1-C) in DAC. MATERIALS AND METHODS: Using a human duodenal cancer cell line, HuTu80, proliferation, migration, invasion, ALDH activity was assessed by cell counting kit-8, scratch wound healing, matrigel invasion, and ALDEFUOR assays, respectively. The function of MUC1 protein was evaluated with knockdown using specific siRNA as well as anti-MUC1-C peptide, GO203. MUC1 expression in human DAC was evaluated immunohistochemically in surgically resected tumors. RESULTS: The positive expression of MUC1 in HuTu80 was confirmed by RT-PCR and flow cytometry. In vitro cell growth was inhibited by the addition of 50-100 µM GO203 as well as treatment with siRNA for MUC1-C. Silencing of MUC1-C also significantly reduced migration, invasion, ALDH activity. Local injection of GO-203 (14 mg/kg) significantly suppressed the growth of subcutaneous HuTu80 tumors in nude mice. Immunohistochemically, MUC1 was strongly detected in seven DAC cases, but not in 11 others. The outcome of patients with high MUC1 expression was significantly worse than those without MUC1 expression. CONCLUSIONS: These results suggest that MUC1 is functionally associated with the malignant potential of DAC and could be a novel therapeutic target for this rare tumor.

Usefulness of miRNA profiles for predicting pathological responses to neoadjuvant chemotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer.

Pathological complete response (pCR) is considered to be a useful prognostic marker for neoadjuvant chemotherapy to improve the survival rate of patients with operable breast cancer. In the present study, we identified differentially expressed microRNAs (miRNAs) between pCR and non-pCR groups of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who received neoadjuvant chemotherapy with trastuzumab. Expression profiles were examined by miRNA microarrays using total RNA extracted from formalin-fixed, paraffin-embedded tissues from pretreatment biopsy specimens. Significant differences were observed in miRNAs associated with pCR between the luminal B-like (HER2-positive) and HER2-positive (nonluminal) subtypes, which were further classified according to their estrogen receptor (ER) status. Prediction models constructed with differentially expressed miRNAs performed well. In conclusion, the combination of miRNA profiles and ER status may improve the accuracy of pCR prediction in patients with HER2-positive breast cancer and enable the development of personalized treatment regimens.

Comparison between the antiemetic effects of palonosetron and granisetron in breast cancer patients treated with anthracycline-based regimens.

Chemotherapy-induced nausea and vomiting is a serious adverse side-effect of anthracycline-based chemotherapy regimens, in patients with breast cancer. A combination of three drugs, 5-hydroxytryptamine (5-HT3) receptor antagonist, aprepitant and dexamethasone, is recommended for antiemetic therapy. Palonosetron (PALO), a novel 5-HT3 receptor antagonist has been identified to be effective against delayed nausea and vomiting. In this study, the results of PALO for patients who received anthracycline-based chemotherapy were compared with that of granisetron (GRA) using a crossover study design. This study evaluated the efficacy of antiemetics in the first cycle of chemotherapy, as well as the second and third cycles. A total of 21 patients and 19 patients were assigned to PALO and GRA treatment groups during the first cycle of chemotherapy, respectively. The patients switched to the other antiemetic drug for the second chemotherapy cycle (PALO followed by GRA or GRA followed by PALO). The patients could select PALO or GRA antiemetics for the third cycle, according to their preference. A total of 21 patients selected PALO and 18 patients selected GRA in the third cycle, and one patient was withdrawn from the study as their third cycle questionnaire was not obtained. No significant differences between PALO and GRA were identified in first and second cycles. However, during the third cycle, a significant difference was observed in acute-phase complete control of emetic events between the PALO and GRA groups, which was defined as no emetic episode, no additional antiemetic treatment and no more than mild nausea, between PALO and GRA. These results demonstrated that changing antiemetics may affect the efficacy of antiemetics. This study indicates that alteration of antiemetic regimens, including drug combination and order, may improve the efficacy of antiemetic treatment.

[Use of sugammadex in a patient with limb girdle muscular dystrophy].

Limb girdle muscular dystrophy, a chronic progressive muscular atrophic disease, leads to high sensitivity to depolarizing and non-depolarizing neuromuscular blocking agents. We report the successful use of the sugammadex in a patient with limb girdle muscular dystrophy (dysferlinopathy, Miyoshi distal myopathy) to reverse rocuronium-induced neuromuscular block. After neuromuscular recovery to a train-of-four ratio = 43%, we administered 3.2 mg x kg(-1) of sugammadex (200 mg) intravenously, reversing neuromuscular blockade to a train-of-four ratio = 95% within 3 min. Sugammadex can be used to reverse rocuronium-induced neuromuscular blockade in patients with limb girdle muscular dystrophy.