Shou Jen Kuo

Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells.

There has been considerable evidence recently demonstrating the anti-tumour effects of flavonols. Quercetin, an ubiquitous bioactive flavonol, inhibits cells proliferation, induces cell cycle arrest and apoptosis in different cancer cell types. The precise molecular mechanism of quercetin-induced apoptosis in human breast cancer cells is unclear. The purpose of this study was to investigate effects of quercetin on cell viability and to determine its underlying mechanism in human breast cancer MDA-MB-231 cells. Quercetin decreased the percentage of viable cells in a dose- and time-dependent manner, which was associated with cell cycle arrest and apoptosis. Quercetin did not increase reactive oxygen species generation but increased cytosolic Ca2+ levels and reduced the mitochondrial membrane potential (ΔΨm). Quercetin treatment promoted activation of caspase-3, -8 and -9 in MDA-MB-231 cells. Caspase inhibitors prevented the quercetin-induced loss of cell viability. Quercetin increased abundance of the pro-apoptotic protein Bax and decreased the levels of anti-apoptotic protein Bcl-2. Confocal laser microscope examination indicated that quercetin promoted apoptosis-inducing factor (AIF) release from mitochondria and stimulated translocation to the nucleus. Taken together, these findings suggest that quercetin results in human breast cancer MDA-MB-231 cell death through mitochondrial- and caspase-3-dependent pathways.

Triple negative breast carcinoma is a prognostic factor in Taiwanese women

BackgroundCurrently, there is a debate as to whether triple negative breast carcinoma (TNBC) has a worse prognosis than non-TNBC. Our aim was to determine whether TNBC is a prognostic factor for survival.MethodsWe identified 1,048 Taiwanese breast carcinoma patients, of whom 167 (15.9%) had TNBC. Data used for analysis were derived from our cancer registry database for women with breast cancer who were diagnosed between 2002 January and 2006 December.ResultsIn the Kaplan-Meier analysis, tumor subgroup (TNBC vs. non-TNBC) was a prognosis factor related to 5-year overall survival. In the univariate analysis, tumor subgroup (TNBC vs. non-TNBC) was a significant factor related to 5-year overall survival, in addition to age, tumor size, lymph node, metastasis, grade, stage, estrogen receptor status, progesterone receptor status, and HER2 overexpression status. In the multivariate analysis, tumor subgroup was not a significant factor related to 5-year disease-free survival (DFS). In node-positive patients, tumor subgroup was a significant factor related to 5-year overall survival, in addition to age, tumor size, metastasis, and grade. In node-negative patients, tumor subgroup was not a significant factor related to 5-year disease-free survival and 5-year overall survival.ConclusionOur results indicated that TNBC patients in Taiwan have worse 5-year overall survival than non-TNBC patients. Notably, in node-positive patients, TNBC played a prognostic role in 5-year overall survival.

Current Trends in and Indications for Endoscopy-Assisted Breast Surgery for Breast Cancer: Results from a Six-Year Study Conducted by the Taiwan Endoscopic Breast Surgery Cooperative Group

Background Endoscopy-assisted breast surgery (EABS) performed through minimal axillary and/or periareolar incisions is a possible alternative to open surgery for certain patients with breast cancer. In this study, we report the early results of an EABS program in Taiwan. Methods The medical records of patients who underwent EABS for breast cancer during the period May 2009 to December 2014 were collected from the Taiwan Endoscopic Breast Surgery Cooperative Group database. Data on clinicopathologic characteristics, type of surgery, method of breast reconstruction, complications and recurrence were analyzed to determine the effectiveness and oncologic safety of EABS in Taiwan. Results A total of 315 EABS procedures were performed in 292 patients with breast cancer, including 23 (7.8%) patients with bilateral disease. The number of breast cancer patients who underwent EABS increased initially from 2009 to 2012 and then stabilized during the period 2012–2014. The most commonly performed EABS was endoscopy-assisted total mastectomy (EATM) (85.4%) followed by endoscopy-assisted partial mastectomy (EAPM) (14.6%). Approximately 74% of the EATM procedures involved breast reconstruction, with the most common types of reconstruction being implant insertion and autologous pedicled TRAM flap surgery. During the six-year study period, there was an increasing trend in the performance of EABS for the management of breast cancer when total mastectomy was indicated. The positive surgical margin rate was 1.9%. Overall, the rate of complications associated with EABS was 15.2% and all were minor and wound-related. During a median follow-up of 26.8 (3.3–68.6) months, there were 3 (1%) cases of local recurrence, 1 (0.3%) case of distant metastasis and 1 (0.3%) death. Conclusion The preliminary results from the EABS program in Taiwan show that EABS is a safe procedure and results in acceptable cosmetic outcome. These findings could help to promote this under-used surgical technique in the field of breast cancer.

A 10-year Follow-up of Triple-negative Breast Cancer Patients in Taiwan

OBJECTIVE This study aimed to investigate whether triple-negative breast cancer has a worse prognosis; here, we present the 10-year follow-up results of triple-negative breast cancer patients in Taiwan. METHODS We identified 2858 breast cancer patients in Taiwan, of whom 416 (14.6%) had triple-negative breast cancer. Data used for analysis were derived from those breast cancer patients who were diagnosed between January 1996 and December 2006. RESULTS In the Kaplan-Meier analysis, tumor subgroup (triple-negative breast cancer vs. non-triple-negative breast cancer) was a prognostic factor related to 10-year breast cancer death-specific survival and disease-free survival. The results of univariate analysis showed that tumor subgroup was a significant factor related to 10-year disease-free survival and breast cancer death-specific survival, as well as menopausal status, tumor size, lymph node, metastasis, grade, stage, estrogen receptor status, progesterone receptor status and her2/neu gene expression status. Similarly, the multivariate analysis also revealed that tumor subgroup was a significant factor related to 10-year breast cancer death-specific survival and disease-free survival, in addition to tumor size, lymph node, metastasis and grade. CONCLUSIONS It was suggested that triple-negative breast cancer patients in Taiwan have worse 10-year survival. Notably, in node-positive patients, triple-negative breast cancer played a prognostic role in 10-year breast cancer death-specific survival.

Endoscopy-Assisted Total Mastectomy Followed by Immediate Pedicled Transverse Rectus Abdominis Musculocutaneous (TRAM) Flap Reconstruction: Preliminary Results of 48 Patients

Background. Endoscopy-assisted breast surgery performed through minimal axillary and/or periareolar incisions is a viable option for patients with breast cancer. In this study, we report the preliminary results of patients with breast cancer who underwent endoscopy-assisted total mastectomy (EATM) followed immediately by pedicled transverse abdominis musculocutaneous (TRAM) flap reconstruction. Methods. Patients in this study comprised women with breast cancer who received EATM and pedicled TRAM flap reconstruction. Clinicopathologic characteristics, type of surgery, complications, and rate of recurrence were recorded. The cosmetic outcomes were evaluated objectively by the surgeons and subjectively by the patients at 3-month postoperative follow-up. Results. A total of 48 patients underwent 49 EATM procedures followed by pedicled TRAM flap reconstruction. Of them, 79.6% underwent endoscopic-assisted nipple-sparing mastectomy and 20.4% received endoscopic-assisted skin-sparing mastectomy. The types of cancer among these patients included ductal carcinoma in situ in 34.7%, stage I cancer in 36.7%, stage II cancer in 24.5%, and stage IIIa cancer in 4.1% patients. Mean tumor size was 2.1 ± 1.4 cm. There were no cases of flap failure. Partial nipple areolar complex ischemia/necrosis occurred in 4 (10.3%) patients; however, all cases resolved after conservative treatment. In the aesthetic outcome evaluation, EATM + TRAM were associated with 89.8% good, 8.2% fair, and 2% unsatisfactory result. No local recurrence was observed during the follow-up period. Conclusion. EATM followed immediately by pedicled TRAM flap reconstruction is a safe procedure and results in good cosmetic outcome in women with early-stage breast cancer.

Adjuvant Tamoxifen Influences the Lipid Profile in Breast Cancer Patients

Background: Currently there is a debate regarding whether tamoxifen used in breast cancer has an impact on lipid profiles. The aim of this study was to determine whether tamoxifen has an impact on the serum lipid profile in Taiwanese women. Patients and Methods: Data of 109 patients were collected from the routine clinical follow-up for women with hormone receptor-positive breast cancer who were treated between July 2005 and March 2008. These patients were divided into 2 subgroups, based on their tumor grade and lymph node status. Subgroup 1 patients had tumor grade I/II and a negative lymph node status. Those patients with tumor grade III or a positive lymph node status were defined as subgroup 2. Results: In the 109 patients, the mean serum total cholesterol (TC) levels after tamoxifen treatment, as well as the serum low-density lipoprotein cholesterol (LDL-C) levels, were lower than the baseline levels, with statistically significant differences. Treatment with tamoxifen lowered the serum TC and LDL-C levels in both subgroups. Conclusions: The results indicate that tamoxifen has an impact on the serum lipid profile of breast cancer patients in Taiwan. Physicians should follow up the lipid profile in these patients.

The learning curve of endoscopic total mastectomy in Taiwan: A multi-center study

Introduction Laparoscopic techniques are commonly used in abdominal and gynecologic surgery, while breast cancer surgery has remained largely unchanged. In Asia, especially in Japan, many surgeons have started to use endoscopic surgery for breast cancer. In Taiwan, endoscopy-assisted breast surgery started in 2010. The benefits of this surgical method include smaller incisions, an axillary anatomic approach, clear vision, no oncologic compromise, and good cosmetic outcomes. This is the first report to discuss the learning curve of endoscopy-assisted breast surgery, including the difficulties experienced. Materials and methods From June 2011 to December 2013, data were collected from 134 patients who received an endoscopic total mastectomy at the Taipei Medical University Hospital (TMUH) or Changhua Christian Hospital (CCH). We divided these patients into a learning group (TMUH, n = 15; CCH, n = 15) and a mature group (TMUH, n = 50; CCH, n = 54). Patient data and perioperative variables were recorded by retrospective chart review. Variables were compared using the χ2 test and Student’s t-test. Results There was a significant difference in operation time (275.3 vs. 228.9 minutes, p < 0.01) between the learning and mature groups. Perioperative variables (lymph node dissection method, nipple preservation, and reconstruction method) were also analyzed, but there were no demographic differences between the groups. The complication rate was higher in the learning group, although this difference was also not statistically significant. Conclusion Our study is the first to discuss the learning curve of endoscopic total mastectomy. The operation time decreased significantly after 15 cases at each hospital. Although the operation is still more time-consuming than traditional methods, it has the benefit of smaller wounds and improved cosmetic outcomes if combined with immediate reconstruction.

Effect of Lipodox in combination with bevacizumab in a patient with a metastatic malignant phyllodes breast tumor: A case report

A 76-year-old female patient with a malignant phyllodes tumor underwent modified radical mastectomy and wide excision. Multiple nodules were observed in the operated wound area. Positron emission tomography-computed tomography (PET-CT) revealed recurrent disease in the left breast, the adjacent left third rib, the left internal mammary region and the left ilium. A novel formulation of bevacizumab (5 mg/m2, first day) in combination with liposomal doxorubicin (Lipodox, 30 mg/m2, second day) was administered for 3 cycles every 2 weeks, and subsequently wide excision was performed. Lipodox (40 mg/m2) was administered for 3 cycles every 3 weeks, starting 4 weeks after the surgery. Follow-up whole body PET-CT scanning, 3 and 6 months later, indicated no sign of residual hypermetabolic malignancy. Malignant phyllodes tumors do not usually respond to chemotherapy or radiotherapy. In the present case report, a novel formulation of bevacizumab in combination with Lipodox was administered as neoadjuvant chemotherapy in a patient with a malignant phyllodes tumor and preoperative tumor shrinkage was achieved, resulting in clear resection margins.

Myoid hamartoma of the breast with focal chondromyoxid metaplasia and pseudoangiomatous stromal hyperplasia: A case report.

Hamartomas of the breast, also known as fibroadenolipomas, lipofibroadenomas or adenolipomas, are benign lesions. Hamartomas account for between 0.04 and 1.15% of all benign breast tumors in females. Myoid hamartoma of the breast (MHB) is extremely rare. The present study describes a case of MHB in a 44-year-old female. Screening mammography revealed a lobulated partial indistinct isodense mass measuring ~3.8 cm in the upper outer quadrant of the left breast. Sonographic examinations revealed a 2–3-cm mass in the left breast, which was fairly well circumbscribed and demonstrated complex scattered echogenic areas and isoechoic tissue. A core needle biopsy demonstrated fibrocystic changes, with small focal ductule aggregations. As malignancy could not be excluded, a partial mastectomy was performed using a circumareolar incision. The mass was histopathologically diagnosed as MHB with focal chondromyoxid metaplasia and pseudoangiomatous stromal hyperplasia. The histological diagnosis was based upon the findings of the well-circumscribed tumor, which was composed of entrapped mammary ducts, fat cells and myoid stromal components, with focal chondromyxoid metaplasia and pseudoangiomatous stromal hyperplasia. The tumor cells exhibited diffuse cluster of differentiation 34-positive immunoreactivity, which was consistent with a diagnosis of pseudoangiomatous stromal hyperplasia.