Incidental Axillary Dose of Tomotherapy in Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer: A Dosimetrical Analysis.

Background and Objectives: Intensity-modulated radiation therapy (IMRT) is becoming a more common method of performing whole breast irradiation (WBI) for early breast cancer. This study aimed to examine the incidental dose to the axillary region using tomotherapy, a unique form of IMRT. Patients and Methods: This study included 30 patients with early-stage breast cancer who underwent adjuvant WBI using TomoDirect IMRT. A hypofractionation scheme of 42.4 Gy delivered in 16 fractions was prescribed. The plan comprised of two parallel-opposed beams, along with two additional beams positioned anteriorly at gantry angles of 20° and 40° from the medial beam. The incidental dose received at axillary levels I, II, and III was evaluated using several dose-volume parameters. Results: The study participants had a median age of 51 years, and 60% had left-sided breast cancer. The mean dose of the axilla for levels I, II, and III were 15.5 ± 4.8 Gy, 14.9 ± 4.2 Gy, and 1.5 ± 1.6 Gy, respectively. Adequate coverage of the axilla, defined as V95%[%], was achieved for 4.7 ± 3.9%, 4.8 ± 3.7%, and 0 ± 0% for levels I, II, and III, respectively. The results were compared with those of previously published studies, and the axillary mean dose and V95%[%] of TomoDirect IMRT were low, comparable to other IMRT techniques, and lower than those of traditional tangential therapy. Conclusions: While incidental axillary radiation during WBI has been proposed to assist in regional disease control, the TomoDirect plan was demonstrated to decrease this dose, and a hypofractionation scheme would further lower its biological effectiveness. Future clinical studies should incorporate dosimetrical analysis of incidental axillary dose, in order to facilitate hypofractionated IMRT planning with risk-adjusted axilla coverage in early breast cancer.

Specific activation of insulin-like growth factor-1 receptor by ginsenoside Rg5 promotes angiogenesis and vasorelaxation.

Ginsenoside Rg5 is a compound newly synthesized during the steaming process of ginseng; however, its biological activity has not been elucidated with regard to endothelial function. We found that Rg5 stimulated in vitro angiogenesis of human endothelial cells, consistent with increased neovascularization and blood perfusion in a mouse hind limb ischemia model. Rg5 also evoked vasorelaxation in aortic rings isolated from wild type and high cholesterol-fed ApoE(-/-) mice but not from endothelial nitric-oxide synthase (eNOS) knock-out mice. Angiogenic activity of Rg5 was highly associated with a specific increase in insulin-like growth factor-1 receptor (IGF-1R) phosphorylation and subsequent activation of multiple angiogenic signals, including ERK, FAK, Akt/eNOS/NO, and Gi-mediated phospholipase C/Ca(2+)/eNOS dimerization pathways. The vasodilative activity of Rg5 was mediated by the eNOS/NO/cGMP axis. IGF-1R knockdown suppressed Rg5-induced angiogenesis and vasorelaxation by inhibiting key angiogenic signaling and NO/cGMP pathways. In silico docking analysis showed that Rg5 bound with high affinity to IGF-1R at the same binding site of IGF. Rg5 blocked binding of IGF-1 to its receptor with an IC50 of ∼90 nmol/liter. However, Rg5 did not induce vascular inflammation and permeability. These data suggest that Rg5 plays a novel role as an IGF-1R agonist, promoting therapeutic angiogenesis and improving hypertension without adverse effects in the vasculature.

Limited resections for duodenal gastrointestinal stromal tumors and their oncologic outcomes.

PURPOSE: Limited resection is considered a treatment option for duodenal gastrointestinal stromal tumors (GISTs) whenever technically feasible, but the optimal technique for this is still not well defined. We present the various types of limited resections for duodenal GISTs and analyze their postoperative outcomes. METHODS: The subjects of this retrospective clinicopathologic analysis were 21 patients who underwent limited resections for duodenal GIST between May, 2001 and June, 2014. The median follow-up period was 52 months (range 5-125 months). RESULTS: The patients comprised 12 men and 9 women, with a median age of 59 years (range 45-75 years), all of whom were treated by various forms of limited resection with clear margins. There were ten wedge resections with primary closure (eight open/two laparoscopic), two wedge resections with Roux-en Y duodenojejunostomy, three segmental duodenectomies with end-to-end duodenoduodenostomy, and six segmental duodenectomies with end-to-end duodenojejunostomy. Hepatic metastasis was found 27 months after surgery in one patient, who was given imatinib mesylate for 17 months to slow disease progression. The other 20 patients were alive and recurrence free at the time of writing. CONCLUSION: Excellent recurrence-free survival was achieved after limited resections, supporting the consideration of various methods of limited resection as the treatment of choice for duodenal GISTs.

Prognostic Value of Axillary Lymph Node Texture Parameters Measured by Pretreatment 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Locally Advanced Breast Cancer with Neoadjuvant Chemotherapy.

BACKGROUND: This study investigated the prognostic value of axillary lymph node (ALN) heterogeneity texture features through 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with locally advanced breast cancer (LABC). METHODS: We retrospectively analyzed 158 LABC patients with FDG-avid, pathology-proven, metastatic ALN who underwent neoadjuvant chemotherapy (NAC) and curative surgery. Tumor and ALN texture parameters were extracted from pretreatment 18F-FDG PET/CT using Chang-Gung Image Texture Analysis software. The least absolute shrinkage and selection operator regression was performed to select the most significant predictive texture parameters. The predictive impact of texture parameters was evaluated for both progression-free survival and pathologic NAC response. RESULTS: The median follow-up period of 36.8 months and progression of disease (PD) was observed in 36 patients. In the univariate analysis, ALN textures (minimum standardized uptake value (SUV) (p = 0.026), SUV skewness (p = 0.038), SUV bias-corrected Kurtosis (p = 0.034), total lesion glycolysis (p = 0.011)), tumor textures (low-intensity size zone emphasis (p = 0.045), minimum SUV (p = 0.047), and homogeneity (p = 0.041)) were significant texture predictors. On the Cox regression analysis, ALN SUV skewness was an independent texture predictor of PD (p = 0.016, hazard ratio 2.3, 95% confidence interval 1.16-4.58). CONCLUSIONS: ALN texture feature from pretreatment 18F-FDG PET/CT is useful for the prediction of LABC progression.

The prognoses of metaplastic breast cancer patients compared to those of triple-negative breast cancer patients.

Metaplastic breast carcinoma (MBC) is a rare, heterogeneous breast cancer characterized by admixture of adenocarcinoma with metaplastic elements, low hormone receptor expression, and poor outcomes. The authors retrospectively reviewed the medical records of 47 MBC patients and 1,346 invasive ductal carcinoma (IDC) patients. Two hundred eighteen of the IDC patients were triple-negative (TN-IDC) for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (ER-/PR-/HER2-). Patients were surgically treated at the Samsung Medical Center between 2005 and 2009. The MBC patients presented with a larger tumor size, lower lymph node involvement, higher histological and nuclear grades, higher triple negativity (ER-/PR-/HER2-) and higher p53, CK5/6, and EGFR expressions compared with those of the IDC group. However, there were no significant differences in clinicopathological characteristics between MBC and TN-IDC. During the follow-up period (median duration of 30.3 months, range 2.6-56.3 months), seven (14.9%) MBC patients, and 98 (7.1%) IDC patients had disease recurrence. The three-year disease-free survival (DFS) rate was 78.1% in the MBC group and 91.1% in IDC group (P < 0.001). The three-year DFS rate was not significantly different between the MBC and TN-IDC groups (78.1 vs. 84.9%, P = 0.114). However, in patients with lymph node metastasis who underwent adjuvant chemotherapy, the three-year DFS rate was 44.4% in the MBC group and 72.5% in the TN-IDC group (P = 0.025). The authors found that MBC had a poorer clinical outcome than did IDC. In breast cancer patients with nodal metastasis, MBC had a poorer prognosis than did TN-IDC, despite adjuvant chemotherapy.

The efficacy of lateral neck sentinel lymph node biopsy in papillary thyroid carcinoma.

BACKGROUND: Although occult lymph node metastasis to the lateral neck compartment is common in papillary thyroid carcinoma, the incidence and patterns of lateral neck node metastasis in papillary carcinoma are not known. We hypothesized that sentinel lymph node biopsy (SLNB) with radioisotope in the detection of occult lateral neck node metastasis would be useful in characterizing metastasis in papillary carcinoma. METHODS: Ninety-four patients with papillary thyroid carcinoma were included from June 2009 to March 2010 for lateral neck SLNB. Preoperative lymphoscintigraphy was obtained after intratumoral injection of a (99m)Tc-tin colloid under ultrasound guidance. Total thyroidectomy or lobectomy preceded SLN detection to avoid radioactivity interference with the primary tumor, after which SLNB was performed in the lateral neck nodes. In the cases where metastasis was detected in SLNs upon frozen biopsy, an immediate modified radical neck node dissection was performed. RESULTS: A total of 174 SLNs were identified in 60 patients (63.8%). The identification rate of the SLNs with isotope increased with time. Sentinel lymph node metastasis was found in 19 patients (31.7%). This clinically occult metastasis was only related to the total number of metastatic LNs in the central compartment. Patient age, gender, tumor size, location, extent of tumor invasion, multiplicity, and presence of thyroiditis were not related to metastasis in the lateral compartment. Detection of lateral neck SLNs upon biopsy with radioisotope was also feasible in level II and contralateral neck. CONCLUSIONS: Sentinel lymph node biopsy is a useful method for evaluating the occult lateral neck lymph node status in patients with papillary thyroid carcinoma, especially in the cases of central neck node metastasis.

Is robotic surgery superior to endoscopic and open surgeries in thyroid cancer?

BACKGROUND: Endoscopic thyroidectomies have been performed using various approaches, and indications have expanded with the development of new surgical techniques and instruments. Endoscopic thyroid surgery using bilateral axillo-breast approaches have excellent cosmetic results and a symmetrical, optimal operative view. However, because of the two-dimensional view and the nonflexible instruments, these approaches are not easy to use in performing a central lymph node dissection (CND). Robotic surgery has drawn attention as a potentially safe and effective method for treating thyroid cancer. The aim of the present study was to determine whether robotic surgery is superior to endoscopic and open surgery through comparing technical aspects and surgical outcomes. METHODS: From October 2008 to December 2009, 302 patients had total thyroidectomies and CND with cancer less than 1 cm. Patients were divided into three groups according to operation methods (open group; n = 138), (endo group; n = 95), (robot group; n = 69). RESULTS: Young patients preferred the robotic and endoscopic surgery. The number of retrieved lymph nodes in the open group (4.8 ± 2.8) was not different from the robot group (4.7 ± 2.7) and the endo group (4.6 ± 3.7). The operative time of the robot group was longer than the open and the endo group. The total drain amount in the robot group was more than the open and endo groups; however, there was no difference in the length of hospitalization and complication rates. There were no differences between the open (0.8 ± 2.0) and robot groups (0.8 ± 1.4), but the endo group (2.4 ± 6.3) showed higher postoperative serum thyroglobulin off thyroid hormone (Off-Tg) when compared to the open and robot groups. CONCLUSIONS: Robotic surgery was equal to open surgery except with respect to operative time and was superior to endoscopic surgery in Off-Tg levels presenting completeness of the operation in thyroid cancer surgery. Because it has excellent cosmetic results and various technical advantages, it should be considered in young, low-risk patients with thyroid carcinoma less than 1 cm.

Ileal metastasis of breast cancer in a patient with a BRCA2 gene mutation: report of a case.

Breast cancer is the most common malignancy in females. Common sites of metastases include the liver, lung, bone, and brain, while metastases to the extrahepatic digestive system are very rare. This report presents a patient diagnosed with breast carcinoma metastasis in the terminal ileum. The patient underwent breast-conserving surgery on both breasts because of breast cancer at the age of 46 years. Both breast cancers were consistent with stage I invasive ductal carcinomas. Colonoscopy during an investigation for hematochezia revealed a 2-cm ulceration in the terminal ileum 22 months later, and microscopic examination of a biopsy specimen of the ulceration revealed a poorly differentiated mass that was strongly suggestive of metastatic adenocarcinoma with endolymphatic tumor emboli. She underwent hand-assisted laparoscopic ileocecectomy because of ileal metastasis. She had a family history of breast cancer (sister) and colon cancer (brother). She exhibited HER2/neu discordance and carried the BRCA2 gene mutation. Surgeons should remain aware that breast cancer can metastasize to the gastrointestinal tract.

Safety of immediate use of totally implantable venous access ports in adult patients with cancer: a retrospective single-center study.

Purpose: Totally implantable venous access ports (TIVAPs) can be used long-term for safe administration of intravenous drugs. TIVAP complications include catheter-related infections, venous thrombosis, extravasation, TIVAP migration, and pain. The relationship between the timing of the first chemotherapy administration after port implantation and complications is controversial. This study aimed to investigate the safety of immediate use of TIVAPs and the associated risk factors for complications. Methods: Between January 2016 and December 2018, 305 patients (median age, 53 years; 256 women) who underwent TIVAP placement at our institution were included. Chemotherapy was administered within 2 days of implantation. A retrospective analysis of patients' clinical data was performed to investigate catheter days and complications of TIVAPs. Results: Overall, 305 patients were evaluated over 57,324 catheter days (median, 168 catheter days; interquartile range, 105). The median interval between placement and first use of TIVAPs was 0.98 days. The overall morbidity rate was 2.95%. Nine complications occurred in nine patients, including TIVAP-related infection (4), pain (2), port occlusion (1), thrombosis (1), and scar disunion (1), of which five required port removal (1.64%). The median number of catheter days before complications occurred was 61 (range, 10-457 days; interquartile range, 51). No complications occurred within 7 days of implantation. Body mass index was an independent risk factor for TIVAP-related complications in the Cox proportional hazards model (multivariable analysis: hazard ratio, 1.221; 95% confidence interval, 1.054-1.414; P=0.008). Conclusion: This study suggests the safe long-term use of TIVAPs following their immediate chemotherapy administration within 2 days of implantation.

Pyoderma Gangrenosum Mimicking Wound Infection after Breast Cancer Surgery.

Postoperative pyoderma gangrenosum (PPG) is rare, and its diagnosis is often delayed because of its wound infection-mimicking course. A 53-year-old breast cancer patient who underwent breast-conserving surgery of the right breast presented with fever, leukocytosis, C-reactive protein elevation, and redness of the right breast on postoperative day (POD) 3. The breast wound showed desquamation with painful ulcerative changes from POD 6, and fever was sustained under antibiotic administration. Wound irrigation was attempted; however, inflammatory skin damage progressed to involvement of the entire skin overlying the breast. With clinical suspicion of PPG, skin biopsy and systemic corticosteroid initiation were performed on POD 12. Wound damage progression ceased, and the systemic inflammation subsided. The patient underwent split-thickness skin grafting under intravenous corticosteroid administration, and the wound healed after 30 days. PPG is a rare clinical scenario. Early diagnosis is critical to avoid unnecessary treatment and aggravation of the surgical wound.

A Nationwide Study on the Incidence of Breast Cancer in Korean Women with Osteoporosis Receiving Raloxifene Treatment.

PURPOSE: Raloxifene is a selective estrogen receptor modulator (SERM), and raloxifene treatment for osteoporosis is reimbursable under the Korean National Health Insurance. Evidence suggests that SERMs use reduces the risk of breast cancer in Asian population. Herein, we retrospectively investigated the protective effect of raloxifene on breast cancer rates in Korean population. METHODS: Using the Health Insurance Review and Assessment Service database, we selected women with osteoporosis aged 50 years and above. Patients treated for at least 2 years with raloxifene were assigned to the user group, whereas the remaining patients were assigned to the non-user group. The effect on breast cancer risk was assessed using the Cox proportional-hazards model with a time-dependent covariate to adjust for immortal time bias. RESULTS: A total of 322,870 women who were registered between 2010 and 2011 were included. The user group comprised 0.7% (n = 2,307) of the total population. The mean age was 65.7 ± 8.0 years and 67.2 ± 8.6 years in the user and non-user groups, respectively (p < 0.001). There was no difference in the previous use of estrogen replacement between the 2 groups (p = 0.087). The incidence of breast cancer per 1,000 person-years was 0.49 (n = 8) and 0.68 (n = 1,714) in the user and non-user groups, respectively (hazard ratio [HR], 0.63, 95% confidence interval [CI], 0.32-1.27). HR decreased with increase in the treatment duration, but this change was not statistically significant (HR, 1.00, 95% CI, 0.32-3.11 in 2-3 years; HR, 0.63, 95% CI, 0.20-1.94 in 3-4 years; and HR, 0.41, 95% CI, 0.10-1.65 in 4-5 years). CONCLUSION: Long-term treatment with raloxifene in women with osteoporosis was not significantly associated with a reduction in breast cancer rates. However, further investigation is required for a conclusive proof.

Late recurrence of papillary thyroid cancer from needle tract implantation after core needle biopsy: A case report.

BACKGROUND: Papillary thyroid cancer (PTC) has good prognosis so that the local recurrence or distant metastasis can occur later on the lifetime follow up. In this study, we report recurrence of PTC in subcutaneous area combined with lymph node metastasis. A suspicion of needle tract implantation after core needle biopsy was found. CASE SUMMARY: A 66-year-old female patients who underwent right thyroid lobectomy for PTC complained of palpable nodule on anterior neck area. The location of the palpable nodule was not associated with her postoperative scar. After excision of the skin tumor, it was diagnosed as recurrence of PTC. Furthermore, results of subsequent imaging showed lymph node metastasis on her right cervical area. According to the previous medical records, the patient received core needle biopsy through the neck of the patient midline and hematoma was noted after the procedure. The time interval from the first diagnosis to local recurrence or metastasis to the skin and lymph nodes was ten years. As treatment, the patient underwent lymph node dissection in the right and completion thyroidectomy for radioisotope treatment. CONCLUSION: Needle tract implantation can occur after core needle biopsy. Further studies are needed to compare core-needle biopsy and fine-needle aspiration.

Prognostic Factors in Male Breast Cancer: A Retrospective Nationwide Study in South Korea by the Study of SMARTSHIP Group.

This study evaluated the incidence, the survival outcomes and its prognostic factors for male breast cancer (MBC) in Korea. Using the National Health Insurance Service database of Korea, we identified MBC patients who had the new claim code of C50. Medical records including type of surgeries and radiotherapy within one year of the first claim and death records were reviewed. Between 2005 and 2016, 838 newly diagnosed MBC patients were included (median follow-up, 1,769 days). The 70-74-year age group had the highest incidence of MBC. The 5-year survival rate was 73.7%. Age > 65 years, low income, no surgical intervention, no tamoxifen use, and > 2 comorbidities correlated with a worse outcome. MBC incidence has increased over time, and its peak is noted at age > 70 years. Age > 65 years, > 2 comorbidities, no surgical intervention, and no tamoxifen use correlate to poor prognosis.

The prediction of lymph node metastasis in ductal carcinoma in situ with microinvasion by assessing lymphangiogenesis.

BACKGROUND AND OBJECTIVES: Lymph node (LN) metastasis of ductal carcinoma in situ with microinvasion (DCISM) is variable (0-14%). To ascertain the role of lymphangiogenesis in LN metastasis in DCISM, we compared the lymphatic vessel density with the presence of LN metastasis in a group of patients that underwent axillary dissection with breast surgery due to DCISM. METHODS: We identified 46 patients with a diagnosis of DCISM who underwent breast surgery with axillary dissection to evaluate LN status from June 1996 to March 2008. Microvessel density (MVD) and lymphatic vessel density (LVD) was measured by immunohistochemical staining with two markers, CD34 and D2-40. RESULTS: LVD of the patients with LN metastasis was significantly higher than that of the patients without LN metastasis (P = 0.04). Correlation in the total score of progesterone receptor and LN metastasis was also noted (P = 0.017). There was no statistically significant relation between LVD and clinicopathologic parameters such as size and type of underlying DCIS, nuclear grade, presence of lymphovascular invasion, hormone receptor, and HER-2 status. CONCLUSIONS: Lymphangiogenesis may be significantly associated with LN metastasis in DCISM. This is the first attempt to predict axillary LN metastasis in DCISM by quantifying the LVD.

Characteristics of metastasis in the breast from extramammary malignancies.

BACKGROUND AND OBJECTIVE: Breast metastasis from extramammary neoplasm is rare. We present the cases of metastasis to the breast after review of results in one institute and we want to show the difference of previous report. METHODS: The surgical and pathology databases of Samsung Medical Center from November 1994 to March 2009 were investigated to identify all patients with a diagnosis of metastasis to the breast. RESULTS: Thirty-three patients with breast metastases from extramammary neoplasm were studied. Gastric carcinoma was most common metastatic origin in this study. There were four cases with microcalcifications in their metastatic lesions. This is the first report of microcalcification of metastatic lesions to the breast from hepatocellular carcinoma and gastric cancer. CONCLUSIONS: Pathologic examination and considering known clinical history may be helpful to differentiate the primary breast cancer and metastatic cancer. Metastasis to the breast from an extramammary neoplasm usually indicates disseminated metastatic disease and a poor prognosis. An accurate diagnosis of breast metastases, differentiating primary from metastatic breast carcinoma, is important for proper management.

Pifithrin-α, an inhibitor of p53 transactivation, up-regulates COX-2 expression through an MAPK-dependent pathway.

Cyclooxygenase-2 (COX-2) has been reported to be elevated in many cancers, including breast and colorectal cancers, resulting in accumulation of prostaglandin E2 in the cancer cell environment. In this study, we investigated the effect of pifithrin (PFT)-α, an inhibitor of p53 transactivation, on COX-2 expression in breast and fibrosarcoma cells. Our results showed that COX-2 expression was dose-dependently increased by PFT-α in MDA-MB231 breast cancer cells with mutant p53. In addition, the expression level of COX-2 was also increased by PFT-α in normal fibroblasts as well as in HT1080 fibrosarcoma cells with p53 wild-type cells. To verify the regulatory mechanism of COX-2 in response to PFT-α, we pretreated cells with a mitogen-activated protein kinase (MAPK) kinase (MEK)1/2 inhibitor (UO126) and a phosphoinositide-3 (PI-3K) inhibitor (LY294002). PFT-α-induced COX-2 expression was significantly decreased by UO126 and LY294002 in MDA-MB231 cells. However, the phosphorylation of extracellular signal-regulated kinase (ERK) was increased by PFT-α, but not Akt phosphorylation. Finally, we confirmed the correlation of the MEK and PI-3K pathway and COX-2 expression using the constitutively active (CA)-MEK and myr-Akt adenovirus systems. COX-2 expression was increased by CA-MEK transfection, but not by myr-Akt. Taken together, we have demonstrated that PFT-α-induced COX-2 expression is regulated through a MEK/ERK pathway in MDA-MB231 human breast cancer cells.

Risk of osteoporosis and fracture in long-term breast cancer survivors.

Purpose: High incidence of osteoporosis has been reported in breast cancer patients due to early menopause triggered by adjuvant treatment and temporary ovarian function suppression. In this study, we sought to determine whether long-term breast cancer survivors had an elevated risk of low bone density compared to the general population. Methods: Long-term breast cancer survivors who had been treated for more than 5 years were selected for this study. Data were obtained from medical records and using a questionnaire from the Korea National Health and Nutrition Examination Survey (KNHANES). An age-matched non-cancer control group was selected from the KNHANES records. Incidence of fracture and bone mineral density (BMD) were compared between the two groups. Results: In total, 74 long-term breast cancer survivors and 296 non-cancer controls were evaluated. The incidence of fracture did not differ between the two groups (P=0.130). No differences were detected in lumbar BMD (P=0.051) following adjustment for body mass index, while hip BMD was significantly lower in breast cancer survivors (P=0.028). Chemotherapy and endocrine treatment were not related to low BMD in breast cancer survivors. In more than half of the survivors, the 10-year risk of osteoporotic fracture was less than 1%. Conclusion: Long-term breast cancer survivors had low bone density but a comparable risk of fracture compared to non-cancer age-matched controls. Further studies on the factors related to low bone density in long-term breast cancer survivors are required.

Effect of Tamoxifen on the Risk of Osteoporosis and Osteoporotic Fracture in Younger Breast Cancer Survivors: A Nationwide Study.

Background: Although international guidelines recommend bone screening for premenopausal breast cancer patients taking adjuvant tamoxifen, the effects of tamoxifen on osteoporosis and related risks remain controversial. The objective of this study was to investigate the incidence of and risk factors for osteoporosis and osteoporotic fractures in younger breast cancer patients. Methods: A nationwide retrospective cohort study was conducted using South Korea Health Insurance Review and Assessment Service claims data. The rates of osteoporosis and osteoporotic fracture were calculated as incident cases per person-year and disease-free probability rates were analyzed with the Kaplan-Meier method. To identify risk factors for osteoporosis and osteoporotic fracture, a multivariable Cox proportional hazard regression model was applied. Results: From January 2009 to December 2014, a total of 47,649 breast cancer patients were included. The incidence rates of osteoporosis and osteoporotic fracture were 23.59 and 2.40 per 1,000 person-years, respectively. In the overall population, tamoxifen was significantly associated with a decreased risk of osteoporosis and osteoporotic fractures 0.76). However, tamoxifen was not associated with the risk of osteoporosis (HR 1.24, CI 0.85-1.82) and osteoporotic fracture (HR 8.15, CI 0.36-186.70) in patients under age 40. In the 40-49 years subgroup, tamoxifen significantly decreased the risk of osteoporosis (HR 0.74, CI 0.65-0.84) and osteoporotic fracture (HR 0.49, CI 0.31-0.76). Conclusions: Tamoxifen is not associated with an increased risk of osteoporosis and osteoporotic fracture in premenopausal breast cancer patients. Tailored screening strategies for breast cancer survivors with different osteoporosis risks are needed. Precis: Tamoxifen is not associated with an increased risk of osteoporosis and osteoporotic fracture in premenopausal breast cancer patients. Tailored screening strategies for breast cancer survivors who are at different risks of developing osteoporosis are needed.

Silibinin suppresses TNF-alpha-induced MMP-9 expression in gastric cancer cells through inhibition of the MAPK pathway.

Tumor necrosis factor (TNF)-alpha is one of the pro-inflammatory cytokines highly expressed in Helicobacter pylori that inhibits gastric acid secretion. In this study we determined the effect of silibinin on TNF-alpha-induced MMP-9 expression in gastric cancer cell lines. MMP-9 mRNA and protein expression was dose-dependently increased by TNF-alpha in SNU216 and SNU668 gastric cancer cells. On the other hand, TNF-alpha-induced MMP-9 expression was dose-dependently suppressed by silibinin. To verify the regulatory mechanism of silibinin on TNF-alpha-induced MMP-9 expression, the gastric cancer cell lines were pretreated with silibinin prior to TNF-alpha. TNF-alpha-induced MMP-9 expression was inhibited by the MEK1/2 specific inhibitor, UO126. Finally, we investigated the effect of adenoviral constitutively active (CA)-MEK and CA-Akt on MMP-9 expression. The expression of MMP-9 was significantly increased by CA-MEK overexpression, but not by CA-Akt overexpression. Taken together, we suggest that silibinin down-regulates TNF-alpha- induced MMP-9 expression through inhibition of the MEK/ERK pathway in gastric cancer cells.

Pegfilgrastim for primary prophylaxis of febrile neutropenia in breast cancer patients undergoing TAC chemotherapy.

PURPOSE: Primary prophylaxis with granulocyte colony-stimulating factor can effectively prevent febrile neutropenia (FN) during breast cancer treatment. The aims of this study were to evaluate the incidence of FN and the ANC profile in patients undergoing chemotherapy and pegfilgrastim primary prophylaxis. METHODS: Patients receiving 6 cycles of adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy were included in this study. Pegfilgrastim was administered with analgesics 24 hours after treatment. Laboratory tests were performed on day 0 (before chemotherapy) and ANC was measured daily starting day 5 until it were restored to 1,000/mm3. Bone pain was checked via the numeral rating scale (NRS). RESULTS: A total of 61 patients and 366 cycles were evaluated. Mean age was 49.2 ± 7.1 years. FN was seen in 5 patients (16.4%) and 12 cycles (3.3%) with pegfilgrastim. Grades 3 and 4 neutropenia was seen in 91.5% of cycles with FN. The ANC nadir was most commonly seen at day 7 and the mean ANC nadir depth was 265.7/m3. Age was negatively correlated with nadir depth (r = -0.137, P = 0.009). Severe pain higher than NRS 7 occurred in less than 20% of patients after the administration of pegfilgrastim. CONCLUSION: Incidence of FN was low during the chemotherapy by primary prophylaxis with pegfilgrastim. The ANC nadir was seen on day 7 after chemotherapy. Bone pain with pegfilgrastim was well tolerated during TAC chemotherapy.