Unique Breast Cancer Features Within the Vietnamese Population

BACKGROUND: Breast cancer is known to be a heterogeneous disease across women, and even within individual tumors. However, relatively little is known about heterogeneity across cultures. There has been some evidence to suggest that Asian women are more likely to have HER2+ breast cancer than their Caucasian counterparts. PURPOSE: The aim of this study was to further investigate the unique pattern of breast cancer incidence and subtype in the Vietnamese population. METHODS: We retrospectively collected data on all Vietnamese women diagnosed with invasive breast cancer at the Lester & Sue Smith Breast Center in Houston, Texas over a four year period. We recorded the subtype of breast cancer, tumor grade, age at diagnosis, and menopausal status for each woman. We then compared these characteristics between our population of Vietnamese breast cancer patients, and an ethnically diverse group of American women from the 2010 SEER registry. RESULTS: We discovered that 15 of 33 Vietnamese patients diagnosed in our breast center had HER2 over-expressing breast cancer, resulting in a 45% rate of HER2 positivity. Compared with the 2010 Surveillance, Epidemiology, and End Results (SEER) registry data that encompasses 28% of all US breast cancer patients diagnosed that year, regardless of race, the Smith Clinic Vietnamese cohort had a statistically significant higher rate of HER2+ breast cancer, with an odds ratio of 4.7 (45% vs. 15%, p CONCLUSIONS: Vietnamese breast cancer patients, especially those older than 50 years old, tend to have higher rates of HER2+ breast cancer than the general population. This unique pattern of breast cancer merits further study, as it may reflect a genetic mutation or environmental exposure which is more common among Vietnamese women

Chronological Effect on Insulin and Glycemic Status in Cancer Pain Patients

Pain is the first sign of malignancy and prevalent symptom experienced by cancer patients. Circadian rhythm is the best known and probably most general rhythm in living creatures. It plays a very important role in the pattern of pain produced by various diseases. Time dependent variation affects perception of pain, its neurochemistry, and drug treatment. Endogenous insulin plays a critical role in the modulation of pain has been documented in clinical and preclinical studies. The aim of this study was to determine the insulin’s antinociceptive effect and also to study the influence of circadian rhythm on cancer pain. This study was done in Erode Cancer centre, Erode wherein we recruited 22 patients for the study. Patients were categorized as Group A, Group B, Group C. Group A included patients taking opiod drugs, Group B-patient taking nonopiods and Group C control patients without pain. Pain was assessed in patients using Visual Analogue Scale. Blood samples were collected from patients four times a day (6AM, 12PM, 6PM, 12AM)with their consent. Serum Insulin level were determined by ELISA method using DRG INSULIN KIT. Results were analyzed using computerized statistical package of Graphpad Instat Software. The statistical significance was tested by the analysis of variance(ANOVA) and Tukey - Kramer Multiple Comparisons Test. In opioid taking patients serum insulin level showed a increase in morning 6AM(31.3125±20.812 ) and afternoon 12PM (33.05±12.757). Whereas in nonopioid taking group increase in insulin level was found at evening 6PM (69.1875±21.290) and midnight 12AM(67.337±30.728). The serum insulin level in opioid and nonopioiod taking patients was increased and found highly significant(p value<0.0001) than control group although no significant differences in mean values of blood glucose were observed . In this study it was found that endogenous insulin play an important role in the modulation of pain in cancer pain and also circadian rhythm influences cancer pai

Patient-reported symptoms and discontinuation of adjuvant aromatase inhibitor therapy

BACKGROUND: Aromatase inhibitor (AI) therapy results in substantial survival benefits for patients with hormone receptor-positive breast cancer. The rates of poor adherence and discontinuation of AI therapy are high, primarily because of treatment-related toxicities like musculoskeletal pain. Although pain-related symptoms may worsen during AI therapy, the authors hypothesized that nonpersistence with AI therapy was associated with symptoms that were present before treatment initiation. METHODS: Postmenopausal women initiating AI therapy who were enrolled in a prospective clinical trial completed questionnaires at baseline to assess sleep, fatigue, mood, and pain. Reasons for treatment discontinuation during the first year of treatment were recorded. Associations between baseline patient-reported symptoms and treatment discontinuation because of toxicity were identified using logistic regression. RESULTS: Four hundred forty-nine patients were evaluable. The odds of treatment discontinuation were higher in patients who reported a greater number of symptoms before AI initiation. Baseline poor sleep quality was associated with early treatment discontinuation, with an odds ratio (OR) of 1.91 (95% confidence interval [CI], 1.26-2.89; P = .002). Baseline presence of tired feeling and forgetfulness had similar ORs for discontinuation (tired feeling: OR, 1.76; 95% CI, 1.15-2.67; P = .009; forgetfulness: OR, 1.66; 95% CI, 1.11-2.48; P = .015). An increasing total number of baseline symptoms was associated with an increased likelihood of treatment discontinuation, with an OR of 1.89 (95% CI, 1.20-2.96; P = .006) for 3 to 5 symptoms versus 0 to 2 symptoms. CONCLUSIONS: Symptom clusters in breast cancer survivors that are present before the initiation of adjuvant AI therapy may have a negative impact on a patient's persistence with therapy. Interventions to manage these symptoms may improve breast cancer outcomes and quality of life

The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast

BACKGROUND: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004–2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. RESULTS: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. CONCLUSION: In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding

TBCRC023: A Randomized Phase II Neoadjuvant Trial of Lapatinib Plus Trastuzumab Without Chemotherapy for 12 versus 24 Weeks in Patients with HER2-Positive Breast Cancer

Purpose: Prior neoadjuvant trials with 12 weeks of dual anti-HER2 therapy without chemotherapy demonstrated a meaningful pathologic complete response (pCR) in patients with HER2-positive breast cancer. In this trial, we sought to determine whether longer treatment would increase the rate of pCR. Patients and Methods: TBCRC023 (NCT00999804) is a randomized phase II trial combining a Simon phase II design in the experimental arm with a pick-the-winner design, not powered for direct comparison. Women with HER2-positive breast tumors measuring ≥2 cm (median = 5 cm) were randomized in a 1:2 ratio to 12 versus 24 weeks of lapatinib and trastuzumab. Letrozole (along with ovarian suppression if premenopausal) was administered in patients whose tumors were also estrogen receptor (ER) positive. All evaluable patients were assessed for in-breast pCR. Results: Ninety-seven patients were enrolled (33 in 12-week arm and 64 in 24-week arm), of whom 94 were evaluable. Median age was 51 years, and 55% were postmenopausal. Median tumor size was 5 cm, and 65% were ER-positive. The rate of pCR in the 24-week arm was 28% and numerically superior to the 12-week arm (12%). This was driven by increased pCR in the ER-positive subgroup (33% vs. 9%). Study treatment was well tolerated, with grade 1–2 diarrhea and acneiform rash being the most common toxicities. Conclusions: Treatment with dual anti-HER2 therapy for 24 weeks led to a numeric increase in pCR rate in women with HER2-positive breast cancer, without using chemotherapy. If validated, this approach may help identify patients who may benefit from deescalation of therapy

RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt

BACKGROUND: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. METHODS: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. RESULTS: Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. CONCLUSIONS: The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area

High Pressure Neutron Time-of-Flight Diffraction Studies on Zirconium Silicate

High pressure structural effects on solids can be studied using neutron (Time of Flight) diffraction. Such an experimental system is now available in the Solid State Science Division of Argonne National Laboratory, under the direction of Dr. T.G. Worlton. It is of interest to compare the results from different experimental approaches and the data from neutron (TOF) diffraction is to be compared to data derived from high pressure x-ray diffraction methods. The neutron (TOF) diffraction system at Argonne National Laboratory has been set up by Dr. T.G. Worlton and considerable aid has been received from him both in the general procedures and also in the particular details of the determination of the constants of the apparatus