The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial

Objective To assess the effects of tibolone on climacteric symptoms, endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer. Design Double-blind, randomised, placebo-controlled, multicentre pilot study. Setting Hospital outpatient clinic. Sample Seventy postmenopausal women receiving tamoxifen following surgery for early breast cancer. Methods Women received 20 mg/day oral tamoxifen plus either 2.5 mg/day oral tibolone or placebo for 12 months. Main outcome measures Frequency and severity of hot flushes (diary cards); intensity of hot flushes and sweats (Landgren scale); interference of hot flushes and sweats with normal life; frequency and intensity of other climacteric symptoms; endometrial thickness and histology; vaginal bleeding; breast cancer recurrence and serum lipid/lipoproteins. Results Daily card data showed no change in the daily number of hot flushes with either tibolone or placebo (P= 0.219) after three months. There was a significant reduction in the severity of flushes with tibolone compared with placebo (-0.4 vs 0.2, P= 0.031). The Landgren scale showed a mean change in the number of hot flushes of -0.6 with tibolone and +1.1 with placebo after 12 months (P= 0.022). Endometrial biopsies were normal and vaginal bleeding was similar in both groups. A significant decrease in triglycerides (-23%vs 1.4%) and HDL (-12%vs 19%) was seen with tibolone compared with placebo after 12 months. Conclusion Tibolone prevented an increase in hot flushes in postmenopausal women given tamoxifen following surgery for breast cancer without untoward effects on the endometrium. Beneficial effects on serum lipid profile were noted

Concomitant and antecedent deep venous thrombosis and cancer survival in male US veterans

Survival is reportedly worse in cancer patients concurrently diagnosed with deep venous thrombosis. However, information on specific malignancies is limited. From a cohort study of male U.S. veterans we identified incident cancer cases (n=412,008) and compared survival patterns among those with versus without a history of deep venous thrombosis. Using Cox-proportional hazard models, we estimated hazard ratios (HR) and 95% confidence intervals as measures of the relative risk of dying. Individuals with (versus without) a concomitant deep venous thrombosis and cancer diagnosis had a higher risk of dying (HR=1.38; 1.28–1.49). The most prominent excess mortality (HRs=1.29–2.55) was observed among patients diagnosed with deep venous thrombosis at the time of diagnosis of lung-, gastric-, prostate-, bladder-, or kidney cancer. Increased risk of dying was also found among cancer patients diagnosed with deep venous thrombosis 1 year (HR=1.14; 1.07–1.22), 1–5 years (HR=1.14; 1.10–1.19) and >5 years (HR=1.27; 1.23–1.31) before cancer; this was true for most cancer sites (HRs=1.17–1.64). In summary, antecedent deep venous thrombosis confers a worse prognosis upon cancer patients. Advanced stage at diagnosis, treatment effects, lifestyle factors, and comorbidity could explain differences by cancer site and time frame between a prior deep venous thrombosis diagnosis and cancer outcome

DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma

We previously described PASD1 as a new cancer testis antigen in multiple myeloma (MM) that is retained post-therapy, suggesting the use of vaccination strategies to induce anti-PASD1 immunity in a setting of minimal residual disease. We have focused on DNA fusion gene vaccines, coupling fragment C domain (DOM) of tetanus toxin with PASD1 sequence, and examined efficacy in Human Leukocyte Antigen (HLA)-A2 (HHD) transgenic mice using a human MM cell line expressing PASD1 protein and chimeric HLA-A2 class I molecules as target. DNA vaccines encoded two HLA-A2-restricted epitopes (p.DOM-PASD1(1), p.DOM-PASD1(2)) and full-length PASD1 (p.DOM-PASD1FL). p.DOM-PASD1(1) proved superior to p.DOM-PASD1(2) in generating T-cell responses in HHD mice, able to lyse the chimeric murine RMA-HHD cells. Boosting by electroporation significantly enhanced p.DOM-PASD1(1). Only p.DOM-PASD1(1) induced cytotoxic T-lymphocytes (CTLs) were able to lyse human MM target cells expressing endogenous antigen. The p.DOM-PASD1FL vaccine predominantly induced strong PASD1(1) over PASD1(2) T-cell immune responses, indicative of immunodominance. Importantly, p.DOM-PASD1FL generated immune-mediating killing of native chimeric MM cells, in the absence of exogenous added peptide, implicating PASD1(1) specific CTLs. These data demonstrate that PASD1-derived epitopes are both efficiently and selectively processed and presented by native human MM cells. Notably, they permit the use of PASD1-encoding DNA vaccine therapy in a clinical setting