Biomedical subjects

John Eden

Publications and source records attributed to John Eden.

4 recordsLinked to original sources

PubMed2005

Is mammographic density, as currently measured, a robust surrogate marker for breast cancer?

In order to determine current beliefs concerning the relevance of breast mammographic percent density (MPD) as a surrogate marker for breast cancer, the panel and the delegates completed a questionnaire. There was general agreement between the panel and delegates on most aspects, although the delegates were unsure whether high breast MPD is a contraindication for hormone therapy and tended to err on the side of caution in suggesting that estrogen and estrogen/progestogen therapy should be stopped before screening mammography. The overall consensus of the panel and the delegates was that breast MPD should become an important clinical tool, and that carefully designed studies are needed to determine exactly how it can be best used to guide clinical decision-making.

Adult↗

PubMed2005

The need for tissue selective menopausal agents.

For decades, hormone therapy (HT) has been the mainstay for managing menopausal symptoms. However, fear of breast cancer, as well as side-effects such as breast pain and return of vaginal bleeding, have made many women stop HT or refuse to take it. There is therefore a clear need for alternative treatments. Recent years have seen the development of hormonal agents with selective effects, such as tibolone. Tibolone has a unique mode of action and is described as a STEAR (Selective Tissue Estrogenic Activity Regulator). The main action of tibolone is mediated through two 3-hydroxy metabolites; small amounts of a third metabolite are also found in the circulation. In the brain, the effect is estrogenic and perhaps androgenic and, as such, tibolone relieves hot flushes and improves energy and sexual well-being. The uterus converts tibolone and its hydroxy metabolites into a Delta4 metabolite that has a progestogenic effect. In the breast, the metabolites of tibolone inhibit key enzymes that result in estrogen depletion within the breast itself. Clinically, tibolone does not stimulate the breast and it does not increase mammographic density. There are several key large, placebo-controlled international trials of tibolone currently underway, one of which (LIBERATE) aims to test the safety of tibolone (vs placebo) in women with a history of breast cancer who are suffering from climacteric symptoms.

Breast↗

PubMed2003

Progestins and breast cancer.

The relationship between the use of menopausal hormone therapy (ERT, unopposed estrogen therapy; HRT, combined estrogen and progestin therapy) and the development of breast cancer remains controversial. Mechanistic studies examining progestins in human breast cancer cell lines have demonstrated a biphasic cellular response to progesterone; initial exposure to hormone results in a proliferative burst with sustained exposure resulting in growth inhibition. To date, there is no definitive evidence that progestins act in the pathogenesis of breast cancer. Epidemiologic studies have produced inconsistent results, and data from randomized, placebo-controlled trials are limited. Although recent results from the continuous combined therapy arm of the Women's Health Initiative trial showed a small increase in the risk of invasive breast cancer in women on therapy for 5 years or more, a clear consensus regarding the relationship between HRT and breast cancer risk cannot yet be drawn from existing data. Studies have consistently documented that HRT use is associated with improved mortality and survival rates for women with breast cancer. Large-scale, randomized studies on different progestin regimens are needed to critically assess the effect of progestin on breast cancer.

Animals↗

PubMedDate not supplied

Transition from estrogen therapy to raloxifene in postmenopausal women: effects on treatment satisfaction and the endometrium-a pilot study.

OBJECTIVE: To compare the effects of transferring from low-dose, transdermal estrogen to raloxifene with a phase of alternate-day raloxifene therapy with or without low-dose transdermal estrogen on patient satisfaction, endometrial changes, and overall safety in healthy, postmenopausal women previously administered hormone therapy. DESIGN: Healthy postmenopausal women were randomized to one of two treatment groups: raloxifene + low-dose, transdermal estrogen (RLX+E) and raloxifene + placebo (RLX+P). The study consisted of four equal phases of 8 weeks each: Phase I (low-dose, transdermal estrogen, 25 microg/day), phase II (double-blind, alternate-day raloxifene 60 mg + low-dose, transdermal estrogen or placebo patch), phase III (alternate-day RLX 60 mg + placebo patch), and phase IV (raloxifene 60 mg/day + placebo patch). Primary endpoints included patient satisfaction, endometrial changes, overall safety, and quality of life. RESULTS: Sixty women were randomized in this study. Baseline characteristics were similar between the two treatment groups. For the primary analysis (phase II to phase IV, inclusive), there were no significant differences between the therapy sequences for patient satisfaction, endometrial thickness, or quality of life. In the therapy comparison phase (phase II), mean change in patient satisfaction score was 3.2 mm (SD = 16.2) for RLX+E and -17.1 mm (SD = 38.7) for RLX+P (P = 0.003), whereas mean change in endometrial thickness was 0.8 mm (SD = 2.7) for RLX+E and -0.9 mm (SD = 1.5) for RLX+P (P = 0.021). The RLX+P group showed a significantly greater increase in vasomotor events, with a mean score change of 1.7 (SD = 1.9) compared with a mean score change of 0.2 (SD = 1.8) in the RLX+E group (P = 0.005). There were no statistically significant differences between the two therapy groups in the reporting of treatment-emergent adverse events. CONCLUSION: Gradual conversion to raloxifene from low-dose estrogen, with a progression from 60 mg every alternate day to 60 mg/day, is a viable option in potentially symptomatic, postmenopausal women.

Administration, Cutaneous↗