F.A.R.O.G. FORUM, Vol. 5 No. 4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1062/thumbnail.jp

Recent trends in hormone therapy utilization and breast cancer incidence rates in the high incidence population of Marin County, California

<p>Abstract</p> <p>Background</p> <p>Recent declines in invasive breast cancer have been reported in the US, with many studies linking these declines to reductions in the use of combination estrogen/progestin hormone therapy (EPHT). We evaluated the changing use of postmenopausal hormone therapy, mammography screening rates, and the decline in breast cancer incidence specifically for Marin County, California, a population with historically elevated breast cancer incidence rates.</p> <p>Methods</p> <p>The Marin Women's Study (MWS) is a community-based, prospective cohort study launched in 2006 to monitor changes in breast cancer, breast density, and personal and biologic risk factors among women living in Marin County. The MWS enrolled 1,833 women following routine screening mammography between October 2006 and July 2007. Participants completed a self-administered questionnaire that included items regarding historical hormone therapy regimen (estrogen only, progesterone only, EPHT), age of first and last use, total years of use, and reason(s) for stopping, as well as information regarding complementary hormone use. Questionnaire items were analyzed for 1,083 non-Hispanic white participants ages 50 and over. Breast cancer incidence rates were assessed overall and by tumor histology and estrogen receptor (ER) status for the years 1990-2007 using data from the Northern California Surveillance, Epidemiology and End Results (SEER) cancer registry.</p> <p>Results</p> <p>Prevalence of EPHT use among non-Hispanic white women ages 50 and over declined sharply from 21.2% in 1998 to 6.7% by 2006-07. Estrogen only use declined from 26.9% in 1998 to 22.4% by 2006-07. Invasive breast cancer incidence rates declined 33.4% between 2001 and 2004, with drops most pronounced for ER+ cancers. These rate reductions corresponded to declines of about 50 cases per year, consistent with population attributable fraction estimates for EPHT-related breast cancer. Self-reported screening mammography rates did not change during this period. Use of alternative or complementary agents did not differ significantly between ever and never hormone users. Of women who reported stopping EPHT in the past 5 years, 60% cited "health risks" or "news reports" as their primary reasons for quitting.</p> <p>Conclusion</p> <p>A dramatic reduction in EPHT use was followed temporally by a significant reduction in invasive and ER+ breast cancer rates among women living in Marin County, California.</p

First pregnancy characteristics, postmenopausal breast density, and salivary sex hormone levels in a population at high risk for breast cancer

Background: It remains unknown if later life breast cancer risk as determined by reproductive history is mediated by postmenopausal breast density and/or sex steroid levels. Methods: Increased breast density is a strong surrogate for future breast cancer risk. A cross-sectional study with a longitudinal follow-up for breast health outcomes evaluated women without breast cancer (n = 1023; 682 = parous), drawn from a high risk postmenopausal population, with questionnaire- reported reproductive histories. The questionnaire was linked to prospective screening mammogram breast density measurements, and saliva biospecimens that were used to assess sex steroid hormone levels. Results: Expected age- and postmenopause- related declines in salivary estradiol (E), progesterone (P), dehydroepiandrosterone (DHEA) and testosterone (T) levels were observed. This was most pronounced for DHEA and T, which were also the only postmenopausal hormone levels significantly associated with any reproductive characteristics: parity and breast feeding for DHEA, and age-at-first birth for T. Postmenopausal breast density was borderline significantly lower with parity and higher body mass index (BMI). After multivariate analysis, T was the only hormone level to retain any association (negative, p < 0.05) with breast density. Conclusions and general significance: While reproductive characteristics, in particular parity, generally demonstrated independent associations with postmenopausal breast density and E, P and DHEA levels, T levels showed concordant inverse associations with age-at-first birth and breast density. These findings suggest that reproductive effects and later life salivary sex steroid hormone levels may have independent effects on later life breast density and cancer risk

Development and validation of the JAX Cancer Treatment Profile™ for detection of clinically actionable mutations in solid tumors.

BACKGROUND: The continued development of targeted therapeutics for cancer treatment has required the concomitant development of more expansive methods for the molecular profiling of the patient\u27s tumor. We describe the validation of the JAX Cancer Treatment Profile™ (JAX-CTP™), a next generation sequencing (NGS)-based molecular diagnostic assay that detects actionable mutations in solid tumors to inform the selection of targeted therapeutics for cancer treatment. METHODS: NGS libraries are generated from DNA extracted from formalin fixed paraffin embedded tumors. Using hybrid capture, the genes of interest are enriched and sequenced on the Illumina HiSeq 2500 or MiSeq sequencers followed by variant detection and functional and clinical annotation for the generation of a clinical report. RESULTS: The JAX-CTP™ detects actionable variants, in the form of single nucleotide variations and small insertions and deletions (≤50 bp) in 190 genes in specimens with a neoplastic cell content of ≥10%. The JAX-CTP™ is also validated for the detection of clinically actionable gene amplifications. CONCLUSIONS: There is a lack of consensus in the molecular diagnostics field on the best method for the validation of NGS-based assays in oncology, thus the importance of communicating methods, as contained in this report. The growing number of targeted therapeutics and the complexity of the tumor genome necessitate continued development and refinement of advanced assays for tumor profiling to enable precision cancer treatment. Exp Mol Pathol 2015 Feb; 98(1):106-112