Increased Sex and Growth Hormone Levels Raise Risk of Breast Cancer

Harvard University researchers reported that multiple sex and growth hormones with high circulating levels substantially increase the risk of breast cancer in post-menopausal women (Breast Cancer Research 2011;13:R99). Although further research is warranted to confirm their conclusions, the authors suggest that the findings should prompt researchers in future studies to consider all these hormones when evaluating risk prediction models.

Sex hormones and growth hormones separately have been associated with risk of breast cancer, but little is known about any combined effect of simultaneously high levels of multiple hormones. The authors tested the hypothesis that women with all hormone levels below the age-adjusted mean had a substantially lower risk of breast cancer in comparison to those with one or more hormone level above the age-adjusted mean.

The study involved 265 cases and 541 controls. The cases had been diagnosed with breast cancer after blood collection. The researchers analyzed values for estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate, and prolactin, and in a subset of cases and controls, insulin-like growth factor 1 (IGF-1) and c-peptide. They also created several hormone scores using different methodologies to consider the biological influence of hormones.

Women in the top versus bottom quintile of individual estrogen or androgen levels had about double the risk of post-menopausal breast cancer. Women with seven or eight hormones versus no hormones above the geometric mean had a relative risk of 2.7, and 3.4 when ER-positive was elevated. The risk further increased when IGF-1 and c-peptide were included in the scores.

More Evidence Needed before Routine HPV Screening is Adopted

An evidence review commissioned by the U.S. Preventive Services Task Force (USPSTF) found support for using liquid-based cytology (LBC) or conventional cytology for cervical cancer screening but concluded that more evidence would be needed before human papillomavirus (HPV) testing as a primary screening strategy is adopted in women age 30 or older (Ann Intern Med 2011;155:687–97). The Evidence-based Practice Center at Oregon Health and Science University (OSHU) conducted the study, with funding from the Agency for Healthcare Research and Quality (AHRQ).

The review sought to look at evidence published since the USPSTF's 2003 recommendations calling for cervical cancer screening in sexually active women with a cervix, but concluding that there was not sufficient evidence to recommend for or against the routine use of LBC or HPV testing as adjuncts or alternatives to cytology screening. The authors sought to address four questions: how does LBC perform in comparison to conventional cytology; what are the harms of LBC; what are the benefits of using HPV testing as a screening test, either alone or in combination with cytology versus not using HPV testing in women age 30 and older; and what are the harms of using HPV testing, either alone or in combination with cytology in this cohort of women.

The researchers concluded that there is no substantial difference between LBC and conventional cytology in relative or absolute sensitivity or specificity in detecting cervical intraepithelial neoplasia at any cytologic threshold.

On the question of the utility of HPV testing, the investigators determined that one-time testing is more sensitive, but less specific, than cytology. They also found that the overall harms and costs of work-up for false-positive HPV test results were unclear.

Novel Protein, GFAP-BDP, linked to Traumatic Brain Injury

A consortium of researchers found that serum glial fibrillary acidic protein breakdown products (GFAP-BDP) is detectable within an hour of mild and moderate traumatic brain injury (TBI) and is associated with measures of injury severity such as the Glasgow Coma Scale (GCS) and positive computed tomography results (Ann Emerg Med doi:10.1016/j.annemergmed.2011.08.021). TBI is a significant cause of death and disability in the U.S., and emergency physicians "liberally" use head CT to detect it, according to the authors. However, CT exposes patients to ionizing radiation and can still miss intracranial injuries. There are no rapid, definitive neurochemical biomarkers for TBI despite numerous studies. However, recent reports have suggested that GFAP might be a useful marker for various types of brain damage, including TBI.

The study involved 108 patients with TBI and 199 controls. The TBI subjects presented within 4 hours of injury to the emergency department with suspected TBI based on a history of blunt head trauma followed by loss of consciousness, amnesia, disorientation and a GCS 9–15. The investigators developed a GFAP-BDP-specific enzyme-linked immunosorbent assay. All TBI patients underwent CT scan, which detected traumatic intracranial lesions in 30% of this cohort. The average time to serum collection from TBI was 2.7 hours.

The researchers found that GFAP-BDP levels distinguished patients with TBI from uninjured controls with an area under the curve of 0.90. GFAP-BDP concentrations also were significantly higher in patients with GCS 15 who had lesions than in those without, but the largest elevations in GFAP-BDP occurred in patients with traumatic intracranial lesions on CT, regardless of GCS.

The authors concluded that acute elevations of GFAP-BDP could be a useful clinical tool for determining injury severity early-on after an injury, and that it might be useful in the decision-making around which patients to order CT on, when to seek neurosurgical consultation, or when to transfer to specialized neurosurgical facilities. They cautioned, however, that further research is needed to validate their findings.