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The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region ofBRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation inBRCA1 was estimated to be 3.8% (95% Cl 0.3-12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence. [ABSTRACT FROM AUTHOR]

No controlled trials regarding management of chronic Achilles tendon ruptures have been published. We conducted an online survey of orthopedic surgeons affiliated with US medical schools. One hundred twenty-seven surgeons responded, but not all responded to each survey question. Thirty-six percent had foot and ankle fellowship training. Nearly all respondents diagnosed tendon rupture by using palpation of the tendon gap (97%) and the Thompson calf-squeeze test (96%). The Matles test was used by 37% of respondents, with foot and ankle specialists nearly 5 times more likely to use it than nonspecialists (P<.001). For surgical repair of a ruptured tendon, most surgeons used the end-to-end Bunnell technique for gaps of a few centimeters, transitioning to the flexor hallucis longus procedure or V-Y tendinoplasty for larger gaps. Ninety-three percent of respondents used nonabsorbable sutures; absorbable suture use tended to increase with years of practice. Most surgeons (72%) preferred postoperative immobilization for up to 6 weeks and non-weight-bearing for up to 6 weeks (96%). In most instances, the responses of foot and ankle specialists did not differ significantly from those of other orthopedic surgeons, allowing generalization of the survey results to practice trends among all orthopedic surgeons. Practice trends tended to follow published expert opinions.

There has been recent interest in the risk of various cancers in cystic fibrosis (CF) patients and carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. It has been proposed that a CFTR mutation may protect against breast cancer, based on evidence that elevated extracellular adenosine triphosphate (ATP) is known to inhibit breast cancer cell line growth and that CFTR pumps ATP out of epithelial cells. A CFTR mutation would therefore result in higher concentrations of serum ATP. A CFTR knockout mouse model had high serum concentrations of ATP and showed reduced breast tumour implantibility and decreased breast cancer growth rates. We have evaluated the relationship between the deltaF508 CFTR mutation and the risk of breast cancer before the age of 40. The deltaF508 CFTR mutation carrier rate in 272 cases (2.2%) was no different from the carrier rate observed in 171 controls (1.8%). If there was a protective effect resulting from the postulated elevation in serum ATP levels, tumours arising in deltaF508 CFTR carriers would have been expected to be generally less aggressive. When the histological features of the breast cancers with a deltaF508 CFTR mutation were reviewed and graded using a combined architectural and cytological grading system, all were found to be grade III, poorly differentiated tumours, contrary to the predictions. A combination of our data with other large population-based samples of cases and controls is required to resolve this issue.