Do BRCA1 and BRCA2 mutation carriers have earlier natural menopause than their noncarrier relatives? Results from the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer.

PURPOSE: Limited data suggest that germline BRCA1 mutations are associated with occult primary ovarian insufficiency and that BRCA1 and BRCA2 mutation carriers might have earlier natural menopause (NM) than their noncarrier relatives. PATIENTS AND METHODS: Eligible women were mutation carriers and noncarriers from families segregating a BRCA1 or BRCA2 mutation. Data were self-reported using uniform questionnaires at cohort entry and every 3 years thereafter. NM was defined as the cessation of menses for 12 months without another cause. Cox proportional hazards analysis modeled time from birth to NM, adjusting for multiple potential confounders. Analysis time was censored at the earliest of the following: last follow-up, bilateral oophorectomy, hysterectomy, commencement of hormone therapy, insertion of intrauterine device, or any cancer diagnosis. Hazard ratios (HRs) were estimated as a measure of how likely mutation carriers are, relative to noncarriers, to reach NM at a given age. RESULTS: A total of 1,840 women were eligible for analysis. Overall only 19% reached NM. A lower proportion of BRCA1 and BRCA2 mutation carriers reached NM compared with noncarriers. Conversely, a higher proportion of mutation carriers were censored at cancer diagnosis or oophorectomy than noncarriers. The adjusted HR estimates for NM were 1.03 (95% CI, 0.75 to 1.40; P = .9) for 445 BRCA1 mutation carriers and 559 noncarrier relatives and 1.01 (95% CI, 0.71 to 1.42; P = .9) for 374 BRCA2 mutation carriers and 462 noncarrier relatives. CONCLUSION: We found no evidence that BRCA1 and BRCA2 mutation carriers are at higher risk of NM at a given age than their noncarrier relatives.

Do spirometry and regular follow-up improve health outcomes in general practice patients with asthma or COPD? A cluster randomised controlled trial.

OBJECTIVE: To determine whether spirometry with regular medical review improves the quality of life or other health outcomes among patients with asthma or chronic obstructive pulmonary disease (COPD) managed in general practice. DESIGN, SETTING AND PARTICIPANTS: Cluster randomised controlled trial conducted in 31 general practices in Melbourne during 2007-2008. Practices recruited 305 adult patients who had been prescribed inhaled medication in the preceding 6 months. INTERVENTION: Practices were randomly assigned to one of three groups: Group A patients received 3-monthly spirometry performed by a respiratory scientist with results returned to the practice and regular medical review; Group B patients received spirometry only before and after the trial; and Group C patients received usual care. MAIN OUTCOME MEASURES: Quality of life, assessed with the 36-item Short Form (SF-36) Australian (English) Version 2 questionnaire at baseline and 3, 6, 9 and 12 months. Secondary outcomes were assessed with the European Community Respiratory Health Survey at baseline and 12 months. RESULTS: The trial was completed by 253 participants: 79 in Group A, 104 in Group B, and 70 in Group C. Median age was 58 years (range, 18-70 years), and 167 participants (66%) were women. There were no significant changes in SF-36 Physical and Mental Component Summary scores from baseline to 12 months, or significant differences between groups on either scale or any subscale of the SF-36. There were also no significant differences in respiratory symptoms, asthma attacks, written asthma action plans, days lost from usual activities or health care utilisation. CONCLUSION: Three-monthly spirometry and regular medical reviews by general practitioners are not associated with any significant improvement in quality of life or other health outcomes for patients with asthma and/or COPD. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12606000378527.