Vernon M Chinchilli — Page 3

PubMed2002

The relationship between menstrual factors and breast cancer according to estrogen receptor status of tumor: a case-control study in African-American women.

BACKGROUND: Exposure to estrogen is a risk factor for breast cancer. Since estrogen executes its effect through estrogen receptors (ERs), the relationship between menstrual factors, which are estrogen-related, and breast cancer may be different depending upon ER status of tumors. This case-control study aimed to examine such a relationship according to ER status of breast cancer in African-American women. METHODS: Cases were 304 African-American patients pathologically diagnosed with breast cancer during 1995-1998, who were 20-64 years old and lived in 3 Tennessee counties. Controls were 305 African-American women without breast cancer, selected through random-digit dialing and frequency matched to cases by age and county. Information on menstrual factors (age at menarche, age at menopause, time from menarche to menstrual regularity, cycle length, and length of flow) and other risk factors were collected through telephone interviews. Estrogen receptor status of tumor samples was defined based on immunohistochemical measurement. Logistic regression analysis was used to calculate odds ratios and 95% confidence interval (CI). RESULTS: Compared to women with an average cycle length less than 28 days, the risks of breast cancer for those with longer length were 0.62 (95% CI, 0.36-1.06) and 0.56 (95% CI, 0.32-1.00) for ER-positive and ER-negative tumors, respectively. The corresponding odds ratio (OR) estimates were 0.42 (95% CI, 0.20-0.86) and 0.38 (95% CI, 0.16-0.90) for postmenopausal women. Other menstrual factors were not significantly associated with breast cancer for either ER status. CONCLUSIONS: Our results did not show a different menstrual factor/breast cancer relationship in terms of ER status in African-American women, although there might be an association between menstrual cycle length and the disease.

Adult↗

PubMedDate not supplied

Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial.

BACKGROUND: The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial. Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine (Arg/Arg), rather than glycine (Gly/Gly), at aminoacid residue 16 of the beta2-adrenergic receptor. However, the existence of any genotype-dependent difference has not been tested in a prospective clinical trial. METHODS: Patients with mild asthma, not using a controller medication, were enrolled in pairs matched for forced expiratory volume in 1 s (FEV1) according to whether they had the Arg/Arg (n=37; four of 41 matches withdrew before randomisation) or Gly/Gly (n=41) genotype. Regularly scheduled treatment with albuterol or placebo was given in a masked, cross-over design, for 16-week periods. During the study, as-needed albuterol use was discontinued and ipratropium bromide was used as needed. Morning peak expiratory flow rate (PEFR) was the primary outcome variable. The primary comparisons were between treatment period for each genotype; the secondary outcome was a treatment by genotype effect. Analyses were by intention to treat. FINDINGS: During the run-in period, when albuterol use was kept to a minimum, patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min (p=0.0162); the change in patients with the Gly/Gly genotype was not significant (2 L/min; p=0.8399). During randomised treatment, patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo (14 L/min [95% CI 3 to 25]; p=0.0175). By contrast, patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period, when albuterol use was limited (-10 L/min [-19 to -2]; p=0.0209). The genotype-attributable treatment difference was therefore -24 L/min (-37 to -12; p=0.0003). There were similar genotype-specific effects in FEV1, symptoms, and use of supplementary reliever medication. INTERPRETATION: Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use. Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype.

Administration, Inhalation↗