A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.

INTRODUCTION: The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. METHODS: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. RESULTS: After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7-3.9%), 10.7% (95% CI 6.3-14.9%), and 15.5% (95% CI 7.6-22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5-7.9%), 17.8% (95% CI 11.8-23.3%), and 19.9% (95% CI 14.2-25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. CONCLUSION: In this large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients.

Physical activity and menstrual cycle characteristics in two prospective cohorts.

Relations between physical activity and prospectively collected menstrual cycle characteristics were examined in two large cohorts. One cohort consisted of women employed in the semiconductor industry in 1989 who participated in a prospective study of reproductive outcomes (n = 367). The other consisted of women living in Tecumseh, Michigan, who completed both the 1992-1993 and 1993-1994 examinations for the Michigan Bone Health Study (n = 328). Mean cycle length, variability of cycle length, and mean bleed length were calculated from daily diaries (Semiconductor cohort) or monthly menstrual calendars (Michigan cohort) for a median of five and 11 cycles, respectively. Physical activity was assessed by self-report at baseline and expressed as metabolic equivalent-minutes per week. In the Semiconductor study, women also reported daily minutes of vigorous exercise in their diaries. In the Michigan cohort, total physical activity, total recreational physical activity, and vigorous recreational activity were positively associated with cycle length. The magnitude of these associations declined as body mass index increased. In the Semiconductor cohort, the minutes of daily vigorous exercise were positively associated with cycle length only in a repeated-measures analysis. These findings lend modest support to the hypothesis that moderate levels of physical activity can lengthen the menstrual cycle.