Roles of radiation dose, chemotherapy, and hormonal factors in XXXX following @entity978 .

@entity1 @entity0 @entity5 @entity978 @entity105
BACKGROUND: Female survivors of @entity978 ( @entity978 ) have a strongly elevated risk of @entity0 , but factors responsible for the increased risk are not well known. METHODS: We investigated the effects of radiation dose, chemotherapy (CT), and reproductive factors on @entity0 risk in a nested case-control study in The Netherlands in a cohort of 770 female @entity1 who had been diagnosed with @entity978 before age 41. Detailed treatment information and data on reproductive factors were collected for 48 case @entity1 who developed @entity0 5 or more years after diagnosis of @entity978 and 175 matched control subjects. The radiation dose was estimated to the area of the breast where the case @entity1 's @entity5 had developed and to a comparable location in matched control subjects. Relative risks (RRs) of @entity0 were calculated by conditional logistic regression. Statistical tests were two-sided. RESULTS: The risk of @entity0 increased statistically significantly with radiation dose (P(trend) =.01); @entity1 who received 38.5 Gy or more had an RR of 4.5 (95% confidence interval [CI] = 1.3 to 16) times that of @entity1 who received less than 4 Gy. @entity1 who received both CT and radiotherapy (RT) had a statistically significantly lower risk than those treated with RT alone (RR = 0.45, 95% CI = 0.22 to 0.91). @entity0 risk increased with increasing radiation dose among @entity1 who received RT only (RR = 12.7, 95% CI = 1.8 to 86, for @entity1 receiving > or =38.5 Gy) but not among @entity1 treated with CT and RT. Sixty-nine percent of control subjects treated with RT and more than six cycles of CT, but only 9% of those who received RT alone, reached menopause before age 41. Reaching menopause before age 36 was associated with a strongly reduced risk of @entity0 (RR = 0.06, 95% CI = 0.01 to 0.45). CONCLUSION: @entity0 risk increases with increasing radiation dose up to at least 40 Gy. The substantial risk reduction associated with CT may reflect its effect on menopausal age, suggesting that ovarian hormones promote @entity105 after radiation has produced an initiating event.
