© 2005 Oxford University Press
IN THIS ISSUE
Surveillance Bias and Cancer Risk in the Relatives of PatientsThe diagnosis of the first cancer in a family may lead to the screening of the patient's relatives and their subsequent diagnosis of cancer. To determine if surveillance bias was associated with an overestimation of cancer risk in the relatives of patients with a first cancer diagnosis, Lorenzo Bermejo and Hemminki (p. 1575) followed 1 677 722 offspring and siblings of 846 468 probands from the year of diagnosis of the proband's first cancer to the diagnosis of the first familial tumor or cancer using the Swedish Family Cancer Database. The risk of in situ breast cancer in daughters of women with breast cancer and the risk of invasive melanoma in the offspring of invasive melanoma patients was higher during the year of the parents' diagnosis than 5 or more years later. Sibling risks of in situ breast and cervical cancer and invasive prostate cancer also decreased with time. The authors conclude that overestimation of familial risk shortly after diagnosis of the first cancer in the family should be considered before clinical and genetic counseling is implemented.
In an editorial (p. 1556), Zelen discusses the methodology used in the study and agrees that some of the increased cancer diagnoses observed in offspring may be due to surveillance bias.
Paternity Rates After Testicular Cancer Treatment
Testicular cancer has a very high cure rate. However, because most diagnoses of this disease are made in young men, many patients have concerns about how the disease and its treatment will affect their subsequent ability to father children. In this issue, Brydøy et al. (p. 1580) report the paternity outcomes of 1433 men in Norway who were treated in various ways for unilateral testicular cancer in 1980 through 1994 and who participated in a follow-up survey in 1998 through 2002. By 15 years after treatment, 71% of the 554 men who reported having attempted post-treatment conception had become biological fathers without the use of cryopreserved semen. The paternity rate ranged from 48% in men who received high doses of chemotherapy after orchiectomy to 92% in men who received no treatment after orchiectomy. The time to first child after treatment also varied with the treatment group.
In an editorial, Saxman (p. 1557) notes that studies of fertility in testicular cancer patients are often limited by the use of surrogate endpoints, by the inherent difficulties of follow-up in men of this age group, and by changes in treatment that occur during the long follow-up necessary to assess paternity success rates. He suggests that national collaborative efforts will be required to understand the long-term quality- of-life implications of treatment for young adults with testicular cancer.
Transcription Factor E2F1, Telomerase, and Glioblastoma
Alonso et al. (p. 1589) investigated the functional role of the retinoblastoma-E2F1 pathway in regulating telomerase activity in malignant gliomas, in glioma cell lines, and patients with malignant glioma. They found that ectopic expression of E2F1 increased the activity of hTERT (the catalytic subunit of human telomerase) and that E2F1 interacted with the hTERT promoter. They noted that E2F1 mRNA expression and hTERT mRNA expression were correlated in human glioblastoma specimens and that the expression of E2F1 mRNA and protein in tumors was statistically significantly associated with survival. They conclude that E2F1 may participate in the regulation of telomerase activity in malignant glioma cells and that E2F1 expression appears to be strongly associated with the survival of patients with malignant brain tumors.
Alcohol, Steroid Receptors, and Breast Cancer
To determine the relationship between alcohol intake, estrogen (ER) and progesterone receptor (PR) status, and postmenopausal breast cancer risk, Suzuki et al. (p. 1601) followed 51 847 women in the Swedish Mammography Cohort who selfreported alcohol intake in 1987 and 1997 for an average of 8.3 years. A total of 1188 women developed invasive breast cancer with known steroid receptor status. After adjusting for other factors, the authors observed a direct association between alcohol intake and risk of developing ERpositive tumors. The age-adjusted absolute rates of ER-positive breast cancer for women in the highest category of alcohol intake and for nondrinkers were 232 and 158 per 100,000 person-years, respectively. The authors also observed a statistically significant interaction between postmenopausal hormone use and alcohol on the risk of developing ER-positive/ PR-positive tumors. They conclude that their findings may be important because most postmenopausal breast tumors are ER-positive.
Improving Cancer Outcomes Measurement
Policy makers seeking to improve the quality of cancer care are increasingly recognizing the importance of including patient perspectives. The challenge is developing rigorous ways to assess patient-reported outcomes such as healthrelated quality of life (HRQOL), patient needs and satisfaction, and economic burden. The US National Cancer Institute convened a working group of experts to consider measurement of outcomes in these three areas for four major cancers (breast, lung, colorectal, and prostate). In this issue, Gotay et al. (p. 1568) highlight some of the themes that emerged from the group's work, focusing on assessment of HRQOL. The authors conclude that HRQOL assessment is feasible in a research context and that methods for HRQOL assessment have improved and should continue to improve with the application of new methodologies that are under development. However, more work is needed to understand the impact of interventions on HRQOL and other patientreported outcomes and to translate this information to policy makers.
Coronary Heart Disease Among Tamoxifen Users
Between 1983 and 1992, a randomized trial of 4610 breast cancer patients evaluated mortality among patients randomly assigned to receive either 2 years or 5 years of adjuvant tamoxifen therapy. Nordenskjöld et al. (p. 1609) report that, after a median follow-up of 10.6 years, all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were lower in the group treated with tamoxifen for 5 years than in the group treated for 2 years but that the incidence of endometrial cancer was higher in the group treated with tamoxifen for 5 years. In addition, they reported that mortality from coronary heart disease was lower in the group treated for 5 years with tamoxifen than the group treated for 2 years. No increases in mortality from other heart diseases, cerebrovascular disease, or other vascular diseases were observed.
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