Kathleen M. Egan

Epidemiologic aspects of uveal melanoma

Although the underlying cause or causes of uveal melanoma have yet to be elucidated, important insights may be gained by examining the epidemiologic features of the disease. Uveal melanoma is an uncommon cancer with an incidence of only six cases per million population per year. It is most often diagnosed in the sixth decade and is somewhat more common in males. Apart from sporadic reports of family clusters, uveal melanoma is not considered an inherited disease. Whether some environmental exposure triggers the development of uveal melanoma remains an open question. Sunlight has been proposed as an environmental risk factor because sunlight is known to cause melanoma of the skin and both diseases are rare in nonwhite races. Unlike cutaneous melanoma, however, rates have not been increasing over time and do not vary by latitude. This paper evaluates the available evidence for sunlight and other potential risk factors for uveal melanoma, highlighting areas requiring further research.

Physical Activity and Survival after Diagnosis of Invasive Breast Cancer

Previous studies suggest that increased physical activity may lower the risk of breast cancer incidence, but less is known about whether levels of physical activity after breast cancer diagnosis can influence survival. We prospectively examined the relation between postdiagnosis recreational physical activity and risk of breast cancer death in women who had a previous invasive breast cancer diagnosed between 1988 and 2001 (at ages 20-79 years). All women completed a questionnaire on recent postdiagnosis physical activity and other lifestyle factors. Among 4,482 women without history of recurrence at the time of completing the questionnaire, 109 died from breast cancer within 6 years of enrollment. Physical activity was expressed as metabolic equivalent task-hours per week (MET-h/wk); hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. After adjusting for age at diagnosis, stage of disease, state of residence, interval between diagnosis and physical activity assessment, body mass index, menopausal status, hormone therapy use, energy intake, education, family history of breast cancer, and treatment modality compared with women expending <2.8 MET-h/wk in physical activity, women who engaged in greater levels of activity had a significantly lower risk of dying from breast cancer (HR, 0.65; 95% CI, 0.39-1.08 for 2.8-7.9 MET-h/wk; HR, 0.59; 95% CI, 0.35-1.01 for 8.0-20.9 MET-h/wk; and HR, 0.51; 95% CI, 0.29-0.89 for ≥21.0 MET-h/wk; P for trend = 0.05). Results were similar for overall survival (HR, 0.44; 95% CI, 0.32-0.60 for ≥21.0 versus <2.8 MET-h/wk; P for trend <0.001) and were similar regardless of a woman’s age, stage of disease, and body mass index. This study provides support for reduced overall mortality and mortality from breast cancer among women who engage in physical activity after breast cancer diagnosis. (Cancer Epidemiol Biomarkers Prev 2008;17(2):379–86)

Survival of Patents with Metastases from Uveal Melanoma

The authors evaluated a series of 145 consecutive patients with metastases from uveal melanoma, after proton beam irradiation, to assess the effect of early diagnosis and treatment for metastases on survival. Metastases were diagnosed between 7 weeks and 8.3 years (median, 2.4 years) after proton beam irradiation. Most patients (n = 94) were symptomatic before diagnosis; the remainder were first detected during screening examination. Liver involvement was documented in nearly all patients (n = 136). The majority of patients had died from metastases by the close of the study (n = 137). Significantly longer survival occurred among patients diagnosed during screening examination (P = 0.004) and among young patients (P = 0.03). The majority of patients received some form of treatment for metastases (69%). Median survival was 2.0 months for patients receiving no treatment compared with 5.2 months for those receiving treatment for metastases (P = .0001). However, the overall 1-year survival rate was poor (13%). Prophylactic adjuvant therapy could be explored as a means to increase disease-free survival in patients with uveal melanoma.

Hormone replacement therapy and risk of breast cancer: Results from epidemiologic studies

OBJECTIVE We combined data from published reports of the relation between estrogen use and breast cancer. We specifically addressed the hypothesis that the addition of progestins to estrogen therapy reduces the risk of breast cancer. STUDY DESIGN A meta-analysis was performed. RESULTS Replacement hormone therapy is not associated with increased risk of breast cancer in women who have ever used it (relative risk 1.02, 95% confidence interval 0.93 to 1.12). However, current use is associated with increased risk (relative risk 1.40, 95% confidence interval 1.20 to 1.63). Although there was no significant trend with increasing duration of use, women with > or = 10 years of estrogen use had a relative risk of 1.23 (95% confidence interval 1.08 to 1.40). However, data on use of estrogen plus progestins combined from four studies indicate that risk is not reduced and that the overall relative risk is 1.13 (95% confidence interval 0.78 to 1.64). Further, risk did not vary in strata of family history or benign breast disease. CONCLUSION Although these results exclude a large effect of hormone therapy on risk of breast cancer, we are unable to rule out some risk associated with current or long-term estrogen use.

Ocular Blood Flow Velocity in Age-related Macular Degeneration

BACKGROUND Changes in the structure of the ocular blood vessels associated with age-related macular degeneration (AMD) have been described in some detail, but comparatively little is known of the concomitant circulatory changes. The goal of this study is to evaluate changes in the ocular circulation that may be associated with AMD. METHODS Ocular blood flow velocities and vessel pulsatilities were measured in volunteers with and without AMD using a color Doppler imaging unit. Spectral analyses were recorded from the ophthalmic artery, central retinal artery and vein, the temporal and nasal short posterior ciliary arteries, and the four vortex veins. RESULTS Adjusting for age, pulsatility indices of all arteries were higher in subjects with AMD (central retinal artery [P = 0.02]; temporal and nasal short posterior ciliary arteries [P = 0.06 and 0.002, respectively]; and ophthalmic artery [P = 0.24]). End-diastolic blood flow velocity of the short posterior ciliary arteries tended to decrease in the presence of AMD. CONCLUSIONS The combination of increased pulsatility and decreased velocity of the short posterior ciliary arteries, observed in the presence of AMD, are interpreted as evidence of increased vascular resistance. The clinical signs of AMD may be related to degradation of the metabolic transport function of the retinal pigment epithelium, resulting from impaired choroidal perfusion.

Long-term results of proton beam irradiated uveal melanomas

The first 128 consecutive patients with uveal melanomas treated with proton beam irradiation were studied in order to evaluate survival and visual acuity status of patients with relatively long-term follow-up. The median follow-up was 5.4 years, and no patient was lost to follow-up. All tumors showed regression. The most recent visual acuity was 20/40 or better in 35% and 20/100 or better in 58%. Eight eyes were enucleated because of complications. Metastasis developed in 26 patients (20.5%) from 3 months to 7 years after treatment. Results indicate that proton irradiation is quite successful for achieving local control of uveal melanomas. A large proportion of the treated eyes maintained useful vision. Five-year follow-up data indicate that proton irradiation has no deleterious effect on the likelihood of the development of metastasis.

Body mass index before and after breast cancer diagnosis: Associations with all-cause, breast cancer, and cardiovascular disease mortality

Background: Factors related to improving outcomes in breast cancer survivors are of increasing public health significance. We examined postdiagnosis weight change in relation to mortality risk in a cohort of breast cancer survivors. Methods: We analyzed data from a cohort of 3,993 women with ages 20 to 79 years living in New Hampshire, Massachusetts, or Wisconsin with invasive nonmetastatic breast cancers diagnosed in 1988 to 1999 identified through state registries. Participants completed a structured telephone interview 1 to 2 years after diagnosis and returned a mailed follow-up questionnaire in 1998 to 2001 that addressed postdiagnosis weight and other factors. Vital status information was obtained from the National Death Index through December 2005. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models and adjusted for prediagnosis weight, age, stage, smoking, physical activity, and other important covariates. Results: During an average 6.3 years of follow-up from the postdiagnosis questionnaire, we identified 421 total deaths, including 121 deaths from breast cancer and 95 deaths from cardiovascular disease. Increasing postdiagnosis weight gain and weight loss were each associated with greater all-cause mortality. Among women who gained weight after breast cancer diagnosis, each 5-kg gain was associated with a 12% increase in all-cause mortality (P = 0.004), a 13% increase in breast cancer–specific mortality (P = 0.01), and a 19% increase in cardiovascular disease mortality (P = 0.04). Associations with breast cancer mortality were not modified by prediagnosis menopausal status, cigarette smoking, or body mass index. Conclusion: These findings suggest that efforts to minimize weight gain after a breast cancer diagnosis may improve survival. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1403–9)

Relative Survival Rates after Alternative Therapies for Uveal Melanoma

Survival in a group of 556 patients with uveal melanoma treated by proton beam irradiation with a median follow-up of 5.3 years was compared with that of 238 patients enucleated during the same 10-year period as irradiated patients (July 1975 to December 1984) with a median follow-up of 8.8 years, and 257 patients enucleated during the preceding 10 years (January 1965 to June 1975) with a median follow-up of 17.0 years. Adjustments were made for known prognostic factors including age, tumor location, tumor height, and clinical estimate of tumor diameter (for enucleated patients this was estimated in a regression equation relating histologic to clinical measurement). The overall rate ratio for all cause mortality was 1.2 (95% confidence interval, 0.9-1.6) for the concurrent enucleation series versus proton beam, and 1.6 (95% confidence interval, 1.2-2.1) for the earlier enucleation series versus proton beam. Relative rates of metastatic death, cancer death, and all cause mortality comparing alternative treatments were found to vary with time after treatment. Interval-specific rate ratios were evaluated using proportional hazards models fitted to separate time intervals after treatment. For all three outcomes, rate ratios were over two and statistically significant for the first 2 years after treatment and closer to one and nonsignificant after year 6 comparing the two enucleation groups with proton beam. Results suggest that treatment choice has little overall influence on survival in patients with uveal melanoma.

Weight change and risk of postmenopausal breast cancer (United States)

AbstractObjective: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case–control study of postmenopausal breast cancer. Methods: Participants included women aged 50–79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from drivers license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (≤45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84–0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95–1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06–1.11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk. Conclusions: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.

Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses

The double-strand break DNA repair pathway has been implicated in breast carcinogenesis. We evaluated the association between 19 polymorphisms in seven genes in this pathway (XRCC2, XRCC3, BRCA2, ZNF350, BRIP1, XRCC4, LIG4) and breast cancer risk in two population-based studies in USA (3,368 cases and 2,880 controls) and Poland (1,995 cases and 2,296 controls). These data suggested weak associations with breast cancer risk for XRCC3 T241M and IVS7-14A>G (pooled odds ratio (95% confidence interval): 1.18 (1.04–1.34) and 0.85 (0.73–0.98) for homozygous variant vs wild-type genotypes, respectively), and for an uncommon variant in ZNF350S472P (1.24 (1.05–1.48)), with no evidence for study heterogeneity. The remaining variants examined had no significant relationships to breast cancer risk. Meta-analyses of studies in Caucasian populations, including ours, provided some support for a weak association for homozygous variants for XRCC3 T241M (1.16 (1.04–1.30); total of 10,979 cases and 10,423 controls) and BRCA2 N372H (1.13 (1.10–1.28); total of 13,032 cases and 13,314 controls), and no support for XRCC2 R188H (1.06 (0.59–1.91); total of 8,394 cases and 8,404 controls). In conclusion, the genetic variants evaluated are unlikely to have a substantial overall association with breast cancer risk; however, weak associations are possible for XRCC3 (T241M and IVS7-14A>G), BRCA2 N372H, and ZNF350 S472P. Evaluation of potential underlying gene–gene interactions or associations in population subgroups will require even larger sample sizes.