Reproductive factors and histologic subtype in relation to mortality after a breast cancer diagnosis.

Evidence suggests that certain reproductive factors are more strongly associated with the incidence of lobular than of ductal breast cancer. The mechanisms influencing breast cancer incidence histology may also affect survival. Women with invasive breast cancer (N = 22,302) diagnosed during 1986-2005 were enrolled in a series of population-based studies in three US states. Participants completed telephone interviews regarding reproductive exposures and other breast cancer risk factors. Histologic subtype was obtained from state cancer registries. Vital status and cause of death were determined through December 2006 using the National Death Index. Women were followed for 9.8 years on average with 3,050 breast cancer deaths documented. Adjusted hazard rate ratios (HR) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazards regression models for breast cancer-specific and all-cause mortality. Parity was inversely associated with breast cancer-specific mortality (P (Trend) = 0.002). Associations were similar though attenuated for all-cause mortality. In women diagnosed with ductal breast cancer, a 15% reduction in breast cancer-specific mortality was observed in women with five or more children when compared to those with no children (HR = 0.85, 95% CI: 0.73-1.00). A similar inverse though non-significant association was observed in women with lobular subtype (HR = 0.70, 95% CI: 0.43-1.14). The trend did not extend to mixed ductal-lobular breast cancer. Age at first birth had no consistent relationship with breast cancer-specific or all-cause mortality. We found increasing parity reduced mortality in ductal and lobular breast cancer. The number of full-term births, rather than age at first birth, has an effect on both breast cancer-specific and overall mortality.

Inverse association of NSAID use and ovarian cancer in relation to oral contraceptive use and parity.

We examined the association between non-steroidal anti-inflammatory drug (NSAID) use and ovarian cancer by potential effect modifiers, parity and oral contraceptive use, in a population-based case-control study conducted in Wisconsin and Massachusetts. Women reported prior use of NSAIDs and information on risk factors in a telephone interview. A total of 487 invasive ovarian cancer cases and 2653 control women aged 20-74 years were included in the analysis. After adjustment for age, state of residence and other covariates, ever use of NSAIDs was inversely associated with ovarian cancer in never users of oral contraceptives (odds ratio (OR)=0.58, 95% confidence interval (CI) 0.42-0.80) but not for ever users (OR=0.98, 95% CI 0.71-1.35) (P-interaction=0.03). A reduced risk with NSAID use was also noted in nulliparous women (OR=0.47, 95% CI 0.27-0.82) but not among parous women (OR=0.81, 95% CI 0.64-1.04) (P-interaction=0.05). These results suggest that use of NSAIDs were beneficial to women at greatest risk for ovarian cancer.

A matched study of primary scleral buckle placement during repair of posterior segment open globe injuries.

AIMS: To compare the visual and anatomical outcomes of patients who underwent primary scleral buckle (SB) placement during posterior segment open globe repair with matched control patients who did not undergo primary SB placement. METHODS: Patients who underwent open globe repair alone or with SB placement at Duke University Eye Center (November 1994-September 1997) and the Massachusetts Eye and Ear Infirmary (July 1993-July 1997) were identified. 19 open globe patients who received primary SB placement were matched with control patients who did not receive a primary SB based on three important prognostic factors: (1) visual grade; (2) zone of injury; and (3) mechanism of injury. The outcomes of interest were: (1) visual outcome; (2) anatomical outcome; (3) subsequent retinal detachment (RD); and (4) number of subsequent surgeries. RESULTS: Baseline characteristics between the groups were similar. Patients who received primary SB placement had a better final visual grade (p = 0.02), logMAR vision (p = 0.007), and anatomical grade (p = 0.01) compared with control patients. Primary SB patients had an average final vision of 20/270, whereas control patients had an average final vision of hand movement. Primary SB placement also resulted in fewer subsequent RDs (26% versus 53%), but this difference did not reach statistical significance (p = 0.10). There were no complications associated with primary SB placement. CONCLUSION: Primary SB placement during posterior segment open globe repair may decrease the risk of subsequent RD and improve final visual and anatomical outcome.

Electric blanket or mattress cover use and breast cancer incidence in women 50-79 years of age.

Previous research has demonstrated inconsistent associations between electromagnetic radiation, especially from electric blanket use, and breast cancer. Breast cancer risk according to electric blanket or mattress cover use was examined as part of a multicenter population-based case-control study. Breast cancer patients 50-79 years of age (N = 1949) were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from the period June 1994 to July 1995. Women of similar age were randomly selected from population lists as controls. Information regarding electric blanket and mattress cover use and breast cancer risk factors was obtained through telephone interviews. After adjustment for age, body mass index, and other breast cancer risk factors, the risk of breast cancer was similar among ever-users (relative risk = 0.93; 95% confidence interval = 0.82-1.06) and lower among current users than among never-users (relative risk = 0.79; 95% confidence interval = 0.66-0.95). There was no evidence of a dose-response relation with increasing number of months that electric blankets had been used. This study provides evidence against a positive association between electric blanket or mattress cover use and breast cancer.

Color Doppler imaging of untreated and irradiated choroidal melanomas.

PURPOSE: We examined untreated and irradiated choroidal melanomas with color Doppler imaging (CDI), a noninvasive method providing quantitative measures of blood flow, to determine if the tumor vessel damage associated with irradiation can be detected using this technology. METHODS: CDI was performed on 122 untreated and 76 previously irradiated tumors using a Q2000 color Doppler ultrasound unit. Spectral analysis was performed on all detectable vascular regions within the tumor to obtain estimates of the peak systolic and end diastolic flow velocities and resistive index ((syst-diast)/syst). RESULTS: Vessels were detected in 93% of the untreated tumors and in 63% of the treated tumors (p<0.001, X2), and the median number of vascular regions found was higher among untreated tumors (3 vs 1, p=0.001, Wilcoxon Rank Sum). The effect of treatment status on the detection of tumor vessels was significant (p=0.039), controlling for age, sex, largest tumor pretreatment diameter, and tumor height at CDI in a logistic regression model. Mean resistive index was lower in the untreated tumors (0.53 vs 0.58, p=0.0050), controlling for tumor height and other covariates in an analysis of variance. CONCLUSIONS: On examination with CDI, irradiated tumors had fewer detectable vascular regions and greater resistance to flow than untreated tumors, a pattern consistent with known radiation effects.

Collection of genomic DNA from adults in epidemiological studies by buccal cytobrush and mouthwash.

Blood samples are an excellent source of large amounts of genomic DNA. However, alternative sources are often needed in epidemiological studies because of difficulties in obtaining blood samples. This report evaluates the buccal cytobrush and alcohol-containing mouthwash protocols for collecting DNA by mail. Several DNA extraction techniques are also evaluated. The study was conducted in two phases. In phase 1, we compared cytobrush and mouthwash samples collected by mail in two different epidemiological studies: (a) cytobrush samples (n = 120) from a United States case-control study of breast cancer; and (b) mouthwash samples (n = 40) from a prospective cohort of male United States farmers. Findings from phase 1 were confirmed in phase 2, where we randomized cytobrush (n = 28) and mouthwash (n = 25) samples among participants in the breast cancer study to directly compare both collection methods. The median human DNA yield determined by hybridization with a human DNA probe from phenol-chloroform extracts was 1.0 and 1.6 microg/2 brushes for phases 1 and 2, respectively, and 27.5 and 16.6 microg/mouthwash sample for phases 1 and 2, respectively. Most (94-100%) mouthwash extracts contained high molecular weight DNA (>23 kb), in contrast to 55-61% of the brush extracts. PCR success rates for amplification of beta-globin gene fragments (268, 536, and 989 bp) were similar for cytobrush and mouthwash phenol-chloroform extracts (range, 94.4-100%). Also, we obtained high success rates in determining the number of CAG repeats in the androgen receptor gene, characterizing tetranucleotide microsatellites in six gene loci, and screening for mutations in the BRCA1/2 genes in a subset of phenol-chloroform DNA extracts. Relative to DNA extracted by phenol-chloroform from cytobrush samples, DNA extracted by NaOH had lower molecular weight, decreased PCR success rates for most assays performed, and unreliably high spectrophotometer readings for DNA yields. In conclusion, although DNA isolated from either mouthwash or cytobrush samples collected by mail from adults is adequate for a wide range of PCR-based assays, a single mouthwash sample provides substantially larger amounts and higher molecular weight DNA than two cytobrush samples.

Fracture history and risk of breast and endometrial cancer.

Fractures in postmenopausal women may serve as a surrogate measure of bone density, reflecting long-term lower estrogen levels, and lower estrogen levels appear to be inversely associated with breast and endometrial cancer. Breast cancer cases aged 50-79 years (n = 5,559) and endometrial cancer cases aged 40-79 years (n = 739) were enrolled in a US case-control study in 1992-1994 to evaluate the relation between fractures and risk of breast and endometrial cancer. Controls for the breast cancer analysis (n = 5,829) and the endometrial cancer analysis (n = 2,334) were randomly selected from population lists (driver's license and Medicare files). Information on fracture history and other risk factors was obtained by telephone interview. Compared with women without a fracture in the past 5 years, the odds ratios for women with a history of fracture were 0.80 (95% confidence interval (CI): 0.68, 0.94) for breast cancer and 0.59 (95% CI: 0.40, 0.89) for endometrial cancer. Height loss (> or =2.5 cm) and recent fracture history were associated with the lowest risk of breast cancer (odds ratio = 0.62, 95% CI: 0.46, 0.83) and endometrial cancer (odds ratio = 0.15, 95% CI: 0.05, 0.43). These data suggest that the endogenous hormonal factors associated with increased fracture risk are also related to decreased breast cancer risk and, more strongly, to endometrial cancer risk.

A population-based case-control study of carotenoid and vitamin A intake and ovarian cancer (United States).

OBJECTIVE: To evaluate the association between dietary intake of carotenoids and vitamin A and the incidence of ovarian cancer. METHODS: We conducted a population-based case-control study of ovarian cancer in Massachusetts and Wisconsin. Incident cases diagnosed between 1991 and 1994 were identified through statewide tumor registries. We selected community controls at random from lists of licensed drivers and Medicare recipients; 327 cases and 3129 controls were included in the analysis. Data were collected by telephone interview, which included an abbreviated food and supplement list to quantify typical consumption of carotenoids (lutein/zeaxanthin, alpha-carotene, beta-carotene), retinol and total vitamin A at 5 years prior to diagnosis in cases, or to a comparable reference date in controls. Results were adjusted for age, state, and other risk factors. RESULTS: Participants with the highest dietary intake of lutein/zeaxanthin (> or =24,000 microg/week) experienced a 40% lower risk of ovarian cancer (95% CI = 0.36-0.99) compared to those with the lowest intake. Intake of alpha-carotene, beta-carotene, retinol and total vitamin A was unrelated to risk. Among foods, we observed non-significantly lower risks with high consumption of spinach, carrots, skim/lowfat milk and liver. CONCLUSION: These results support previous findings suggesting an inverse relationship between carotenoid intake and ovarian cancer risk.

Metabolic disorders and breast cancer risk (United States).

OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.

Left-handedness in relation to breast cancer risk in postmenopausal women.

Breast cancer risk may be influenced by intrauterine exposure to steroid hormones. We evaluated left-handedness, a marker of intrauterine hormone exposure, in relation to breast cancer risk in our population-based, case-control study. Case women 50-79 years of age with a first diagnosis of invasive breast cancer were ascertained through statewide cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control women were identified in each state through lists of licensed drivers (for ages 50-64) and Medicare beneficiaries (for ages 65-79), and selected at random to correspond with the age distribution of case women. Exposure information, including handedness, was obtained through a telephone interview. Our results indicated a modest association between left-handedness and breast cancer risk (OR = 1.42; 95% CI = 1.10-1.83). The effect of left-handedness was modified by age; we observed the greatest risk ratio in the oldest age group. Left-handedness was not associated with breast tumor laterality. Our results are consistent with the hypothesis that intrauterine hormone exposures play a role in the development of breast cancer.

Metastatic melanoma death rates by anatomic site after proton beam irradiation for uveal melanoma.

BACKGROUND: Ciliary body location is an established prognostic factor for metastasis-related death from uveal melanoma. We evaluated alternative approaches for classifying this covariate when constructing predictive models of patient survival. METHODS AND DESIGN: The analyses were based on a consecutive series of 1848 primary choroidal and/or ciliary body melanoma patients treated with proton beam irradiation (70 cobalt gray equivalent in 5 fractions) at the Harvard Cyclotron Laboratory, Boston, Mass, between July 1975 and December 1995. For each patient, the anatomic site of the tumor was classified according to an estimate of the proportion of the tumor base lying anterior to the ora serrata. Using proportional hazards regression, we estimated relative risk ratios and death rates from melanoma metastasis according to the extent of ciliary body involvement. All estimates were adjusted for other established prognostic factors. RESULTS: Patients were followed up through April 30, 1998; none were lost to follow-up. Of 1848 patients analyzed, 378 died of melanoma metastasis. The median follow-up period among survivors was 9.5 years. Ciliary body origin (>50% of tumor base anterior to the ora serrata) was positively associated with tumor pigmentation (P<.001), tumor height (P<.001), and extrascleral extension of the tumor (P<.001). Compared with tumors involving only the choroid, melanoma-associated death rates increased with the proportion of the tumor base lying within the ciliary body (P =. 006); the multivariate-adjusted relative risk ratio for greater than 75% involvement was 2.30 (95% confidence interval [CI], 1.26-4.23). The covariate-adjusted 5-year death rates for ciliary body origin and choroidal origin were 15.9% (95% CI, 11.3%-21.2%) and 9.8% (95% CI, 8.3%-11.7%), respectively. CONCLUSION: Patients with melanomas of presumed ciliary body origin seem to be subject to a higher risk of death resulting from melanoma metastasis. Arch Ophthalmol. 2000;118:1066-1070

Patterns of tumor initiation in choroidal melanoma.

This study attempts to document the occurrence of tumors with respect to clock hour location and distance from the macula and to evaluate tumor location in relation to retinal topography and light dose distribution on the retinal sphere. Analysis of patterns of tumor initiation may provide new evidence to clarify the controversy regarding the possible light-related etiology of choroidal melanoma. Incident cases of choroidal and ciliary body melanoma in Massachusetts residents diagnosed between 1984 and 1993 were the basis for analysis. Conventional fundus drawings and photos were used to assess the initiation site of each tumor. The initiation site was defined as the intersect between the largest tumor diameter and the largest perpendicular diameter of the tumor. Initiation sites were recorded using spherical coordinates. The retinal sphere was divided into 61 mutually exclusive sectors defined according to clock hour and anteroposterior distance from the macula. Rates of initiation were computed for each sector, overall, and according to gender and other clinical factors. Results were similar in left and right eyes; therefore, these were combined in analysis. Tumor initiation had a predilection for the macula (P < 0.0001). Overall, no significant clock hour preference was observed (P = 0.63). However, the parafoveal zone showed a strong circular trend (P < 0.01), with highest rates occurring in the temporal region, and the lowest rates occurring in the nasal region. Rates of occurrence in six progressively more anterior concentric zones (designated as the foveal, parafoveal, posterior, peripheral, anterior, and ciliary body zones) were 21.4, 14.2, 12.1, 8.9, 4.5, and 4.3 counts per spherical unit per 1000 eyes, respectively. Concentric zone location did not vary by gender (P = 0.93) or laterality (P = 0.78). However, posterior location was associated with light iris color (P = 0.01). Tumor diameters were largest in the peripheral region of the fundus and smallest in the macular and ciliary body zone (P < 0.001). Clock hour location was not influenced by gender (P = 0.74), laterality (P = 0.53), iris color (P = 0.84), or tumor diameter (P = 0.73). Results suggest that tumor initiation is not uniformly distributed, with rates of occurrence concentrated in the macular area and decreasing monotonically with distance from the macula to the ciliary body. This pattern is consistent with the retinal topography and correlates positively with the dose distribution of solar light on the retinal sphere.

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

OBJECTIVE: 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 driver's 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.

A randomized controlled trial of varying radiation doses in the treatment of choroidal melanoma.

OBJECTIVE: To determine if a reduction in proton radiation dose from the standard dose of 70 cobalt gray equivalents (CGE) to 50 CGE would decrease radiation-induced complications, thereby improving visual prognosis, without compromising local tumor control for patients with uveal melanoma at high risk of these complications. DESIGN: Randomized, double-masked clinical trial. PARTICIPANTS: A total of 188 patients with small or medium-sized choroidal melanomas (<15 mm in diameter and <5 mm in height) near the optic disc or macula (within 4 disc diameters of either structure). METHODS: Patients were treated with proton beam therapy at doses of either 50 CGE or 70 CGE between October 1989 and July 1994, and followed up biannually through April 1998. Outcomes included visual acuity, radiation complications, melanoma recurrence, and metastasis. RESULTS: Proportions of patients retaining visual acuity of at least 20/200 were similar in the 2 dose groups at 5 years after radiation (approximately 55%). Similar numbers of patients in each group experienced tumor regrowth (2 patients at 50 CGE vs 3 patients at 70 CGE; P>.99) and metastasis (7 patients at 50 CGE vs 8 patients at 70 CGE;P=.79). Five-year rates of radiation maculopathy also were similar (for both groups, approximately 75% for tumors within 1 disc diameter and 40% for tumors >1 disc diameter from the macula). Rates of radiation papillopathy were nonsignificantly decreased in the 50-CGE treatment group when tumors were located 1 disc diameter or less from the optic disc (P=.20). Patients treated with the lower dose also experienced significantly less visual field loss. CONCLUSIONS: This level of dose reduction did not result in a lesser degree of visual acuity loss. The lower-dose group did experience significantly less visual field loss. Local tumor recurrence and metastatic death rates were similar in both dose groups. Arch Ophthalmol. 2000;118:773-778

Risk factors for radiation maculopathy and papillopathy after intraocular irradiation.

PURPOSE: To evaluate rates of occurrence and risk factors for radiation maculopathy and radiation papillopathy in patients with choroidal melanoma at high risk for these complications. DESIGN: Cohort study. PARTICIPANTS: A total of 558 patients treated with proton irradiation for choroidal melanoma between 1986 and 1996 with small to moderate sized tumors (less than 5 mm in height and 15 mm in diameter) located within 4 disc diameters of the macula or optic nerve and with a median ocular follow-up of 4 years. METHODS: Annual and cumulative rates of each endpoint were estimated using life table approaches. Prognostic factors were evaluated using the Cox proportional hazards regression. MAIN OUTCOME MEASURES: Radiation maculopathy, radiation papillopathy, and vision loss to worse than 20/100. RESULTS: Cumulative 5-year rates for radiation maculopathy, radiation papillopathy, and vision loss were 64%, 35%, and 68%, respectively. Complication rates rose as a function of radiation exposure to the macula (P for trend = 0.04) or optic disc (P for trend < 0.001), although dose-response patterns were nonlinear. History of diabetes was a significant risk factor for maculopathy (P < 0.001) and optic neuropathy (P = 0.009). CONCLUSIONS: The onset of radiation vasculopathy is determined primarily by the degree of irradiation exposure to the macula and optic disc. Risk may be enhanced among those with underlying vascular disorders.

Childbearing history associated with improved survival in choroidal melanoma.

BACKGROUND: Research in cutaneous melanoma suggests that women may experience better tumor-dependent survival than men, and some studies have shown that the advantage is specific to childbearing. OBJECTIVE: To examine whether childbearing may be a favorable prognostic factor in melanoma of the uveal tract. DESIGN: Prospective follow-up study. SETTING: Hospital. MAIN OUTCOME MEASURE: Death from metastatic choroidal melanoma. METHODS: We evaluated a consecutive series of 1818 patients with choroidal melanoma, 748 parous and 165 nulliparous women and 905 men, after treatment with proton irradiation. Three hundred fifty-two deaths from metastasis were documented in follow-up. RESULTS: Overall multivariate-adjusted death rates from metastasis were approximately 25% higher in nulliparous women (relative risk [RR], 1.23; 95% confidence interval [CI], 0.83-1.82) and men (RR, 1.25; 95% CI, 1.00-1.56) than in women who had given birth. The protective influence of parity was strongest in the early period following diagnosis and treatment (RR, 1.58; 95% CI, 0.88-2.86, and RR, 1.51; 95% CI, 1.04-2.19, in nulliparous women and men, respectively, during the first 36 months of follow-up). The level of protection increased with the number of live births (P for trend, .04). CONCLUSION: These data provide support for the hypothesis that a history of childbearing confers protection from death in choroidal melanoma.

Germline brca2 sequence variants in patients with ocular melanoma.

On the basis, chiefly, of anecdotal reports of cases of ocular melanoma (OM) occurring in families with inherited susceptibility to breast cancer due to brca2 germline mutations, we examined the frequency of brca2 alterations in a series of 62 ocular melanoma cases. These cases were preferentially selected on the basis of reported family history of breast or ovarian cancer, or OM, although the series also included a randomly selected set of cases without family history of cancer. A total of 7 germline alterations were found, of which 3 were likely to be associated with disease. While all 3 deleterious mutations were found in patients who also had a personal history of breast cancer, only 1 of the 3 families had a family history of breast/ovarian cancer or OM. Although germline brca2 mutations may account for a small proportion of all OM cases, there may be additional loci that contribute to familial aggregation of OM and to the familial association between OM and breast cancer.

Lactation in relation to postmenopausal breast cancer.

A modest inverse association between lactation and breast cancer risk has most consistently been observed in premenopausal women, and certain breastfeeding patterns, such as prolonged duration and early age at first lactation, may be important determinants of risk. However, these associations have not generally been observed in relation to postmenopausal breast cancer. As part of a multicenter population-based case-control study, the authors examined postmenopausal breast cancer risk according to breastfeeding characteristics. Breast cancer patients aged 50-79 years were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from July 1992 through July 1995. Similarly aged control women were randomly selected from population lists. Information regarding lactation history and breast cancer risk factors was obtained through telephone interviews. This analysis included only data on parous postmenopausal women (3,633 cases and 3,790 controls). After adjustment for age, parity, age at first birth, and other breast cancer risk factors, breastfeeding for at least 2 weeks was associated with a slightly reduced risk of breast cancer in comparison with women who had never lactated (relative risk = 0.87, 95% confidence interval 0.78-0.96). There was only a modest suggestion that increasing cumulative duration of lactation was inversely associated with breast cancer risk; the relative risk for women who had breastfed for > or =24 months was 0.73 (95% confidence interval 0.56-0.94) (p-trend for duration = 0.10). Age at first lactation was not consistently associated with risk. Modest inverse associations appeared to persist even up to 50 years since first lactation. Use of hormones to suppress lactation was not associated with postmenopausal breast cancer, nor was inability to breastfeed related to risk. These results suggest that lactation may have a slight and perhaps long-lasting protective effect on postmenopausal breast cancer risk.

Iris color as a prognostic factor in ocular melanoma.

BACKGROUND: Ocular melanoma may be more prevalent among patients with light irises than those with dark irises. OBJECTIVE: To examine a large clinical series of patients with intraocular melanoma to determine if light irises are associated with increased risk of death from these tumors. METHODS: A total of 1162 patients treated with proton irradiation between 1984 and 1996 were observed through 1997. RESULTS: Iris color in the patients was blue or gray in 48%, green or hazel in 30%, and brown in 23%. Tumors in patients with blue or gray irises were less heavily pigmented (P<.001) and closer to the optic disc and macula (P<.001). Five- and 10-year metastasis-related death rates were 0.14 and 0.21, respectively, for those with blue or gray irises and 0.10 and 0.15, respectively, for those with darker irises (P = .02). In a Cox proportional hazards regression controlling for tumor characteristics, patients with blue or gray irises died of metastatic disease at a rate 1.90 times (95% confidence interval, 1.26-2.85) that of patients with brown irises. The rate of metastatic death was not significantly elevated for those with green or hazel irises (relative risk, 1.43; 95% confidence interval, 0.91-2.23). CONCLUSION: Patients with blue or gray irises appear to be at increased risk of metastatic death from choroidal melanoma, independent of other risk factors.