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Biomedical subjects

A J Coldman

Publications and source records attributed to A J Coldman.

At least 19 recordsLinked to original sources

Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer.

BACKGROUND: Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began to decline in the 1980s because it failed to improve overall survival. We prospectively tested the efficacy of combining radiotherapy with chemotherapy. METHODS: From 1978 through 1986, 318 premenopausal women with node-positive breast cancer were randomly assigned, after modified radical mastectomy, to receive chemotherapy plus radiotherapy or chemotherapy alone. Radiotherapy was given to the chest wall and locoregional lymph nodes between the fourth and fifth cycles of cyclophosphamide, methotrexate, and fluorouracil. RESULTS: After 15 years of follow-up, the women assigned to chemotherapy plus radiotherapy had a 33 percent reduction in the rate of recurrence (relative risk, 0.67; 95 percent confidence interval, 0.50 to 0.90) and a 29 percent reduction in mortality from breast cancer (relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.99), as compared with the women treated with chemotherapy alone. CONCLUSIONS: Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer.

Adult

Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma.

The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P < .01), DFS (32% v 66%, P < .001), and RFS (25% v 59%, P < .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P < .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.

Adolescent

Compliance with practice guidelines for node-negative breast cancer.

PURPOSE: Practice guidelines for cancer management have been in use in the province of British Columbia (BC), Canada, since the mid 1970s. To evaluate practice guideline compliance, treatment received was compared with treatment recommended in a population-based cohort of women with breast cancer. METHODS: All incident cases (n = 939) of invasive, pathologically node-negative breast cancer diagnosed in 1991 were identified from the BC Cancer Registry. Treatment details were abstracted from cancer clinic records for cases referred to the BC Cancer Agency (BCCA) (n = 661) and original source documents for nonreferred cases. Management decisions were considered compliant if the patient received the recommended treatment or was entered onto a randomized trial of the modality being assessed. RESULTS: Overall compliance with adjuvant therapy guidelines was 97% for radiotherapy, 96% for chemotherapy, and 89% for tamoxifen. An oncology specialist was consulted by 94% of patients with an indication for adjuvant treatment and by 58% of those without an indication (odds ratio [OR] = 10.7; 95% confidence interval, 7.0 to 16.4). Compliance with a guideline to deliver radiotherapy was 95%; with chemotherapy, 77%; and with tamoxifen, 68%. Compliance with a guideline that stated no adjuvant treatment was indicated was 99% for radiotherapy, 98% for chemotherapy, and 92% for tamoxifen. Noncompliance among patients with an indication for treatment was related to nonreferral to an oncology specialist and less complete implementation of guideline changes in the community as compared with cancer center practices. CONCLUSION: Compliance was high, but scheduled updating and more effective community implementation could further improve consistency of care.

Aged

Cohort study of Air Canada pilots: mortality, cancer incidence, and leukemia risk.

Despite the special working environment and exposures of airline pilots, data on risk of death and cancer incidence in this occupational group are limited. The authors investigated a cohort of 2,740 Air Canada pilots who contributed 62,449 person-years of observation. All male pilots employed for at least 1 year on and since January 1, 1950, were studied. The cutoff date for outcome information was December 31, 1992. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were used to compare mortality rates and cancer incidence rates of the cohort with the respective Canadian population rates. Ninety percent confidence intervals of the SMR and SIR were calculated. Statistically significant decreased mortality was observed for all causes (SMR = 0.63, 90% confidence interval (CI) 0.56-0.70), for all cancers (SMR = 0.61, 90% CI 0.48-0.76), and for all noncancer diseases (SMR = 0.53, 90% CI 0.45-0.62). Mortality from aircraft accidents was significantly raised (SMR = 26.57, 90% CI 19.3-35.9). Significantly decreased cancer incidence was observed for all cancers (SIR = 0.71, 90% CI 0.61-0.82), rectal cancer (SIR = 0.42, 90% CI 0.14-0.96), lung cancer (SIR = 0.28, 90% CI 0.16-0.46), and bladder cancer (SIR = 0.36, 90% CI 0.12-0.82). Prostate cancer (SIR = 1.87, 90% CI 1.38-2.49) and acute myeloid leukemia (SIR = 4.72, 90% CI 2.05-9.31) were significantly increased. The preferred relative risk model for radiation-induced nonchronic lymphoid leukemia (Beir V report) was applied to the cohort by using published estimates of in-flight radiation exposures. The estimated relative risk ranged from 1.001 to 1.06 and did not differ significantly from the observed SIR (SIR = 1.88, 90% CI 0.80-3.53). However, the incidence rate of acute myeloid leukemia was significantly increased. Monitoring of in-flight radiation exposure and long-term follow-up of civil aviation crew members is needed to further assess cancer incidence and leukemia risk in this special occupational group.

Accidents, Aviation

Effects of intermittent androgen suppression on the stem cell composition and the expression of the TRPM-2 (clusterin) gene in the Shionogi carcinoma.

The proportion of tumorigenic stem cells and the expression of the apoptosis-related gene, TRPM-2 (clusterin), were studied in populations of Shionogi carcinoma cells subjected to multiple cycles of androgen withdrawal and replacement (intermittent androgen suppression). The parent androgen-dependent cell line was initially transplanted into a male mouse which was castrated when the estimated weight of the resultant tumour became approximately 3 g. After the tumour had regressed to 40% or less of the original weight, it was transplanted into the next non-castrated male. This was repeated for four cycles of transplantation and castration-induced apoptosis before the tumour progressed to an androgen-independent state. The proportion of total stem cells in the tumour, as determined by in vivo limiting dilution assays in male mice, was constant during the first three cycles but increased 15-fold between the third and fourth cycles. In the parent androgen-dependent tumour before androgen ablation, the androgen-independent stem cell population formed 0.8% of the total stem cell compartment. After the fourth cycle this population increased to 47%; a population of similar size (33%, P = 0.8) was found in the androgen-independent recurrent form of the tumour induced by one-time castration. Whether androgen withdrawal therapy was intermittent or continuous, conversion to androgen independence thus occurred when one-third to one-half of the total stem cell compartment was populated by androgen-independent stem cells. The androgen-repressed TRPM-2 (clusterin) gene was actively expressed in regressing tumours after androgen ablation, and also became constitutively expressed in non-regressing tumours after the first and subsequent cycles of androgen withdrawal. Staining of cytoplasm and nuclei with anti-clusterin antibody was observed in androgen-dependent tumour cells after each cycle of intermittent androgen suppression; the nuclear staining was more intense in recurrent androgen-independent cells. The anomalous nuclear localization of clusterin, an anti-cytolytic TRPM-2 encoded protein, may serve to inhibit early events in the apoptotic process and thereby foster the generation and outgrowth of androgen-independent stem cells in an androgen-depleted environment.

Androgens

Forty years of repeated screening: the significance of carcinoma in situ.

Two cohorts of women born in 1914-18 and 1929-33 who participated in a cervical screening programme have been followed for over 40 years. Age-specific incidence rates of squamous carcinoma of the cervix by rank of smear and length of interval between smears are reported. The younger cohort, who had undergone more frequent screening, had lower rates of invasive disease. From these incidence rates, estimates of false-negative rates and regression rates for carcinoma in situ have been made. The false-negative rate was estimated to be about 15%. Regression seemed more frequent in younger than in older women. For the younger cohort it was estimated to be 72% and in the older 47%. A comparison of the rates of in situ carcinoma with those of invasive disease suggests that the screening of the younger cohort reduced the rate of invasive disease to at least one-half or one-third of what it would have been if screening had commenced later. Rates of disease appear less dependent on age than previously thought and are consistent with causation by an infective agent.

Adult

Clinical determinants of mammographic dysplasia patterns.

The association between the clinical manifestations of benign breast disease (BBD) and mammographic patterns was investigated among 1394 women (923 pre-menopausal and 471 post-menopausal) participating to the Canadian National Breast Screening Study in Vancouver, who completed a questionnaire designed to collect detailed information on the symptoms and signs of BBD, hormonal, reproductive and dietary factors. Mastalgia was present in 637 (46%) women and was cyclical in 505 (79%). Breast swelling was noted in 331 women (23%) and mammary dysplasia involving 50% or more of the breast parenchyma in 733 (43%). Mastalgia was highly associated with breast swelling (odds ratios [OR] = 29.9, 95% confidence interval [CI] = 21.3-41.8), particularly when cyclical and characterized by tenderness with pain (OR = 58.4, 95% CI = 39.1-87.0). The relative risk for mammary dysplasia involving 50% or over of the breast parenchyma was significant in pre-menopausal women having breast swelling (OR = 2.96, 95% CI = 1.81-4.83), being highest in women with cyclical mastalgia associated with tenderness and pain (OR = 3.43, 95% CI = 1.49-7.92); similar associations were noted in post-menopausal women. This study indicates that mastalgia is strongly related to breast swelling, especially when tenderness is associated with pain. Furthermore, mastalgia associated with breast swelling is highly related to the presence of mammary dysplasia involving 50% or more of the breast parenchyma in both pre- and post-menopausal women, suggesting that cyclical tenderness and breast swelling may carry an increased breast cancer risk.

Adult

Physical activity, medical history, and risk of testicular cancer (Alberta and British Columbia, Canada).

In order to evaluate risk factors for germ cell cancers, we conducted a case-control study of 510 men with testicular cancer aged 15 to 79 years and 996 randomly selected age-matched controls in the provinces of British Columbia and Alberta, Canada. Subjects completed a mailed questionnaire providing data on education level, ethnic origin, medical history, smoking, occupation, and recreational and sports activity. The response rate among cases was 80.3 percent and among controls was 68.1 percent. After controlling for age and ethnic origin, undescended testis was associated positively with risk of testicular cancer (odds ratio [OR] = 3.5; 95 percent confidence interval [CI] = 2.2-5.7) as was inguinal hernia requiring surgery (OR = 2.0, CI = 1.3-2.9), and hydrocoele (OR = 2.6, CI = 1.4-5.1). Risk of testicular cancer increased with height, with subjects taller than 180 cm having a significantly increased risk compared with those 174 cm or less (OR = 1.5, CI = 1.1-2.1). A moderate to high level of recreational activity level was associated inversely with testicular cancer risk (OR = 0.6, CI = 0.5-0.8).

Adolescent

Comparison of cytogenetic analysis, southern analysis, and polymerase chain reaction for the detection of t(14; 18) in follicular lymphoma.

This study was undertaken to compare the ability of cytogenetic analysis (CG), Southern analysis (SA) and the polymerase chain reaction (PCR) to detect the t(14; 18) in follicular lymphoma (FL). All methodologies were performed by standard techniques. The probes used for SA included major breakpoint region (mbr) and minor cluster region (mcr) probes. The primers for PCR were identical or similar to those used by other investigators. One hundred fifteen cases of FL were ascertained by morphologic criteria, from which sufficient fresh tissue was available for both CG and molecular analysis. Eleven cases failed by both methods (nonrepresentative sampling). One hundred four cases showed evidence of an abnormal clone by CG and/or immunoglobulin gene rearrangement (IgH) studies. Cytogenetic analysis failed in 2 cases, was positive for t(14; 18) in 91 of the remaining 102 cases (89%) and detected a non-t(14; 18) close in 11 cases. An IgH clonal rearrangement was confirmed in all 104 cases. Southern analysis detected a mbr or mcr rearrangement in 78 of 104 cases (75%). Polymerase chain reaction detected an mbr or mcr rearrangement in 68 of 104 cases (65%). The use of PCR as a clinical test to detect t(14; 18)-positive lymphomas, with single primer sets for the mbr and mcr, will result in a high false-negative rate. The use of additional primers to detect uncommon breakpoints sites will be required to enhance the sensitivity of PCR for detection of t(14; 18) in malignant lymphoma.

Base Sequence

Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma.

BACKGROUND AND DESIGN: Basal cell carcinoma (BCC) of the skin is the most common neoplasm in white populations, and solar radiation is generally accepted to be the dominant environmental risk factor for this disease. However, little information is available on the nature of the relationship between BCC and sunlight. The purpose of this study was to evaluate the nature of the relationship between sunlight exposure, pigmentary factors, and BCC of the skin. A population-based case-control study of 226 male patients with BCC diagnosed from January 1, 1983, through December 31, 1984, and 406 randomly selected male control subjects was conducted in Alberta, Canada. The study was conducted using a standardized questionnaire, administered in person by trained interviewers. Data were analyzed using conditional logistic regression methods. RESULTS: After controlling for other host and pigmentary factors, the risk of BCC was increased in subjects with light skin color and those who freckled in childhood. A history of severe sunburn in childhood also increased risk. Subjects of southern European ethnic origin were at significantly lower risk of BCC. Surprisingly, no association was seen between mean annual cumulative summer sunlight exposure and risk of BCC. A significantly increased risk of BCC was seen in subjects with increased recreational sunlight exposure in adolescence and childhood (age, 0 to 19 years), although an inverse relationship was seen with lifetime recreation exposure. The relationship with childhood sun exposure was most pronounced among sun-sensitive subjects whose skin tended to burn rather than tan in the sun. CONCLUSIONS: The lack of association between cumulative sun exposure and BCC contradicts conventional wisdom about the cause of this tumor, and the increased risk with sun exposure at age 0 to 19 years suggests that childhood and adolescence may be critical periods for establishing adult risk for BCC.

Adult

Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma.

INTRODUCTION AND DESIGN: Squamous cell carcinoma of the skin (SCC), a common cancer in white populations, is related to sunshine exposure; however, relatively little information is available on how timing and character of exposure affect the relationship. The purpose of this study was to investigate the nature of the relationship of SCC to individual solar UV exposure after control for phenotype and pigmentary factors. All newly diagnosed cases of SCC were in men aged 25 through 79 years, ascertained in the province of Alberta from January 1, 1983, through December 31, 1984, who were approached for participation; 80% completed a standardized etiologic interview that was conducted in their homes by a trained interviewer. Control subjects were chosen at random from the Alberta Health Care Insurance Plan subscribers list, matched only by sex (male) and age (within a 5-year age group). The response rate among controls was 71%. RESULTS: Subjects with pale skin and red hair had an elevated risk of SCC. Subjects whose mother was of southern European ancestry had a reduced risk of SCC. After accounting for pigmentary factors, no association was seen between risk of SCC and cumulative lifetime sun exposure. However, a strong trend toward increasing risk was seen with increasing chronic occupational sun exposure in the 10 years prior to diagnosis. CONCLUSION: The results suggest that recent sun exposure (in the 10 years prior to diagnosis) may be important in accounting for individual risk of SCC.

Adult

Human pharmacokinetic study of immediate-release (codeine phosphate) and sustained-release (codeine Contin) codeine.

The authors compared, in a double-blind, randomized, crossover study in 13 healthy adult volunteers, the single- and multiple-dose pharmacokinetics, relative bioavailability, and side effects of a new oral sustained-release formulation of codeine (SRC) containing 150 mg codeine base, with oral immediate-release codeine phosphate (IRC). Sustained-release codeine was given at a dose of 150 mg every 12 hours for 5 doses; IRC was given at a dose of 60 mg (2 x 30 mg) every 4 hours for the first 3 doses, and 30 mg every 4 hours thereafter for 12 doses. Plasma codeine levels were determined using a sensitive and specific high-performance liquid chromatography method and corrected for dose administered and codeine base equivalent. Mean values for single-dose pharmacokinetic parameters for SRC and IRC, respectively, were: Cmax of 217.8 and 138.8 ng/mL; Tmax of 2.3 and 1.1 hours; AUC0-inf of 1202.3 and 1262.4 ng.mL-1.hour-1; and t1/2el of 2.6 hours for both formulations. Their respective mean steady-state pharmacokinetic parameters were: Cmax of 263.8 and 222.9 ng/mL; Tmax of 3.2 and 1.1 hours; AUC0-12h of 1576.4 and 1379.1 ng.mL-1.hour-1; and t1/2el of 2.8 and 2.3 hours. These results indicate comparable bioavailability between both formulations with SRC providing delayed peak plasma levels. The sustained-release character of SRC can be explained by a delayed absorption, which is not limiting to drug elimination. Sustained-release codeine provides higher plasma codeine levels over a broader time interval and is expected to improve pain management.

Adult

Relationship between variant forms of estrogen receptor RNA and an apoptosis-related RNA, TRPM-2, with survival in patients with breast cancer.

BACKGROUND: Although smaller variant forms of estrogen receptor (ER) messenger RNA (mRNA) have been detected in breast tumors, neither their prevalence nor their prognostic significance have been evaluated. Similarly, TRPM-2 mRNA, the product of a gene induced principally during the onset of apoptosis, is present in mouse and human breast cancer cell lines, but whether it also occurs in primary breast tumors and is related to disease outcome is unknown. METHODS: The relative expression and transcript size of ER mRNA and TRPM-2 mRNA in 126 primary breast tumors were measured by Northern analysis and compared with tumor grade, hormone receptor status, extent of tumor necrosis, and survival. RESULTS: In ER-positive tumors, 64% of the tumors had only the normal 6.5 kb ER mRNA, an additional 9% had the normal plus smaller ER mRNA, and 2% had variant forms. Only 8% of ER-negative tumors had ER mRNA transcripts. There were significant relationships between the occurrence of ER mRNA and low tumor grade, ER-positive receptor status, and better survival. In contrast, TRPM-2 mRNA was found in only 17% of breast tumors, none of which could be grouped with respect to grade, hormone receptor status, or survival. CONCLUSIONS: The presence of smaller variant forms of ER mRNA either alone or in association with the normal ER transcript is not indicative of an unfavorable prognosis, whereas TRPM-2 mRNA occurs in many primary breast tumors, but has no apparent relationship to survival.

Adult

Chromatographic analysis and pharmacokinetics of liposome-encapsulated doxorubicin in non-small-cell lung cancer patients.

A sensitive and specific quantitative assay for total doxorubicin concentrations in plasma containing liposome-encapsulated doxorubicin hydrochloride (TLC D-99) was developed, with solvent extraction and reversed-phase high-performance liquid chromatography (HPLC). Separation of doxorubicin from its metabolites was accomplished with a 15 cm x 3.9 mm i.d., microBondapak phenyl analytical HPLC column. Optimum chromatographic conditions, obtained with a mobile phase gradient from 85 to 50% (v/v) 16 mM ammonium formate buffer in tetrahydrofuran at a flow rate of 2 mL/min, gave a detection limit of 0.3 pmol/injection. Eleven-point standard curves with from 0.00595 to 29.8 microM TLC D-99 and 0.1 microM internal standard in plasma were analyzed on three separate occasions to formally validate this assay. An overall correlation coefficient of 0.9985 was found for the logarithmic transformed data. The pharmacokinetic characteristics of doxorubicin were investigated after administration of TLC D-99 to 12 non-small-cell lung cancer patients as an intravenous infusion at doses of 60 and 75 mg/m2. The data are best described by a three-compartment model with alpha, beta, and gamma elimination half-lives of 0.0721, 2.84, and 25.2 h for the 60-mg/m2 group and 0.103, 2.56, and 14.9 h for the 75-mg/m2 patients. A mean plasma clearance of 9.89 L/h (range: 1.95 to 23.4 L/h) was found for the 60-mg/m2 patients, with that from the 75-mg/m2 group being within these values. Mean area under the plasma concentration versus time curve estimates of 37.1 and 47.9 microM/h were observed for the patients receiving 60 and 75 mg/m2, respectively. The plasma concentration-time course for total doxorubicin following administration of TLC D-99 suggests that the disposition of the liposomal formulation is determined more by the pharmacokinetics of the liposome than the encapsulated drug.

Adult

Calculating the prevalence of cancer.

Incidence, prevalence and mortality are commonly used measures to assess the impact of disease on human populations. Prevalence, although regularly assessed for a number of different diseases, has only had recent use to measure the impact of cancer. The calculation of the prevalence of cancer presents several difficulties since there is no reporting mechanism established to measure the proportion of the community that has the disease. In the absence of such a mechanism, mortality data linked to incidence data from cancer registries have been used. The assumption is made that once diagnosed with cancer an individual remains a prevalent case until death. In this paper we present alternatives to this assumption and use them to produce estimates of cancer prevalence. We illustrate the effect of these assumptions on the calculated prevalence of cancer using data from the British Columbia Cancer Registry.

Algorithms

Cigarette and alcohol use in patients with adenocarcinoma of the gastric cardia or lower esophagus.

The authors studied the cigarette and alcohol use of 243 patients with adenocarcinoma of the cardia or lower esophagus, including 66 with Barrett's metaplasia (esophagocardia group). They compared results of that investigation with the cigarette and alcohol use of 303 patients with squamous carcinoma of the esophagus, a cancer in which an etiologic association is proven, and of 338 patients with stomach cancer not involving the cardia, a cancer in which there is little or no association with cigarettes or alcohol. Controlled for other variables, patients with squamous cancer used more cigarettes and alcohol than the other two groups. There was no significant difference in cigarette or alcohol use between patients with esophagocardia and stomach cancer or between those in the esophagocardia group with or without Barrett's metaplasia. Because cigarette and alcohol use was not greater in patients with esophagocardia than in those with stomach cancer, the authors do not think that such factors explain the increasing incidence of adenocarcinoma of the cardia or lower esophagus.

Adenocarcinoma

Reliability of dietary information from surrogate respondents.

A self-administered food frequency questionnaire was included as part of a case-control study of breast cancer in 1980-82. In 1986-87, a second food frequency questionnaire was sent to surviving cases and husbands of deceased cases; 30 spouses (86% response rate) and 263 surviving cases (88% response rate) returned questionnaires. The dietary questions concerned consumption of specific food items by the case before diagnosis of breast cancer. Missing values were less common in the second questionnaire; there was no significant difference in missing values between surviving cases and spouses of deceased cases. Kappa statistics comparing responses in the first and second questionnaires were significantly lower for spouses of deceased cases than for surviving cases. Reported level of confidence by the husbands regarding knowledge about their wives' eating habits did not influence the kappa statistics or the frequencies of missing values. The lack of good agreement has important implications for the use of proxy interviews from husbands in retrospective dietary studies.

Breast Neoplasms