Multiple chemical sensitivity: discriminant validity of case definitions.

In this study, the authors used the University of Toronto's Health Survey self-administered questionnaire to determine discriminant validity of multiple chemical sensitivity definitions. The authors distributed a total of 4,126 questionnaires to adults who attended general, allergy, occupational, and environmental health practices. The authors then matched responses to features selected from existing case definitions posited by Thomson et al.; the National Research Council; Cullen; Ashford and Miller; Randolph; Nethercott et al.; and the 1999 Consensus (references 4-7, 2, 9, and 10, respectively, herein). The overall response rate was 61.7%. The prevalence of reported symptoms was lowest in general practices, was intermediate in occupational health and allergy practices, and was highest in environmental health practices. Features from the definitions presented by Nethercott et al. and the 1999 Consensus (references 9 and 10, respectively, herein) correctly identified more than 80% of environmental health practice patients and more than 70% of general practice patients. Combinations of 4 symptoms (i.e., having a stronger sense of smell than others, feeling dull/groggy, feeling "spacey," and having difficulty concentrating) also discriminated successfully. In summary, features from 2 of 7 case definitions assessed by the University of Toronto Health Survey achieved good discrimination and identified patients with an increased likelihood of multiple chemical sensitivity.

Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years.

BACKGROUND: Screening for breast cancer with mammography in women aged 50 years or more has been shown to reduce mortality from breast cancer. However, the extent to which mammography contributes to the reduction of mortality in women who also undergo physical examination of the breasts is not known. This study was designed to compare breast cancer mortality following annual screening consisting of two-view mammography and physical examination of the breasts with mortality following annual screening by physical examination only. Breast self-examination was taught to all participants. METHODS: This trial randomly and individually assigned 39 405 women aged 50-59 years, recruited from January 1980 through March 1985, to one of the study arms. The women were followed by record linkage with the Canadian National Cancer Registry and National Mortality Database to December 31, 1993, and by active follow-up of breast cancer patients to June 30, 1996. RESULTS: Randomization achieved virtually equal distribution of demographic and breast cancer risk variables. At the first annual screen, 21% of the cancers found by mammography alone (in the mammography plus physical examination group) were 20 mm or more in size compared with 46% of those found by physical examination in the mammography plus physical examination group and 56% in the physical examination-only group. The corresponding percentages for screens 2-5 were 10%, 42%, and 50%, respectively. Screening detected 267 invasive breast cancers in the mammography plus physical examination group compared with 148 in the physical examination-only group. By December 31, 1993, 622 invasive and 71 in situ breast carcinomas were ascertained in the mammography plus physical examination group, and 610 and 16 were ascertained in the physical examination-only group. At 13-year follow-up, with 107 and 105 deaths from breast cancer in the respective groups, the cumulative rate ratio was 1.02 (95% confidence interval = 0.78-1.33). CONCLUSION: In women aged 50-59 years, the addition of annual mammography screening to physical examination has no impact on breast cancer mortality.

Reproducibility of the University of Toronto self-administered questionnaire used to assess environmental sensitivity.

Environmental sensitivity patients report symptoms provoked by low-level exposure to a wide range of substances. Features of published case definitions include nature of onset, chronicity, symptom provocation by multiple substances, symptom provocation by an escalating number of exposures, involvement of multiple body systems including the nervous system, provocation by unrelated substances, and addictive behaviors. This study assessed the reproducibility of a Canadian self-administered questionnaire, the University of Toronto Health Survey, designed to determine the prevalence of the features described in these case definitions. A total of 191 eligible respondents aged 16-70 years who attended several types of medical practices in 1994 were invited to complete a second questionnaire 5-7 months after the first; 134 (70.2%) complied. Total agreement on whether patients satisfied each of seven case definitions ranged from 80% to 90%. After adjustment for chance, major agreement was observed for three of the seven case definitions (kappa = 0.69, 0.68, and 0.78). The survey achieved good reproducibility regarding self-report of symptoms described in published case definitions of environmental sensitivity.

Breast milk contamination and silicone implants: preliminary results using silicon as a proxy measurement for silicone.

In response to concerns about contamination of human breast milk from silicone gel-filled breast implants, and because silicon levels are assumed to be a proxy measurement for silicone, we compared silicon levels in milk from lactating women with and without implants. Two other sources of infant nutrition, cow's milk and infant formulas, were also analyzed for silicon. The survey took place at the Breast-feeding Clinic at Women's College Hospital in Toronto. A convenience sample of lactating women, 15 with bilateral silicone gel-filled implants and 34 with no implants, was selected. Women with foam-covered or saline implants or with medically related silicone exposures were ineligible. Collection of samples was scrupulously controlled to avoid contamination. Samples were prepared in a class 100 "ultraclean" laboratory and analyzed using graphite furnace atomic absorption spectrophotometry. Silicon levels were analyzed in breast milk, whole blood, cow's milk, and 26 brands of infant formulas. Comparing implanted women to controls, mean silicon levels were not significantly different in breast milk (55.45 +/- 35 and 51.05 +/- 31 ng/ml, respectively) or in blood (79.29 +/- 87 and 103.76 +/- 112 ng/ml, respectively). Mean silicon level measured in store-bought cow's milk was 708.94 ng/ml, and that for 26 brands of commercially available infant formula was 4402.5 ng/ml (ng/ml = parts per billion). We concluded that lactating women with silicone implants are similar to control women with respect to levels of silicon in their breast milk and blood. Silicon levels are 10 times higher in cow's milk and even higher in infant formulas.

Effect of breast self-examination techniques on the risk of death from breast cancer.

OBJECTIVE: To measure the effect of breast self-examination (BSE) technique and frequency on the risk of death from breast cancer. DESIGN: Case-control study nested within the Canadian National Breast Screening Study (NBSS). SETTING: The Canadian NBSS, a multicentre randomized controlled trial of screening for breast cancer in Canadian women. SUBJECTS: The case subjects were 163 women who had died from breast cancer and 57 women with distant metastases. Ten control subjects matched by 5-year age group, screening centre, year of enrolment and random allocation group were randomly selected for each case subject. EXPOSURE MEASURES: Self-reported BSE frequency before enrolment in the NBSS, annual self-reports of BSE frequency during the program and annual objective assessments of BSE technique. OUTCOME MEASURES: Odds ratios (ORs) associated with BSE practice were estimated by conditional multiple logistic regression modelling, which permitted control of covariates. RESULTS: Relative to women who, when assessed 2 years before diagnosis, examined their breasts visually, used their finger pads for palpation and examined with their 3 middle fingers, the OR for death from breast cancer or distant metastatic disease for women who omitted 1, 2 or 3 of these components was 2.20 (95% confidence interval [CI] 1.30 to 3.71, p = 0.003). The OR for women who omitted 1 of the 3 components was 1.82 (95% CI 1.00 to 3.29, p = 0.05), for those who omitted 2 of the 3 components, 2.84 (95% CI 1.44 to 5.59, p = 0.003), and for those who omitted all 3 components, 2.95 (95% CI 1.19 to 7.30, p = 0.02). The results remained unchanged after adjustment for potential confounders. CONCLUSION: The results, obtained with the use of prospectively collected data, suggest that the performance of specific BSE components may reduce the risk of death from breast cancer.

Impact of menstrual phase on false-negative mammograms in the Canadian National Breast Screening Study.

BACKGROUND: The efficacy of breast carcinoma screening should be enhanced if false-negative mammography were reduced. Prospectively collected data from the Canadian National Breast Screening Study were used to examine whether menstrual cycle phase was associated with false-negative outcomes for mammographic screening. METHODS: Of 8887 women ages 40-44 years at the onset of screening, randomized to receive annual mammography and clinical breast examination, reporting menstruation no more than 28 days prior to their screening examination, and with a valid radiologic report, 1898 had never used oral contraceptives or replacement estrogen with or without progesterone. The remainder were past (6573) and current (416) estrogen users. Similar selection criteria were applied at subsequent screens. The distribution of false-negative and false-positive mammography in relation to true-negative and true-positive mammography was examined with respect to the follicular (Days 1 to 14) and luteal (Days 15-28) menstrual phases. RESULTS: Comparing luteal with follicular mammograms in 6989 patients who ever used estrogen, the unadjusted odds ratio (2-sided P-values) for false-negatives versus true-negatives was 2.16 (0.05) and the adjusted odds ratio was 1.47 (0.05). In 1898 never-users, parallel odds ratios for luteal false-negatives were 0.55 (1.0) and 0.74 (1.0), respectively. CONCLUSIONS: These results suggest that menstruating women who have used hormones may have an increased risk of false-negative results for screening mammograms performed in the luteal phase of the menstrual cycle. An increased risk of false-negative mammography might adversely affect screening efficacy. The impact of menstrual phase on mammographic interpretation, especially for women who ever used hormones, requires further investigation.

The Canadian National Breast Screening Study: update on breast cancer mortality.

The Canadian National Breast Screening Study (CNBSS), conducted on women age 40-49, was designed to evaluate the efficacy of combined annual mammography and physical examination of the breasts in reducing breast cancer mortality in comparison to usual care (UC) controls. From January 1980 through March 1985, 25,214 women were individually randomized to the mammography/physical exam (MP) arm and 25,216 to the UC. The integrity of the randomization has been reviewed and confirmed to be unbiased. During an average, follow-up of 10.5 years from entry (range: 8.75-13 years), 82 women died from breast cancer in the MP arm and 72 in the UC, for a rate ratio of 1.14 (95% confidence interval: 0.83-1.56). All-cause mortality was almost identical comparing the two groups; the nonsignificant excess of breast cancer deaths in the MP arm was balanced by an excess of other cancer deaths in the UC arm.

Mammography versus clinical examination of the breasts.

Using published data from screening trials, this article compares two-modality (mammography and clinical examination) and single-modality (clinical examination alone) screening by evaluating cancer detection rates, program sensitivities, mode of cancer detection in two-modality screening, nodal status at time of detection, survival 10 years post-diagnosis, and breast cancer mortality 10 years after entry. Consistently, two-modality screening achieved higher cancer detection rates and program sensitivity estimates than either modality alone; mammography alone achieved higher rates than clinical examination alone; interval cancer detection rates between screening examinations were higher following clinical examination alone than mammography alone; single-modality screening with mammography failed to detect breast cancers identified by clinical examination alone; the sensitivity of mammography was lower in younger than older women, while the reverse was true for clinical examination; and mammography identified a higher proportion of node-negative breast cancer than clinical examination. We conclude that combining clinical breast examination with mammography is desirable for women age 40-49 because mammography is less sensitive in younger than older women. Careful training and monitoring are, however, as essential with clinical examiners as with mammographers.

The Canadian National Breast Screening Study. Why? What next? And so what?

Why the National Breast Screening Study (NBSS)? In 1979, after reviewing the Breast Cancer Detection Demonstration Projects (BCDDP), the Beahrs Working Group made 11 recommendations. The NBSS protocol reflected a number of these recommendations, particularly the evaluation of screening women age 40-49 and the still unanswered question of the incremental benefit of mammography versus physical examination of the breasts among women age 50-59. Three years after publication of NBSS's 7-year results and in light of other published evidence from screening trials (as opposed to observational studies), it is reasonable to recommend screening with mammography and physical examination every 2 years for women age 50-59. In contrast, it is not reasonable to offer screening mammography to women age 40-49 other than in the context of a controlled trial, an opportunity currently available in the United Kingdom. The Beahrs recommendation, that "physical examinations should be continued in the Breast Cancer Detection Demonstration Projects as a routine screening modality for all ages," remains justifiable as long as so many women age 40-49 are having mammograms performed, given the relatively poor sensitivity of mammography in this age group. Criticism of the NBSS, mainly by radiologists, will continue until the NBSS yields results that support its critics' belief in the efficacy of screening. To date, responses to critics of the NBSS have focused on correcting misinformation and clarifying NBSS procedures. Useful critical commentary should await the results of a 10-year NBSS follow-up and the U.S. National Cancer Institute-sponsored meta-analysis of screening trials. Rigorous critical scrutiny should be directed at all trials.