F. de Waard

EVALUATION OF SCREENING FOR BREAST CANCER IN A NON-RANDOMISED STUDY (THE DOM PROJECT) BY MEANS OF A CASE-CONTROL STUDY

In 1974 a non-randomised study of the effect of mass screening by physical examination and xeromammography on mortality from breast cancer was started. Of the 20 555 eligible women in the city of Utrecht born between 1911 and 1925 (aged 50-64 at the start of the study), 14 796 attended for screening. Four rounds of screening were carried out. The relative risk of dying from breast cancer among women ever screened compared with women never screened was 0.30 (95% confidence interval 0.13-0.70).

A prospective study in general practice on breast-cancer risk in postmenopausal women

A prospective study of breast‐cancer risk in postmenopausal women has been carried out with the cooperation of 50 general practitioners. A total of 7,259 women have been followed up for an average period of 5.4 years (maximum 8.1 years); 70 cases of breast cancer occurred. The main finding was a pronounced effect of body weight and height on breast cancer risk; the significance of this in explaining international differences in incidence is stressed. High parity counteracted the risk of high weight regarding breastcancer. Single women did not show a high risk because of their relatively low body weight. The relative risk in women with a previous mastectomy was five‐fold.

Breast cancer incidence according to weight and height in two cities of the Netherlands and in Aichi prefecture, Japan

A study was made in the cities of Rotterdam and The Hague, the Netherlands, and in Aichi prefecture, Japan, to assess the effect of weight and height (and their combinations) on the age‐specific incidence of breast cancer. It is based on a comparison between 1006 cases of breast cancer and 4201 women from the general population, 35–69 years old. The results suggest that about one‐half of the differences in incidence between the regions in Holland and Japan can be attributed to differences in body weight and height. In breast cancer patients in Rotterdam and The Hague those with metastases in axillary nodes were significantly heavier but not taller than those without nodal involvement. A hormonal factor related to body weight and/or height might be responsible for the increased incidence and the more rapid course of breast cancer in women with a large body mass.

Risk of strut fracture of Björk-Shiley valves

The incidence of and factors that predispose to outlet strut fracture of Björk-Shiley heart valves are still not known. To obtain such information a retrospective cohort study was conducted on all 2303 patients in the Netherlands with a 60 degrees convexo-concave (60 degrees CC) or a 70 degrees convexo-concave (70 degrees CC) Björk-Shiley heart valve. Patients have been followed-up for a mean of 6.6 years (range 1-4271 days). 42 cases of mechanical failure due to outlet strut fracture have been recorded-6 of the 7 patients with fracture of the aortic valve died, as did 18 of the 35 patients with fracture of the mitral valve. Multivariate analysis identified wide opening angle (70 degrees), large valve size (greater than or equal to 29 mm diameter), and young age (less than 50 years) as risk factors for outlet strut fracture. For large 70 degrees CC mitral valves the cumulative risk of outlet strut fracture after 8 years was 17.4% (95% CI 9.1-31.6). Unlike previous findings, this excessive risk applied to late as well as to early batches of valves. In patients with a large 60 degrees CC mitral valve the cumulative risk after 8 years was 4.2% (95% CI 2.7-6.5). The incidence rate of outlet strut fracture in 60 degrees CC and 70 degrees CC valves (aortic and mitral) was constant over time. Overall survival since implantation was better for patients with 60 degrees CC prostheses than for those with 70 degrees CC prostheses; the adjusted hazard ratio for mortality for patients receiving a 70 degrees CC prosthesis was 1.5 (95% CI 1.1-2.0). Together with the low (24%) necropsy rate, this ratio suggests that the reported incidence of strut fracture for the 70 degrees CC valves is an underestimate. The data indicate that prophylactic replacement of 60 degrees CC and 70 degrees CC valves is advisable for selected groups of patients. Since the case-fatality rate is 50% for emergency replacement of faulty valves, patients suspected of Björk-Shiley heart-valve failure should be referred without delay to a cardiothoracic centre.

A feasibility study on weight reduction in obese postmenopausal breast cancer patients.

An attempt was made to undertake a randomized clinical trial of weight reduction in obese postmenopausal breast cancer patients as an adjuvant to primary surgical and radiotherapeutic treatment. The rationale was to improve prognosis which has been shown to be worse in the obese (probably because of its effect on extra-ovarian oestrogen production). Difficulties in recruiting a sufficient number of patients and the introduction of tamoxifen as anti-oestrogenic adjuvant therapy led to the decision to modify the aim of the study by limiting it to a feasibility study in 102 patients. In three hospitals in The Netherlands and in two hospitals in Poznan, Poland these patients were randomized in intervention and control groups according to a 3:2 ratio. Weight reduction in the intervention group was achieved by dietary means, ie caloric restriction was adapted to personal needs and behaviour of the patients. After 1 year a median weight loss of 6 kg was reached in both countries. In the Netherlands further follow-up indicated that this result could be maintained for another 2 years.

The epidemiology of breast cancer; Review and prospects

In the epidemiology of a disease, which is multifactorial to such an extent as we believe breast cancer to be, attention should be paid even to “weak” factors and an attempt should be made to assign a place to them in an aetiologic system which is biologically sound. Medical knowledge will help us in doing this, and the exercises in “metabolic epidemiology” will be as useful as statistical manipulations and computer programming.

Age at menarche and breast cancer risk in nulliparous women

SummaryEarly age at menarche is a known risk factor for breast cancer, some inconsistency in the literature not withstanding. Relative risks for an early menarcheal onset as compared to a late onset vary from 1.0 to 1.9.To avoid (residual) confounding by parity-related factors a case-control study was conducted among nulliparous women. 135 cases and 540 controls were selected from two population-based screening projects for breast cancer in The Netherlands. Four controls were matched to each case for year of birth, for screening-centre, and for number of screening examinations.Women with a menarcheal age of 10 or 11 years showed a 2.2 times (95% confidence interval: 1.2-4.0) higher risk for breast cancer compared to women who had their first menstrual period at 12 years of age or older.

Plasma oestrone, oestradiol and androstenedione levels in post-menopausal women: relation to body weight and height.

To study the relation between body weight and height and the plasma sex-hormone levels wer measured the plasma levels of oestrone (E1), oestradiol (E2) and androstenedione (A) in a group of healthy post-menopausal women with a wide range of body weight. The sex hormones were measured by radioimmunoassay with highly specific antisera after purification of the plasma extract by column chromatography. Our findings show that there is significant positive correlation between the E1 level and body weight as well as A level and, to a lesser extent, between the E1 level and Quetelet index. For E2 there is no correlation with these parameters. There is also a very slight correlation between A level, body weight and Quetelet index. Calculation of the partial correlation coefficient shows that E1 correlates to the same degree with body weight and A level, whereas the A level does not correlate with body weight at a fixed value for the E1 level. We conclude that variation in the E1 level depends to the same degree on the variation in body weight as well as the variation in A level.

Urinary cotinine and lung cancer risk in a female cohort.

In a cohort of women aged 40-64 at entry, 12 h urine samples were obtained at the beginning of a follow-up period of up to 15 years in which incident cases of lung cancer were registered as well as deaths from lung cancer. In this cohort a nested case-control study (n = 397) was carried out by measuring urinary cotinine. The method for quantitation of cotinine was sensitive enough to study lung cancer risk not only in active smokers but also in passive smokers. The results seem to indicate that cotinine estimations in single 12 h samples of urine are enough to predict lung cancer risk. Relative risk rose with increasing levels of nicotine intake already in the range associated with passive smoking. The smoking-related risk of adenocarcinoma was much less than that of other lung carcinomas.

A prospective study on obesity and subcutaneous fat patterning in relation to breast cancer in post-menopausal women participating in the DOM project

The associations of body fat and body fat distribution with breast cancer risk were examined in a prospective study in 9,746 post-menopausal women with a natural menopause, aged 49-66 at intake, participating in a breast cancer screening project (the DOM project in Utrecht). During a follow-up period of 15 years (mean follow-up time 12.5 years) 260 women developed breast cancer. Fat distribution, assessed by contrasting groups of subcapsular and triceps skinfold thickness, was found to be unrelated to breast cancer incidence. No significant relationship between body fat, measured either by weight, Quetelets index, triceps skinfold or subscapular skinfold, and breast cancer risk was found when analysed in quartiles. However, women in the upper decile compared with the lower decile of the distribution of Quetelets index were found to have a 1.9 times (95% CI 1.1-3.3) higher risk for breast cancer. These results seemed to be in contrast with the significant positive association between fatness, analysed in quartiles, and breast cancer observed in a cross-sectional study, based on mammographic screening, carried out previously in the same population. Although the differences between the present, prospective, study and our cross-sectional study may be due to chance it may be that there are differences between characteristics of breast cancer detected at screening and subsequently, which influence the associations between measures of fatness and risk of breast cancer.