A prospective cohort study of postmenopausal hormone use and risk of breast cancer in US women.

The association between history of postmenopausal hormone use as of 1976 and breast cancer incidence during 1976-1980 was examined prospectively among 33,335 married, postmenopausal registered nurses aged 30-55 years at entry. Half the women reported postmenopausal hormone use, and one fourth had taken these drugs for over five years. During 1976-1980, 221 new cases of breast cancer were identified. The relative risk (RR) for those who had used postmenopausal hormones when compared with women who had never used them was 1.1 (95% confidence limits (CL) 0.8, 1.4); for current and past users, the relative risks were 1.0 (95% CL 0.7, 1.4) and 1.3 (95% CL 0.9, 1.8), respectively. These ratios were not substantially modified by whether or not a woman's ovaries had been removed or by other known breast cancer risk factors. No increase in breast cancer risk was apparent among women who had used postmenopausal hormones for less than five years (RR = 1.0, 95% CL 0.5, 1.6). An apparent effect among the subgroup of women who had used them for five to nine years (RR = 1.5, 95% CL 1.0, 2.2) was not present among the few women with longer-term use (RR = 0.9, 95% CL 0.4, 1.6). These findings are moderately reassuring, but since there are as yet few women in this cohort with long-term durations of use and, particularly, with long intervals since first use, continued follow-up of this and other cohorts will be required before firm conclusions can be drawn, especially among specific subgroups.

Oral contraceptives and breast cancer. A prospective cohort study.

In 1976, information on oral contraceptive (OC) use as well as numerous risk factors for breast cancer was provided by 121,964 married female registered nurses aged 30 to 55 years. Ninety-two percent of women in the cohort completed follow-up questionnaires, and vital records were systematically searched to ascertain deaths among nonrespondents. After four years of follow-up, 592 incident cases of breast cancer were identified. Compared with never users, the age-adjusted relative risk (RR) of breast cancer, regardless of menopausal status, among all women who had ever used OCs was 1.0. Among premenopausal women compared with those who had never used OCs, the RR of breast cancer was 1.5 for current use of OCs in 1976 and 1.0 for past use. Among postmenopausal women, the RR for past use of OCs was 1.0. These estimates were essentially unaltered after controlling for other known risk factors for breast cancer in multiple logistic regression analysis. Furthermore, there was no modification of these effects by family history of breast cancer, age at first use, timing of the first birth, or other breast cancer risk factors. Data on past use of OCs provide substantial reassuring evidence that there is no large excess risk of breast cancer within a few years of cessation of pill use. The observed moderate elevation of breast cancer risk with current use was of borderline statistical significance. However, the observation was based on 29 cases and may reflect the effect of sampling variability, as most other studies have not observed a relationship between current use of OCs and breast cancer in women of this age.

Parity and breast cancer risk: possible effect on age at diagnosis.

We examined the effect of parity on breast cancer risk on the basis of information from 107,146 married female nurses followed prospectively between 1976-1980. For everparous women, a significant protective effect against breast cancer was observed with increasing parity (chi 12 for trend = 14.2, p less than 0.001). Adjustment for age at first birth and other potential confounders by multiple logistic regression did not materially affect this trend. After controlling for these risk factors, the overall relative risk of breast cancer for women with four or more pregnancies lasting 6 months or longer was 0.68 (95% confidence limits 0.51-0.90) compared with women with only one pregnancy. When nulliparous and everparous women were compared, an interaction of age and everparous status in 1976 was observed. The logistic regression coefficient for the interaction was 0.3419 (95% confidence limits 0.0374-0.6464). Specifically, for women of parity 2 relative to nulliparous, the relative risk of breast cancer and the 95% confidence intervals were 1.85 (1.09, 3.14), 1.32 (0.92, 1.89), and 0.93 (0.62, 1.41) for 30-39, 40-49 and 50-55-year-old women, respectively. This points to the need of presenting age-specific, rather than age-adjusted, relative risks in future studies of breast cancer and parity.

Relative weight and risk of breast cancer among premenopausal women.

Although higher relative weight is generally considered to increase the risk of breast cancer, several case-control studies have suggested that the reverse may be true among premenopausal women. The association between Quetelet's index (a measure of relative weight calculated as weight/height) and the subsequent incidence of breast cancer was therefore examined during four years of follow-up among a cohort of 121,964 US women who were 30-55 years of age in 1976. In contrast to women who had experienced natural menopause or bilateral oophorectomy, the incidence of breast cancer among premenopausal women decreased with higher levels of relative weight. Age-adjusted relative risks for increasing quintiles of Quetelet's index were 1.00, 0.90, 0.90, 0.73, and 0.66 (Mantel extension test for trend = -2.82, p = 0.005). This inverse association was not explained by known risk factors for breast cancer and was somewhat stronger when Quetelet's index was computed using reported weight at age 18 years. The excess incidence of breast cancer among lean premenopausal women, however, was limited to tumors that were less than 2.0 cm in diameter, were not associated with metastases to lymph nodes, and were well-differentiated. These findings suggest that the apparent excess risk of breast cancer among lean premenopausal women may result at least in part from easier, and thus earlier, diagnosis of less aggressive tumors.

Increased green and yellow vegetable intake and lowered cancer deaths in an elderly population.

In a prospective cohort study of 1271 Massachusetts residents 66 years of age or older, we examined the association between consumption of carotene-containing vegetables and subsequent five year mortality. Dietary information was obtained by food frequency questionnaire in 1976. The relative risk of cancer mortality was examined within quintiles of green and yellow vegetable score (calculated from intake of carrots or squash, tomatoes, salads or leafy vegetables, dried fruits, fresh strawberries or fresh melon, and broccoli or brussel sprouts). After controlling for age and smoking behavior, those in the highest quintile of intake of these carotene-containing vegetables had a risk of cancer mortality which was 0.3 (95% confidence limits 0.10-0.96) that of those in the lowest quintile. The trend of decreased cancer risk with increasing intake of carotene containing vegetables was significant (p = .026). This relationship is consistent with the hypothesis that carotene may act as an inhibitor of carcinogenesis.

Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis.

Although thrombolysis with streptokinase has been compared with heparin anticoagulation for treating acute proximal deep venous thrombosis in several randomized trials, no individual study has had a sample of sufficient size to determine with adequate power both efficacy and safety. Therefore, results were pooled from six randomized studies in which phlebography was used to confirm the diagnosis and to assess therapy. Thrombolysis was achieved 3.7 times more often among patients treated with streptokinase than among patients treated with heparin (95 percent confidence limits 2.5, 5.7; p less than 0.0001). Only three studies allowed comparison of these drugs for major bleeding complications, which were 2.9 times greater with streptokinase than with heparin (95 percent confidence limits 1.1, 8.1; p = 0.04). Thus, in aggregate, streptokinase-treated patients achieved thrombolysis but also seemed to experience major bleeding complications more frequently than those assigned at random to receive heparin. Future trials of sufficient sample size should be undertaken to evaluate efficacy and safety. Such trials, which should include newer fibrinolytic agents, are necessary to determine optimal therapy for acute proximal deep venous thrombosis.

Interruption of the inferior vena cava by clip or filter.

Interruption of the inferior vena cava is usually performed with either external clipping or transvenous filter placement. For patients unable to tolerate general anesthesia and laparotomy, the advantages of transvenous filters rather than clips are obvious. However, for some patients, the use of either clips or filters is possible. In general, retrospective observational studies of inferior vena caval interruption have not adequately accounted for baseline patient characteristics such as age, presence of cancer, and history of prior venous thromboembolism. These confounding factors can independently affect subsequent rates of both recurrent embolism and overall mortality. A comparative, controlled, prospective evaluation of inferior vena caval clipping versus transvenous filter placement among patients who are appropriate candidates for either procedure has not been undertaken. It is suggested that, among patients with good long-term prognoses, a randomized controlled trial would be necessary to help determine whether clipping or transvenous filter placement is more efficacious.

A case-control study of oral contraceptive use and breast cancer.

Among 989 cases of breast cancer and 9,890 controls selected from a cohort of married, female registered nurses aged 30-55 years, the relative risk (RR) of breast cancer for women who had ever used oral contraceptives (OC) compared with those who had never used them was 1.0, with 95% confidence limits 0.9-1.2. Among OC users, there was no consistent pattern of excess risk with increasing duration; in fact, the few women who had used OC longest (greater than 10 yr) had a slightly lower risk than never-users. Moreover, there was no association between OC use and breast cancer among women with a positive history of breast cancer in the mother or sister or with OC use before their first pregnancy. The only subgroup of women among whom any adverse effect was apparent was current OC users aged 50-55 years (two onsets expected vs. seven observed). This finding is consistent with earlier reports of an increased risk of breast cancer among older OC users; however, it is also likely to reflect, at least to some extent, the play of chance, since at ages 45-49 and in each younger age group fewer cases than expected were observed among current OC users.