The CancerWeb Report, What's New In Cancer: July, 1996
Breast Cancer

• Does an intensive program of screening, counselling, surveillance and preventive intervention increase women's anxiety about breast cancer? - Although much effort is being used to extend the coverage of screening programs for breast cancer, especially to currently under-screened populations, such as minorities and the economically-disadvantaged, and to carry out long term surveillance and prevention programs, concerns have been expressed that such efforts may increase anxiety levels among women. A study from several medical institutions in London, England, found that women at risk through family history of the disease and attending specialist clinics as part of the Tamoxifen Prevention Trial, were no more likely to be anxious than those recruited under the general National Breast Screening Programme who had no family history of breast cancer. Most anxious were those in the screening program who did have such a family history. (Thirlaway, Br J Cancer 73:1422, 1996)

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• A more convenient way to identify BRCA1 mutations that underlie familial breast cancer? - Although mutations in the cancer susceptibility gene BRCA1 account for a half of family-related breast cancers, there are so many different types of mutations that identifying them is a slow laborious business. An article from Finnish researchers in the July 1, 1996 issue of Cancer Research describes a simple histochemical method that permits the carriers of these mutations to be identified with a specificity and sensitivity of more than 95% . The technique involves testing for the amount of messenger RNA transcribed by the gene, which is reduced compared with normal tissue in the carriers of mutant BRCA1. Sporadic breast tumors which have no family association, on the other hand, showed a much higher level of the BRCA1 RNA. (Kainu, Cancer Res 56:2912, 1996)

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• Progesterone levels, the menstrual cycle, and prognosis in operable breast cancer - There have been a number of reports indicating that women who undergo surgery for breast cancer do better if their operations occur during the luteal phase of their menstrual cycle. However, variability in findings might reflect uncertainty regrading exact menstrual status or existence of anovulatory cycles. The luteal phase (following ovulation and preceding menstrual bleeding) is the point at which progesterone levels are raised. A report from Guy's, St. Mary's and St. Thomas' Hospitals in London, England, showed a clear relationship to progesterone levels. Among 239 premenopausal women with breast cancer, those with progesterone levels above 4 ng/mL had a significantly better survival after ongoing modified radical mastectomy or conservative surgery than those with progesterone levels below this value (relative risk 1.76). The difference was especially marked for those women with positive nodes (relative risk for low progesterone 2.22). Progesterone level is a more reliable measure of menstrual status and of prognosis than estrogen levels which are more variable. (Mohr, Br J Cancer 73:1552, 1996)

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• Estrogen levels in the urine and breast cancer risk - Doctors in Australia, Britain and the US looked at estrogen levels in 24- hour urine specimens from 1,000 women in the island of Guernsey between 1977 and 1984. There were 69 reported breast cancer cases up to December 1994. In those women who were premenopausal at the time of urine collection, urinary estrogen was significantly lower (risk was about halved) in breast cancer cases than in controls, whereas for those who were post- menopausal, the cases had almost doubled levels of estrogen. (Br J Cancer 73:1613, 1996)

  Editor's Comment: - The post-menopausal findings are in accord with many other studies suggesting high estrogen levels as a risk factor for breast cancer, but the premenopausal results are unexpected. The authors consider there is less of a mid-cycle surge in estrogen in their breast cancer cases, and review data from 14 studies in 6 of which luteal estrogen was lowered. The present study also suffers from some potential confounding from smoking prevalence, since it was originally set up as two studies, with one looking at the effect of smoking.

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• Microvessel numbers as a predictor of tamoxifen efficacy - Angiogenesis, the development of new blood supply through the growth of vessels and microvessels, has been discussed before in several issues of CancerWeb Report as a critical factor in whether a tumor grows, remains static, or disappears. A study was carried out in Vicenza in Italy and Oxford in the UK, on 178 patients with lymph-node-positive breast cancer treated with adjuvant tamoxifen. The results showed that when the count of microvessels within tumor specimens was expressed in a common standard (the Chalkley score), it constituted a strong predictor of both relapse-free and overall survival, along with estrogen- receptor status, number of positive nodes, histology, and tumor size. Patients with highly angiogenic tumors showed poor response when treated with tamoxifen, irrespective of their estrogen-receptor status, indicating that therapy aimed at preventing angiogenesis would likely be profitable. (Gasparini, Clin Cancer Res 2:1191, 1996)

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• Diet and breast cancer, a clearer view of the role of fiber? - Reports on the relation of fat and fiber in the diet to the development of human breast cancer have been confusing, although animal studies have been somewhat more consistent in suggesting that the two dietary components have opposing effects. Much of the problem in both human and animal studies may result from the complexity of diet, and the likelihood that various interactions between dietary components may either obscure the effects of changing just one component, or may be responsible for effects that are observed. A preclinical study of rats on a high-fat diet treated with the carcinogen, N-methylnitrosourea, to induce breast cancer, which was performed at the American Health Foundation in Valhalla, New York, clearly shows this interaction in operation. The rats were fed wheat bran, an insoluble fiber, and psyllium, a soluble fiber, alone and at different ratios in the diet. As the ratio of psyllium to bran increased, there were fewer tumors produced by the carcinogen. Wheat bran alone was least effective. The best results in terms of anticarcinogenic effect were achieved with a 4%-4% mixture of the two fibers in the diet. Interestingly, this coincides with the findings of epidemiology studies of some types of human cancer which suggested that mixed types of dietary fibers, rather than excess supplementation with one, offered the best protection. (Cohen, J Natl Cancer Inst 88:899, 1996)