The CancerWeb Report, What's New In Cancer: February, 1997
Breast Cancer

• The risk of being overweight for developing breast cancer - Although there is considerable evidence that being overweight or obese increases the risk for breast cancer, no studies have looked at the time line. Does the risk stay constant with time, decrease with age, or increase with duration of time during which the overweight condition prevails? Using the body mass index (Quetelet's index relating weight to body surface area) as a criterion of excess weight, researchers at several Italian Universities reported in the February, 1997 issue of the British Journal of Cancer that the risk rose from an 18% excess in the women aged 50-59, to 59% in those aged over 70. These scientists concluded that it is important to control weight gain in elderly women, since nearly 20% of all post-menopausal breast cancer, rising to 27% in those over 70, is attributable to overweight and obesity. (La Vecchia, Br J Cancer 75:441, 1997)

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• Tobacco and breast cancer: is it all in the genes? - Although many of the components of tobacco smoke are carcinogenic in animals, there have not been any consistent findings implicating smoking as a factor in human breast cancer. Among the most potent carcinogens in tobacco smoke are nitrosamines and many of these need to be metabolized before they are active. In work published in the November, 1996 issue of Molecular Carcinogenesis, researchers at the National Cancer Institute in Bethesda, MD, and the State University of New York at Buffalo, tested DNA extracted from the blood of 219 pre- and 387 postmenopausal white women. This DNA was amplified by the PCR technique to obtain enough material to determine which of the two genes C or D for the enzyme (called cytochrome P4502E1) that metabolizes nitrosamines each woman had. The C-type is less common, about 7% had either one or both gene copies in the C-form, and there was no overall connection with breast cancer. When the women were further categorized according to their smoking habits, it was found that those who smoked and had one or two copies of the C-form of the enzyme had an 11-fold adjusted increased risk for breast cancer. (Shields, Mol Carcinogen 17:144, 1996)

  Editor's Comment: Unfortunately the numbers of women having the C-form of the gene was small; a larger study would be needed to be sure of the actual increase in risk. The implication goes beyond smoking, however, since nitrosamines are very common substances, and the greatest human intake may be by way of the diet. The authors of the study were well aware of its limitations, in terms both of statistics and racial composition of the study group.

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• A new form of Vitamin D more suitable for cancer prevention? - The active form of Vitamin D, 1 alpha 25-dihydroxyvitamin D3, appears to have a protective effect against development of breast cancer, but it is quite toxic at the doses needed for activity. Researchers at the University of Illinois in Chicago reported in the February 5, 1997 issue of the Journal of the National Cancer Institute that a newly synthesized form of Vitamin D, 1 alpha hydroxyvitamin D5, is a potent antagonist of carcinogens that produce breast cancer in rats. The important thing about this new vitamin is not only that it is more potent than 1 alpha 25-dihydroxyvitamin D3, but also that it has only one quarter of the latter's undesirable effect of raising blood calcium levels. (Mehta, J Natl Cancer Inst 89:212, 1997)

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• Laboratory evidence supporting a protective effect of fish oil EPA and DHA - Epidemiologic studies suggest that fish consumption lowers the risk for breast cancer. Studies carried out in animals have also indicated that the n-3 unsaturated fatty acids in fish oils, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), antagonize tumor formation resulting from exposure to carcinogens. However, the ratios of n-3 acids to other (n-6) polyunsaturates, from 1:1 to 1:2, needed to do this would require very large amounts of these fatty acids in the diet for cancer prevention, amounts only known to be consumed by Eskimo populations. Japanese scientists at Kanazawa Hospital described a study in the February, 1997 issue of the British Journal of Cancer in which low dietary intake of EPA and DHA (1:6.36) reduced the incidence of breast tumors produced by the carcinogen DMBA in rats by one third to one sixth, even if the levels were not adequate to slow the growth of the tumors that did develop. (Noguchi, Br J Cancer 75:348, 1997)

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• Breast cancer surgery and the menstrual cycle - There has been much interest in a number of reports that women fare better when undergoing breast surgery if they are in the luteal phase (between ovulation and menstruation) of their cycles at the time of the operation. This is believed to be due to the effect of higher progesterone levels at that time of the cycle inhibiting the spread of tumor cells. However, given the known sensitivity of menstruation to physical and psychological stress, the emotional stress surrounding a diagnosis of cancer, and scheduling for and undergoing surgery, might be expected to play havoc with a woman's cycle. Such disruption would affect the planned scheduling of surgery for optimal timing during the cycle. A group of researchers at the University of Auckland in New Zealand set about determining if there is any change in cycle due to these factors. Their results, published in the February, 1997 issue of the British Journal of Cancer, indicated that cycle characteristics were generally well maintained in four women diagnosed with breast cancer and undergoing mastectomy in whom the full complement of blood hormone levels were studied. Even in two patients who had delayed menstruation it was the length of the optimal luteal phase which was extended. (Holdaway, Br J Cancer 75:413, 1997)

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• The role of lymph node removal in conservative surgery for breast cancer, is it always necessary? - Clinical researchers at Yale University reported, in an article published in the February, 1997 issue of the Journal of Clinical Oncology, a study of 292 patients who underwent conservative surgery in the past 3 years (current practice), and 955 who had conservative surgery and radiation therapy before December, 1989 (long-term). Those who did or did not have lymph node dissections were compared. The status of the nodes only affected the treatment chosen for current-practice patients aged below 50 and those over 50 with breast tumors that could be felt; these two groups had above average incidence of positive nodes (20-30%) . Positive nodes were rare in patients over 50 who did not have palpable tumor masses. The outcome of patients from the long-term study, in terms of survival and distant metastases, was not affected by whether the nodes were dissected or not. (Haffty, J Clin Oncol 15:691, 1997)

  Editor's Comment: - As these clinicians point out, earlier detection of breast cancer has reduced the finding of positive nodes from 30% in the long-term group to less than 18% in current practice. At the same time, there is no question that adjuvant therapy, in the form of cytotoxic chemotherapy, tamoxifen or radiation, is now being given to most women whether they are node-positive or node-negative. In view of this situation, it is not hard to agree that node dissection is unnecessary. However, coming on the heels of controversy over the need for mammograms in younger women, the suggestion of these authors that the role of lymph node dissection should be reevaluated may have a cold reception.

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• Assessing how effective adjuvant chemotherapy is by the toxicity it produces - Dose intensity, the amount of drug given per unit time, usually correlates with the response achieved when the results of completed trials (retrospective analysis) are examined. However, when trials are set up to study this correlation prospectively, the correlation does not hold up. Retrospective studies often suffer from various biases and errors, and even dose intensity of placebo may correlate with outcome in some circumstances. To overcome this, Researchers at Helsinki University Central Hospital, in Finland treated Stage II and III breast cancer patients with cyclophosphamide, doxorubicin and ftorafur (CAFt) and analyzed the results. As reported in the February, 1997 issue of the British Journal of Cancer, they found that the best disease-free and overall survivals were achieved in those patients whose white blood cell counts were lowest after treatment. Dose intensity failed to correlate with survival on more rigorous (multivariate) statistical analysis, whereas low levels of WBCs did. The authors discussed the possibility of using the WBC nadir as a marker to establish the optimum dose intensity required for each individual patient. (Saarto, Br J Cancer 75:301, 1997)