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

• DNA repair and susceptibility to breast cancer - The cellular genetic material, DNA, is constantly being damaged, not only by toxic materials in the environment, but also by reactive products of our own metabolism, even by the vital but potentially damaging oxygen. Cells have enzyme systems to patch and repair damaged DNA, but if the damage is too extensive, or the repair system is deficient, permanent damage remains. This is frequently the basis for later development of cancer. It is known that ability to repair DNA varies among people, and a feature of the disease xeroderma pigmentosum, for example, is reduced ability to repair damage caused by UV light. A brief article in the June 1, 1996 issue of the Journal of the National Cancer Institute by researchers at several institutions, including the Johns Hopkins University, reported that 17 women at high risk for breast cancer, by reason of having the disease in close family members, were five times as likely to have lower levels of repair enzymes than were 19 women without such risk factors. Low levels also were found in each of four women with breast cancer, but in less than one third of 19 without a personal or family history of benign or malignant breast disease. (Helzlsouer, J National Cancer Institute 88:754, 1996)

  Editor's Comment: - This is an interesting report, but the study was very small and should be repeated in a larger group of women.

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• Obesity and breast cancer risk - It has been known for more than ten years that heavy premenopausal women have a lower risk of breast cancer. More recently it was shown that this relationship does not hold for heavy women after menopause, in whom the risk may even increase. Why should this switchover occur? A brief report from a group at the National Cancer Institute, appearing in the June 1, 1996 issue of the Institute's Journal, provided the likely reason. With increasing weight expressed as body mass index, there was a significant trend towards increase in blood estradiol (the most active natural estrogen) in postmenopausal women, whereas a decrease occurred in heavier premenopausal women. This was more clearly seen in those of the premenopausal group who were studied in the same phase of their cycle. Sustained higher levels of estrogens are considered to be a risk factor for breast cancer, and are the probable causes in the findings of this study. This situation deserves further follow up. (Potischman, J National Cancer Institute 88:756, 1996)

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• Bone marrow metastases as indicators of prognosis - An article from the H. Lee Mofitt Cancer Center in Tampa, Florida, described measurement of cytokeratin K19 as a good indicator of metastatic disease in the bone marrow. This material is characteristic of epithelial cells, but not of bone marrow cells, so it is out of place in the marrow. The researchers used a very sensitive method based on the polymerase chain reaction (PCR) technique, finding the incidence of K19 message to be 52% for 19 Stage II, 57% for 14 Stage III, and 82% for 50 Stage IV patients. After the patients received autologous bone-marrow transplants, relapse rates three years later were 32% and 94% for Stage II/III and Stage IV K19-positive patients, but only 10% and 14% for Stage II/III and Stage IV K19-negative patients. As with another cytokeratin (number 18) in the bone marrow of stomach cancer patients (See this month's Cancer Web Report Stomach Cancer section), K19 in the bone marrow of breast cancer patients indicates a poor prognosis. (Fields, J Clin Oncol 14:1868)

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• The best sequence for chemotherapy and radiation therapy after conservative surgery? - Patients with early breast cancer, whose disease characteristics place them in the category of having a high risk of metastases, receive chemotherapy. However, at present it is not known what is the best sequence in which to give this treatment. In an article in the May 23, 1996 issue of the New England Journal of Medicine, a group of researchers from hospitals in Boston described their approach to this problem. They randomly treated 244 patients with Stage I or II breast cancer with 12-week courses of chemotherapy either before or after radiation therapy. Five-year rates for recurrence at any site were 38 and 31%, and those for distant metastases were 36 and 25%, in the radiation-first and chemotherapy-first groups, respectively. Five-year crude rates of first recurrence by site were 5 and 14% for local, and 32 and 20% for distant or regional recurrence in the radiation-first and chemotherapy-first groups, respectively. The evidence suggests that in these higher-risk patients, it is better to give the chemotherapy before radiotherapy. (Recht, New England J Medicine 334:1356, 1996)

  Editor's Comment: - Other trials not specifically designed to investigate the sequence question, such as the National Surgical Adjuvant Breast and Bowel Project, Protocol B-15, and the International Breast Cancer Study Group Trials VI and VII, also support the same conclusion. This Boston study is, however, the first such study specifically on the effect of the treatment order. It should be kept in mind in interpreting the data that there were relatively few patients accrued over a long time period, and the patient population was not necessarily representative of the whole group of higher-risk patients with early breast cancer. Also, it is necessary to be very sure that control of local disease is not compromised. This underlines the need for further larger studies to clarify this important issue.

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• Paclitaxel and metastatic breast cancer - Reports of studies of the efficacy of paclitaxel (taxol) and the related docetaxel continue to accumulate, with many having the goal of defining the optimum treatment schedule. A multicenter trial in Belgium, Canada, France, Germany, Italy, and the Netherlands, claimed that a dose of 175 mg/m2 as a three-hour infusion gave superior results to 135 mg/m2. Differences were not impressive, however, with findings for high-dose compared with low-dose of: overall response rates 29% versus 22%; time to disease progression 4.2 versus 3.0 months and median survival time 11.7 versus 10.5 months. Although drug-induced side effects (lowered white blood cell count, and tingling, numbness and disturbed sensations in the extremities) increased with increased dose, overall assessments of quality of life were better for the higher dose. (Nabholtz, J Clin Oncol 14:1858, 1996)

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• Breast implants - The June 6, 1996 issue of the New England Journal of Medicine, contained the text of the Shattuck lecture delivered by Dr. Marcia Angell at the Annual Meeting of the Massachusetts Medical Society on May 4, 1996. While the focus is on the claimed relationship of silicone implants to connective tissue disease, the article is relevant to cancer for at least two reasons: the use of such implants in reconstructive surgery; and the problems that implants may create for obtaining satisfactory mammograms. The article also presents an overview of how the controversy originated, and the course of the legal and business actions that followed. It is a fascinating story with wider implications for medicine and science. (Angell, NEJ Med 334:1513, 1996)