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

• BRCA1 mutations and breast cancer - Two papers in the January 18 issue of the New England Journal of Medicine examined this subject. In the first study from the Fred Hutchinson Cancer Center in Seattle, alterations in BRCA1, mostly mutations, but also some rare sequences, were found in about 10% of young women with breast cancer who developed the disease before they were 35 years old. None of the mutations and only one variant was seen among 73 control referents. (Langston, NEJ Med 334:137, 1996)

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• The second study from the Massachusetts General Hospital and the Dana-Farber Cancer Institute in Boston examined 418 women who developed breast cancer before the age of 40. Among 30 women developing breast cancer before the age of 30, 13% had chain- terminating mutations and one had a nonsense mutation. The authors described a specific germ-line BRCA1 mutation termed 185delAG associated with 21% of the cases of early onset of breast cancer in Jewish women. (FitzGerald, NEJ Med 334:143, 1996)

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• Another predictor of distant metastasis? - A study from Yale University, New Haven, CT, reporting on 973 patients with invasive cancer treated between 1970 and 1989, confirmed earlier conclusions of the National Surgical Adjuvant Breast and Bowel Project, that recurrence in the breast treated with lumpectomy and radiation was a good indicator of distant disease. 71% survived for 10 years. Of 32 patients developing recurrence within 4 years, 50% developed metastases compared with 17% of those with recurrence later than 4 years after diagnosis. The disease tended to be of more aggressive type in those patients whose disease recurred, making it very critical to consider optimizing local and systemic therapy at time of diagnosis. (Haffty, J Clin Oncol 14:52, 1996)

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• Combination chemotherapy with epirubicin - The International Collaborative Cancer Group, a group of European Hospitals and Medical Centers, used a randomized trial of 759 premenopausal patients with axillary-node-positive operable disease on either the standard three drug therapy for women with positive-node operable breast cancer (CMF - cyclophosphamide, methotrexate, 5- fluorouracil), or one that substituted epirubicin for methotrexate (FEC). Two different dose schedules were used for each combination. Both relapse-free survival and overall survival were significantly improved in FEC patients. (Coombes, J Clin Oncol 14:35, 1996)

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• Tamoxifen and bone loss - An interesting finding reported by doctors from the Royal Marsden Hospital and Sheffield University in the UK is that whereas tamoxifen given to postmenopausal women prevents bone loss, in premenopausal women it has the opposite effect, causing significant bone loss. This finding is important for any consideration of the benefits of both adjuvant treatment of cancer and the possible use of this drug in cancer chemoprevention. (Powles, J Clin Oncol 14:78, 1996)

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• Breast-conserving surgery - The use of breast conserving surgery (BCS) with or without radiation for early cancers (ductal carcinoma in situ or DCIS) trades less extensive physical changes for a slight decrease in survival rate, according to a report from the Massey Cancer Center in Richmond, Virginia. Rates for survival at 10 years after surgery were: mastectomy, 91.7 and 74.1%; BCS and radiotherapy 91.0 and 72.1%, and BCS alone 89.6 and 68.2%. At 20 years, breast cancer-free survival rates were: mastectomy 74,5%, BCS plus radiation 63.3%, and BCS alone 46.8%. The critical question is the quality-of-life-adjusted survival, how much reduction in survival outweighs the less tangible factors in loss of a breast? (Hillner, J Clin Oncol 14:70, 1996)

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• Tumor cell shedding during cancer surgery - The possibility that surgery could spread cancer cells into the blood circulation has been of concern for a long time. However, there has been no definitive information on the subject, and the issue has languished. In a study from the Royal Liverpool University Hospital in the UK, immunochemical detection of tumor cell components called cytokeratins was made during surgery, either simple mastectomy or lumpectomy, on 18 patients. Blood was sampled through a catheter threaded into the subclavian vein draining the breast undergoing surgery. Tumor cells were detected by the stain in one patient before operation, in six during surgery, and in none of the patients post-operatively. The study did demonstrate that shedding of tumor cells occurs, but was too small to derive definitive rates for the shedding process. (Choy, British Journal Cancer 73:79, 1996)