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Paired DNA samples from the neoplastic and nonneoplastic cells of 118 patients with the sporadic, nonfamilial form of breast cancer were analyzed for evidence of genetic alteration at a polymorphic microsatellite mapped to intron 6 within the MUC1 gene at 1q21. Two other microsatellite loci, D1S104 and APO-A2, which also map to 1q21, were analyzed as well. The frequency of alteration at the microsatellite within the MUC1 locus was significantly higher than D1S104 or APO-A2 (P < 0.001). Analysis by Southern blotting of the VNTR region of the MUC1 gene revealed an amplification of one allele in 34 of 54 informative cases (63%). There was no significant association between these alterations and alterations of the microsatellite within the same locus, suggesting independent mechanisms were responsible for the genetic changes. Microsatellite loci D17S579 at 17q21, the site of the BRCA1 gene, and D18S34 at 18q21-qter, the deleted in colorectal cancer locus, were also analyzed by PCR. Alterations at D17S579 and D18S34 were detected in 18.8% and 6.2% of patients, respectively (P < 0.001, and P < 0.1 relative to the frequency of alteration at D1S104 or APO-A2). A previously described polymorphism of hMSH2 was altered in 16.4% of cases.

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BACKGROUND: Axillary dissection remains a standard component of the treatment of invasive carcinoma of the breast. The presence of metastases to the regional lymph nodes guides adjuvant therapy and aids in determining prognosis. Mammography results in the discovery of small and often node-negative carcinomas of the breast. STUDY DESIGN: This 15-year, retrospective analysis investigated whether certain patients with small tumors could be spared the morbidity of axillary dissection. RESULTS: Medical records showed that from January 1980 to May 1995, 4,543 needle localization biopsies were done at York Hospital because of abnormalities detected on mammograms. Of these, 703 (15.5 percent) proved to be carcinoma. Of the carcinomas, 68 percent were infiltrating ductal carcinoma, 26 percent were ductal carcinoma in situ, and 5.4 percent were infiltrating lobular carcinoma. Axillary dissection was done on 588 patients, and 88.1 percent of the patients had no metastases to axillary lymph nodes. No axillary metastases were present in 109 patients with ductal carcinoma in situ who underwent axillary lymph node dissection or in 21 patients with microscopic invasive tumors. Only two of 54 patients with a T1a tumor (tumor [T], < or = 0.5 cm) had positive axillary nodes. Only one of 29 patients with a well-differentiated T1b tumor (T, > 0.5 to < or = 1 cm) had metastatic axillary nodes. In the presence of negative axillary lymph nodes, 19.2 percent of patients with a T1a tumor, 33.7 percent of patients with a T1b tumor, 60 percent of patients with a T1c tumor (T, > 1 to < or = 2 cm), and 78.9 percent of patients with a T2 tumor (T, > 2 cm) were given adjuvant chemotherapy or hormonal therapy. CONCLUSIONS: Patients with ductal carcinoma in situ and microscopic invasive tumors do not require node dissections. Possibly patients with T1a tumors and patients with well-differentiated, estrogen-receptor positive, progesterone-receptor positive, T1b tumors can also be spared axillary node dissection. By following this approach on occasion, patients with positive nodes might not undergo axillary lymph node dissection, but they may still be offered adjuvant therapy.

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Carcinoma of the breast was studied in 100 women who underwent needle localization and open breast biopsy for lesions found by screening mammography from January 1980 to May 1987. The average age of the patients found to have carcinoma was 59.2 years, and 16 percent of patients were younger than 50 years of age. Pathologic examination revealed 62 patients with infiltrating ductal carcinoma, 31 patients with ductal carcinoma in situ, and seven patients with infiltrating lobular carcinoma. In 34 patients the carcinoma was microscopic. Thirty-six patients had carcinomas less than or equal to 1 centimeter, and 30 patients had carcinomas greater than 1 centimeter. Eighty-four patients were treated with total mastectomy and axillary dissection. Seven patients were treated with wide excision, axillary dissection and radiation therapy. Nine patients underwent lesser treatments. Among the 91 patients undergoing axillary dissection, 82 were node negative, eight had one to three positive nodes, and one had four or more positive nodes. One hundred percent of patients with ductal carcinoma in situ who underwent axillary dissections (24 of 31) were node negative. Only two patients received adjuvant hormonal therapy, and one woman received adjuvant chemotherapy. All patients were under observation for at least five years or to the time of death (mean follow-up period, 5.8 years). Of the 100 patients with complete follow-up, 92 are alive and disease free. Four patients with carcinoma that metastasized have died. Three patients are alive with known recurrence. One patient died of other causes six months after carcinoma was diagnosed. Widespread use of screening mammography coupled with judicious use of needle-localization biopsy will lead to the early diagnosis of carcinoma of the breast. Such early diagnosis of carcinoma does lead to an excellent (95 percent) five-year survival rate.

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A ten year experience with 2,077 consecutive mammographically guided needle-localization biopsies at a large community hospital is presented. By using this technique, 13.8 per cent of the biopsies were positive, yielding 284 carcinomas. The nonpalpable carcinomas discovered by mammography and the needle-localization technique were compared with those palpable carcinomas diagnosed during the same time period at York Hospital. In the final year of the study, 42.1 per cent of carcinomas treated at the York Hospital were diagnosed by the needle-localization technique. The mammographically detected carcinomas were smaller, more often node-negative and found, on average, at an earlier patient age than palpable carcinomas. The results of this study demonstrate that screening mammography, coupled with an aggressive biopsy policy, will lead to the discovery of many early, node-negative carcinomas of the breast.

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