Michael D. Lagios

BACKGROUND: There is controversy and confusion regarding therapy for patients with ductal carcinoma in situ (DCIS) of the breast. The Van Nuys Prognostic Index (VNPI) was developed to aid in the complex treatment selection process. METHODS: The VNPI combines three significant predictors of local recurrence: tumor size, margin width, and pathologic classification. Scores of 1 (best) to 3 (worst) were assigned for each of the 3 predictors and then totaled to give an overall VNPI score ranging from 3 to 9. Three hundred thirty-three patients with pure DCIS treated with breast preservation (195 by excision only and 138 by excision plus radiation therapy) were studied with detection of local recurrence as the end point. RESULTS: There was no statistical difference in the 8 year local recurrence free survival in patients with VNPI scores of 3 or 4, regardless of whether or not radiation therapy was used (100% vs. 97%; P = not significant). Patients with VNPI scores of 5, 6, or 7 received a statistically significant 17% local recurrence free survival benefit when treated with radiation therapy (85% vs. 68%; P = 0.017). Patients with scores of 8 or 9, although showing the greatest relative benefit from radiation therapy, experienced local recurrence rates in excess of 60% at 8 years. CONCLUSIONS: DCIS patients with VNPI scores of 3 or 4 can be considered for treatment with excision only. Patients with intermediate scores (5, 6, or 7) show a 17% decrease in local recurrence rates with radiation therapy. Patients with VNPI scores of 8 or 9 exhibit extremely high local recurrence rates, regardless of irradiation, and should be considered for mastectomy.

BACKGROUND: Ductal carcinoma in situ is a non-invasive carcinoma that is unlikely to recur if completely excised. Margin width, the distance between the boundary of the lesion and the edge of the excised specimen, may be an important determinant of local recurrence. METHODS: Margin widths, determined by direct measurement or ocular micrometry, and standardized evaluation of the tumor for nuclear grade, comedonecrosis, and size were performed on 469 specimens of ductal carcinoma in situ from patients who had been treated with breast-conserving surgery with or without postoperative radiation therapy, according to the choice of the patient or her physician. We analyzed the results in relation to margin width and whether the patient received postoperative radiation therapy. RESULTS: The mean (+/-SE) estimated probability of recurrence at eight years was 0.04+/-0.02 among 133 patients whose excised lesions had margin widths of 10 mm or more in every direction. Among these patients there was no benefit from postoperative radiation therapy. There was also no statistically significant benefit from postoperative radiation therapy among patients with margin widths of 1 to <10 mm. In contrast, there was a statistically significant benefit from radiation among patients in whom margin widths were less than 1 mm. CONCLUSIONS: Postoperative radiation therapy did not lower the recurrence rate among patients with ductal carcinoma in situ that was excised with margins of 10 mm or more. Patients in whom the margin width is less than 1 mm can benefit from postoperative radiation therapy.

Seventy-nine patients with mammographically detected foci of duct carcinoma in situ (DCIS) of histologically confirmed extents of 25 mm or less, were treated by tylectomy without irradiation or axillary dissection. Adequacy of excision was confirmed histologically, by radiographic-pathologic correlation and by postoperative mammographic examination. Eight patients (10.1%) have recurred locally in the immediate vicinity of the biopsy site. Four patients developed recurrent in situ disease identified mammographically, and all were initially treated by reexcision. One of these patients subsequently elected to undergo mastectomy; no residual in situ or invasive disease was detected in the breast or in axillary lymph nodes. Four patients developed recurrent invasive disease; 50% of these recurrences were detected mammographically. All patients were treated by mastectomy with node dissection. Three had confirmed minimal invasive carcinomas and were N0, one patient had a 13-mm invasive lobular carcinoma with a single Group I micrometastasis. All patients, including those treated for a recurrence, are presently free of disease but three patients died of heart disease. Nuclear grade would appear to identify subsets of DCIS more likely to produce local failure after tylectomy alone. Duct carcinoma in situ with high-grade nuclear morphology and comedo-type necrosis was associated with a 19% local recurrence rate after an average interval of 26 months; only one of ten patients with intermediate-grade DCIS developed a local recurrence at 87 months; and none of 33 patients with DCIS of micropapillary/nonnecrotic cribriform type and low-grade nuclear morphology developed local recurrence in the follow-up period.

Fifty-three breasts resected for a biopsy diagnosis of duct carcinoma in situ were studied with a serial subgross and correlated radiographic method of examination designed to permit quantitation of the extent of the noninvasive lesion in the breast. Overall frequencies of occult invasion and multicentricity were 21 and 32%, respectively. Among 24 lesions 25 mm or larger in extent (average, 63; median, 56 mm) 11 showed occult foci of invasion, 13 had multicentric foci and six had nipple involvement. Among 29 lesions less than 25 mm in extent (average, 10; median, 8 mm) there were no instances of occult invasion, four were multicentric and two had nipple involvement (P = less than 0.05 for multicentricity and occult invasion). Twenty patients with lesions averaging 8 mm in extent are being followed after excision only in an experimental program. There have been three local recurrences at an average follow-up of 44 months. All recurrences occurred ipsilaterally, two were within the prior biopsy site. All patients with recurrence are free of disease following local resection in two and modified radical mastectomy in one. For lesions with associated microcalcifications, the distribution of the mammographic microcalcifications closely approximates the extent of disease as confirmed histologically. These findings suggest that an important predictive factor for the presence of occult invasion and multicentricity in the resected breast is the extent of the noninvasive lesion.