Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial

Seventy-eight examples of intraductal carcinoma (DCIS) were identified after pathologic review of 2072 specimens obtained from National Surgical Adjuvant Breast Project protocol 6. This randomized clinical trial compares the therapeutic merit of total mastectomy (TM) with lumpectomy (L), with (LX) and without (LO) postoperative irradiation. All patients were subjected to axillary lymph node dissection. Seven (14%) of the 51 patients with DCIS treated by L exhibited breast recurrence within or close to the site of the initial lesion 4 to 53 months (average, 16 months) after L. Only 2 (7%) of these events occurred in the 29 women treated by LX, as opposed to 23% in the LO group. No pathologic features were noticed that might have been considered predictive of local breast recurrence. The three DCIS recurrences and the four invasive forms noted are considered to represent overlooked or incompletely excised foci of cancer because of the multifocality (not multicentricity) of some breast cancers. The possibility that DCIS may represent a marker of risk for the development of cancer rather than a precursor lesion per se is suggested. Despite apparent difficulties in the pathologic diagnosis of DCIS as well as uncertainty concerning its natural history, no evidence was found to indicate that it represents a more ominous disease than invasive cancer. Indeed, treatment failure occurred in only one patient treated by LX and a similar number subjected to TM (4% versus 2%). Although these observations are short term (average follow-up, 39 months), estimates of the probability of local recurrence or survival suggest that they will not be significantly altered after longer periods of surveillance. Thus, there are no compelling reasons why DCIS may not be treated in a cosmetically acceptable manner by LX. A randomized clinical trial addressing this issue is now in progress.

Pathologic findings from the National Surgical Adjuvant Breast Project (protocol 6). I. Intraductal carcinoma (DCIS).

Background and Methods Women with ductal carcinoma in situ have been treated both by lumpectomy and by lumpectomy followed by radiation therapy, but the benefit of combined therapy is uncertain. A group of 818 women with ductal carcinoma in situ were randomly assigned to undergo lumpectomy or lumpectomy followed by breast irradiation (50 Gy). Sufficient tissue was removed that the margins of the resected specimens were histologically tumor-free. The mean duration of follow-up was 43 months (range, 11 to 86). The principal end point of the study was event-free survival, as defined by the presence of no new ipsilateral or contralateral breast cancers, regional or distant metastases, or other cancers and by no deaths from causes other than cancer. Results Five-year event-free survival was better in the women who received breast irradiation (84.4 percent, vs. 73.8 percent for the women treated by lumpectomy alone; P = 0.001). The improvement was due to a reduction in the occurrence of second ipsilateral breas...

Lumpectomy Compared with Lumpectomy and Radiation Therapy for the Treatment of Intraductal Breast Cancer

Ductal carcinoma in situ of the breast (also called intraductal carcinoma), a clonal proliferation of malignant-appearing cells within the mammary duct lumens without evidence of invasion beyond the epithelial basement membrane, is the precursor lesion of invasive breast cancer In the past 20 years, concomitant with the wide use of screening mammography, its detected incidence has risen dramatically Data from large cohort studies and randomized trials have emerged to guide treatment This review summarizes progress in the understanding, pathogenesis, and treatment of ductal carcinoma in situ

Ductal Carcinoma in Situ of the Breast

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. Cancer 1996;77:2267-74.

A prognostic index for ductal carcinoma in situ of the breast.

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.

Mammographically detected duct carcinoma in situ. Frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence.

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.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819821001%2950%3A7%3C1309%3A%3AAID-CNCR2820500716%3E3.0.CO%3B2-%23

Duct carcinoma in situ. Relationship of extent of noninvasive disease to the frequency of occult invasion, multicentricity, lymph node metastases, and short-term treatment failures

Based on a serial subgross and correlated radiographic examination technique, the frequency of carcinomatous involvement of the nipple was found to be 30.2 per cent in a consecutive series of 149 mastectomy specimens. This is significantly higher than that in other reported series. Carcinomatous nipple changes in this series were equally divided between invasive and noninvasive types. The most common type of noninvasive cancer found was subclinical, microscopic pagetoid involvement of a lactiferous duct and associated microscopic Paget's disease of the skin of the nipple. Of the nipples with invasive carcinoma, 95.4 per cent were associated with primary tumors less than 25 mm from the nipple. Invasive nipples were more likely to be associated with primary tumors that were poorly differentiated, greater than 20 mm in diameter, and contained axillary metastases than were benign or noninvasive nipples. Fifty per cent of nipples with invasive changes had macroscopic clinical abnormalities. There appeared to be no way to predict the presence of noninvasive carcinomatous involvement of a nipple other than by thorough direct sampling. The associated primary tumor locations were evenly distributed, and only 4.3 per cent of nipples involved with noninvasive cancer were clinically evident. However, removal of the nipple per se and skeletonization of the remaining areola would virtually eliminate the chance of residual noninvasive carcinoma. The higher incidence of nipple-areolar involvement in breast carcinoma found in this series compared to previous reports probably reflects the sampling technique. These data should be considered when approaching the problem of mastectomy and potential reconstruction for carcinoma of the breast. They are not to be interpreted to mean that the investigators are advocates of the procedure.

A guide to the frequency of nipple involvement in breast cancer. A study of 149 consecutive mastectomies using a serial subgross and correlated radiographic technique

Philip R. Westdahl

Papers

Mammographically detected duct carcinoma in situ. Frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence.

Duct carcinoma in situ. Relationship of extent of noninvasive disease to the frequency of occult invasion, multicentricity, lymph node metastases, and short-term treatment failures

A guide to the frequency of nipple involvement in breast cancer. A study of 149 consecutive mastectomies using a serial subgross and correlated radiographic technique

A letter to Jim: Advice to a resident: The importance of being aware