Rosen's Breast Pathology, 4e

397

Ductal Carcinoma In Situ

randomized trials comparing the results of excision alone to excision with radiotherapy. Initial reports published in the 1980s described selected patients and noted a recurrence rate in the conserved breast of 10% or less after a median follow-up of approximately 5 years. 381–383 Bornstein et al. 384 reported an actuarial 8-year breast recurrence rate of 27% in a series of 38 selected patients. Five of the eight recurrences were invasive, and one of these women developed metastatic carcinoma. Solin et al. 385 identified 259 women treated in nine institutions in the United States and Europe and found a 10-year actuarial breast failure rate of 16%. Fifty percent of the 28 recurrences were invasive, and four patients devel- oped metastatic carcinoma. A later follow-up report by Solin et al. 386 described an expanded cohort of 1,003 patients from 10 institutions with a median follow-up of 8.5 years (range, 0.2 to 24.6 years). Initial recurrences of carcinoma limited to the breast were documented in 82 patients (8.2%). One addi- tional patient had angiosarcoma (0.1%), and the nature of the breast recurrence was unknown in two cases. The calculated 15-year rates of breast recurrence and systemic metastases were 19% and 3%, respectively. The histology of the 82 initial documented breast carcinoma recurrences was as follows: invasive ductal 46 (57%), intraductal 34 (41%), and other 2 (2%). Five additional patients had invasive breast recurrences concurrently with systemic recurrences. The risk of breast re- currence was significantly lower in women who had a nega- tive surgical margin or were 50 years of age or older at the time of treatment. During the course of follow-up, contralat- eral breast carcinoma was reported in 71 (7%) patients, and 56 (6%) women had a nonmammary malignant neoplasm. Two large-scale randomized trials have compared local control in the breast after excision alone and excision plus ra- diotherapy. The NSABP B17 study revealed a 50% reduction in breast recurrence when radiation was added to lumpec- tomy. 387 The 12-year risk of breast recurrence was 31.7% with surgery alone and 15.7% for surgery with radiotherapy. A similar randomized trial by the European Organization for Research and Treatment of Cancer (EORTC) yielded a 4-year breast recurrence rate of 16% after surgery alone and 9% when radiation was added to surgery. 388 Updated results from the EORTC study with a median follow-up of 10.5 years revealed a 10-year breast recurrence-free rate of 74% for exci- sion alone and 85% for surgery followed by radiation. 296 The risk reduction attributed to radiotherapy for recurrent DCIS was 48%, and for invasive carcinoma it was 42%. 389 Patho- logic features significantly associated with breast recurrence in both treatment groups were intermediate to poorly differ- entiated grade and cribriform or solid growth. A low-risk subset of DCIS patients who could be spared radiation treatment was characterized in a prospective East- ern Cooperative Oncology Group and North Central Cancer Treatment Group trial. 339 Patients with either low- or inter- mediate-grade DCIS spanning less than 2.6 cm or high-grade DCIS measuring less than 1.1 cm who had margin clearance of more than 3 mm and no residual mammographic calcifica- tions were eligible for this 1997 to 2002 trial. In a median fol- low-up of 6.2 years, the 5-year rate of ipsilateral breast events in 565 patients in the low- or intermediate-grade group was

6.1% (95% CI, 4.1% to 8.2%). With a median follow-up of 6.7 years, the incidence of recurrence for 105 patients in the high-grade stratum was 15.3% (95% CI, 8.2% to 22.5%). Patients with lower grade DCIS and clear margins 3 mm or wider were deemed to have an acceptably low rate of ipsilat- eral breast events at 5 years without irradiation. Patients with high-grade lesions had a much higher rate of recurrence, suggesting that excision alone would be inadequate. Although patient outcome is maximized when treatment is tailored to patient and disease characteristics, the num- ber of events prevented per 1,000 radiation-treated women is typically less than 10%. 390 Radiation treatment offers an increase in the chances of successful breast conservation, but this positive feature is somewhat offset by the likelihood that mastectomy will be necessary in the event of recurrence, the detection of a new primary carcinoma, or as a result of vari- ous radiation-associated complications. 391 Accelerated partial breast irradiation, that is, brachy- therapy using Mammosite (Hologic, Boxborough, MA), has emerged as a substitute for whole-breast irradiation (in- cluding three-dimensional conformal external beam) in the treatment of breast carcinoma. 392,393 Preliminary outcome results indicate similar results regardless of either radiation modality used. A radiotherapy boost to the surgical cavity improves local control in DCIS. 394 The interpretation of radiation-induced cytologic changes in mammary epithelium may occasionally pose diagnostic difficulty. It should be noted that recurrent disease exhibits a histopathologic appearance that is generally similar to the index lesion. 395 As such, histopathologic review of the previ- ously diagnosed DCIS is critical for the optimal evaluation of all “recurrences.” Factors associated with an increased risk of breast recur- rence after surgery alone are also significant for recurrence after surgery and radiotherapy. Necrosis in DCIS or com- edo-type DCIS imparts an especially high risk of breast re- currence after breast conservation with radiotherapy. Solin et al. 396 found that the presence of necrosis was a significant risk factor when it occurred in DCIS with poorly differen- tiated nuclear grade. Kuske et al. 397 reported significantly poorer local control in patients with comedo (75%) than in those with noncomedo (98%) carcinoma, but did not of- fer a definition of “comedo” DCIS. In the NSABP B17 trial comparing excision alone and excision plus radiotherapy, features associated with increased risk of local recurrence after either form of treatment were the presence of moderate to marked comedonecrosis, regardless of histologic subtype, margins that were positive or indeterminate, multifocality, and a moderate to marked lymphocytic infiltrate. 398 The size of the lesion (less than 10 or greater than or equal to 10 mm) did not prove to be a statistically significant predictor for breast recurrence. Necrosis proved to be the only statisti- cally significant independent risk factor for recurrence in both treatment groups in multivariate analysis. Risk Factors for Breast Recurrence after Conservation Surgery with Radiotherapy