What is Ductal carcinoma in situ?
Ductal carcinoma in situ (DCIS) is a noninvasive, precancerous condition. Ductal carcinoma in situ can progress to become invasive cancer, but estimates of the likelihood of this vary widely. Some people include Ductal carcinoma in situ in breast cancer statistics. The frequency of the diagnosis of Ductal carcinoma in situ has increased markedly in the United States since the widespread use of screening mammography. In 1998, Ductal carcinoma in situ accounted for about 18% of all newly diagnosed invasive plus noninvasive breast tumors in the United States.
Very few cases of Ductal carcinoma in situ present as a palpable mass; 80% are diagnosed by mammography alone. Ductal carcinoma in situ comprises a heterogeneous group of histopathologic lesions that have been classified into several subtypes based primarily on architectural pattern: micropapillary, papillary, solid, cribriform, and comedo. Comedo-type Ductal carcinoma in situ consists of cells that appear cytologically malignant, with the presence of high-grade nuclei, pleomorphism, and abundant central luminal necrosis. Comedo-type Ductal carcinoma in situ appears to be more aggressive, with a higher probability of associated invasive ductal carcinoma.
Treatment option overview
Until recently, the customary treatment of Ductal carcinoma in situ was mastectomy. The rationale for mastectomy included a 30% incidence of multicentric disease, a 40% prevalence of residual tumor at mastectomy following wide excision alone, and a 25% to 50% incidence of breast recurrence following limited surgery for palpable tumor, with 50% of those recurrences being invasive carcinoma. The combined local and distant recurrence rate following mastectomy is 1% to 2%.
Because of the success of breast-conserving surgery for invasive carcinoma, this conservative approach was extended to the noninvasive entity. No randomized comparisons are available of mastectomy versus breast-conserving surgery plus breast irradiation. In an effort to determine whether breast-conserving surgery was a reasonable approach to the management of Ductal carcinoma in situ, the National Surgical Adjuvant Breast and Bowel Project (NSABP) study B-17 randomly assigned 818 women with localized Ductal carcinoma in situ and negative surgical margins following excisional biopsy to breast irradiation (50 Gy) or to no further therapy. In this study, 80% of the patients were diagnosed by mammography, and 70% of the patients had small lesions (≤1 cm). Events were defined as the presence of new ipsilateral disease, contralateral disease, metastases, a second primary tumor, or death from any cause. Event-free survival at 8 years for the irradiated patients was 75% compared with 62% for patients with lumpectomy alone (P = .00003). [Level of evidence: 1iiDi] The cumulative incidence of recurrent ipsilateral breast cancer was reduced from 26% to 12% (P < .000005) by the addition of radiation to surgery. Specifically, the occurrence of invasive cancer decreased from 13.4% to 3.9% with the addition of radiation (P < .001), and recurrent Ductal carcinoma in situ was reduced from 13.4% to 8.2% (P = .007). Thus far, only 1% of patients in this trial have died from breast cancer, which is similar to the historical data after mastectomy. This trial indicates that local excision and breast irradiation is an acceptable therapy for localized Ductal carcinoma in situ. These results have been confirmed in a trial of the same design conducted by the EORTC.
To determine whether patients at high risk for recurrence of Ductal carcinoma in situ could be identified, the NSABP analyzed the pathologic material submitted for central review from 623 of the original cohort of 814 women randomized in B-17. Moderate/marked comedonecrosis was the only pathologic feature that was an independent predictor for ipsilateral breast tumor recurrence. The original intent of this study was to include only patients with histologically negative margins of excision; however, central pathology review found a small cohort of patients with positive or unknown margins. An insufficient number of patients was in this group to allow a statistically valid observation of the prognostic significance of positive margins. In spite of the higher risk of local recurrence with comedonecrosis, the local recurrence rate was not high enough to rule out breast conservation as a therapeutic option. Margins of <1 mm have shown an unacceptable local recurrence rate, even with radiation therapy.
Given that lumpectomy and radiation therapy are generally applicable for most patients with Ductal carcinoma in situ, can a subset of patients be identified with such a low risk of local recurrence that postoperative radiation therapy can be omitted? In an effort to identify such a favorable group of patients, several pathologic staging systems have been developed and tested retrospectively, but consensus recommendations have not been achieved. The Van Nuys Prognostic Index, which combines 3 predictors of local recurrence (i.e., tumor size, margin width, and pathologic classification), was used to retrospectively analyze 333 patients treated with either excision alone or excision and radiation therapy. Using this prognostic index, patients with favorable lesions, who received surgical excision alone, had a low recurrence rate (i.e., 2% with median follow-up of 79 months). A subsequent analysis of these data was performed to determine the influence of margin width on local control. Patients whose excised lesions had margin widths ≥10 mm in every direction had an extremely low probability of local recurrence with surgery alone (4% with mean follow-up of 8 years). These reviews are retrospective, noncontrolled, and are subject to substantial selection bias. By contrast, no subset of patients was identified in the prospective NSABP trial that did not benefit from the addition of radiation therapy to lumpectomy in the management of Ductal carcinoma in situ.
To determine if tamoxifen adds to the efficacy of local therapy in the management of Ductal carcinoma in situ, the NSABP performed a double-blind prospective trial of 1,804 women. Patients were randomly assigned to lumpectomy, radiation therapy (50 Gy), and placebo versus lumpectomy, radiation therapy, and tamoxifen (20 mg/day for 5 years). Positive or unknown surgical margins were present in 23% of patients. Approximately 80% of the lesions measured ≤1 cm and >80% were detected mammographically. Breast cancer events were defined as the presence of new ipsilateral disease, contralateral disease, or metastases. Women in the tamoxifen group had fewer breast cancer events at 5 years than did those on a placebo (8.2% vs. 13.4%; P = .0009). [Level of evidence: 1iDi] With tamoxifen, ipsilateral invasive breast cancer decreased from 4.2% to 2.1% at 5 years (P = .03). Tamoxifen also decreased the incidence of contralateral breast neoplasms (invasive and noninvasive) from 0.8% per year to 0.4% per year (P = .01). The benefit of tamoxifen extended to those patients with positive or uncertain margins.
Treatment options for patients with Ductal carcinoma in situ
