Duct carcinoma in situ: A personal perspective.

In the recent past, DCIS was a rare diagnosis established by biopsy of palpable breast masses or nipple changes. Mammography increased the frequency of a DCIS diagnosis by 20 × resulting in a tsunami of small circa 10 mm lesions detected only by mammography. The impact of pathologic technique in examining and characterizing such lesions is reviewed, and the development of algorithms incorporating prognostic factors and histology based on serial sequential processing techniques are described and contrasted with those which relied on tissue sampling. The development of the initial clinical trails of irradiation all demonstrated the significant benefit of irradiation but none could identify subsets with a more favorable outcome. The latter was precluded by their common practice of tissue sampling: Size could not be calculated and margin width and microinvasion could not be reliable demonstrated. Multigene signature assays are increasingly being utilized, most prominently Oncotype DCIS. However, these assays must be interpreted in conjunction with the limitations set forth in the validating studies-in the case of Oncotype DCIS-the size, margin width, and grade which defined the baseline study (E5194). Tamoxifen and other anti-hormonal agents (aromatase inhibitor therapy) have been shown to have a limited impact on ipsilateral recurrence which makes their use given their morbidities problematic. Such interventions do impact the frequency of contralateral occult in situ and invasive lesions. In the one study which permitted a comparison of local recurrence in irradiated vs nonirradiated breast, there was no added benefit of Tamoxifen in irradiated breasts. Some are attempting to identify a low-risk subset of DCIS which can be treated without surgical re-excision for margins or adjuvant irradiation. These studies are in progress but surrogates identified within the Van Nuys prospective series defined by grade and inadequate margins (≤ 1 mm) would suggest a significant recurrence and progression rate. DCIS remains a work in progress both in terms of classification and treatment. However, limited our progress in these areas we have certainly advanced from the oft-proclaimed mantra: "Radiation and Tamoxifen are standard of care."

Are We Overtreating Ductal Carcinoma in Situ (DCIS)?

OBJECTIVE: During 2015, the media was flooded with the issue of whether ductal carcinoma in situ (DCIS) was being overtreated and whether favorable cases could be simply watched (core biopsy only followed by surveillance). To answer this question, we looked at DCIS patients treated with excision alone with margin width <1 mm as inadequate and a surrogate for no treatment (surveillance group) and margin ≥1 mm as adequate surgical excision (excision group). METHODS: A total of 720 patients with pure DCIS treated with excision alone were stratified into two groups based on margin width and further subdivided by nuclear grade. Kaplan-Meier analysis was used to determine local recurrence-free survival. Differences in outcome were analyzed using the log-rank test. RESULTS: The 10-year local recurrence probabilities are statistically significant for low-grade versus high-grade and surveillance alone versus excision alone. The comparison of excision alone group with margins ≥1 mm for low-grade DCIS versus high-grade DCIS shows a 10-year local recurrence-free survival rate of 13 versus 35 % (p < 0.0001). The surveillance group had (margins <1 mm) had higher rates of recurrence in both the low-grade group (51 %) and high-grade group (70 %) (p < 0.001). CONCLUSIONS: This study indicates that there is not an acceptable level of local control in DCIS patients with tumor margins <1 mm that undergo active surveillance, regardless of tumor grade. Leaving even low-grade DCIS untreated would lead to local recurrence in more than half the patients in 10 years. Needle biopsy and surveillance for DCIS, regardless of grade, is just not adequate at this time.

Treatment selection for patients with ductal carcinoma in situ (DCIS) of the breast using the University of Southern California/Van Nuys (USC/VNPI) prognostic index.

The University of Southern California/Van Nuys Prognostic Index (USC/VNPI) is an algorithm that quantifies five measurable prognostic factors known to be important in predicting local recurrence in conservatively treated patients with ductal carcinoma in situ (DCIS) (tumor size, margin width, nuclear grade, age, and comedonecrosis). With five times as many patients since originally developed, sufficient numbers now exist for analysis by individual scores rather than groups of scores. To achieve a local recurrence rate of less than 20% at 12 years, these data support excision alone for all patients scoring 4, 5, or 6 and patients who score 7 but have margin widths ≥3 mm. Excision plus RT achieves the less than 20% local recurrence threshold at 12 years for patients who score 7 and have margins <3 mm, patients who score 8 and have margins ≥3 mm, and for patients who score 9 and have margins ≥5 mm. Mastectomy is required for patients who score 8 and have margins <3 mm, who score 9 and have margins <5 mm and for all patients who score 10, 11, or 12 to keep the local recurrence rate less than 20% at 12 years. DCIS is a highly favorable disease. There is no difference in mortality rate regardless of which treatment is chosen. The USC/VNPI is a numeric tool that can be used to aid the treatment decision-making process.

Ductal carcinoma in situ: recent history and areas of controversy.

The authors provide a perspective on the rapidly evolving field of prognostic analyses designed to quantify the risk of local recurrence in conservatively treated ductal carcinoma in situ (DCIS). These include morphologic features variously defined, nomograms, algorithms and multi-gene expression assays-all of which have completed against the perceived conclusions of the randomized trials of irradiation and Tamoxifen for DCIS: "all subsets benefit". At present the majority of newly diagnosed DCIS can be adequately treated with surgery alone. A number will require irradiation to achieve acceptable local control, and a minority will require mastectomy regardless of adjuvant treatments. Differences in the definition of prognostic factors and in the methods used to establish them is a major reason for the lack of consensus in treatment recommendation.

DCIS treated with excision alone using the National Comprehensive Cancer Network (NCCN) guidelines.

BACKGROUND: In 2008, the NCCN published guidelines allowing low-risk DCIS patients to be treated by excision alone. The goal of this study was to determine local and distant recurrence and breast-cancer specific survival in patients with DCIS that meet NCCN criteria and are treated with excision alone. METHODS: A prospective, single institution database was analyzed for patients with the following: pure ductal carcinoma in situ (no microinvasion), tumor extent 20 mm or less, age ≥50 years, margin width ≥2 mm, and nuclear grade 1 or 2 (non-high grade). Patients were treated with excision alone. Kaplan-Meier analysis was used to determine recurrence and survival rates. RESULTS: A total of 205 patients were treated with excision alone. The median age was 59 years. The median time of follow-up was 51 months. The median extent of disease was 8 mm. There were a total of nine local recurrences. The 6-year probability of local recurrence was 6.6 %. The 12-year probability of local recurrence was 7.8 %. The 12-year breast cancer-specific survival probability was 100 %. CONCLUSIONS: The 12-year local recurrence rate for DCIS patients in NSABP Protocol B-17 treated with excision alone was 32 %, and for excision plus radiation therapy, it was 16 %. In this study, retrospectively applying the NCCN Guidelines to our patients, the 12-year local recurrence rate for excision alone was 7.8 %. Patients with a low risk of local recurrence, if treated by excision alone, can be safely selected using the NCCN Guidelines.

Choosing treatment for patients with ductal carcinoma in situ: fine tuning the University of Southern California/Van Nuys Prognostic Index.

The University of Southern California/Van Nuys Prognostic Index is an algorithm that quantifies five measurable prognostic factors known to be important in predicting local recurrence in conservatively treated patients with ductal carcinoma in situ (tumor size, margin width, nuclear grade, age, and comedonecrosis). With three times as many patients since originally developed, sufficient numbers now exist for analysis by individual scores rather than groups of scores. To achieve a local recurrence rate of less than 20% at 12 years, these data support excision alone for all patients scoring 4, 5, or 6 and patients who score 7 but have margin widths ≥ 3 mm. Excision plus RT achieves the less than 20% local recurrence requirement at 12 years for patients who score 7 and have margins < 3 mm, patients who score 8 and have margins ≥ 3 mm, and for patients who score 9 and have margins ≥ 5 mm. Mastectomy is required for patients who score 8 and have margins < 3 mm, who score 9 and have margins < 5 mm, and for all patients who score 10, 11, or 12 to keep the local recurrence rate less than 20% at 12 years. These recommendations in this article represent substantial changes from those previously published.

Invasive local recurrence increased after radiation therapy for ductal carcinoma in situ.

BACKGROUND: It is thought that equal numbers of invasive and noninvasive recurrences develop after conservative treatment for ductal carcinoma in situ. We analyzed our data to see if this was true. METHODS: A prospective database of 878 conservatively treated patients with ductal carcinoma in situ was analyzed. RESULTS: Among 551 excision patients, there were 88 recurrences. Thirty-five percent were invasive. Among 327 excision plus radiotherapy patients, there were 59 recurrences. Fifty-three percent were invasive. In an attempt to predict which patients develop invasive recurrences, prolonged time to recurrence was the only statistically significant factor. CONCLUSIONS: The median time to local recurrence for irradiated patients was more than twice as long when compared with nonirradiated patients, during which there is more time for local recurrence to progress to invasion. Irradiated patients had more breast scarring, making diagnosis by palpation and mammography harder. Irradiated patients develop invasive recurrences at a statistically higher rate than nonirradiated patients. Follow-up evaluation with magnetic resonance imaging should be considered.

Outcomes for women with ductal carcinoma-in-situ and a positive sentinel node: a multi-institutional audit.

BACKGROUND: A positive sentinel lymph node (SLN) has been reported in 6% to 13% of patients with ductal carcinoma in situ (DCIS). Although it is well established that nodal status for invasive disease is prognostically important, the clinical relevance of a positive SLN in patients with DCIS remains undetermined. METHODS: SLN biopsy was performed on 470 high-risk patients with DCIS (22% of all patients with DCIS) at 3 institutions. Of these, 43 (9%) had SLN metastases. Pathology findings of positive cases were reviewed, and follow-up was obtained. At 2 of the 3 institutions, data were also collected on DCIS patients who had negative findings on SLN biopsy. For these 414 patients, univariate analyses of tumor characteristics were performed to identify factors associated with node positivity. RESULTS: Extensive disease requiring mastectomy (p = 0.02) and the presence of necrosis (p = 0.04) were associated with an increased risk of nodal positivity. Three (7%) of the 43 SLN-positive patients had macrometastases (pN1), 4 (9%) had micrometastases (pN1mi), and 36 (84%) had single tumor cells or small clusters (pN0(i+)). Of the 25 women that underwent completion axillary dissection, one was found to have a macrometastasis. On pathological review of the primary lesion, 2 (5%) of 43 patints were found to have microinvasion, and 2 (5%) lymphovascular invasion. Nine of 43 (21%) high-risk DCIS patients with a positive SLN and 9/470 (2%) of all high-risk DCIS patients were upstaged to AJCC stage I or II as a result of the SLN biopsy. At a median (range) follow-up of 27 (3-88) months, 1 patient had developed hepatic metastases. This patient had immunohistochemistry detected isolated tumor cells in her SLN (N0(i+)), and upon pathologic review, was found to have high-grade DCIS with microinvasion. CONCLUSION: SLN biopsy for high-risk DCIS patients is a mean of detecting those who may have unrecognized invasive disease and therefore are at risk for distant disease.

Breast cancer-specific mortality after invasive local recurrence in patients with ductal carcinoma-in-situ of the breast.

BACKGROUND: Previous studies on the efficacy of primary treatments for ductal carcinoma-in-situ (DCIS) have focused on local recurrence rates. Our objective was to detail the outcomes of local invasive recurrence, distant recurrence, and breast cancer mortality in patients previously treated for DCIS. METHODS: Clinical, pathologic, and outcome data were collected prospectively for 1236 patients with pure DCIS accrued from 1972 through 2005. RESULTS: There were 150 recurrences (87 DCIS and 63 invasive). Invasive local recurrence after mastectomy was rare (0.5% of patients) and after breast preservation was more frequent (12.0% of patients). The 12-year probabilities of breast cancer-specific mortality after mastectomy and after breast preservation were 0.8% and 1.0%, respectively. The 12-year breast cancer-specific mortality and distant disease probability for the 63 patients with invasive recurrences were 12% and 15%, respectively. CONCLUSIONS: Regardless of initial treatment, most patients with invasive local recurrence after treatment for DCIS can be treated and cured.