Understanding of the biology and clinical behavior of ductal carcinoma in situ (DCIS) is currently inadequate. The aim of this comprehensive review was to identify important molecular biological markers associated with DCIS and candidate markers associated with increased risk of ipsilateral recurrence after diagnosis of DCIS. A comprehensive systematic review was performed to identify studies published in the past 10 years that investigated biological markers in DCIS. To be included in this review, studies that investigated the rate of biological expression of markers had to report on at least 30 patients; studies that analyzed the recurrence risk associated with biomarker expression had to report on at least 50 patients. There were 6,252 patients altogether in our review. Biological markers evaluated included steroid receptors, proliferation markers, cell cycle regulation and apoptotic markers, angiogenesis-related proteins, epidermal growth factor receptor family receptors, extracellular matrix-related proteins, and COX-2. Although the studies in this review provide valuable preliminary information regarding the expression and prognostic significance of biomarkers in DCIS, common limitations of published studies (case-series, cohort, and case-control studies) were that they were limited to small patient cohorts in which the extent of surgery and use of radiotherapy or endocrine therapy varied from patient to patient, and variable methods of determining biomarker expression. These constraints made it difficult to interpret the absolute effect of expression of various biomarkers on risk of local recurrence. No prospective validation studies were identified. As the study of biomarkers are in their relative infancy in DCIS compared with invasive breast cancer, key significant prognostic and predictive markers associated with invasive breast cancer have not been adequately studied in DCIS. There is a critical need for prospective analyses of novel and other known breast cancer molecular markers in large cohorts of patient with DCIS to differentiate indolent from aggressive DCIS and better tailor the need and extent of current therapies.

Background This study examines a modern cohort of women with ductal carcinoma-in-situ (DCIS) in order to identify potential differences in clinical presentation, treatments, and outcome based on age. Methods From 1996 to 2009, a total of 2037 patients with pure DCIS were treated. Clinical presentation, pathologic factors, type of surgery and adjuvant therapy, and local recurrence rates among age groups were compared and analyzed. Median follow-up was 5.2 years. Results There were 132 patients (6.5 %) aged <40, 1,690 (83 %) aged 40–70, and 215 (10.5 %) aged >70. Younger patients (<40) were significantly more likely to have a family history of breast cancer, present with clinical symptoms, undergo mastectomy with immediate reconstruction, and have a contralateral prophylactic mastectomy (P < 0.05). Older patients (>70) were significantly less likely to use adjuvant radiotherapy and tamoxifen (P <0.05). No significant differences were found in DCIS size, estrogen receptor status, necrosis, or contralateral breast cancer based on age. Among women <40, 29.3 % had evidence of multicentric disease versus 17.7 and 13.3 % in the women aged 40–70 and those >70, respectively (P = 0.004). On multivariate analysis, younger age (<40), larger-size DCIS (≥1.5 cm), and no use of radiotherapy were significant independent predictors of locoregional recurrence. The 5 year rates of local recurrence were 10.1 % in women <40 compared with 3.2 % in older women (P = 0.005). Conclusions Younger patients with DCIS more often have multicentric disease, present with clinical findings, and opt for or require mastectomy with immediate reconstruction. Conservative surgery is only appropriate for younger patients if adjuvant radiotherapy is delivered.

Background The impact of close margins in patients with ductal carcinoma-in situ (DCIS) treated with mastectomy is unclear; however, this finding may lead to a recommendation for postmastectomy radiotherapy (PMRT). We sought to determine the incidence and consequences of close margins in patients with DCIS treated with mastectomy. Methods The records of 810 patients with DCIS treated with mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors were analyzed with respect to final margin status. Median follow-up was 6.3 years. Results Overall, 94 patients (11.7 %) had close margins (positive, n = 5; negative but ≤1 mm, n = 54; 1.1–2.9 mm, n = 35). Independent risk factors for close margins included multicentricity, pathologic lesion size ≥1.5 cm, and necrosis, but not age, use of skin-sparing mastectomy, or immediate reconstruction (p >0.05). Seven patients received PMRT, and none had a locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR rate was 1 % (5.0 % for margins ≤1 mm, 3.6 % for margins 1.1–2.9 mm, and 0.7 % for margins ≥3 mm [p <0.001]). The 10-year rate of contralateral breast cancer was 6.4 %. On multivariate analysis, close margins was the only independent predictor of LRR (p = 0.005). Conclusions Close margins occur in a minority of patients undergoing mastectomy for DCIS and is the only independent risk factor for LRR. As the LRR rate in patients with close margins is low and less than the rate of contralateral breast cancer, PMRT is not warranted except for patients with multiple close/positive margins that cannot be surgically excised.

DM after a diagnosis of pure DCIS is rare. Although most patients with DM have a preceding invasive LRR, some present with subsequent DM alone. Further study is required to identify clinical and pathologic predictors of this more rapid disease progression.

Background The clinicopathologic, mammographic, and sonographic findings in patients with pure ductal carcinoma in situ (DCIS) were assessed by estrogen receptor (ER) expression. Methods After institutional review board approval, patients with pure DCIS evaluated from January 1996 to July 2009 with known ER status and available imaging were identified. Images were reviewed per the ACR BI-RADS® lexicon (4th edition). Clinical, pathologic, and imaging characteristics were analyzed by ER status using t-test, chi-square test, and Fisher’s exact test. Results Of 1219 patients with pure DCIS and known ER status identified, 1187 with complete data were included. Mammography was performed in all 1187 patients and sonography in 519 (44%). There were 972 (82%) patients with ER-positive and 215 (18%) with ER-negative disease. ER-negative DCIS was more likely to be high grade (93% vs 44%, p<0.0001), associated with comedonecrosis (64% vs 29%, p<0.0001), and multifocal (23% vs 15%, p=0.009). On sonography, ER-negative DCIS was more likely to be visible (61% vs 46%, p=0.004), larger (mean size, 2.3 vs 1.6 cm, p=0.006), and show posterior shadowing (53% vs 28%, p=0.006). Mastectomy was more frequently performed for ER-negative DCIS (47% vs 37%, p=0.008). Palpable DCIS was visible on sonography in 55% of cases and mammography in 81%. Compared with ER-positive palpable DCIS, ER-negative palpable DCIS was larger and more likely to be visible on sonography. Compared with ER-positive noncalcified DCIS, ER-negative noncalcified DCIS was less likely to be visible on mammography. Conclusion ER-positive and ER-negative pure DCIS have different clinicopathologic and imaging characteristics. ER-negative DCIS is associated with worse prognostic factors then ER-positive DCIS. On sonography, ER-negative DCIS is more frequently visible than ER-positive DCIS, tends to be larger, and more frequently demonstrates posterior shadowing.