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Purpose: A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions., Methods: Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC)., Results: Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5-12%), 23% (95% CI 13-32%), and 51% (95% CI 26-75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well., Conclusions: This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.

We examined the clinical/pathologic features of ipsilateral second breast cancers (IP-SBCs) following breast-conserving surgery (BCS) for DCIS among community-treated patients and ascertained the degree of correlation between the features of index DCIS and IP-SBC events. From a Cancer Research Network cohort of DCIS patients diagnosed 1990-2001 and treated with BCS, we identified women who subsequently developed an ipsilateral DCIS or invasive breast cancer. All index DCIS tumors underwent expert pathology review. Pathologic characteristics of IP-SBCs were abstracted from available medical records. Logistic regression was used to examine associations between pathologic characteristics and identify factors associated with invasive versus non-invasive IP-SBC. Of 1969 DCIS patients, 182 developed an IP-SBC within a median of 38 months (range 6-160). IP-SBCs were slightly more commonly non-invasive (53 %) versus invasive (47 %). Of invasive IP-SBCs, 31 % were high grade, 67 % were <20 mm, 74 % were estrogen receptor positive, 7 % were HER2 positive, and 16 % were node positive. Of non-invasive IP-SBCs, 33 % were high grade. Comparing index DCIS and IP-SBC specimens, there was moderate-high correlation for HR status and grade. Among patients with IP-SBCs, those who were younger and whose index DCIS tumors were HR negative had shorter intervals (within 3 years) between index and IP-SBC diagnoses. No index DCIS feature was statistically significantly associated with an IP-SBC that was invasive versus non-invasive. Understanding the characteristics of SBCs and identifying correlations between these and index DCIS events could influence treatment choices for DCIS, and may help patients and providers develop treatment paradigms for SBCs.

Background: Various patient, treatment, and pathologic factors have been associated with an increased risk of local recurrence (LR) following breast-conserving therapy (BCT) for ductal carcinoma in situ (DCIS). However, the strength and importance of individual factors has varied; whether combining factors improves prediction, particularly in community practice, is uncertain. In a large, population-based cohort of women with DCIS treated with BCT in three community-based practices, we assessed the validity of the Memorial Sloan-Kettering Cancer Center (MSKCC) DCIS nomogram, which combines clinical, pathologic, and treatment features to predict LR., Methods: We reviewed slides of patients with unilateral DCIS treated with BCT. Regression methods were used to estimate risks of LR. The MSKCC DCIS nomogram was applied to the study population to compare the nomogram-predicted and observed LR at 5 and 10 years., Results: The 495 patients in our study were grouped into quartiles and octiles to compare observed and nomogram-predicted LR. The 5-year absolute risk of recurrence for lowest and highest quartiles was 4.8 and 33.1 % (95 % CI 3.1-6.4 and 24.2-40.9, respectively; p < 0.0001). The overall correlation between 10-year nomogram-predicted recurrences and observed recurrences was 0.95. Compared with observed 10-year LR rates, the risk estimates provided by the nomogram showed good correlation, and reasonable discrimination with a c-statistic of 0.68., Conclusions: The MSKCC DCIS nomogram provided good prediction of the 5- and 10-year LR when applied to a population of patients with DCIS treated with BCT in a community-based practice. This nomogram, therefore, is a useful treatment decision aid for patients with DCIS.

Purpose: The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences., Methods: We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182)., Results: Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09)., Conclusion: We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.

We aimed to identify clinicopathologic factors associated with local recurrence (LR) in a large population of DCIS patients treated with breast-conserving therapy between 1990-2001 in three health plans. Regression methods were used to estimate relative risks (RR) of LR. Among 2,995 patients, 325 had a LR [10.9 %; median follow-up 4.8 years (range 0.5-15.7)]. After adjusting for health plan and treatment, risk of LR was increased among women <45 years (RR = 2.1, 95 % CI 1.5-2.8), African-Americans (RR = 1.6; 95 % CI 1.1-2.1) and those with DCIS detected because of signs/symptoms (RR = 1.6; 95 % CI 1.2-2.0). After also adjusting for age and diagnosis year, pathologic features associated with increased LR were larger lesion size (RR = 2.9 for ≥20 low power fields of DCIS; 95 % CI 1.6-5.6) and involved (RR = 2.9; 95 % CI 1.6-5.2), or close margins (RR = 2.4; 95 % CI 1.6-3.8). Presentation with symptoms/signs was associated with increased risk of invasive recurrence; while African-American race, larger tumor size, and involved/close tumor margins were more strongly associated with increased risk of DCIS recurrence. Our findings suggest some risk factors differ for non-invasive and invasive LRs and that most factors are only moderately associated with increased LR risk. Future research efforts should focus on non-clinicopathologic factors to identify more powerful risk factors for LR.

Background: Breast-conserving surgery (BCS) is the most common treatment for ductal carcinoma in situ (DCIS); however, how often women experience subsequent diagnostic evaluations over time is not known., Methods: We identified 2948 women with DCIS who were treated with BCS from 1990 to 2001 and followed for up to 10 years at three integrated health-care delivery systems. We calculated the percentages of diagnostic mammograms and ipsilateral invasive procedures following the initial breast excision to treat DCIS, estimated the 10-year cumulative incidence of these procedures, and determined hazard ratios for both types of procedures with Cox regression modeling. All statistical tests were two-sided., Results: Over 10 years, 907 women (30.8%) had 1422 diagnostic mammograms and 1813 (61.5%) had 2305 ipsilateral invasive procedures. Diagnostic mammograms occurred in 7.3% of women in the first 6 months and continued at a median annual rate of 4.3%. Ipsilateral invasive procedures occurred in 51.5% of women in the first 6 months and continued at a median annual rate of 3.1%. The estimated 10-year cumulative risk of having at least one diagnostic mammogram after initial DCIS excision was 41.0% (95% confidence interval [CI] = 38.5% to 43.5%); at least one invasive procedure, 65.7% (95% CI = 63.7% to 67.8%); and either event, 76.1% (95% CI = 74.1% to 78.1%). Excluding events in the first 6 months following initial DCIS excision, corresponding risks were 36.4% (95% CI = 33.8% to 39.0%) for diagnostic mammograms, 30.4% (95% CI = 26.9% to 33.8%) for invasive procedures, and 49.5% (95% CI = 45.6% to 53.5%) for either event., Conclusions: Women with DCIS treated with BCS continue to have diagnostic and invasive breast procedures in the conserved breast over an extended period. The frequency of ongoing diagnostic breast evaluations should be included in discussions about treatment.

Background: We examined whether mammographic density predicts risk of second breast cancers among patients with ductal carcinoma in situ (DCIS)., Methods: The study included DCIS patients diagnosed during 1990 to 1997 and treated with breast-conserving surgery at Kaiser Permanente Northern California. Medical records were reviewed for clinical factors and subsequent breast cancers (DCIS and invasive). Ipsilateral mammograms from the index DCIS were assessed for density without knowledge of subsequent cancer status. Cox regression modeling was used to examine the association between mammographic density and risk of breast cancer events., Results: Of the 935 eligible DCIS patients, 164 (18%) had a subsequent ipsilateral breast cancer, and 59 (6%) had a new primary cancer in the contralateral breast during follow-up (median, 103 mo). Those with the greatest total area of density (upper 20% of values) were at increased risk for invasive disease in either breast [hazard ratio (HR), 2.1; 95% confidence interval (95% CI), 1.2-3.8] or any cancer (DCIS or invasive) in the ipsilateral (HR, 1.7; 95% CI, 1.0-2.9) or contralateral (HR, 3.0; 95% CI, 1.3-6.9) breast compared with those with the smallest area of density (bottom 20%). HRs for these same end points comparing those in the highest with those in the lowest American College of Radiology Breast Imaging Reporting and Data System category were 1.6 (95% CI, 0.7-3.6), 1.3 (95% CI, 0.7-2.6), and 5.0 (95% CI, 1.4-17.9), respectively. There was a suggestion of increasing risk of contralateral, but not ipsilateral, cancer with increasing percent density., Conclusions: Women with mammographically dense breasts may be at higher risk of subsequent breast cancer, especially in the contralateral breast., Impact: Information about mammographic density may help with DCIS treatment decisions., (©2010 AACR.)

Prior studies have shown that young patient age at diagnosis is associated with an increased risk of local recurrence among women with ductal carcinoma in situ (DCIS) treated with breast-conserving therapy. Whether this can be explained by differences in clinical or pathologic features of DCIS according to age is an unresolved issue. We compared clinical and pathologic features of DCIS among 657 women in 4 age groups: <45 years (n=111), 45 to 54 years (n=191), 55 to 64 years (n=160), and 65+ years (n=195). DCIS presented as a mammographic abnormality less often in younger than in older women (68%, 82%, 81%, and 86% for women <45, 45 to 54, 55 to 64, and 65+ y, respectively; P=0.003). Among the pathologic features analyzed, DCIS extent as determined by the number of low power fields was greater in younger than in older women (mean number of low power fields were 18.6, 14.2, 10.8, and 11.3 in women <45, 45 to 54, 55 to 64 and 65+ y; P<0.001). In addition, cancerization of lobules was present more often in younger than in older women (77%, 73%, 66%, and 50% for women <45, 45 to 54, 55 to 64 and 65+ y, respectively; P<0.0001). Of note, we found no statistically significant relationship between age and DCIS architectural pattern, nuclear grade, comedo necrosis or expression of estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2. We conclude that DCIS in younger women is more often symptomatic, is more extensive, and more often shows cancerization of lobules than DCIS in older women. Whether these features contribute to the higher local recurrence risk in young women with DCIS treated with the breast-conserving therapy requires further study.

Flat epithelial atypia is an alteration of mammary terminal duct lobular units that is considered to be a precursor to, or early stage in, the development of some forms of ductal carcinoma in situ. No prior study has systematically evaluated the relationship between various clinico-pathologic features of ductal carcinoma in situ and the presence of coexistent flat epithelial atypia. An understanding of such relationships could provide insight into the connection between flat epithelial atypia and ductal carcinoma in situ. We reviewed slides from 543 ductal carcinoma in situ patients enrolled in a case-control study assessing epidemiologic and pathologic risk factors for local recurrence. We examined the association between the presence of flat epithelial atypia and various clinical factors, pathologic features of the ductal carcinoma in situ, and the presence of coexistent atypical ductal hyperplasia, lobular neoplasia, and non-atypical columnar cell lesions. In univariate analysis, the presence of flat epithelial atypia was significantly related to ductal carcinoma in situ nuclear grade (most common in low grade, least common in high grade; P<0.0001), architectural pattern (most common in micropapillary and cribriform, least common in comedo; P<0.0001), absence of comedo necrosis (P<0.001), absence of stromal desmoplasia (P=0.02) and absence of stromal inflammation (P=0.03). In multivariable analysis, features of ductal carcinoma in situ independently associated with flat epithelial atypia were micropapillary and cribriform patterns and absence of comedo necrosis. Additionally, flat epithelial atypia was significantly associated with the presence of atypical ductal hyperplasia, lobular neoplasia, and columnar cell lesions in both univariate and multivariable analyses. These observations provide support for a precursor-product relationship between flat epithelial atypia and ductal carcinoma in situ lesions that exhibit particular features such as micropapillary and cribriform patterns and absence of comedo necrosis.