Initial Diagnosis Of Ductal Carcinoma In Situ Research Articles

Abstract IA021: Challenges of conducting active surveillance for ductal carcinoma in situ (DCIS)

Abstract The COMET (Comparing an Operation to Monitoring, with or without Endocrine Therapy) multicenter Phase III prospective trial randomizes women with low-risk DCIS to either standard of care (surgery +/- radiation therapy) or active surveillance (AS), a management approach in which mammograms and physical exams are used to monitor breast changes and determine when, or if, surgery is needed. It is currently open at 85 Alliance for Clinical Trials in Oncology sites and has accrued 905 patients as of 08/01/22. Initial recruitment challenges related to standardizing pathology eligibility criteria, with re-evaluation regarding the merits of central versus second pathology review, and discordance among pathologists regarding DCIS grade and necrosis. These discussions resulted in evidence-based protocol amendments that subsequently increased accrual. Patients that express a specific treatment preference often decline the arm to which they are randomized (not uncommon in trials of surgery de-escalation). Two consultants were recruited to implement the Quintet Recruitment Intervention, an initiative that utilizes qualitative/quantitative strategies to better understand recruitment in trials with very different treatment arms; acceptance rates in each randomized arm stabilized following this intervention. Patient and provider attitudes also presented a potential barrier to recruitment. Some surgeons lacked equipoise with the concept of AS and possess a “more is more” mentality; others express concern about younger patients undergoing AS; there are also financial implications of conducting AS rather than surgery for some surgeons. Radiologists often provide the initial diagnosis of DCIS to the patient; if the patient is told “DCIS is breast cancer”, they will expect to have surgery. Potential to consider AS may be limited if this preconceived notion about the need for surgery becomes established at the outset. DCIS has been disproportionately influenced by its terminology and classification, which may contribute to women feeling rushed into treatment decisions. Because of the way that DCIS is described to them, women considering AS may feel anxious knowing that the ‘threat’ of invasive breast cancer (IBC) has not been removed. Specific challenges to conducting AS for patients include those with a family history of breast cancer who express a strong desire for surgery. Women who undergo AS may experience ‘anticipatory anxiety’ regarding ongoing surveillance for the disease. Insufficient research exists about how relevant the outcomes of undergoing AS are to women and how patient perception around the potential ‘risk’ of IBC may impact upon their acceptance of AS. Collection of patient-reported outcomes in currently enrolling studies enables the challenges of undergoing AS to be understood from a patient perspective. Changing the treatment paradigm for DCIS requires multidisciplinary collaboration to drive change. However, providing more safe options for patients with low-risk DCIS will significantly reduce treatment-related harms. Citation Format: Thomas Lynch. Challenges of conducting active surveillance for ductal carcinoma in situ (DCIS) [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA021.

Abstract P1-22-02: Subsequent risk of ipsilateral breast events in a multinational DCIS cohort of 48.619 patients: A meta-analysis within the PRECISION consortium

Abstract Background: The PRECISION (PREvent ductal Carcinoma In Situ Invasive Overtreatment Now) CRUK Grand Challenge project focusses on discriminating hazardous from indolent ductal carcinoma in situ (DCIS). Aim of these analyses is to identify factors associated with a lower or higher risk of developing invasive breast cancer after an initial DCIS diagnosis. Knowledge of these factors is crucial in our quest to reducing overtreatment for women with DCIS. Many clinicopathological features are hypothesized to be important factors affecting the risk of a subsequent breast lesion. Most studies performed so far are from trial or single country studies, we now present an integrated analysis of four different cohorts from three countries.Methods: Four cohorts from the three countries participating in PRECISION were identified. A population based cohort from the Netherlands cancer registry (Dutch cohort); a population based, prospective, screening cohort from the United Kingdom (Sloane cohort); a single center cohort from MD Anderson Cancer Center (MDACC) and a subset of DCIS patients abstracted from a population based National Cancer Database Special Study cohort (NCDB subset) in the United States. Patient-level data from these cohorts were combined for this analysis. Subsequent ipsilateral invasive breast cancer (iIBC) and subsequent ipsilateral DCIS (iDCIS) were assessed at five and ten years by Kaplan Meier analysis. The cumulative incidence of iIBC was assessed in three treatment groups: breast conserving surgery only (BCS), breast conserving surgery with radiotherapy (BCS+RT) and mastectomy (MST). Cumulative incidence of iDCIS was assessed in patients receiving BCS or BCS+RT. Additionally, cumulative incidences were calculated for iIBC and IDCIS in patients who received endocrine treatment (ET) after BCS or BCS+RT versus patients who did not receive ET. All cumulative incidences were calculated with death as competing risk. Results: The joint PRECISION cohort consisted of 48,619 patients, diagnosed between 1999 and 2017. Median follow-up was 7.4 years (0.6-17.9). In preliminary analyses, Kaplan Meier curves showed broadly similar risks in iIBC and iDCIS between the four different cohorts. The cumulative incidence of iIBC was 1.6% at five years and 3.5% at 10 years. Five-year cumulative incidence of iIBC was highest in patients receiving BCS (3.4%) compared with patients receiving BCS+RT or MST (1.3%). The cumulative incidence of iDCIS was 1.7% at 5 years and 2.4% at 10 years. Five-year cumulative incidence of iDCIS was higher in patients receiving BCS (3.5%) compared to patients receiving BCS+RT (1.9%). In univariate analyses, the effect of ET on cumulative incidence of both iIBC and iDCIS was modest, especially with respect to radiotherapy. Conclusion: Overall, 5- and 10-year incidence of an ipsilateral in situ or invasive breast lesion was low and similar between the four different cohorts. The incidence of iIBC and iDCIS was higher in patients receiving BCS, compared to women receiving BCS+RT or MST. Table 1.Cohort and patient characteristicsDutch Cohort Sloane MDACCNCDB subsetTotal CohortN=18,995N=8,425N=1,820N=19,379N=48,619Cohort descriptionProspectiveNoYesNoNoPopulation basedYesYesNo, single centerYesScreening and non-screeningYesScreening onlyYesYesMean (min - max)Mean (min - max)Mean (min - max)Mean (min-max)Mean (min-max)Age diagnosis DCIS58.3 (21-94)59.8 (46-88)55.6 (20-90)59.7 (20-98)59.0 (20-98)Year of diagnosis (range)1999-20152003-20121999-20172007-20151999-2017Follow-up in years10.4 (0.5-21.1)5.3 (0.5-9.7)8.7 (0.25-17.8)5.8 (0.5-10.7)7.6 (0.25-2.1)N (%)N (%)N (%)N (%)N (%)GradeGrade 12,844 (15.0)784 (9.3)141 (7.8)3,158 (16.3)6,927 (14.3)Grade 25,952 (31.3)2,328 (27.6)737 (40.5)6,844 (35.3)15,861 (32.6)Grade 38,944 (47.1)5,305 (62.9)933 (51.3)7,848 (40.5)23,030 (47.3)Unknown grade1,255 (6.6)8 (0.1)9 (0.5)1,529 (7.9)2,801 (5.8)Type of surgeryBreast conserving surgery (BCS)11,790 (62.1)5,830 (69.2)1,031 (56.7)14,504 (74.8)33,155 (68.2)Mastectomy (MST)7,205 (37.9)2,595 (30.8)789 (43.4)4,875 (25.2)15,464 (31.8)Adjuvant treatmentRadiotherapy (RT)9,650 (50.8)3,418 (40.6)762 (41.9)10,620 (54.8)24,450 (50.3)Endocrine treatmentNA1,151 (13.6)999 (54.9)8,849 (45.7)10,999 (37.0)5 years Cumulative IncidencesiIBC1.4%2.3%1.6%1.7%1.6%iDCIS1.5%2.0%1.6%1.7%1.7%Vital statusAlive16,472 (86.7)8,147 (96.7)1,668 (91.7)18,161 (93.7)44,448 (91.4)Deceased2,523 (13.3)278 (3.3)152 (8.4)1,218 (6.3)4,171 (8.6)This work was supported by Cancer Research UK and by KWF Dutch Cancer Society (ref.C38317/A24043) Citation Format: Renée SJM Schmitz, Sandra W van den Belt-Dusebout, Chiara Cresta, Yat-Hee Liu, Michael Schaapveld, Karen Clements, Jasmine Timbres, Danalyn T Byng, Marc D Ryser, Yi Ren, Thomas Lynch, Terry Hyslop, Brian Menegaz, Deborah Collyar, Shelley Hwang, Alastair Thompson, Elinor Sawyer, Jelle Wesseling, Esther H Lips, Marjanka K Schmidt, Grand Challenge PRECISION consortium. Subsequent risk of ipsilateral breast events in a multinational DCIS cohort of 48.619 patients: A meta-analysis within the PRECISION consortium [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-22-02.

Racial and Ethnic Disparities in Rates of Invasive Second Breast Cancer Among Women With Ductal Carcinoma In Situ in Hawaiʻi

Women with ductal carcinoma in situ (DCIS) may develop a subsequent invasive second breast cancer (SBC). Understanding the association of racial and ethnic factors with the development of invasive SBC may help reduce overtreatment and undertreatment of women from minority groups. To evaluate risk factors associated with developing invasive ipsilateral SBC (iiSBC) and invasive contralateral SBC (icSBC) among women with an initial diagnosis of DCIS who are from racial and ethnic minority populations. This retrospective cohort study used deidentified data from the Hawai'i Tumor Registry of 6221 female Hawai'i residents aged 20 years or older who received a diagnosis of DCIS between January 1, 1973, and December 31, 2017. The 5 most populous ethnic groups were compared (Chinese, Filipino, Japanese, Native Hawaiian, and White). Data analysis was performed from 2020 to 2021. Patient demographic and clinical characteristics and the first course of treatment. The a priori study outcome was the development of invasive SBC. Logistic regression was used to identify factors associated with invasive SBC. Factors that were significant on unadjusted analyses were included in the adjusted models (ie, age, race and ethnicity, diagnosis year, DCIS histologic characteristics, laterality, hormone status, and treatment). The racial and ethnic distribution of patients with DCIS across the state's most populous groups were 2270 Japanese women (37%), 1411 White women (23%), 840 Filipino women (14%), 821 Native Hawaiian women (13%), and 491 Chinese women (8%). Women of other minority race and ethnicity collectively comprised 6% of cases (n = 388). A total of 6221 women (age range, 20 to ≥80 years) were included in the study; 4817 (77%) were 50 years of age or older, 4452 (72%) received a diagnosis between 2000 and 2017, 2581 (42%) had well or moderately differentiated histologic characteristics, 2383 (38%) had noninfiltrating intraductal DCIS, and 2011 (32%) were treated with mastectomy only. Of these 6221 women, 444 (7%) developed invasive SBC; 190 developed iiSBC (median time to SBC diagnosis, 7.8 years [range, 0.5-30 years]) and 254 developed icSBC (median time to SBC diagnosis, 5.9 years [range, 0.5-28.8 years]). On adjusted analysis, women who developed iiSBC were more likely to be younger than 50 years (adjusted odds ratio [aOR], 1.49; 95% CI, 1.08-2.06), Native Hawaiian (aOR, 3.28; 95% CI, 2.01-5.35), Filipino (aOR, 1.94; 95% CI, 1.11-3.42), Japanese (aOR, 1.58; 95% CI, 1.01-2.48), and untreated (aOR, 2.29; 95% CI, 1.09-4.80). Compared with breast-conserving surgery (BCS) alone, there was a decreased likelihood of iiSBC among women receiving BCS and radiotherapy (aOR, 0.45; 95% CI, 0.27-0.75), BCS and systemic treatment with or without radiotherapy (aOR, 0.40; 95% CI, 0.23-0.69), mastectomy only (aOR, 0.23; 95% CI, 0.13-0.39), and mastectomy and systemic treatment (aOR, 0.57; 95% CI, 0.33-0.96). Women who developed an icSBC were more likely to be Native Hawaiian (aOR, 1.69; 95% CI, 1.10-2.61) or Filipino (aOR, 1.70; 95% CI, 1.10-2.63). Risk of both iiSBC and icSBC decreased in the later years of diagnosis (2000-2017) compared with the earlier years (1973-1999). This study suggests that Native Hawaiian and Filipino women who initially received a diagnosis of DCIS were more likely to subsequently develop both iiSBC and icSBC. Japanese women and younger women were more likely to develop iiSBC. Subpopulation disaggregation may help guide clinical treatment and screening decisions for at-risk subpopulations.

Predictors of Sentinel Lymph Node Metastasis in Postoperatively Upgraded Invasive Breast Carcinoma Patients

Simple SummaryRoutine sentinel lymph node (SLN) biopsy (SLNB) is not necessary for breast-conserving surgery (BCS)-treated ductal carcinoma in situ (DCIS) but is indicated for underestimated invasive carcinoma (IC) postoperatively. In this retrospective study, we aimed to investigate the factors contributing to SLN metastasis in underestimated IC patients with an initial diagnosis of DCIS by core needle biopsy. We found that only the features related to IC, including an IC tumor size (>0.5 cm) and the presence of LVI, could be used as risk predictors of SLN metastasis. In the absence of any predictors, the incidence of positive SLNs was very low (2.6%) in the total population and extremely low (1.3%) in the BCS subgroup. Therefore, we suggest that SLNB may be omitted in patients who initially underwent BCS without risk predictors on final pathological assessment. However, further prospective studies are warranted before its clinical application.Sentinel lymph node (SLN) biopsy (SLNB) usually need not be simultaneously performed with breast-conserving surgery (BCS) for patients diagnosed with ductal carcinoma in situ (DCIS) by preoperative core needle biopsy (CNB), but must be performed once there is invasive carcinoma (IC) found postoperatively. This study aimed to investigate the factors contributing to SLN metastasis in underestimated IC patients with an initial diagnosis of DCIS by CNB. We retrospectively reviewed 1240 consecutive cases of DCIS by image-guided CNB from January 2010 to December 2017 and identified 316 underestimated IC cases with SLNB. Data on clinical characteristics, radiologic features, and final pathological findings were examined. Twenty-three patients (7.3%) had SLN metastasis. Multivariate analysis indicated that an IC tumor size > 0.5 cm (odds ratio: 3.11, p = 0.033) and the presence of lymphovascular invasion (odds ratio: 32.85, p < 0.0001) were independent risk predictors of SLN metastasis. In the absence of any predictors, the incidence of positive SLNs was very low (2.6%) in the total population and extremely low (1.3%) in the BCS subgroup. Therefore, omitting SLNB may be an acceptable option for patients who initially underwent BCS without risk predictors on final pathological assessment. Further prospective studies are necessary before clinical application.

Abstract P5-08-05: Risk of subsequent events after initial diagnosis of ductal carcinoma in situ - A large multi-center registry study

Abstract Introduction: Ductal carcinoma in situ (DCIS) is a pre-malignant lesion but 14-53% will not progress to an invasive cancer. Large, well characterized DCIS datasets with long term follow up are sparse, and there is uncertainty regarding the long term effects of various treatment modalities on subsequent breast events (SBE). Here, we analyze trends identified in the SBE rates from patients treated at two large academic breast care centers in California, UCSF and UCSD. Methods: Institutional Cancer Registries were used to collect demographic, clinical, imaging and pathologic data. Patients aged 18 years and older without any prior history of breast disease whose first diagnosed breast neoplasm was DCIS and who had at least 6 months of follow up were included. Only SBE beyond 6 months after initial diagnosis were included. All mastectomy types and associated adjuvant treatment were grouped. All patients not undergoing surgery were grouped. Differences between patients in the various treatment groups were assessed using χ2, Student’s t-test, and one-way ANOVA. Poisson regression was used to compare differences in SBE rates between treatment groups. For analysis, follow up times were divided into three 5 years periods (0-5, 6-10, 11-15 years) after initial DCIS diagnosis. Results: 2730 patients - 1575 (57.7%) at UCSF and 1155 (42.3%) at UCSD - were diagnosed between 1985 and 2017 and included in the study. 1910 (70.0%) underwent breast conserving surgery (BCS), 672 (24.6 %) had mastectomy, 144 (5.3%) did not have surgery, and 4 (0.1%) had missing surgery status. 623 (22.8%) received adjuvant endocrine therapy (ET), 2081 (76.2%) did not and 26 (1.0%) had missing adjuvant endocrine therapy status. 1092 (40.0%) received adjuvant radiation therapy (RT), 1619 (59.3%) did not and 19 (0.7%) had unknown radiation therapy status. Median follow up time for all patients was 7.9 years. 305 patients were diagnosed with SBE. Of these, 144 (47.2%) were in situ and 147 (48.2%) were invasive including 16 (5.2%) metastatic lesions, and 14 (4.6%) had missing invasiveness. Of the 289 patients who did not have a metastatic second lesion, 176 (60.9%) SBE were ipsilateral, 88 (30.4%) were contralateral, and 25 (8.7%) had missing SBE laterality. The overall incidence (i) for any SBE over the entire study period was 1.4%/yr. Compared to women who were treated with BCS alone (N=642, i=2.14%/yr, 95% CI 1.76-2.51), SBE rates were lower in women undergoing BCS with RT (N=719, i=1.13%/yr, 95% CI 0.87-1.40, p&amp;lt;0.001), BCS with RT and ET (N=356, i=0.63%/yr, 95% CI 0.30-0.97, P&amp;lt;0.001), and mastectomy (N=672, i=1.00%/yr, 95% CI 0.75-1.25, p&amp;lt;0.001) but were not significantly different for patients undergoing BCS with ET (N=159, i=2.25%/yr, 95% CI 1.35-3.15, p=0.813). Within the first 5 years of diagnosis, mastectomy, BCS with RT, and BCS with RT and ET all lowered the SBE rate of ipsilateral in situ and invasive SBE (p&amp;lt;0.05, in each case). In contrast, no treatment modalities impacted the rate of contralateral SBE rate during any of the time periods. Importantly, the majority of patients, even with BCS alone never had a subsequent event and only 147 had an invasive event overall. Conclusion: This large two-center registry study reveals that the rate of invasive and in situ SBE after an initial DCIS diagnosis are comparable. The effect of each treatment modality on SBE incidence rates are consistent with other published studies, with the notable exception of BCS and ET which requires deeper investigation. As expected, local treatment affects mostly ipsilateral events within the first 5 years after initial diagnosis, without impacting the rate of contralateral SBE. Complementary molecular and cellular profiling of selected specimens are underway to help build a more precise BSE risk model and prevent overtreatment. Citation Format: Thomas O'Keefe, Christina Yau, Eliza Jeong, Emma Iaconetti, Paul Kim, Ann Griffin, Joseph McGuire, Rita Mukhtar, Laura Esserman, Olivier Harismendy, Gillian L. Hirst. Risk of subsequent events after initial diagnosis of ductal carcinoma in situ - A large multi-center registry study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-05.

Relationship Between Anthropometric Factors and Risk of Second Breast Cancer Among Women With a History of Ductal Carcinoma In Situ.

BackgroundWomen with ductal carcinoma in situ (DCIS) have an elevated risk of a second breast cancer, but few data are available regarding the impact of modifiable lifestyle factors on this risk.MethodsIn a population-based case–control patient study of women with a history of DCIS in western Washington diagnosed between 1996 and 2013, 497 patients diagnosed with DCIS and a second ipsilateral or contralateral invasive or in situ breast cancer were enrolled. There were 965 matched control patients with one DCIS diagnosis. Associations between anthropometric factors and risk of an invasive or in situ second breast cancer event were evaluated using conditional logistic regression. Statistical tests were two-sided.ResultsObesity (body mass index [BMI] ≥ 30 kg/m2) at initial DCIS diagnosis was associated with a 1.6-fold (95% confidence interval [CI] = 1.2 to 2.2) increased risk of any second breast cancer and a 2.2-fold increased risk of a contralateral second breast cancer (95% CI = 1.4 to 3.3) compared with normal weight women (BMI < 25 kg/m2). BMI and weight, both at initial DCIS diagnosis and at the time of the second breast cancer diagnosis, were positively associated with risk of any second and second invasive breast cancers (odds ratio = 1.01–1.04, all P ≤ .03).ConclusionsAlthough additional confirmatory studies are needed, obesity appears to be an important contributor to the risk of second breast cancers within the growing population of women with DCIS. This has potential clinical relevance with respect to identifying which women with a history of DCIS may require more careful monitoring and who may benefit from lifestyle modifications.

Treating Second Breast Events After Breast-Conserving Surgery for Ductal Carcinoma in Situ.

Background: Because of screening mammography, the number of ductal carcinoma in situ (DCIS) survivors has increased dramatically. DCIS survivors may face excess risk of second breast events (SBEs). However, little is known about SBE treatment or its relationship to initial DCIS care. Methods: Among a prospective cohort of women who underwent breast-conserving surgery (BCS) for DCIS from 1997 to 2008 at institutions participating in the NCCN Outcomes Database, we identified SBEs, described patterns of care for SBEs, and examined the association between DCIS treatment choice and SBE care. Using multivariable regression, we identified features associated with use of mastectomy, radiation therapy (RT), or antiestrogen therapy (AET) for SBEs. Results: Of 2,939 women who underwent BCS for DCIS, 83% received RT and 40% received AET. During the median follow-up of 4.2 years, 200 women (6.8%) developed an SBE (55% ipsilateral, 45% invasive). SBEs occurred in 6% of women who underwent RT for their initial DCIS versus 11% who did not. Local treatment for these events included BCS (10%), BCS/RT (30%), mastectomy (53%), or none (6%); only 28% of patients received AET. Independent predictors of RT or mastectomy for SBEs included younger age, shorter time to SBE diagnosis, and RT or AET for the initial DCIS. Conclusions: A sizable proportion of patients with SBEs were treated with mastectomy, most especially those who previously received RT for their initial DCIS and those who developed an ipsilateral SBE. Despite the occurrence of an SBE, relatively few patients received AET. Future studies should investigate optimal treatment approaches for SBEs, including the benefit of mastectomy versus lumpectomy for an ipsilateral SBE and the benefit of AET for a hormone-receptor-positive SBE contingent on AET use for the initial DCIS diagnosis.

Abstract P3-01-06: Can axillary evaluation be omitted in patients preoperatively diagnosed with ductal carcinoma in situ by core needle biopsy?

Abstract Background Patients diagnosed with ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) have a great chance of upgrading invasive cancer on the final pathology. Positive axillary lymph nodes can be found in these patients. The present study sought to identify clinicopathological factors associated with upgrading and axillary lymph nodes metastasis in patients preoperatively diagnosed with DCIS by CNB. Materials and Methods This study identified 604 patients (cT1-3N0M0) with preoperative diagnosis of pure DCIS by CNB who had undergone axillary evaluation from August 2006 to December 2015 at Fudan University Shanghai Cancer Center (FUSCC). Predictors of upgrading and axillary lymph nodes metastasis were analyzed, respectively. Results Of all 604 patients, 513 (84.93%) and 91 (15.07%) patients had undergone sentinel lymph nodes biopsy (SLNB) and axillary lymph nodes dissection (ALND), respectively. Overall, 121 (20.03%) and 193 (31.95%) patients were upgraded to DCIS with microinvasion (DCISM) and IDC on final pathology, respectively. Positive axillary lymph nodes were identified in 41 (6.79%) patients, of which 35 (5.80%) patients had 1-2 positive axillary lymph nodes, 6 (0.99%) patients had 3 or more positive axillary lymph nodes. Among patients with axillary lymph nodes metastasis, 4 (9.76%), 4 (9.76%) and 33 (80.48%) patients were in DCIS, DCISM and IDC group, respectively. Predictors of upgrading included tumor size on ultrasonography (P=0.001), Ki-67 (P=0.046) and molecular subtype (P=0.007) in univariate analysis. In multivariate analysis, patients with larger tumor size on ultrasonography (&amp;gt;2cm) (OR 1.767, P=0.001) were more likely to be upgraded on final pathology. Also, ER+ HER2+ patients were more likely to be upgraded than ER+ HER2- patients (OR 1.659, P=0.047). Factors associated with axillary lymph nodes metastasis included nipple discharge (P&amp;lt;0.001), tumor size on pathology (P=0.037), number of lesions (P=0.039), axillary evaluation methods (P=0.029) and molecular subtype (P=0.049) in univariate analysis. Whereas, only nipple discharge and larger tumor size on pathology (&amp;gt;2cm) reached statistical significance in multivariate analysis (OR 5.959, P&amp;lt;0.001; OR 2.361, P=0.042). In addition, further analysis showed upgrading on final pathology had a significant influence on axillary lymph nodes status (P&amp;lt;0.001). However, this correlation was not shown between patients with DCIS and DCISM in pairwise comparison. Conclusion The data of upgrading and axillary lymph nodes metastasis in patients with an initial diagnosis of DCIS by CNB was comparable in this cohort with published data. Despite of a 51.98% upgrading rate, the rate of axillary lymph nodes metastasis in these patients is low, which supports the omission of axillary evaluation in selected patients. Citation Format: Si J, Yang B, Guo R, Huang N, Quan C, Chen J, Wu J. Can axillary evaluation be omitted in patients preoperatively diagnosed with ductal carcinoma in situ by core needle biopsy? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-06.

Trends in Treatment Patterns and Clinical Outcomes in Young Women Diagnosed With Ductal Carcinoma In Situ

BackgroundAlthough it is known that the risk of a second breast cancer event among young women diagnosed with ductal carcinoma in situ (DCIS) is higher than in older women, the effect of current treatment options on long-term outcomes in this subgroup of women remains poorly defined. We aimed to evaluate national treatment trends and determine their effect on second breast cancer risk and overall survival among young women diagnosed with DCIS. Materials and MethodsSurveillance, Epidemiology, and End Results data from 1998 to 2011 were used to analyze 3648 DCIS patients younger than age 40 years. ResultsAmong all treatment options, breast-conserving surgery (BCS) with radiation therapy (BCS + RT) was the most prevalent (36.1%) followed by mastectomy (MTX) without contralateral prophylactic MTX (CPM; 25.8%), BCS alone (22.2%), and MTX with CPM (15.8%). Risk of a second ipsilateral event was > 5-fold and > 2-fold lower within 2 years and 5 years of initial DCIS diagnosis, respectively, in women who received BCS + RT compared with BCS alone; and overall survival was 3-fold higher in women who received BCS + RT. However, MTX with or without CPM did not show an increase in overall survival compared with BCS + RT. In addition, although the percentage of young women who receive MTX with CPM has increased in recent years, MTX with CPM did not show an increased benefit in survival compared with MTX without CPM. ConclusionThe results of our study suggest that more aggressive treatments do not offer survival benefits over BCS + RT; thus, clinical treatment options in young women with DCIS should be carefully considered.

Evaluating the Risk of Upstaging HER2-Positive DCIS to Invasive Breast Cancer.

Overexpression of human epidermal growth factor 2 (HER2) in invasive breast cancer (IBC) is an independent poor prognostic factor. However, the significance of HER2 overexpression in ductal carcinoma in situ (DCIS) is not well defined. The current study assessed the correlation of HER2+ DCIS with the rate of upstaging to IBC on the final pathology. The study retrospectively analyzed patients with the diagnosis of DCIS on core needle biopsy (CNB) at the authors' institution from 2009 to 2016. Data were analyzed using two-sample t tests. Multivariate analysis was performed using logistic regression. The study found that HER2+ DCIS had significantly higher rates of upstaging to IBC than HER2- DCIS (odds ratio [OR] 1.89; p=0.012). In addition, triple-positive disease was more than two times more likely to be upstaged (OR 2.5; p=0.01), whereas patients with estrogen (ER)-positive, progesterone (PR)-positive, and HER2- diseases were half as likely to be upstaged (OR 0.5; p=0.04). Upstaging did not differ for patients with triple-negative disease (OR 0.89; p=0.8). Additionally, patients with HER2+ DCIS were significantly younger regardless of ER/PR status (p=0.03). The overexpression of HER2 in patients with an initial diagnosis of DCIS on CNB were twice as likely to have IBC on the final pathology as those who did not. The results suggest that overexpression of HER2 may serve as a biomarker for risk stratification of patients with DCIS and may help to guide treatment strategies in the future. For institutions in which HER2 testing may be performed on DCIS, patients should be counseled appropriately about the risk of upgrade to IBC.

Risk prediction for local versus regional/metastatic tumors after initial ductal carcinoma in situ diagnosis treated by lumpectomy.

Among women diagnosed with ductal carcinoma in situ (DCIS), we identified factors associated with local invasive cancer (LIC) and regional/metastatic invasive cancer (RMIC) and provide 10-year risks based on clinically relevant factors. We created a retrospective, population-based cohort of 1492 women with an initial diagnosis of DCIS (1983-1996) treated by lumpectomy alone. Histological and molecular markers (Ki67, ER, PR, COX-2, p16, ERBB2) were collected on DCIS cases with a subsequent tumor (DCIS, LIC, or RMIC) and a subsample of frequency-matched controls without subsequent tumors. Competing risks methods were used to identify factors associated with LIC and RMIC and cumulative incidence methods to estimate 10-year risks for combinations of factors. Median follow-up time was 12.6years (range 0.5-29.5years). The overall 10-year risk of LIC (11.9%) was higher than for RMIC (3.8%). About half of women with initial DCIS lesions are detected by mammography and p16 negative and have a 10-year risk of LIC of 6.2% (95% CI 5.8-6.8%) and RMIC of 1.2% (95% CI 1.1-1.3%). Premenopausal women whose DCIS lesion was p16 positive or p16 negative and detected by palpation had high 10-year risk of LIC of 23.0% (95% CI 19.3-27.4%). Ten-year risk of RMIC was highest at 22.5% (95% CI 13.8-48.1%) for those positive for p16, COX-2, and ERRB2, and negative for ER, but prevalence of this group is low at 3%. Ten-year risk of LIC and RMIC is low for the majority diagnosed with DCIS. Combinations of molecular markers and method of detection of initial DCIS lesion can differentiate women at low and high risk of LIC and RMIC.

Predictive factors for positive surgical margins in the treatment of breast ductal carcinoma in situ.

Surgery is the main form of treatment for ductal carcinoma in situ (DCIS) of the breast. Among other factors, treatment success requires that the surgical margins are free of disease, to reduce the risk of recurrence. The purpose of this study was to analyze factors that might be associated with positive margins in patients diagnosed with DCIS. A retrospective analysis was performed of hospital databases from the year 2006 to 2014, to identify patients with an initial diagnosis of DCIS made by percutaneous biopsy. Age, the presence of disease symptoms, lesion size on mammogram, and the presence of estrogen receptors, and their relationship to the surgical margins were evaluated in 249 patients. Shapiro and Wilcoxon-Mann-Whitney tests were used to verify that the data were normally distributed. Chi-squared test was used to verify the independence of the variables. Lesions measuring 1.55 cm or greater had a relative risk of positive margins after conservative surgery of 1.39 (95% confidence interval [95% CI]: 1.02-1.90). The presence of symptoms had a relative risk of positive margins after conservative surgery of 1.54 (95% CI: 1.17-2.02). Lesions measuring 1.55 cm or greater and the presence of symptoms are risk factors for positive margins in the treatment of ductal carcinoma in situ. Therefore, these patients need a better surgical planning in order to reduce the risk of positive margins. There is a clear need for large prospective studies to validate our findings and define other factors that might contribute to the success of surgical resection for ductal carcinoma in situ.

Risk Factors Associated with Sentinel Lymph Node Biopsy in Patients with a Preoperative Diagnosis of Ductal Carcinoma &amp;lt;i&amp;gt;In Situ&amp;lt;/i&amp;gt;

Purpose: Sentinel lymph node (SLN) biopsy has become the gold standard for axillary staging of invasive breast cancer. However, some controversy has existed concerning the usefulness of SLN biopsy in ductal carcinoma in situ (DCIS). In this study, we tried to identify the usefulness of SLN biopsy in patients with an initial preoperative diagnosis of DCIS. Methods: A retrospective analysis was performed using single-center data of 415 patients with an initial diagnosis of DCIS between January 2003 and December 2013. Many features were correlated with upstaging and positive SLN biopsy using univariate analysis and multivariate analysis. Results: A total of 415 patients with a preoperative diagnosis of DCIS were enrolled in this study. Total 320 of 415 patients (77.1%) underwent axillary evaluation via SLN biopsy, axillary lymph node dissection, or additional axillary lymph node dissection, and 24 of 320 patients (7.5%) were diagnosed with axillary lymph node metastasis or micrometastases in the lymph nodes. Of 415, 296 patients (71.3%) underwent SLN biopsy and 16 patients (5.4%) had positive SLN biopsy. The rate of upstaging to invasive cancer was 4.1% (17 of 415 patients) on final pathology. Of the 17 patients who were upstaged to invasive carcinoma at final pathology, seven patients (41.2%) had a positive SLN biopsy. The statistically significant factors of upstaging were large tumor size (≥2 cm), histologic features of intermediate or high-grade tumor, and positive SLN biopsy. Conclusion: SLN biopsy should be considered in patients with high risk DCIS as a part of the primary surgical procedure. Keywords: Breast; Noninfiltrating intraductal carcinoma; Sentinel lymph node biopsy

Is Sentinel Lymph Node Dissection Warranted for Patients with a Diagnosis of Ductal Carcinoma In Situ?

Positive sentinel lymph node (SLN) findings in ductal carcinoma in situ (DCIS) range from 1 to 22 % but have unknown biologic significance. This study sought to identify predictors of positive SLNs and to assess their clinical significance for patients with an initial diagnosis of DCIS. The study identified 1234 patients with an initial diagnosis of DCIS who underwent SLN dissection (SLND) at our institution from 1997 through 2011. Positive SLN findings were categorized as isolated tumor cells (ITCs) (≤0.2 mm), micrometastases (>0.2-2 mm), or macrometastases (>2 mm). Predictors of positive SLNs were analyzed, and survival outcomes were examined. Positive SLN findings were identified in 132 patients (10.7 %): 66 patients with ITCs (5.4 %), 36 patients with micrometastases (2.9 %), and 30 patients with macrometastases (2.4 %). Upstaging to microinvasive (n = 68, 5.5 %) or invasive (n = 259, 21.0 %) cancer occurred for 327 patients (26.5 %). Factors predicting positive SLNs included diagnosis by excisional biopsy (odds ratio [OR] 1.90; P = 0.007), papillary histology (OR 1.77; P = 0.006), DCIS larger than 2 cm (OR 1.55; P = 0.030), more than three interventions before SLND (4 interventions: OR 2.04; P = 0.022; ≥5 interventions: OR 3.87; P < 0.001), and occult invasion (microinvasive: OR 3.44; P = 0.001; invasive: OR 6.21; P < 0.001). The median follow-up period was 61.7 months. Patients who had pure DCIS with and without positive SLNs had equivalent survival rates (100.0 vs 99.7 %; P = 0.679). Patients with occult invasion and positive SLNs had the worst survival rate (91.7 %; P < 0.001). Occult invasion and more than three total interventions were the strongest predictors of positive SLN findings in patients with an initial diagnosis of DCIS. This supports the theory of benign mechanical transport of breast epithelial cells. Except for patients at high risk for invasive disease, routine use of SLND in DCIS is not warranted.

Metastatic Invasive Breast Cancer Recurrence Following Curative-Intent Therapy for Ductal Carcinoma In Situ

The development of an invasive breast cancer recurrence outside of the breast parenchyma following curative-intent therapy for ductal carcinoma in situ (DCIS) is rare. We describe the patient and tumor characteristics associated with such recurrences. A retrospective review was conducted of 621 patients who were treated for DCIS between 2004 and 2009. Patient, tumor, and treatment characteristics were collected. Descriptive statistics were utilized for data summary and data were compared using χ(2), where appropriate. Of 621 patients who underwent curative-intent therapy for DCIS, 12 (1.9%) developed an invasive metastatic recurrence. Primary local therapy at the time of the initial DCIS diagnosis included 11 patients who underwent mastectomy and one who had lumpectomy and adjuvant radiotherapy. The metastatic recurrences were in chest wall and/or ipsilateral axillary lymph nodes only (n = 6) or distant sites with or without ipsilateral axillary or supraclavicular lymph nodes (n = 6). Of the 12 patients with invasive recurrence, eight had high grade DCIS with comedo necrosis at initial diagnosis. The biomarker profiles of the invasive recurrences included 55% estrogen receptor positivity, 45% progesterone receptor positivity, and 73% Her2/neu amplification. Patient age, tumor grade, presence of comedo necrosis, biomarker profile, and surgical treatment were not predictive of recurrence. Invasive metastatic recurrence following adequate local therapy for DCIS is uncommon and likely represents progression of unidentified invasive disease at the time of diagnosis. The majority of invasive recurrences were Her2/neu amplified. Further studies are necessary to determine if such a unique biomarker profile correlates with metastatic recurrence.

Axillary Failure in Patients Treated with MammoSite Accelerated Partial Breast Irradiation

The risk of axillary failure (AF) after accelerated partial breast irradiation (APBI) using MammoSite brachytherapy is unknown and has been source of concern as the axillary region is not treated with this technique. We aimed to determine the rate of AF in patients treated with APBI and identify factors associated with its occurrence. Data from the American Society of Breast Surgeons MammoSite Registry Trial were reviewed and patients with AF were identified. Clinical, pathologic and treatment-related variables were analyzed to determine which factors were associated with AF. A total of 1440 patients underwent MammoSite APBI. A total of 1449 cases were treated (9 patients received bilateral treatment), 1255 cases (87%) of invasive breast cancer and 194 cases (13%) of ductal carcinoma in situ (DCIS). The median length of follow-up was 59 months. There were 10 patients who had an AF. Of these, 9 patients had an initial diagnosis of invasive cancer and 1 had an initial diagnosis of DCIS. The 5-year actuarial rate of AF was 0.79%. The only independent risk factor for AF identified by multivariate analysis was the presence of high-grade disease (P=.008). The 5-year overall survival rate in patients with an AF was 77.8% (there was 1 death related to breast cancer). The rate of AF after MammoSite APBI is low and appears to be similar to that achieved with whole-breast irradiation.

Ductal carcinoma-in-situ of the breast with subsequent distant metastasis and death.

The rare patient diagnosed with pure ductal carcinoma-in-situ (DCIS) develops distant breast cancer metastases (DM). We sought to identify clinical and pathologic predictors of DM. The clinical and pathologic characteristics of patients with DM after a diagnosis of pure DCIS from 1996 to 2009 were analyzed. Twenty five patients with DM after an initial diagnosis of DCIS were identified; 3 were treated at our institution and 22 were originally treated elsewhere. The rate of DM was 0.14% among 2,123 patients originally treated at our institution. Among all patients with DM, 73.7% had DCIS with necrosis, and 62% had DCIS that did not express estrogen receptor. Twenty-four percent of patients with DM were African American, compared to 11.5% of the total study population. The median time from DCIS to DM was 4.5 years. Sixteen patients (66%) had a preceding or simultaneous invasive locoregional recurrence (LRR); nine (34%) did not. At last follow-up, 14 patients (56%) had died of disease; median time to death was 2.4 years. No dominant variables could be identified in patients who developed DM with or without a LRR. 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.

Ductal CarcinomaIn Situand Sentinel Lymph Node Biopsy

PurposeAxillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to evaluate whether sentinel lymph node biopsy (SLNB) is required in patients with an initial diagnosis of ductal carcinoma in situ (DCIS).MethodsA retrospective analysis was performed of 78 patients with an initial diagnosis of DCIS between December 2002 and April 2010 and who proceeded to have either SLNB or axillary node dissection performed as part of their primary surgical procedure. The study focused on the rates of axillary node metastasis and the underestimation of invasive carcinoma at an initial diagnosis.ResultsForty-eight patients underwent SLNB and 18 patients underwent axillary node dissection. Only 1 of 66 patients (1.5%) had a positive sentinel lymph node. After definite surgery, the final diagnosis was changed to invasive ductal carcinoma (IDC) in 12 patients and DCIS with microinvasion in 2 patients; 14 of 78 patients (17.9%) were therefore underestimated at preoperative histological examinations. In 35 patients who were diagnosed DCIS by core needle biopsy (CNB), 13 patients (37.1%) were upstaged into IDC or DCIS with microinvasion in the final diagnosis. The statistically significant factors predictive of invasive breast cancer were a large tumor size and HER2 overexpression.ConclusionThe rates of SLNB positivity in pure DCIS are very low, and there is continuing uncertainty about its clinical importance. However in view of the high rate of underestimation of invasive carcinoma in patients with an initial diagnosis of DCIS, SLNB appears to be appropriate in these patients, especially in the case when DCIS is diagnosed by a core needle biopsy. In patients with an initial diagnosis of DCIS by CNB, SLNB should be considered as part of the primary surgical procedure, when preoperative variables show a tumor larger than 2.35 cm and with HER2 overexpression.

Risk Factor of Invasive Breast Cancer in Patients with Preoperative Diagnosis of Ductal Carcinoma in Situ

Purpose: Ductal carcinoma in situ (DCIS), unlike invasive ductal carcinoma, does not require sentinel lymph node biopsy or axillary lymph node dissection because the possibility of axillary lymph node metastasis is low. However, occasionally, despite preoperative diagnosis of DCIS, invasive ductal carcinoma can be diagnosed by postoperative biopsy. Therefore, a study of the associated risk factors is necessary. Methods: 198 patients with an initial diagnosis of DCIS, treated between February 2005 and December 2009, were retrospectively analyzed. Associations between clinical and pathologic factors were analyzed for significance using univariate and multivariate analyses. Results: Of the 198 patients, 57 (28.8%) were found to have invasive disease on final pathology. Multivariate analysis revealed 4 independent predictors of invasive cancer upon final pathology: diagnosis by needle biopsy (OR, 3.165; P=0.008), positive p53 on preoperative biopsy (OR, 2.494; P=0.019) DCIS size (＞2 ㎝) on microscopic finding (OR, 2.683; P=0.014), and relatively young age (OR, 0.958, P=0.046). Of the 13 patients with positive axillary lymph nodes, 11 (84.6%) were shown to have invasive cancer on final pathology (P＜0.001). Conclusion: In cases of preoperative diagnosis based on needle biopsy, positive p53, large tumor, and relatively young age, an SLNB procedure can be considered because in almost 30% of the patients an invasive carcinoma is found after surgery.

Ductal Carcinoma in Situ: Dilemma or Denouement

TO THE EDITOR: On the basis of multiple randomized trials for ductal carcinoma in situ (DCIS), it has long been claimed that no low-risk subset defined by favorable clinical or pathologic features could be identified and spared irradiation. The report by Hughes et al successfully identified for the first time a low-risk subset in a prospective trial that was spared radiation therapy. Their results were based on careful mammographic-pathologic correlation and complete sequential tissue processing—methods that are essential to define the size and margin status and to exclude invasion. This type of comprehensive approach has been advocated for some time and was the consensus recommendation of three consecutive image-detected breast cancer consensus conferences and the recently published College of American Pathologists’ guidelines for DCIS. As the accompanying Editorial noted, such methods were not employed by any of the randomized trials. As a result, there were much higher local recurrence rates with or without irradiation and a sizeable number of metastatic first events in B17 and B24, a reflection of unrecognized invasive disease compared with prospective nonrandomized studies. Moreover, this approach was decidedly not part of the prospective study of Wong et al, on which we have previously commented. In our experience, the two therapeutic interventions for which patients have the greatest dread are radiation therapy and axillary lymph node dissection. Relatively few of our patients seek a bilateral mastectomy for DCIS, and most who initially discuss this will choose alternative breast-conserving treatments when they are properly informed. For the lowto intermediate-grade lesions, 25 mm or smaller with 3 mm or more margins, the 7-year rate of IBE was 10.5%, half of which were invasive. In our experience, 10% of patients with invasive recurrences after an initial diagnosis of DCIS die of metastatic breast cancer. That means if 400 patients are not irradiated, we can expect 42 recurrences, 21 of which will be invasive, two of whom will die. If these 400 patients are irradiated, the numbers will be halved to 21 recurrences, 10 of which are invasive, one of whom will die. In other words, we must irradiate 400 patients to save one life. Of the 400 patients, 358 do not benefit from radiation because they would not have recurred. All of them, however, are exposed to the morbidities of radiation therapy. Are we certain that no lives will be shortened because of irradiation? We are not. Long-term data with current techniques do not exist; however, available long-term outcome data of breast irradiation note small increases in mortality related to cardiac disease and smaller risks of lung carcinoma. It hardly seems worth irradiating 400 women to prevent 21 recurrences and one death. Does it not make more sense to carefully follow these patients, re-excise the 42 who recur, and irradiate them at that time, thus sparing 358 the time, expense, and morbidity of breast radiation therapy? Michael D. Lagios The Breast Cancer Consultation Service, Tiburon, CA