Initial Ductal Carcinoma In Situ Research Articles

Endocrine therapy initiation among women diagnosed with ductal carcinoma in situ breast cancer from 2001-2016.

487 Background: Endocrine therapy (ET) initiation in people within 1 year of diagnosis of estrogen-receptor-positive (ER+) ductal carcinoma in situ (DCIS) has ranged from 21-45% in prior studies; however, these studies did not evaluate initiation post-2011 and may not reflect current patterns of use. ET use following ER+ DCIS diagnosis can reduce the relative risks of recurrence and contralateral breast cancer by 30-50%. We evaluated ET initiation over time and by demographic, tumor, and treatment characteristics in the Kaiser Permanente Breast Cancer Survivors Study between 2001-2016. Methods: We included people aged 20+ years diagnosed with unilateral DCIS with at least 1 year of cancer-free follow-up from three U.S. integrated health systems. We excluded people with ER-negative disease, no surgery, and those who received chemotherapy or unknown radiation therapy. ET dispensings (tamoxifen and aromatase inhibitors) were extracted from electronic pharmacy records within 1 year of a person’s initial DCIS breast cancer diagnosis. Using generalized linear models with a log link and Poisson distribution, we estimated relative rates (RRs) of ET use (vs none) over time and by demographic, tumor, and other treatment characteristics. Results: Among 1,782 pre- and postmenopausal people, 577 (32%) initiated ET within 1 year of diagnosis. From 2001-2016, ET use did not change over time (34% vs 36%), tamoxifen use declined slightly (34% vs 29%), and aromatase inhibitor use increased slightly (0% vs 7%). People were less likely to initiate ET if they were ≥65 years, Black, had borderline or unknown ER status, were not tested for ER, had breast conserving surgery (BCS) without radiation, or had a unilateral mastectomy. Conclusions: Only one-third of people with DCIS diagnosed in a community healthcare setting and potentially eligible for ET, initiated treatment within 1 year of their diagnosis. Previous studies have shown long-term benefits of ET use in people with DCIS; however, we saw no increase in use over time. Concerns about side-effects, overdiagnosis and overtreatment of DCIS, and confusion about treatment guidelines may explain relatively low ET initiation.[Table: see text]

Estrogen Receptor-negative Ductal Carcinoma In Situ (DCIS) of the Breast - an Institutional Review of Outcomes.

Estrogen receptor (ER)-negative [ER(-)] invasive breast cancers (IBCs) are known to be more aggressive than their ER(+) counterparts. This is less well defined for ductal carcinoma in situ (DCIS). This study investigated the outcomes following the treatment of ER(-) DCIS. A total of 103 ER(-) DCIS patients diagnosed between 2004-2018 were retrospectively analyzed. Median follow-up was 63.9 months. Statistical analysis included descriptive statistics, non-parametric tests, T-test, logistic regression. The outcomes were compared to a group of 102 ER(+) DCIS patients from our institution. Any breast event (BE) occurred in 10 (9.7%) patients at a median of 3.2 (1.7-7.2) years. The incidence of ipsilateral breast events (IBEs) was 5.8% (6/103). All IBE cases were ER(-) DCIS. All (n=4) contralateral breast events (CBEs) were ER(+) including 3 IBCs. Cumulative incidence of any BEs at 1, 2, and 5 years was 0%, 1.1%, and 9.1%, respectively. Among patients with ER(-) DCIS who developed BE, breast conserving surgery (BCS) had been performed for the initial DCIS in 90% of cases. In those without any BE, the BCS rate (vs. mastectomy) was 58.1% (p=0.08). Adjuvant radiotherapy after BCS was used less often among patients with vs. without subsequent BE (55.5% vs. 77.4%) (p=0.22). Predictors for BE occurrence were not identified. The incidence of any BE among patients with ER(+) DCIS was 6.9% and was not significantly different compared to ER(-) DCIS group (p=0.46). ER(-) DCIS outcomes were similar to our institutional ER-positive DCIS group and the previously reported ones for predominantly ER-positive DCIS cohorts.

Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5–10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.

Mode of detection of second breast cancers in patients undergoing surveillance after treatment of ductal carcinoma in situ.

571 Background: The incidence of ductal carcinoma in situ (DCIS) has increased, resulting in more women undergoing post-treatment surveillance for second breast cancers. National Comprehensive Cancer Network (NCCN) guidelines recommend annual breast imaging and physical exam every 6-12 months for five years, and then annually. We assessed mode of detection (imaging, patient-reported, or physical exam) of secondary DCIS and/or invasive breast cancer in a large cohort of DCIS patients undergoing surveillance after treatment of primary DCIS. Methods: We performed a retrospective cohort study of DCIS patients treated between 1/1/2008 and 1/1/2011 within a large integrated health care system. Patients had a minimum of 5 years of follow up. Patient demographics, treatment for primary DCIS, and tumor characteristics (of both primary DCIS and secondary cancer) were obtained from the electronic health record or from manual chart review. Chart review also included mode of detection of secondary breast cancers. Results: Our study cohort consisted of 1561 women with DCIS, with a median age of 59 years (range 32-92) at time of diagnosis. Among initial DCIS tumors, tumor grade was low/intermediate in 942 (60.3%) and high in 619 (39.7%); 1274 (81.6%) were estrogen receptor positive, and 988 (63.3%) progesterone receptor positive. Surgical treatment for the initial DCIS included lumpectomy (n=1134, 72.6%), unilateral mastectomy (n=320, 20.5%), or bilateral mastectomy (n=61, 3.9%), and included sentinel lymph node biopsy in 211 (14%) of patients. Additionally, 691 (44.3%) received radiation therapy and 440 (28.2%) received endocrine therapy. The cohort was followed for a median of 120 months, during which we identified 179 women (11.5%) with a secondary cancer detected at a median time of 57 months. Of the second breast cancers, 77 (43.0%) were ipsilateral, 98 (54.8%) contralateral, and 4 (2.2%) presented with distant metastases; 110 (61.5%) were invasive, 65 (36.3%) were DCIS, and 4 (2.2%) Paget’s disease. See table for mode of detection of second breast cancers. Conclusions: In our cohort of patients undergoing surveillance following initial diagnosis and treatment of DCIS, 2% of secondary breast cancers were detected by clinical breast exam, a rate similar to incidental detection at time of plastic surgery. These results can help inform future recommendations for surveillance of second breast cancers in DCIS patients. [Table: see text]

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.

Predictive factors of invasion in ductal carcinoma in situ diagnosed by core-needle biopsy.

To identify clinical, radiological, and histopathological characteristics that could be predictive factors of microinvasive/invasive breast carcinoma in patients with diagnosis of ductal carcinoma in situ (DCIS) by core-needle biopsy. This is a retrospective study conducted from 2006-2017, which included women ≥18 years of age with initial DCIS, and who were treated with surgery. Final diagnosis was divided in DCIS and microinvasive/invasive carcinoma. 334 patients were included: 193 (57.8%) with DCIS and 141 (42.2%) with microinvasive/invasive carcinoma (microinvasive 5.1%, invasive 37.1%). Lymph node metastasis occurred in 16.3%. Differences between DCIS and microinvasive/invasive groups included the presence of palpable nodule (36.7% vs. 63.2%), radiological nodule (29% vs. 51%), bigger radiological-tumor size (1.2 cm vs. 1.7 cm), and larger microcalcification extension (2.5 cm vs. 3.1 cm), all of these variables p ≤0.05. Hormonal receptors and HER2 expression were similar. After logistic regression analysis, predictive factor of invasion was the presence of palpable nodule (OR = 4.072, 95%CI = 2.520-6.582, p <0.001) and radiological multicentric disease (OR = 1.677, 95%CI = 1.036-2.716, p = 0.035). In patients with DCIS, palpable nodule, and radiological multicentric disease, upgrade to microinvasive/invasive is high, and sentinel lymph node is recommended.

Association between antidepressant use and second breast cancer event after ductal carcinoma in situ diagnosis: a nested case-control study.

Controversy exists regarding the potential relationship between antidepressant use and risk of breast cancer. No previous studies have evaluated the relationship between antidepressant use after diagnosis of ductal carcinoma in situ (DCIS) and risk of a subsequent breast cancer restricted to women with a history of DCIS. We conducted a population-based, nested case-control study in western Washington State. Cases included 337 women diagnosed with DCIS and a subsequent breast cancer and they were compared to 592 individually matched controls (on age, year of DCIS diagnosis, primary treatment, histology, grade, and disease-free survival time) who were diagnosed with DCIS but not a subsequent breast cancer. Information on antidepressant use after DCIS diagnosis was obtained from comprehensive medical records reviews. Antidepressant use was defined as greater or equal to 3 months of duration. Antidepressant use after initial DCIS was associated with a 1.4-fold increased risk of a subsequent breast cancer event (adjusted OR 1.41, 95% CI 1.02, 1.95). Similar risks were observed when assessing individual antidepressant classes, however, there was no sufficient power across specific classes of antidepressants. Antidepressant use after DCIS diagnosis was associated with an increased risk of subsequent breast cancer in women. Further studies are needed to confirm the associations observed.

The role of stromal immune microenvironment in the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer

AimThe first aim of the study was to compare the scores and types of stromal immune cells in 30 patients with primary DCIS and in the same patients after invasive breast recurrence in order to assess possible differences in both during tumor progression. The second aim was to evaluate possible differences in stromal cells of 30 patients with primary DCIS before progression and in the control group of 11 DCIS patients without recurrence during long-term follow-up.Material and methodsEvaluation of tumor-infiltrating lymphocytes (TILs) and immunohistochemical stains for immune cell markers CD4, CD8, CD20, CD138, FOXP3, CD163 and TGF beta was performed on the stroma of primary DCIS before progression, invasive breast cancer of the same patients after progression and DCIS without progression.ResultsThe comparison of stromal cells in 30 patients with initial DCIS and its invasive recurrence revealed an increased level of CD20 + immune cells (median score 5% vs. 17%, respectively, p < 0.001) and CD163 + cells (median score 1% vs. 5%, respectively, p < 0.001) in invasive breast cancer. The comparison of stromal cells in 30 patients with initial DCIS before recurrence and the control group of 11 patients with DCIS without recurrence showed statistically significant difference for CD138 + cells, which were more prevalent in patients with worse prognosis (median score 0 vs. 2%, respectively, p < 0.001). No similar relationship was found for the other tested cells as well as for TGF-beta.ConclusionsCD138 + immune cells that were more prevalent in patients with a worse prognosis should be explored in further studies to confirm or exclude their role as a potential biological marker of DCIS invasive recurrence.

14 Oral - Risk of subsequent in situ and invasive lesions after a primary diagnosis of ductal carcinoma in situ with follow-up time up to 28 years

Background: Ductal Carcinoma in situ (DCIS) is considered a potential precursor of invasive breast cancer (BC) and is treated by mastectomy or breast conserving surgery (BCS) often supplemented with radiotherapy (RT). This study aimed to assess the long-term risk of ipsilateral subsequent in situ and invasive lesions after a diagnosis of primary DCIS and the association with initial DCIS treatment.

Abstract C108: Race and risk of subsequent aggressive breast cancer in women with ductal carcinoma in situ

Abstract Background: Ductal carcinoma in situ (DCIS) is a heterogeneous group of preinvasive neoplastic lesions in the breast. Black women with DCIS are more likely than White counterparts to subsequently develop invasive cancer in either breast. We examined the association between race and the risk of developing aggressive invasive breast cancer, characterized with hormone receptor (HR) negativity (both estrogen receptor and progesterone receptor negative) or intermediate-to-high risk Oncotype scores (≥18) in HR-positive subtypes, in women with DCIS. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) data, we identified 133,705 women with DCIS diagnosed between 1990 and 2015, and 12.9% were black. Cox proportional hazards regression was used to estimate relative risks (RRs) of subtypes of subsequent invasive breast cancer in either breast and metastatic breast cancer. Results: During a median follow-up of 90 months, 6889 women developed invasive breast cancer and 6384 had HR status available. The risks of HR-defined (Pheterogeneity=0.0004) and Oncotype score-defined (Pheterogeneity=0.046) invasive breast cancer subtypes after initial DCIS significantly varied by race. The RR of HR-negative invasive breast cancer was 1.86 (95% CI 1.57-2.20) and the RR of subsequent invasive subtypes with intermediate-to-high Oncotype scores was 1.29 (95% CI 1.00-1.67) in Black women with DCIS, which was independent of age, pathologic features and treatment. In women who had data on HR status in both primary DCIS and subsequent invasive breast cancer, the HR discordant rate was higher in Black patients than in White patients (21.2% versus 18.9%, P=0.003), which was largely driven by HR loss (15.4% versus 9.5%). Black race was more strongly associated with HR loss (RR=1.92, 95% CI 1.41-2.61, Pheterogeneity=0.03) than HR concordance (RR=1.24, 95% CI 1.09-1.41) and HR gain (RR=1.04, 95% CI 0.67-1.62). Conclusions: Black women with DCIS had higher risks of developing aggressive invasive breast cancer compared with White counterparts, which may contribute to their worse survival. Future studies examining biologic differences in the progression of DCIS for Black patients are warranted. Citation Format: Ying Liu, Graham Colditz. Race and risk of subsequent aggressive breast cancer in women with ductal carcinoma in situ [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C108.

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.

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.

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.

Abstract P4-15-04: A longitudinal cohort study to identify risk factors for the development of invasive cancer in unresected DCIS

Abstract Background: The variable natural history of ductal carcinoma in situ (DCIS) remains poorly understood. Randomized trials of active surveillance versus guideline concordant care are currently underway: the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) trial in the US, LOw Risk dcIS (LORIS) trial in the UK and Low Risk Dcis (LORD) in Europe. Given this context, we examined the outcomes of a contemporary group of women with DCIS who did not undergo initial surgical resection. Methods: A longitudinal cohort of women diagnosed with DCIS on needle biopsy who did not undergo initial surgical excision for ≥1 year were identified through the Cancer Registry with case note and death certificate review for subsequent outcomes. Results: Eighty-nine eligible women with DCIS alone diagnosed on needle biopsy (most with 14-gauge core needle biopsy) between 1998 and 2010 were identified. The mean age at diagnosis was 72 years (range 44-94 years) with mean follow-up (diagnosis to death, invasive disease or last review) of 62 months (range 12-180 months). Twenty-nine women (33%) developed histologically proven invasive breast cancer, 28 at the site of the initial DCIS biopsy, after a mean interval of 54 months (range 12-144 months): 14/29 (48%) women originally had high grade DCIS, 10/31 (32%) intermediate grade and 3/17 (18%) low grade DCIS (initial grade not known in 12). Time to detect a diagnosis of invasive breast cancer was associated with initial grade of DCIS (p=0.0016, log-rank test): after mean intervals of 41 months (high grade), 69 months (intermediate grade) and 78 months (low grade) respectively. Younger age was associated with development of invasive disease (p&amp;lt;0.003, Mann-Whitney U-Test). High grade (grade 3) invasive breast cancer exclusively occurred in women with a prior diagnosis of high grade DCIS. Invasion was more frequent in lesions with calcification as the predominant feature than those without (23/50 v. 5/25; p&amp;lt;0.05, Fisher exact test). Forty-four women were prescribed endocrine therapy, use of which was associated with a lower rate of invasive breast cancer (p&amp;lt;0.05). Ultimately 18 women underwent surgery, 17 for invasive cancer. The mean interval from DCIS diagnosis to death was 76 months for those who developed invasive cancer; 48/89 women died, 12 had a certified cause of death as breast cancer. Conclusion: High grade DCIS, mammographic microcalcification and lack of endocrine therapy were associated with progression to invasion. The findings suggest surgical excision of high grade DCIS should continue but provides support that women with DCIS features which include low grade should be considered for the COMET, LORIS or LORD active surveillance trials. Citation Format: Maxwell AJ, Clements K, Hilton B, Dodwell DJ, Evans A, Olive K, Pinder SE, Thomas J, Matthew WG, Thompson AM. A longitudinal cohort study to identify risk factors for the development of invasive cancer in unresected DCIS [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 P4-15-04.

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.

Abstract 4738: Risk of ipsilateral invasive breast cancer after DCIS: a comparison of primary DCIS and subsequent invasive disease by morphological and immunohistochemical analysis

Abstract INTRODUCTION. The wide spread adoption of population-based breast cancer screening has led to a substantial increase in diagnosis of ductal carcinoma in situ (DCIS). When detected, almost all DCIS is treated to prevent progression to invasive disease, even though the majority of DCIS will never progress. Yet, we are unable to discriminate harmless from potentially hazardous DCIS. Hence, there is an urgent need to find characteristics of DCIS and biomarkers that predict subsequent invasive tumor development. In this study, we compared primary DCIS lesions with their subsequent ipsilateral invasive breast cancer (iIBC), to explore how the initial DCIS lesion and its subsequent iIBC are related. PATIENTS AND METHODS. We used a population-based, nation-wide cohort consisting of 2,654 women who were treated for primary DCIS by breast conserving surgery (BCS) only. Within a median follow-up time of 10.7 years, 316 women developed a subsequent iIBC (12%). FFPE tissue blocks of both DCIS and subsequent iIBC could be collected for 158 of these 316 women. We assessed histology characteristics, tumor location, estrogen and progesterone receptor status, p16 expression, and HER2 and p53 overexpression. Additionally, DNA and RNA were simultaneously isolated from 100 DCIS and 100 matched subsequent iIBC specimens for extensive molecular profiling. RESULTS. More than 95% of the invasive recurrences were located at or near the site of the primary DCIS. Concordant histological grade was found in 94% of the matched pairs and identical immunohistochemical (IHC) marker expression in 58%. Of the 44 patients with HER2 positive DCIS, 36% developed HER2 negative iIBC. Furthermore, this change in HER2 status was also a main cause of a change in surrogate intrinsic subtype (based on ER, PR, HER2) between DCIS and iIBC, which was observed in 16% of the patients. These dissimilarities were not found when we compared invasive disease with synchronous DCIS (present in 83 of 158 patients). Molecular analyses is still ongoing. CONCLUSION. This is the first time that an unbiased comparison could be made between primary DCIS and its subsequent iIBC within such a large patient group, integrating clinical, histological and IHC data. Our results suggest that the majority of invasive breast cancers in our cohort reflect outgrowth of residual disease based on tumor location and histological grade. DCIS and iIBC are very similar when comparing histological grade, but frequently show differences on the IHC level. Remarkably, the dissimilarities in HER2 status and surrogate intrinsic subtype as seen in primary DCIS vs. iIBC are missing when comparing IBC with synchronous DCIS. As a next step, we will analyse the lesions on the molecular level, to verify these findings and to look for molecular characteristics of DCIS that could be associated with progression to invasive disease. Citation Format: Lindy L. Visser, Lotte L. Elshof, Koen van de Vijver, Emma J. Groen, Mathilde Almekinders, Marjanka K. Schmidt, Flora van Leeuwen, Emiel J. Rutgers, Michael Schaapveld, Esther H. Lips, Jelle Wesseling. Risk of ipsilateral invasive breast cancer after DCIS: a comparison of primary DCIS and subsequent invasive disease by morphological and immunohistochemical analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4738. doi:10.1158/1538-7445.AM2017-4738

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.

Predictors of Recurrence in Patients Diagnosed with Ductal Carcinoma In Situ

Although patients diagnosed with ductal carcinoma In Situ (DCIS) enjoy a favorable prognosis, recurrence after definitive management does occur in a subset of these patients. Factors influencing the development of recurrence remain poorly understood. A retrospective chart review of 205 consecutive patients who presented to an academic breast center with DCIS from 2000 to 2003 was conducted under an Institutional Review Board-approved protocol. With a median follow-up of 8.5 years, 14 (6.8%) of the 205 patients who presented with DCIS between 2000 and 2003 had a recurrence of their DCIS. The median age of all patients at the time of diagnosis of their initial DCIS was 55.5 years (range, 35.8 to 88.9 years). Patients who experienced tumor recurrence were more likely to have Grade 3 DCIS on initial diagnosis compared with patients without recurrence (72.7 vs 35.4%, P = 0.032). The odds ratio of tumor recurrence for high-grade compared with low-grade DCIS was 4.39. Patient age, race, tumor size, tumor histologic subtype, or histopathologic features was not associated with recurrence. Patients with high-grade DCIS are more likely to recur than patients with low-grade DCIS, and this seems to be more predictive of recurrence than other clinicopathologic markers.

Abstract P3-14-05: Recurrence in Patients Diagnosed with Ductal Carcinoma in Situ: Predictors and Prognostic Significance

Abstract Background: While patients diagnosed with ductal carcinoma in situ (DCIS) enjoy a favorable prognosis, recurrence after definitive management does occur in a subset of these patients. Factors influencing the development of recurrence, and the ultimate impact of this event on overall survival, remain poorly understood. We sought to determine clinicopathologic factors affecting recurrence and the prognostic role this plays in patients with DCIS. Methods: A retrospective chart review of 205 consecutive patients who presented to an academic breast center with DCIS from 2000 to 2003 was conducted under an IRB-approved protocol. Non-parametric statistical analyses comparing patients who recurred to those who did not were then performed using SPSS Statistical Software. Results: With a median follow-up of 8.5 years, 14 (6.8%) of the 205 patients who presented with DCIS between 2000–2003 had an invasive or in situ recurrence. The median age of all patients at the time of diagnosis of their initial DCIS was 55.5 years (range; 35.8–88.9). 51 (24.9%) had possible (albeit not definitive) microinvasion on their initial specimen. The majority were grade 2 (91; 44.4%), and 99 (48.3%) had comedo histology. The median size of DCIS on the initial excision was 10 mm (range; 0.1–80). All patients underwent definitive surgery to negative margins. The mean time to recurrence was 4.7 years (range; 1.1–10.6). On bivariate analysis, histologic grade of DCIS was the only factor that was significantly correlated with the risk of recurrence. Patients with grade 3 DCIS were more likely to develop a recurrence compared to those with grade 2 or grade 1 DCIS (12.3% vs. 3.3% vs. 0%, respectively, p = 0.032). Patient age, race, extent of DCIS, and histologic subtype were not associated with recurrence (see table below). 5-year actuarial overall survival was no different between those who developed a recurrence and those who did not (92.9 vs. 95.7%, p = 0.171). Conclusions: Approximately 7% of patients diagnosed with DCIS will recur within 10 years. Patients with high grade DCIS are more likely to recur, and this seems to be more predictive of recurrence than other clinicopathologic markers. Irrespective of whether or not patients with DCIS recur, overall survival is not significantly different between these two groups, and patients with DCIS enjoy an outstanding prognosis regardless. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-14-05.

Ten-Year Risk of Diagnostic Mammograms and Invasive Breast Procedures After Breast-Conserving Surgery for DCIS

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. 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. 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. 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.