Breast DCIS Research Articles

Abstract P5-19-01: The impact of streamlined processes and patient-directed messaging to improve enrollment in a remote, pragmatic clinical trial

Abstract Background Recent advances in technology have made it possible to conduct remote clinical trials that allow individuals to participate from home with comfort, privacy, and ease. Despite these advances, challenges persist in running remote trials, such as survey question redundancies, lack of patient-initiated data-sharing tools, and unclear patient communication around critical enrollment steps. The Women Informed to Screen Depending on Measures of risk (WISDOM) Study is a pragmatic, preference-tolerant randomized control breast cancer screening trial comparing personalized risk-based screening to traditional, annual screening. The study population includes women ages 40-74 without a history of breast cancer or DCIS. Since 2016, study enrollment has been available to all women in the U.S. who meet study eligibility criteria. Since October 2020, WISDOM has implemented multiple strategies to improve participant experience: participant-initiated data-sharing tools and clear participant messaging. This abstract presents the efficacy of these interventions as they relate to increasing patient enrollment in remote, pragmatic clinical trials. Methods The WISDOM Study online enrollment process includes registration, participant study arm selection or randomization, online consent, and enrollment (submission of multiple study surveys over a secure, online platform). Barriers to online enrollment were uncovered through an internally-conducted needs assessment of participants who enrolled between 2019-2020, and participant feedback obtained through phone interviews conducted by WISDOM’s embedded ethics study. Improvements to our online enrollment procedures were executed in October 2020 and included: improving the clarity of study arm selection options, streamlining data collection surveys, and enacting a secure, patient-initiated online data-sharing tool and an online portal feature with auto-launch of critical information. Study metrics were obtained through Google Analytics and Salesforce. Results Prior to the end of 2020, only 62% of the 30,046 participants who registered for the WISDOM Study completed study enrollment. After improving the enrollment process, of the 5,334 participants registered for the study between Jan-June 2021, 69% completed the enrollment process finishing both the online consent and survey forms. Conversion from consent to enrollment went from 78% in January 2020 to 93% in June 2021. Currently, 56% participants complete enrollment in one day. Streamlining online patient questionnaires led to an increase in completion rates, with 75% of participants completing their yearly surveys, compared to 59% prior to April 2021. A secure patient upload feature for data sharing led to 1,054 participants successfully sharing their mammogram reports with WISDOM between March - June 2021. Previously, mammogram reports were missing for 20% of enrolled participants. This feature has enabled WISDOM to process 300 additional mammogram reports per month. Integration of an auto-launch feature in the participant’s portal in Feb 2021 has led to a 17% increase in participants viewing their screening recommendations in Yr 1. Prior to auto-launch, only 59% (n=6328) of Yr 1 screening recommendations and 61% (n=3681) of genetic testing reports were viewed by participants. Since implementation, the numbers increased to 78% (n=8406) and 85% (n=5160), respectively. Conclusions. Streamlining data to the most essential elements, and minimizing the steps required to share clinical documents, complete questionnaires and open key study notification is essential to improving enrollment rates in virtual, pragmatic trials. Patient-initiated data-sharing tools such as the ability for participants to share documents through secure, online portals is one example of success. Citation Format: Patricia Choy, Tomiyuri Lewis, Stephanie Flores, Leah Sabacan, Halle Thannickal, Steffanie Goodman, Yiwey Shieh, Lisa Madlensky, Jeffrey A. Tice, Elad Ziv, Martin Eklund, Amie Blanco, Barry Tong, Deborah Goodman, Nancy Anderson, Heather Harvey, Steele Fors, Hannah Lui Park, Antonia Petruse, Skye Stewart, Samrrah Raouf, Janet Wernisch, Barbara Koenig, Celia Kaplan, Robert Hiatt, Neil Wenger, Vivian Lee, Diane Heditsian, Susie Brain, Dolores Moorehead, Barbara A Parker, Alexander Borowsky, Hoda Anton-Culver, Arash Naeim, Andrea Kaster, Laura van 't Veer, Andrea Z LaCroix, Olufunmilayo I. Olopade, Deepa Sheth, Agustin Garcia, Rachel Lancaster, Jennifer James, Galen Joseph, Wisdom Study, Athena Breast Health Network Investigators and Advocates, Allison Stover Fiscallini, Laura Esserman. The impact of streamlined processes and patient-directed messaging to improve enrollment in a remote, pragmatic clinical trial [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 P5-19-01.

Abstract PD7-03: Ultra-accelerated photon, proton, and brachytherapy partial breast irradiation: Primary results of the Mayo 3-fraction trial

Abstract Background: Partial breast irradiation (PBI) is an established option for selected patients with early stage breast cancer. The optimal technique, target volume and dose/fractionation for PBI has yet to be defined. The most studied regimen in North America (38.5 Gy in 10 fractions twice daily) has been associated with cosmetic deterioration. We hypothesized that condensing treatment and reducing the total administered dose could improve the therapeutic ratio in luminal breast cancer and DCIS based on emerging evidence that breast cancer is more sensitive than surrounding normal tissues to high dose fractions. Herein, we report cosmetic, tolerability, disease control, and patient reported outcomes of a novel ultra-accelerated PBI regimen. Methods: We conducted a single arm, three cohort trial of photon, proton, and brachytherapy PBI. Technique was selected at physician and patient discretion. Eligible women were age ≥ 50 years with estrogen receptor positive (ER+), sentinel lymph node negative invasive or in-situ breast cancer measuring ≤ 2.5 cm. The regimen was designed to have comparable biologically equivalent effect as 40 Gy in 15 fractions, assuming an α/β ratio of 3.5. Intracavitary brachytherapy target volume was lumpectomy cavity plus 1 cm and prescribed 21 Gy in 3 fractions. Photon and proton target volumes were post-operative tumor bed plus 1 cm and a 3 mm setup uncertainty margin, prescribed 21.9 Gy (RBE) in 3 fractions, and delivered with image guidance. The primary outcome was the percentage difference in patients with adverse cosmesis (defined as fair or poor cosmesis) at 3 years compared to baseline pre-PBI, as assessed by trained nurses using the 4-point Harvard breast cosmesis scale. Patients also completed quality of life surveys and self-reported cosmesis using the 4-point scale. Locoregional and distant recurrence-free survival was determined using the Kaplan-Meier method. Adverse events were assessed using CTCAE, v 4.0. Results: Between 2015 and 2017, 163 patients were treated: photons in 58, protons in 48, and brachytherapy in 57. Median patient age was 66 years. 129 (79%) patients had invasive breast cancer (all ER+) and 34 (21%) had DCIS (83% ER+). Median tumor size was 1.1 cm. Grade was 2-3 in 102 (63%). The median mean heart/ipsilateral lung doses were photons 0.1/1.6 Gy, protons <0.001/0.1 Gy, and brachytherapy 0.5/0.9 Gy. Median follow-up was 4.1 years (IQR 3.9-5.0). The proportion of patients with adverse cosmesis (by RN assessment) was 14.3% at baseline and 3.8% at 3 years, with four patients (1 photon, 1 proton, 2 brachytherapy) experiencing cosmetic deterioration at 3 years from baseline. The proportion with adverse cosmesis by self-report at 3 years was 2.4%, with three patients (1 photon, 1 proton, 1 brachytherapy) reporting cosmetic deterioration. Four patients developed locoregional recurrence (1 photons, 2 protons, 1 brachytherapy); three were local only and one was local and distant. 4-year locoregional recurrence and distant metastasis-free survival were 97.9% and 97.4%, respectively. There were 2 treatment related ≥ grade 2 late events (grade 2 fibrosis and grade 2 seroma, both brachytherapy associated), and no evidence of deterioration in patient-reported pain, fatigue, breast related or overall quality of life, as assessed by the patient reported outcomes version of the CTCAE, 10-point linear analog scales, and the breast cancer treatment outcomes scale. Conclusions: Ultra-accelerated 3-fraction PBI exquisitely spared normal tissues and was associated with favorable cosmetic outcomes, disease control, and excellent long-term tolerability. This ‘precision-radiotherapy’ approach may optimize the therapeutic ratio over more aggressive radiotherapy options as well as radiotherapy omission, particularly in patients with long life expectancies. Citation Format: Robert Mutter, Tina Hieken, Todd DeWees, Arslan Afzal, Stephanie Kenison, Laura Vallow, Christopher Deufel, Nicholas Remmes, Kathryn Ruddy, Judy Boughey, Keith Furutani, Amy Degnim, James Jakub, Tamara Vern-Gross, Dean Shumway, William Wong, Samir Patel, Lisa McGee, Minetta Liu, Carlos Vargas, Daniel Visscher, Bradley Stish, Deanna Pafundi, Mark Waddle, Michael Golafshar, Michele Halyard, Kimberly Corbin, Sean Park. Ultra-accelerated photon, proton, and brachytherapy partial breast irradiation: Primary results of the Mayo 3-fraction trial [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 PD7-03.

Abstract P5-19-04: The WISDOM study: Reducing sequential steps and implementing parallel workflows in pragmatic trials

Abstract Background:The WISDOM Study is a preference-tolerant pragmatic study, comparing annual mammograms to a risk-based screening. Eligibility includes women ages 40-74 years with no history of breast cancer or DCIS. Participants are enrolled to one study arm: annual screening or risk-based screening (includes genetic testing). Pragmatic trials often involve gathering real-time data over multiple time points. Collecting real-time data sequentially can limit enrollment, delay study assignments, and reduce participant engagement. The WISDOM Study has identified such bottlenecks and has implemented parallel workflows, reducing the overall wait time for participants to complete required study steps. These data highlight how moving participants through the study more efficiently can improve enrollment and retention and inform other pragmatic trials. Methods: WISDOM participants have the option to either choose their study arm or be randomized into one as part of the preference tolerant randomized trial design. Participants then complete breast health questionnaires and genetic testing (if in the risk-based arm). This information is analyzed by the WISDOM breast cancer risk assessment algorithm, the result of which is then communicated to the participant through a screening assignment letter (SAL). Specific data elements, such as breast density found participants’ mammogram reports and genetic testing results are required for study randomization process and risk assessment calculations, respectively. The WISDOM randomization algorithm is stratified by several factors, including breast cancer risk estimated using the Breast Cancer Surveillance Consortium (BCSC) model, which uses mammographic density as a key input variable. The study team changed the workflow to allow participants to proceed to randomization without specific information by imputing both density and risk. Additionally, a parallel workflow improvement process was implemented to obtain mammogram reports while genetic testing was being completed. Results: Before the weighted BCSC and imputed density algorithms were introduced, it took an average of 47 days to randomize participants after completion of the baseline enrollment questionnaires. Now, participants are randomized immediately which has reduced delays by 100%. Prior to implementing the parallel workflow for genetic testing and mammogram ascertainment, genetic testing kits were sent only after mammogram reports were collected and validated. The expected turnaround time for genetic testing results was 30-60 days and on average, results were returned to participants in 42 days. Streamlining the study design to obtain mammogram reports while participants complete their genetic testing has shortened the time for participants to receive their screening assignment letters (SALs) from an average of 160 days to 78 days, a reduction by 49%. In comparison, participants in the annual arm of the study who do not complete genetic testing, receive their SALs after an average of 38 days from enrollment. This is due to long wait times to obtain mammographic densities from outside medical facilities. Conclusions: Creating parallel data ascertainment workflows and reducing sequential steps in the study process has increased completion of individual enrollment activities. Participants now are randomized immediately upon joining the study and have access to their SALs and genetic results more rapidly. This approach eliminated randomization wait times and improved efficiency of the early in the enrollment process. We are evaluating the impact on participant retention going forward. Workflow efficiency is critical to improve the patient experience, and our learnings can inform future trial design, particularly for studies requiring data from outside sources. Citation Format: Tomiyuri Lewis, Stephanie Flores, Leah Sabacan, Patricia Choy, Halle Thannickal, Yiwey Shieh, Jeffrey Tice, Elad Ziv, Lisa Madlensky, Martin Eklund, Christina Yau, Amie Blanco, Barry Tong, Deborah Goodman, Nancy Anderson, Heather Harvey, Steele Fors, Hannah L Park, Samrrah Raouf, Skye Stewart, Janet Wernisch, Barbara Koenig, Celia Kaplan, Robert Hiatt, Neil Wenger, Vivian Lee, Diane Heditsian, Susie Brain, Dolores Moorehead, Barbara A Parker, Alexander Borowsky, Hoda Anton-Culver, Arash Naeim, Andrea Kaster, Laura van ‘t Veer, Andrea Z LaCroix, Olufunmilayo I Olopade, Deepa Sheth, Agustin Garcia, Rachel Lancaster, Michael Plaza, Wisdom Study, Athena Breast Health Network Investigators, Advocate Partners, Allison S Fiscalini, Laura Esserman. The WISDOM study: Reducing sequential steps and implementing parallel workflows in pragmatic trials [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 P5-19-04.

Abstract P5-14-20: Neoadjuvant endocrine therapy (NET) during COVID-19: Single institution survey of patients’ perspectives

Abstract Background: Coronavirus disease 2019 (COVID-19) resulted in a global pandemic, which led to deferral of surgeries for early stage breast cancer during March - June 2020. Institutional guidelines were developed to use neoadjuvant endocrine therapy (NET) as a bridge to surgery. As a follow up to initial data presented at SABCS 2020 demonstrating patient acceptance of NET, the present study provides results from a survey which explored psychosocial factors associated with medication compliance. Objective: Primary objective was to identify any barriers to compliance with NET. Method: This was a single institution, prospective study that surveyed patients diagnosed with DCIS and early stage breast cancer at Perlmutter Cancer Center at NYU Langone Hospital and NYU Langone Hospital - Long Island from March 15, 2020 - June 1, 2020. Questions were based on the Beliefs about Medicines Questionnaire specific for endocrine therapy (BMQ-AET) and the Medication Adherence Report Scale. Responses were recorded on a Likert scale and included 7 questions regarding perceptions about breast cancer treatment, 10 questions addressing experience with NET, and 5 questions gauging at adherence to NET. Inclusion criteria were males and females older than 18 years old, with an initial diagnosis of DCIS or early stage HR+ Her2/neu- breast cancer, who were prescribed NET. Descriptive statistics were calculated and subgroups were compared using Fisher’s exact tests. Analyses were performed using SAS version 9.4. Results: From March 15 - June 1, 2020, 13 patients were diagnosed with DCIS and 29 patients with HR+ Her2/neu- breast cancer for whom NET was recommended. Demographics are shown in Table 1. All 42 patients were female with an average age of 60.9 years. Majority of patients were post-menopause (74%) and predominantly white (64%), with an income of less than $60,000 (52.4%). Average NET duration was 6.7 weeks. Survey responses displayed in Table 2 indicate statistically significant p values in bold. Patients >50 years old, post-menopause and invasive breast cancer had a stronger belief that NET would be helpful, resulting in greater perception to breast cancer treatment and higher adherence to NET. Patients treated with NET for greater than 4 weeks also felt that NET would make them feel well compared to ≤4 weeks. Interestingly, no significant differences in responses based on education or income level were observed. Conclusion: COVID-19 pandemic presented a unique opportunity to use NET, which is often underutilized outside of clinical trials. In this single institution prospective study, we found that post-menopause patients greater than 50 years old with invasive breast cancer perceived hormonal therapy as beneficial to their health, resulting in increased medication compliance. These findings can be used when counseling patients currently treated with NET as well as those patients may be appropriate for NET in the post-COVID era. Table 1.Demographics of early stage breast cancer patients diagnosed during COVID-19.DCIS (n=13)Invasive Breast Cancer (n=29)Total (n=42)Menopause Status (n, %)Pre-menopause7 (53.8)4 (13.8)11 (26.2)Post-menopause6 (46.2)25 (86.2)31 (73.8)Diagnosis (n, %)Self-Palpated06 (20.7)6 (14.3)Screening13 (100)23 (79.3)36 (85.7)Age (n, %)≤504 (30.8)4 (13.8)8 (19)50+9 (69.2)25 (86.2)34 (80.9)Average Age (range)54.9 (40 – 72)63.6 (32 – 85)60.9 (32 – 85)Race (n, %)White7 (53.8)20 (69%)27 (64.3)Non-White6 (46.2)9 (31%)15 (35.7)Education (n, %)K-121 (7.7)6 (20.7)7 (16.7)College and Graduate12 (92.3)23 (79.3)35 (83.3)Income (n, %)$0 – $60,0005 (38.5)17 (58.6)22 (52.4)$>60,0017 (53.8)12 (41.3)19 (45.2)No response1 (7.7)01 (2.4)NET in Weeks (n, %)≤45 (38.5)7 (24.1)12 (28.6)4+8 (61.5)22 (75.9)30 (71.4) Table 2.Perceptions of breast cancer and hormonal therapy.Perceptions About Hormonal TherapyPerceptions About Breast Cancer TreatmentAdherence To Hormonal TherapyMy health at present depends on me taking hormone treatment (p-value)Hormone treatment is a mystery to me (p-value)My health in the future will depend on me taking hormone treatment (p-value)Taking hormone treatment makes me feel I am taking positive steps to remain well (p-value)How much do you feel that your current hormone therapy can help? (p-value)How much do you feel that you need your current hormone therapy? (p-value)I miss out on a dose (p-value)I stop taking medication for a while (p-value)Age >50 vs. ≤500.04020.56510.00580.08330.04770.87370.04831.0000Post-Menopause vs. Pre-Menopause0.00330.02720.00530.13380.00060.24520.01661.0000Invasive vs. DCIS0.00381.00000.00450.16480.01810.00011.00000.0133Non-White vs. White0.47420.04340.76400.05220.91430.77730.61280.1369Duration of NET: ≤4 vs. >4 weeks0.43190.49971.00000.02840.11390.75430.05220.8833Screening vs. Self-Palpated0.51100.02560.62571.00000.44230.05930.47760.6353K-12 vs. College/Graduate0.43660.65400.16151.00000.41450.67531.00000.8321Income: ≤$60,000 vs. >$60,0000.54590.27860.59900.85690.09530.07000.78980.0581 Citation Format: Julie Huang, Joshua Feinberg, Meredith Akerman, Anthony Pasquarella, Abhinav Rohatgi, Bahram Dabiri, Jordan Baum, Shubhada Dhage, Amber Guth, Nina D'Abreo. Neoadjuvant endocrine therapy (NET) during COVID-19: Single institution survey of patients’ perspectives [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 P5-14-20.

Abstract P1-10-06: Effect of aging and mTOR inhibition on human mammary stem cells and early breast cancer progression markers

Abstract Ductal carcinoma in situ (DCIS) is the most common form of breast cancer and is a predecessor to invasive carcinoma development. The origins for early breast cancer have been attributed to aberrant single cells, which may include adult stem and progenitor cells. We performed a window trial with mTOR inhibitor sirolimus in patients with atypical ductal hyperplasia (ADH) or DCIS and investigated the epithelial populations in adjacent normal and ADH/DCIS breast tissues along with their residing stem and progenitor cell activity. Differences associated with age, menopausal status, and treatment by sirolimus have also been explored. While the mammary epithelial populations were seen to be unchanged in aging, we found that age correlates with a decline in stem cell activity. mTOR inhibition was also able to abrogate mammary stem cell activity and decrease luminal progenitor passaging lifespan, particularly in postmenopausal patients. While mTOR inhibition had no effect on myoepithelial populations, it did decrease premenopausal luminal cell populations and reduced prognostic markers associated with breast cancer progression from DCIS to invasive breast cancer. These markers include p16INK4A, COX-2, and Ki67, which were reduced in DCIS breast tissue from patients administered with sirolimus as shown through quantitative analysis of immunohistochemistry. Overall, these findings indicate a link from mTOR signaling to mammary stem cell activity and cancer progression. mTOR inhibitors may have potential for breast cancer prevention. Citation Format: Larry E Broome, Hakim Bouamar, Kate Lathrop, Ismail Jatoi, Andrew Brenner, Michael Garcia, Alia Nazarullah, Karla Moncada, Virginia Kaklamani, Lu-Zhe Sun. Effect of aging and mTOR inhibition on human mammary stem cells and early breast cancer progression markers [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 P1-10-06.

Elevated NRAS expression during DCIS is a potential driver for progression to basal-like properties and local invasiveness

BackgroundDuctal carcinoma in situ (DCIS) is the most common type of in situ premalignant breast cancers. What drives DCIS to invasive breast cancer is unclear. Basal-like invasive breast cancers are aggressive. We have previously shown that NRAS is highly expressed selectively in basal-like subtypes of invasive breast cancers and can promote their growth and progression. In this study, we investigated whether NRAS expression at the DCIS stage can control transition from luminal DCIS to basal-like invasive breast cancers.MethodsWilcoxon rank-sum test was performed to assess expression of NRAS in DCIS compared to invasive breast tumors in patients. NRAS mRNA levels were also determined by fluorescence in situ hybridization in patient tumor microarrays (TMAs) with concurrent normal, DCIS, and invasive breast cancer, and association of NRAS mRNA levels with DCIS and invasive breast cancer was assessed by paired Wilcoxon signed-rank test. Pearson’s correlation was calculated between NRAS mRNA levels and basal biomarkers in the TMAs, as well as in patient datasets. RNA-seq data were generated in cell lines, and unsupervised hierarchical clustering was performed after combining with RNA-seq data from a previously published patient cohort.ResultsInvasive breast cancers showed higher NRAS mRNA levels compared to DCIS samples. These NRAShigh lesions were also enriched with basal-like features, such as basal gene expression signatures, lower ER, and higher p53 protein and Ki67 levels. We have shown previously that NRAS drives aggressive features in DCIS-like and basal-like SUM102PT cells. Here, we found that NRAS-silencing induced a shift to a luminal gene expression pattern. Conversely, NRAS overexpression in the luminal DCIS SUM225 cells induced a basal-like gene expression pattern, as well as an epithelial-to-mesenchymal transition signature. Furthermore, these cells formed disorganized mammospheres containing cell masses with an apparent reduction in adhesion.ConclusionsThese data suggest that elevated NRAS levels in DCIS are not only a marker but can also control the emergence of basal-like features leading to more aggressive tumor activity, thus supporting the therapeutic hypothesis that targeting NRAS and/or downstream pathways may block disease progression for a subset of DCIS patients with high NRAS.

A multi-modal exploration of heterogeneous physico-chemical properties of DCIS breast microcalcifications.

Ductal carcinoma in situ (DCIS) is frequently associated with breast calcification. This study combines multiple analytical techniques to investigate the heterogeneity of these calcifications at the micrometre scale. X-ray diffraction, scanning electron microscopy and Raman and Fourier-transform infrared spectroscopy were used to determine the physicochemical and crystallographic properties of type II breast calcifications located in formalin fixed paraffin embedded DCIS breast tissue samples. Multiple calcium phosphate phases were identified across the calcifications, distributed in different patterns. Hydroxyapatite was the dominant mineral, with magnesium whitlockite found at the calcification edge. Amorphous calcium phosphate and octacalcium phosphate were also identified close to the calcification edge at the apparent mineral/matrix barrier. Crystallographic features of hydroxyapatite also varied across the calcifications, with higher crystallinity centrally, and highest carbonate substitution at the calcification edge. Protein was also differentially distributed across the calcification and the surrounding soft tissue, with collagen and β-pleated protein features present to differing extents. Combination of analytical techniques in this study was essential to understand the heterogeneity of breast calcifications and how this may link crystallographic and physicochemical properties of calcifications to the surrounding tissue microenvironment.

A Comprehensive Prospective Comparison of Acute Skin Toxicity after Hypofractionated and Normofractionated Radiation Therapy in Breast Cancer.

The current study aims to determine whether hypofractionated radiotherapy (HF) leads to lower rates of acute radiodermatitis compared to conventional normofractionated radiotherapy (CF). A total of 166 patients with invasive breast cancer or DCIS were included in a prospective cohort study. Evaluation of acute radiodermatitis was obtained before radiotherapy, at the end of the treatment (T1), and 6 weeks after the treatment (T2) using CTCAE (v5.0) scores, the Skindex-16 questionnaire, and ultrasound measurement of the skin. CTCAE and Skindex-16 scores in the CF-group were significantly higher compared to the HF group indicating more pronounced side effects at the end of the treatment (CTCAE: CF-RT 1.0 (IQR: 0.0) vs. HF-RT 0.0 (0.25); p = 0.03; Skindex-16: CF: 20.8 (IQR: 25.8); HF: 8.3 (27.1); p = 0.04). At 6 weeks after the treatment, no significant differences between the two fractionation schemes were observed. Ultrasound based assessment showed that the skin thickness in the treated breast was higher compared to the healthy breast at all time-points. However, no significant difference between HF and CF was seen either at T1 or T2. The current study complements and confirms pre-existing evidence that HF leads to a lower degree of acute radiodermatitis and better patient reported outcome compared to CF at the end of treatment. This should be considered whenever fractionation of adjuvant breast cancer treatment is being discussed.

Predictors of Acute Radiation Dermatitis and Esophagitis in African American Patients Receiving Whole Breast Radiotherapy

<h3>Purpose/Objective(s)</h3> Adjuvant whole breast radiotherapy following breast conserving surgery is standard of care in the management of early-stage breast cancer. Two common acute toxicities of breast radiotherapy are esophagitis and dermatitis. African Americans are at higher risk for experiencing treatment-related toxicity and are often under-represented in clinical trials. This study investigates clinical factors associated with increased incidence of Grade 2+ radiation esophagitis (G2RE) and dermatitis (G2RD) in African American breast cancer patients undergoing adjuvant breast radiotherapy. <h3>Materials/Methods</h3> An institutional database was developed to include all African American patients with history of breast cancer or DCIS undergoing adjuvant radiotherapy at a single institution from 2013-2019. Records were reviewed to identify patient age, BMI, radiation dose, prone vs supine position, inclusion of boost, and inclusion of regional nodal irradiation (RNI). Radiation treatment plans were reviewed to identify breast size, and volume of breast receiving > 105% and > 107% prescription dose (V105%, V107%). For the subset of patients who received RNI, esophageal dosimetry was reviewed to identify mean/max dose to esophagus (Dmean/Dmax) and volume of esophagus receiving 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy (V5 Gy, V15 Gy, V25 Gy, V35 Gy, and V45 Gy). Medical records were reviewed to identify which patients were prescribed silver sulfadiazine or aluminum hydroxide/magnesium hydroxide/simethicone-lidocaine during or immediately following their course of radiotherapy which was used as a surrogate for G2 or higher toxicity. <h3>Results</h3> 279 patients were included in the final analysis. 44% of patients were obese and 15% were morbidly obese. 40% of patients received hypofractionated treatment. 36% of patients received RNI. 22% of patients were treated in prone position. On univariable analysis, morbidly obese patients were more likely to develop G2RD (OR 4.05, <i>P</i> < 0.001) and obese patients trended towards a higher incidence of G2RD (OR 1.67, <i>P</i> = 0.063). On multivariable analysis, increasing breast volume was associated with higher rates of G2RD (OR 3.25, <i>P</i> < 0.001) while hypofractionated radiotherapy was associated with lower rates of G2RD (OR 0.50, <i>P</i> = 0.027). Patients treated in prone position did trend towards decrease incidence of G2RD (OR 0.46, <i>P</i> = 0.052). For the subset of patients receiving RNI, 19% of patients experienced G2RE with the best predictor on multivariable analysis being esophagus Dmean (OR 5.56, <i>P</i> = 0.057). <h3>Conclusion</h3> Radiation dermatitis and esophagitis are common toxicities in African American patients undergoing adjuvant breast radiotherapy. Breast size, irrespective of patient's BMI, was associated with worse rate of dermatitis. Prone position and hypofractionated radiation reduced rates of G2RD. RNI was associated with increased rate of G2RE and esophagus Dmean was the best dosimetric parameter correlating with G2RE. These results may be used to help select patients who may be at higher risk for G2 or higher toxicity during radiotherapy.

Biosignatures to Optimize Adjuvant Radiation Therapy Use in Patients With DCIS With High Risk Clinicopathologic Features

There is an unmet need to identify women diagnosed with DCIS who have a low recurrence risk and could omit radiotherapy (RT) after breast conserving surgery (BCS), or an elevated recurrence risk after treatment with BCS plus RT.Pathology, clinical data, and FFPE tissue samples were evaluable for 485 women treated for DCIS with BCS with negative margins, with or without whole breast RT, at centers in Sweden, US and Australia. A subset with large tumor size (> 2.5 cm) &/or nuclear grade III DCIS was assessed (n = 250). A validated biosignature (Prelude, Laguna Hills CA) and a novel response subtype biosignature to RT after BCS were determined using protein biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2) assayed on FFPE tissue. The two biosignatures classified women into three risk groups: Low risk, Elevated risk with a good response subtype (Rst) and Elevated risk with a poor Rst to RT after BCS. Ipsilateral breast tumor recurrence (IBTR) included DCIS or Invasive Breast Cancer (IBC) that was local, regional, or metastatic. Hazard ratios and 10-year risks were calculated using Cox proportional hazards and Kaplan-Meier analyses.Of 250 women with nuclear grade III DCIS and/or size > 2.5 cm, biosignatures classified 72% (n = 179) of patients into an Elevated risk group consisting of those with a good (n = 122) or a poor (n = 57) response subtype (Rst) to RT after BCS. The remaining 28% of women were classified into a low-risk group (n = 71). In the low-risk group (n = 71), women treated without RT had good 10-year outcomes with no (0%) 10-year IBC events, and derived no significant RT benefit (1%) in 10-year IBTR rates (IBTR P = 0.81). Of all women treated without RT (n = 102), those in the elevated risk group (good and poor Rst combined, n = 61) had significantly worse 10-year IBTR/IBC rates (31%/17%) than those in the low-risk group, (IBTR HR = 12, P = 0.01). Women treated with RT in the elevated risk group with a good Rst (n = 77) had significantly reduced 10-year IBTR/IBC rates of 5%/3%. However, no significant benefit to RT was noted for women within the elevated risk group with a poor Rst (n = 41) who had 10-year IBTR/IBC rates of 25%/20%. Of all women treated with RT in the elevated risk group (n = 118), those with a poor Rst had significantly worse outcomes than those with a good Rst (IBTR HR = 4.1, P = 0.035, IBC HR = 8, P = 0.053).In women with nuclear grade III DCIS &/or size > 2.5 cm, DCISionRT combined with a novel response subtype biosignature (Rst) identified an elevated risk group with two distinct subtypes of women: (1) a poor Rst that had high IBTR/IBC rates with or without RT and (2) a good Rst deriving significant benefit from adjuvant RT. Women in the corresponding low risk group had low 10-year IBTR/IBC rates and derived no significant benefit from adjuvant RT.

OPAR: A Multicenter Phase II Randomized Trial of Fractionation Schedules for Once-a-Day Accelerated Partial Breast Irradiation (APBI)

<h3>Purpose/Objective(s)</h3> APBI is the delivery of radiotherapy (RT) to the tumor bed after breast conserving surgery (BCS) often given over a week or less. An attractive approach to deliver APBI is by external beam 3DCRT or IMRT. Previous studies have suggested that external beam APBI delivered twice-a-day can lead to increased late effects and poor breast cosmesis. The objective of our trial was to determine if two doses for APBI given once-a-day over 1-week result in acceptable long-term morbidity. <h3>Materials/Methods</h3> Eligible patients were > 50 years with DCIS or invasive breast cancer < 3 cm treated by BCS with negative margins and negative axillary nodes. Consenting patients were planned to receive APBI with 3-5 non-coplanar fields using a 3DCRT or IMRT and randomized to 27.5Gy or 30Gy each given in 5 fractions once-a-day over 5-8 days. Cosmetic evaluation with the EORTC Cosmetic Rating System was performed at baseline and 2 years by: a study nurse directly assessing the breast, and a group of oncologists unaware of RT regimen assessing photographs. Patient assessment of cosmesis was also performed at 3 years. Patients were followed for toxicity using the NCI CTCAE and recurrence. The primary outcome was adverse cosmesis (fair or poor global score) by photographic assessment at 2 years. The rate of adverse cosmesis with standard whole breast irradiation was 17% in our previous trial. Based on this consideration and one-sided α of 5% for each group, the upper bound of a one-sided 95% (two-sided 90%) confidence interval (CI) had to be < 23% for the treatment to be acceptable; 140 patients were required for each group. The proportion of patients with adverse cosmesis at 2 years and cosmetic deterioration from baseline to 2 years (excellent/good to fair/poor) with corresponding two-sided 90% CIs were estimated using the Wilson score method. The proportion of patients with any late breast toxicity (edema, induration, and telangiectasia) grades 2-3 at 2 years and local recurrence (LR) were also determined. <h3>Results</h3> Of the 281 patients: 139 were randomized to 27.5Gy and 142 to 30.0Gy. Median follow-up was 3 years. The mean age was 65 years; mean tumor size was 1.2cm. With respect to photographic assessment both schedules met our criteria for acceptability (Table 1). Adverse cosmesis assessed by nurse or patient and toxicity appeared to be less for 27.5Gy compared to 30Gy. No LRs were observed for 27.5Gy and one LR was observed for 30Gy. <h3>Conclusion</h3> According to the study design 27.5Gy and 30Gy resulted in acceptable cosmetic outcomes. In light of recent studies, the lower dose may be preferable in terms of late adverse effects but requires further evaluation.

Patient- versus physician-reported outcomes in a low-dose tamoxifen trial in noninvasive breast cancer.

We recently conducted a de-escalation trial of low-dose tamoxifen 5mg/day ("babytam", BT) or placebo given for 3years in 500 women with noninvasive breast cancer. Women on babytam had a 52% reduction of recurrence (invasive breast cancer or DCIS) after 5years. Since menopausal symptoms are major reasons for treatment withdrawal during tamoxifen preventive therapy, we compared and analyzed the patient-reported outcomes (PROs) with the physician-reported adverse events and studied their association with recurrence. Menopausal symptoms recorded by physicians using the Common Terminology Criteria (CTCAEs) were compared with a patient self-reported validated questionnaire reviewed by a research nurse at baseline and every 6months up to 36months. Hot flashes (HF), the main outcome measure, were detected through a self-report 7-day diary for frequency and intensity. Treatment adherence and efficacy were assessed by the Kaplan-Meier curves and the Cox model. The number of HF events at 12, 24, and 36months for PROs versus CTCAEs was 246 versus 12, 238 versus 8, and 210 versus 4, respectively. The majority of events were grade 1. There was no difference in PROs between babytam and placebo except for HF daily frequency, which increased by 1.5 events (95% CI, 1.1-1.8) on placebo to 2.1 on babytam (95% CI, 1.7-2.5, p=0.05). The presence of HF at baseline was a favorable prognostic factor for recurrence and a predictive factor for response to babytam. Adherence was similar between babytam and placebo. The use of PROs is effective for identifying frequent mild grade menopausal symptoms which are underestimated by physicians but important prognostic and predictive factors. Research nurse can use these results as a tool to reassure patients about symptoms, improve adherence to treatment, and limit dropouts.

A novel biosignature identifies DCIS patients with a poor biologic subtype with an unacceptably high rate of local recurrence after breast conserving surgery and radiotherapy.

513 Background: There is an unmet need to identify women diagnosed with DCIS who have a low recurrence risk and could omit radiotherapy (RT) after breast conserving surgery (BCS), or an elevated recurrence risk after treatment with BCS plus RT. DCISionRT and its response subtype (Rst) biosignature were evaluated in a contemporary cohort treated with BCS with or without RT to identify these risk groups. Methods: Pathology, clinical data, and FFPE tissue samples were evaluable for 485 women diagnosed with DCIS at centers in Sweden (1996-2004), the USA (1999-2008), and Australia (2006-2011). Patients were treated with BCS (negative margins) with or without whole breast RT. Ipsilateral breast tumor recurrence (IBTR) included DCIS or invasive breast cancer (IBC) that was local, regional, or metastatic. The patients were classified into Low and Elevated risk groups to assess IBTR and IBC rates. Patients in the Elevated risk group were categorized by two subtypes: a good response subtype (good Rst) or a poor response subtype (poor Rst) after BCS plus RT. Biosignatures were calculated using biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2) assayed using IHC on FFPE tissue. Hazard ratios and 10-year risks were calculated using Cox proportional hazards (CPH) and Kaplan-Meier analyses. Results: In the DCISionRT Elevated risk group, RT was associated with significantly reduced recurrence rates, but only for those patients with a good Rst (Table, IBTR HR=0.18, p&lt;0.001, IBC HR=0.15, p=0.003, n=241). For Elevated risk group patients with a poor Rst, no benefit to RT was noted (Table). Additionally, irrespective of RT, patients with a poor Rst had 10-year IBTR/IBC rates of 25%/16%, which were much higher than good Rst rates of 6.6%/4.5% (IBE HR=3.6, p=0.02, IBC HR=4.4, p=0.04, n=190). For patients in the Low risk group, there was no significant difference in 10-year IBTR/IBC rates with and without RT (Table, IBTR p=0.4, IBC p=0.9, n=177). The distribution of clinicopathologic risk factors (age &lt;50 years, grade 3, size &gt;2.5 cm) did not identify poor vs. good response subtypes, and multivariable analysis (n=485) indicated these traditional clinicopathologic factors and endocrine therapy were not significantly associated with IBTR (p≥0.22) or IBC (p≥0.34). Conclusions: Biosignatures identified a Low risk patient group with low 10-year recurrence rates with or without RT who may be candidates for omitting adjuvant RT. Biosignatures also identified an Elevated risk group receiving BCS plus RT with a poor response subtype that had unacceptably high recurrence rates, warranting potential intensified or alternate therapy.[Table: see text]

DUCHESS: an evaluation of the ductal carcinoma in situ score for decisions on radiotherapy in patients with low/intermediate-risk DCIS

Identification of women with DCIS who have a very low risk of local recurrence risk (LRR) after breast-conserving surgery (BCS) is needed to de-escalate therapy. We evaluated the impact of 10-year LRR estimates after BCS, calculated by the integration of a 12-gene molecular expression assay (Oncotype Breast DCIS Score®) and clinicopathological features (CPFs), on its ability to change radiation oncologists' recommendations for RT after BCS for DCIS. Prospective cohort study of women with DCIS treated with BCS. Eligibility criteria were as follows: age > 45years, tumor ≤ 2.5cm, and margins ≥ 1mm. Radiation oncologists provided 10-year LRR estimates without RT and recommendation for RT pre- and post-assay. Primary outcome was change in RT recommendation. 217 patients were evaluable, with mean age = 63years, mean tumor size = 1.1cm, and mean DCIS Score = 32; 140 (64%) were in the low-risk (<39), 32 (15%) were in the intermediate-risk (39-54), and 45 (21%) were in the high-risk groups (≥55). The assay led to a change in treatment recommendation in 76 (35.2%) (95%CI 29.1-41.8%) patients. RT recommendations decreased from 79% pre-assay to 50% post-assay (difference = 29%; 95%CI 22-35%) due to a significant increase in the proportion of patients with a predicted low LRR (< 10%) post-assay and recommendations to omit RT for those with a low predicted risk. The assay was associated with improved patient satisfaction and reduced decisional conflict. The DCIS Score assay combined with CPFs identified more women with an estimated low (<10%) 10-yr LR risk after BCS, leading to a significant decrease in recommendations for RT compared to estimates based on CPFs alone.

Abstract OT-21-01: Personalized breast cancer screening in a population-based study: Women informed to screen depending on measures of risk (WISDOM)

Abstract Background: WISDOM is a 100,000 healthy women preference-tolerant, pragmatic study comparing traditional annual screening to personalized risk-based breast screening. The novelty of WISDOM personalized screening is the integration of previously validated genetic and clinical risk factors (age, family history, breast biopsy results, ethnicity, mammographic density) into a single risk assessment model that directs the starting age, timing, and frequency of screening. The goal of WISDOM is to determine if personalized screening, compared to annual screening, is as safe, less morbid, enables prevention, and is more accepted by women. The study is registered on ClinicalTrials.gov, NCT02620852. Methods: Women aged 40-74 years with no history of breast cancer, DCIS or previous double mastectomy can join the study online at wisdomstudy.org. Participants can either elect randomization or self-select a study arm. Then, they provide electronic consent and sign the Release for Medical Information via DocuSign. For all participants, 5-year risk of developing breast cancer is calculated according to the Breast Cancer Surveillance Consortium (BCSC) model. Participants in the personalized arm undergo panel-based mutation testing (BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, ATM, PALB2, and CHEK2), and their 5-year risk is calculated using the BCSC score combined with a Polygenic Risk Score (BCSC-PRS) that includes 229 single nucleotide polymorphisms (SNPs) known to increase breast cancer risk. The SNPs and mutations are assessed by saliva-based testing through Color Genomics. Five-year risk level thresholds are used to stratify participants as low-, moderate- and high risk. Risk stratification determines age to start, stop, and frequency of screening in the personalized arm. Accrual: As of July 2020 the WISDOM Study is open to all eligible women in the United States. To date, 38,762 eligible women have registered, and 28,706 women have consented to participate in the trial. The median age is 56 years. Seventy-seven percent of participants are Caucasian, 2% African-American, 5% Asian, and 8% of self-reported Hispanic ethnicity. WISDOM is partnering with Blue Cross Blue Shield Association for regional plan opt-in coverage, self-insured companies (Salesforce, Genentech, Qualcomm, CalPERS) and Medi-Cal (Inland Empire Health Plan) using a coverage with evidence progression approach. Accrual expansion and diversity: To ensure that resulting data are meaningful and potentially practice-changing for all populations of women, the WISDOM Study is enhancing the diversity of our participant population by establishing WISDOM sites in diverse areas with large African-American (Alabama, Louisiana, Illinois) and Latina (Florida) populations. These new recruitment sites, intentionally selected for the diverse communities they serve, have established partnerships with community organizations and outreach navigators. Additionally, we have translated the WISDOM Study to Spanish to facilitate access by Latina communities. With the engagement of patient advocates and community partnerships, expanding diversity in the study population will strengthen our scientific knowledge of breast cancer risk and improve access to personalized breast cancer screening recommendations for all women. Enrollment will continue through 2022. Conclusions: Results of 5 years follow-up will enable us to demonstrate whether personalized screening improves outcomes for future patients and it improves healthcare value by reducing screen volumes and costs without jeopardizing outcomes. Citation Format: Irene Acerbi, Allison Stover Fiscalini, Mandy Che, Yiwey Shieh, Lisa Madlensky, Jeffrey Tice, Elad Ziv, Martin Eklund, Amie Blanco, Barry Tong, Deborah Goodman, Lamees Nassereddine, Nancy Anderson, Heather Harvey, Steele Fors, Hannah L Park, Antonia Petruse, Skye Stewart, Janet Wernisch, Larissa Risty, Ian Hurley, Barbara Koenig, Celia Kaplan, Robert Hiatt, Neil Wenger, Vivian Lee, Diane Heditsian, Susie Brain, Leah Sabacan, Tianyi Wang, Barbara A Parker, Alexander Borowsky, Hoda Anton-Culver, Arash Naeim, Andrea Kaster, Melinda Talley, Laura van 't Veer, Andrea Z LaCroix, Olufunmilayo I Olopade, Deepa Sheth, Augustin Garcia, Rachel Lancaster, Wisdom Study and Athena Breast Health Network Investigators and Advocate Partners, Laura Esserman. Personalized breast cancer screening in a population-based study: Women informed to screen depending on measures of risk (WISDOM) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-21-01.

Abstract OT-22-01: Opportunities and lessons learned in using electronic health record patient portal (MyChart) for recruitment to the population-based WISDOM study

Abstract Background: WISDOM is a preference-tolerant, pragmatic study comparing annual mammogram screening to personalized, risk-based breast screening in healthy women with a target accrual of 100,000. This sizable recruitment goal requires creative and broad-based strategies that are not typical for traditional clinical research. One of the recruitment methods is use of an electronic health record patient portal (Epic’s MyChart) to invite patients to participate in research. We tested various MyChart implementation strategies across WISDOM recruitment sites and report response rates, barriers and lessons learned. The study is registered on ClinicalTrials.gov, NCT02620852. Methods: Women aged 40-74 years with no history of breast cancer, DCIS, or double mastectomy can join the WISDOM Study online at wisdomstudy.org. Participants either elect to be randomized or self-select one of the study arms, the control (annual mammogram screening) arm or the treatment (personalized, risk-based breast screening) arm. All study steps can be completed electronically, with no requirement to travel to a study site. University of California, Los Angeles (UCLA) was the first WISDOM site to gain approval to use MyChart as a recruitment tool as part of the Clinical Translational Science Institute pilot in Spring 2018. The pilot was designed to demonstrate feasibility, patient response, and recruitment metrics. Following UCLA’s pilot, additional WISDOM sites received approval to use MyChart; however, implementation differed across sites based on local medical center leadership decisions. MyChart Implementation: As of July 2020, use of MyChart is ongoing at five of WISDOM’s six initial recruitment sites (UCLA, Sanford Health, UCSF, UCSD, UCI). Three sites (UCLA, Stanford, and UCSF) implemented MyChart broadly, and two sites (UCI and UCSD) are phasing in MyChart recruitment. UCLA and Sanford Health implemented MyChart recruitment through a centralized approach targeting all eligible patients and sending a MyChart invitation with a link to the study’s enrollment website. UCSF was approved to send WISDOM information on the MyChart portal, but the patients must opt in to learn more by outreach from a research coordinator. UCSD and UCI approaches are more limited requiring departmental or primary care provider approval for communications to be sent to patients. Results: MyChart enabled direct communication to a large number of potential study participants at UCLA and Sanford Health (UCLA 107,829, Sanford Health 86,684) during a 12-month period. The experiences of both sites were similar in that 50% of individuals read the MyChart message, 2.5-5% registered for additional information, and 1.5-2.5% consented to participate. UCSF’s implementation approach was similar with 8005 individuals invited, 6.6% indicating interest to participate, and 2.4% consenting. Although the number of consented participants represented a small portion of the total women consented to join the study to date, the recruitment rates from using MyChart were 2.5-10X higher compared to sites that did not use it or were in pilot phase. Participating sites saw 30%-50% increased recruitment rates during periods when MyChart messages were in use. Implementations at the departmental (UCSD) and primary care provider level (UCI) demonstrated similar trends (3.8% and 3% consented respectively), albeit with smaller samples. Conclusions: Use of electronic health record patient portal (MyChart) recruitment for the WISDOM Study increased enrollment rate by site and is a cost-effective approach to recruiting for large scale trials with broad eligibility criteria like the WISDOM Study. Citation Format: Antonio Petruse, Alyssa Rocha, Liliana Johansen, Neil Wenger, Mandy Che, Steele Fors, Hannah L Park, Janet Wernisch, Irene Acerbi, Allison S Fiscalini, Jasmin Hassam, Andrea LaCroix, Barbara Parker, Lisa Madlensky, Laura Van't Veer, Celia Kaplan, Hoda Anton-Culver, Andrea Kaster, Skye Stewart, Samrrah Rouf, Alexander Borowsky, Ian Hurley, Robert Hiatt, Vivian Lee, Diane Heditsian, Susie Brain, Olufunmilayo Olopade, Deepa Sheth, Laura Esserman, Wisdom Study and Athena Breast Health Network Investigators and Advocate Partners, Arash Naeim. Opportunities and lessons learned in using electronic health record patient portal (MyChart) for recruitment to the population-based WISDOM study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-22-01.

Abstract SS2-04: Health maintenance and breast cancer screening during the COVID-19 pandemic

Abstract Background: WISDOM is a large (target enrollment&amp;gt;40,000) healthy women preference-tolerant, pragmatic study comparing traditional annual screening to personalized risk-based breast screening. Cancer screening, routine health care, and elective procedures were disrupted due to attempts to manage resources during the COVID-19 pandemic. Understanding of the impact on COVID-19 on trial participants is important to gain a broader understanding of the effect of the pandemic on healthcare activities. Methods: Women aged 40-74 years with no history of breast cancer or DCIS, and no previous double mastectomy can join the WISDOM (NCT02620852) study online at wisdomstudy.org. A total of 28,600 women have consented to participate. As part of the trial, each patient completes a baseline and interval surveys through a Salesforce platform. In May, the study IRB was amended to add a COVID specific survey with questions related to participants COVID risk perceptions, coexisting conditions, and receipt of healthcare services in the 2 months prior to the survey. An initial survey was sent May 2020, with follow-up surveys planned every 2 months. In addition, national surveys on a population-based cross section of individuals across the nation will be performed in parallel. Data was collected, de-identified, and then analyzed using basic descriptive analysis, chi-2 analysis, and logit regression. Results: A total of 7,523 individuals in WISDOM responded to the survey (response rate 27%). Of those that responded, the average age at the time of the survey was 59 (range 40-79). The population was 87% Caucasian, 6% Hispanic, and 4% African-American. Only 3.6% of the sample felt they had COVID-19 either by symptoms or through testing. However, 10.0% felt they were at higher risk compared to similar individuals their age to get COVID-19. Of the sample, 29% had some form of high-risk coexisting condition that put them at higher risk for COVID-19. In terms of healthcare utilization in the prior 2 months, 43% had a routine medical visit cancelled by their primary care provider or health system, whereas 26% cancelled an appointment themselves. In terms of breast cancer screening, 16% had their screening visit either cancelled or delayed. Individuals who believed they were at higher risk (and more likely to have shorter interval screening recommendations on this trial) had a higher Odds Ratio (1.66) for a screening cancellation (p&amp;lt;0.001). Those individuals who held the belief that COVID-19 was no more dangerous than the seasonal flu were more likely to have medical visits and routine care in the preceding 2 months than those that did not share that belief. (OR 1.18, p=0.032). Individuals were significantly more worried about COVID-19 than developing breast cancer (43% moderate to severely worried about COVID compared to 8.2% for breast cancer). Those worried about COVID were more likely to have screening cancellation (OR 1.18, P&amp;lt;0.001) and those more worried about breast cancer were less likely to have a screening cancellation (OR. 0.83, P&amp;lt;0.001). Conclusions: Health maintenance, prevention, and specifically breast cancer screening are important, but these health activities have been significantly disrupted due to the COVID-19 pandemic. Given that the pandemic will likely continue for many months until there is either a vaccine, treatment, or herd immunity, it will be important to define the drivers and messages (healthcare and screening) to ensure patients receive proper health maintenance and prevention to reduce the risks associated with other diseases that are not COVID-19. The preliminary data presented as part of this abstract submission are the early results of an effort to develop a predictive model and targeted strategies for communication and intervention for cancer screening during the course of the COVID-19 pandemic. Citation Format: Arash Naeim, Neil Wenger, Karen Sepucha, Annette Stanton, Ryan Baxter-King, Leah Sabacan, Antonia Petruse, Patricia Choy, Susie Brain, Laura Esserman, Wisdom Study and Athena Breast Health Network Investigators and Advocate Partners, Lynn Vavreck. Health maintenance and breast cancer screening during the COVID-19 pandemic [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS2-04.

Abstract PS14-09: The impact of non-classic LCIS on the natural history of DCIS

Abstract Background: Classic lobular carcinoma in situ (C-LCIS) and non-classic LCIS (NC-LCIS) are histologically and biologically distinct types of lobular neoplasia. Little is known about the impact of NC-LCIS on risk of recurrence when found in association with concomitant malignancy. We sought to assess oncologic outcomes in patients with DCIS and concomitant NC-LCIS as compared to DCIS with concomitant C-LCIS treated with breast conservation. Methods: Upon IRB approval, an institutional database was accessed to identify patients with a diagnosis of C-LCIS + DCIS or NC-LCIS+DCIS in the same core biopsy and/or excisional biopsy specimen. All pathology slides relevant to the diagnosis were confirmed by internal review. Patients with prior or concurrent ipsilateral invasive breast cancer and/or prior ipsilateral DCIS were excluded. Use of adjuvant therapies and the incidence of ipsilateral and contralateral DCIS and invasive breast cancer were compared in the 2 groups. Statistical analysis was performed using the chi-square test. Results: Among patients diagnosed with DCIS between 1996 and 2015 and treated with breast conserving surgery, 69 also had C-LCIS and 13 also had NC-LCIS (the diagnosis of NC-LCIS was not encountered until 2000). Median patient age was 55 years (range 40-88), 42 (51%) had a family history of breast cancer and 5 (6%) had a prior diagnosis of atypical proliferative breast lesions; these factors did not differ between patients with C-LCIS+DCIS and NC-LCIS+DCIS. Patients with NC-LCIS+DCIS were more likely to present with mammographic distortion (25% vs 6%, p=0.03), to have been diagnosed by core biopsy, and less likely to have ER positive (67% vs 91%, p=0.03) or PR positive (50% vs78%, p=0.014) DCIS. In 78% of the patient cohort, final excision margins were negative, and these proportions were not different between the 2 groups The median number of surgeries performed to obtain clear surgical margins which was 2 (range 1-4) for the entire cohort and for C-LCIS+DCIS and NC-LCIS+DCIS, individually. 78.% of C-LCIS+DCIS patients and 54% of NC-LCIS+DCIS patients received adjuvant radiation (p=0.064), and 45% of C-LCIS+DCIS patients took adjuvant hormonal therapy, while none of the NC-LCIS+DCIS patients did (p=0.002). At median follow-up of 78 (1-260) months for C-LCIS+DCIS and 60 (1-197) months for NC-LCIS+DCIS, there were no differences observed in the incidence of ipsilateral and contralateral breast cancer (10.1% vs 7.7% , p=0.19, and 10.1% vs 0%, respectively, p=0.78). One of 13 patients (7.7%) with NC-LCIS+DCIS, who developed an ipsilateral invasive carcinoma, was subsequently diagnosed with bone metastasis. Conclusions: Patients with NC-LCIS+DCIS were more likely to have ER and/or PR negative DCIS and only 54% of this cohort received radiation, yet local-regional recurrence rates were low and not different between NC-LCIS +DCIS and C-LCIS+DCIS patients. Despite the more aggressive histologic features of NC-LCIS, these data do not suggest that NC-LCIS associated with DCIS portends a different prognosis that C-LCIS associated with DCIS. Larger studies are needed to confirm these findings. Citation Format: Faina Nakhlis, Fisher Katlin, Samantha Grossmith, Ashley DiPasquale, Beth Harrison, Tari King. The impact of non-classic LCIS on the natural history of DCIS [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-09.

Atypical ductal hyperplasia on core needle biopsy: Surgical outcomes of 200 consecutive cases from a high-volume breast program.

Atypical ductal hyperplasia (ADH) is an indication for excisional biopsy to rule out occult breast cancer. We analyzed pathological findings on excisional biopsy for ADH diagnosed in a high volume breast center equipped with digital tomosynthesis. Two hundred consecutive patients were diagnosed with ADH on core biopsy with radiographic concordance followed by excisional biopsy. On excisional biopsy, 33 patients (16.5%) were diagnosed with DCIS or invasive breast cancer. Patients with a concurrent diagnosis of papilloma had a higher risk of upstaging on both univariate and multivariate analysis (41.7% vs. 14.9%, p=0.015). No other statistically significant predictors of upgrading were identified (p>0.05).

Clinicopathological Characteristics of Breast Ductal Carcinoma In Situ: An Analysis of Chinese Population of 617 Patients.

Background The purpose of this study was to describe the clinicopathological characteristics of breast DCIS in Chinese women and compare with that of patients in western countries. Method From December 2005 to December 2015, 617 women diagnosed with pure DCIS after surgery at our institution were enrolled, and the clinicopathological characteristics were described. Results In this study, the percentage of patients detected on screening, diagnosed at ≤50 years of age, with tumor size ≤2.0 cm, and with low-intermediate grade was 39.4%, 56.7%, 72.6%, and 77.4%, respectively, as compared to 50–80%, 20–30%, 70–90%, and 40–60% in published reports from western countries. The percentage of ER-positive patients was 76.3% in this study, which is similar to the mean expression rate of ER (mean: 68.7%, range: 49–96.6%) reported previously. Conclusions The clinicopathological characteristics of Chinese DCIS patients include less detection on screening, younger age at diagnosis, and more low-intermediate nuclear grade.