Breast DCIS Research Articles

NRG-BR007: A phase III trial evaluating de-escalation of breast radiation (DEBRA) following breast-conserving surgery (BCS) of stage 1, HR+, HER2-, RS ≤18 breast cancer.

TPS623 Background: Approximately 50% of newly diagnosed invasive breast cancers are stage 1, with the majority being ER/PR-positive, HER2-negative. Genomic assays such as the Oncotype DX have identified patients (pts) with reduced risk of distant metastasis and without benefit from chemotherapy added to endocrine therapy, freeing them from excess toxicity. Genomic assays are also recognized as prognostic for in-breast recurrence (IBR) after BCS and could similarly allow de-escalation of adjuvant radiotherapy (RT). Reducing overtreatment is of interest to pts, providers, and payers. Methods: We hypothesize that BCS alone is non-inferior to BCS plus RT for in-breast recurrence and breast preservation in women intending endocrine therapy (ET) for stage 1 invasive breast cancer (ER &/or PR positive, HER2-negative with an Oncotype DX Recurrence Score [RS] of ≤18). Stratification is by age (<60; ≥60), tumor size (≤1 cm; >1-2cm), and RS (<11, 11-18). Pts are randomized post-BCS to Arm 1 with breast RT using standard methods (hypo- or conventional-fractionated whole breast RT with/without boost, or APBI) with ≥5 yrs of ET (tamoxifen or AI) or Arm 2 with ≥5 yrs of ET (tamoxifen or AI) alone. The specific regimen of ET in both arms is at the treating physician’s discretion. Eligible pts are stage 1: pT1 (≤2 cm), pN0, age ≥50 to <70 yrs, s/p BCS with negative margins (no ink on tumor), s/p axillary nodal staging (SNB or ALND), ER &/or PR positive (ASCO/CAP), HER2-negative (ASCO/CAP), and Oncotype DX RS of ≤18 (diagnostic core biopsy or resected specimen). Primary endpoint is in-breast recurrence (invasive breast cancer or DCIS). Secondary endpoints are breast conservation rate, invasive in-breast recurrence, relapse-free interval, distant disease-free survival, overall survival, patient-reported breast pain, patient-reported worry about recurrence, and adherence to ET. We assume a clinically acceptable difference in IBR of 4% at 10 yrs to judge omission of RT as non-inferior (10-yr event-free survival for RT group is 95.6% vs 91.6% for the omission of RT group). BR007 is powered to detect non-inferiority with 80% power and a one-sided α=0.025, assuming that there would be a ramp-up in accrual in the first two years (leveling off in Yrs 3-5); 1,670 pts (835 per arm) are required for randomization. Conservative loss to follow-up is 1% per yr. Some of the T1a pts screened may have Oncotype DX scores >18, making them ineligible for the study. In the accrual process, 1,714 pts will be required to register to ensure that our final randomized cohort is 1,670 pts. Current accrual (02-08-2023) is 370 screened and 323 randomized (~87% of predicted accrual). Clinical trial information: NCT04852887 .

MELODY (Methods for Localization of Different Types of Breast Lesions): A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET).

TPS626 Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com ). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 20 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Clinical trial information: NCT05559411 .

Contrast enhanced mammography in breast cancer surveillance

PurposeMammography (MG) is the standard imaging in surveillance of women with a personal history of breast cancer or DCIS (PHBC), supplemented with ultrasound. Contrast Enhanced Mammography (CEM) has higher sensitivity than MG and US. We report the performance of CEM compared with MG ± US.MethodsA retrospective study of patients undergoing their first surveillance CEM in an Australian hospital setting between June 2006 and October 2020. Cases where a patient was recalled for assessment were identified, recording radiology, pathology and treatment details. Blinded re-reading of recalled cases was performed to determine the contribution of contrast. Use of surveillance US across the board was assessed for the period.Results73/1191 (6.1%) patients were recalled. 35 (48%) were true positives (TP), with 26 invasive cancers and 9 cases of DCIS, while 38 (52%) were false positive (FP) with a positive predictive value (PPV) 47.9%. 32/73 were recalled due to MG findings, while 41/73 were only recalled due to Contrast. 14/73 had ‘minimal signs’ with a lesion identifiable on MG with knowledge of the contrast finding, while 27/73 were visible only with contrast. 41% (17/41) recalled due to contrast were TP. Contrast-only TPs were found with low and high mammographic density (MD). Screening breast US reduced by 55% in the year after CEM was implemented.ConclusionCompared to MG, CEM as a single surveillance modality for those with PHBC has higher sensitivity and comparable specificity, identifying additional malignant lesions that are clinically significant. Investigation of interval cancer and subsequent round outcomes is warranted.

Abstract GS4-08: 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer

Abstract We have previously shown in a phase 3 trial that tamoxifen 5 mg/day for 3 years decreased by 52% the incidence of recurrence of invasive breast cancer or DCIS after a median follow-up of 5.1 years in women with excised non invasive breast disease, including atypical ductal hyperplasia, DCIS or LCIS (DeCensi et al. JCO 2019; 37:1629). Toxicity was negligible with only an extra hot flash per day in the tamoxifen arm compared with the placebo arm. These findings were incorporated into the ASCO clinical practice guidelines for breast cancer risk reduction as an alternative option to standard doses and duration of tamoxifen or aromatase inhibitors in women with non-invasive disease (Visvanathan et al. JCO 2019; 37:3152). In the present study we update the findings on breast cancer recurrence after a median of 9.14 years (interquartile range, IQR, 7.16-10.73) and a total of 10.57 person years of follow up to see if the treatment effect is retained with more events and after a median of approximately 6 years from treatment cessation. We conducted a national multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. Between November 1, 2008, and March 31, 2015, 1,160 women were screened and 500 aged 75 years of age or younger were included in the study. Women with high-grade or comedo/necrotic DCIS received adjuvant radiotherapy of 50 Gy in 25 courses. The mean age was 54 years (standard deviation, 9 years), and 55% of participants were postmenopausal. The mean (SD) body mass index, kg/m2, was 25.7 (4.8) on tamoxifen and 25.3 (4.2) on placebo. Twenty percent had ADH, 11% had LCIS, and the remaining 69% had DCIS. After a median follow-up of 9.14 years, there were 22 neoplastic events (invasive breast cancer or DCIS) with tamoxifen and 37 with placebo (annual rate 11.09, 95% CI, 7-30-16.84 on T vs 19.71, 95% CI, 14.28-27.21 on P per 1,000 person-years; hazard ratio, 0.56; 95% CI, 0.33 to 0.95; P = .03), which resulted in a 5-year number needed to treat of 18. Overall, 71% of the recurrences were invasive breast cancer. The follow-up was updated with the most recent visit within 12 months in two thirds of the participants, so an update of all participants will be performed by Sept 30th with full analysis of neoplastic events, annual risk rate ratio, serious adverse events and deaths. Moreover, an updated analysis of potential effect modifiers will be conducted, including menopausal status, baseline estradiol levels, menopausal symptoms, BMI, smoking status and Ki-67 of the primary lesion. In conclusion, our findings indicate that low dose tamoxifen given for 3 years still significantly prevents recurrences from non-invasive breast cancer after a median of 6 years from treatment cessation, providing a valid prevention/interception option in this disease group. Supported by Ente Ospedaliero Ospedali Galliera, Genova, Italy, the Italian Ministry of Health (RFPS-2006-1-339898), the Italian Association for Cancer Research (IG 2008 Grant No. 5611), and the Italian League against Cancer (LILT 7-08). Citation Format: Andrea De Censi, Matteo Lazzeroni, Matteo Puntoni, Luca Boni, Aliana Guerrieri Gonzaga, Tania Buttiron Webber, Marianna Fava, Irene Maria Briata, Livia Giordano, Maria Digennaro, Laura Cortesi, Fabio Falcini, Franca Avino, Francesco Millo, Katia Cagossi, Elisa Gallerani, Alessia De Simone, Anna Cariello, Giuseppe Aprile, Maria Renne, Bernardo Bonanni. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-08.

Abstract PD3-06: Robotic Stereotactic APBI for Early-Stage Breast Cancer: 2-year Outcomes of a Prospective Multi-Institutional Trial

Abstract Purpose: Outcomes following adjuvant accelerated partial breast irradiation (APBI) in select women with early-stage breast cancer are comparable to whole breast irradiation. Robotic stereotactic accelerated partial breast irradiation (RSAPBI) with fiducial tracking is an attractive treatment option, but limited outcomes data are available for this approach. We report 2-year outcomes for a prospective multi-institutional trial treating select women with RSAPBI. Materials and Methods: Post-menopausal women with DCIS and Stage IA breast cancer were treated over a five-year period extending from November 2015 to November 2020 and were followed for a minimum of 18 months. Treatments were delivered with a robotic radiosurgery system. Four gold fiducials were implanted around the lumpectomy cavity prior to the start of treatment for tumor bed delineation and target tracking. The CTV was defined as the lumpectomy cavity with a uniform 5-15 mm expansion confined to the breast tissue and the PTV was defined as the CTV with a 0-5 mm uniform expansion. The PTV was prescribed 30 Gy in 5 fractions. Disease status assessments were completed at 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months and yearly intervals thereafter for five years. Results: Eighty-one patients (median age 68 years) with hormone receptor-positive tumors were treated over a median 9 days (range, 5-15). Sixty-eight women had invasive ductal carcinoma (84%) and thirteen had DCIS (16%). The median treated PTV was 108 cm3 (IQR 66-156) and the median prescription isodose line was 81% (IQR 79-83). The median CTV expansion was 10 mm (range 5-10) and the median PTV expansion was 3 mm (range 0-5). At a median follow up of 2 years there was one new ipsilateral breast tumor diagnosed. There were no local, regional, or distant treatment failures. Conclusions: Two-year results suggest that RSAPBI with fiducial tracking is an effective technique for the adjuvant treatment of post-menopausal women with hormone receptor-positive early-stage breast cancer. Additional follow-up is planned to confirm this preliminary finding. Citation Format: Jonathan M. Cantalino, David D’Ambrosio, Arica Hirsch, Brian Collins, Malika Danner, Dawn Matsanka, Sonali Rudra, Simeng Suy, Sean Collins, Monica Pernia Marin, Michael Good, Jing Feng, John Lamond, Deborah Markiewicz, Rachelle Lanciano, Olusola Obayomi-Davies. Robotic Stereotactic APBI for Early-Stage Breast Cancer: 2-year Outcomes of a Prospective Multi-Institutional Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-06.

Abstract P1-10-11: Optical stimulated luminescence dosimeters for skin dose measurements during accelerated partial breast brachytherapy: In vivo dosimetric validation and clinical outcomes

Abstract BACKGROUND: The role of multi-lumen catheter devices in the delivery of high dose rate (HDR) brachytherapy for adjuvant accelerated partial breast irradiation (APBI) for women with DCIS or early-stage breast cancer has been well established. In vivo dosimetry (IVD) using optically stimulating luminescence dosimeters (OSLD) is a feasible way to detect applicator instability that may cause translational and rotational inaccuracies during HDR brachytherapy delivery. Herein, we evaluate the accuracy and effectiveness of IVD to improve patient outcomes following APBI brachytherapy using the Strut Adjusted Volume Irradiation (SAVI) device. METHODS: Single-institution cohort study piloting the use of OSLD on the patient’s skin during HDR brachytherapy APBI to assess the estimated maximum skin dose (skin Dmax) and the achievable accuracy of OSLD for skin Dmax measurements. Women treated with SAVI-based APBI between November 1, 2018 and October 1, 2021 were eligible to enroll in our study. All patients met the American Society for Radiation Oncology “suitable” or “cautionary” criteria and were treated according to the American Brachytherapy Society consensus treatment planning guidelines. A SAVI preplan was created to estimate the probable point of skin Dmax. During CT simulation, a radiopaque marker was placed on the skin for visualization during treatment planning. Correction factors were applied to account for the OSLD tissue-air interface that is not present in the TG-43 expected dose calculations. Measured and calculated IVD doses were analyzed to assess agreement and cause for discrepancies found. Breast phantom IVD measurements repeated seven times with two independent dose points were analyzed to assess the best accuracy achievable under ideal conditions. RESULTS: We enrolled 41 patients with an average age of 68 years. Table 1 details the brachytherapy treatment delivery and dosimetry data. Higher skin Dmax as a percentage of the radiation prescription was associated with the occurrence of breast volume loss noted on subsequent clinical breast exams (OR 1.84 per each 5% increase in skin Dmax; 95% CI 1.21 – 3.32; p=0.016). The graphically estimated skin Dmax threshold was 80% with all cases of noted breast volume loss occurring above this threshold. The overall level of achievable IVD accuracy was ±3.32% based on breast phantom measurements. Under ideal conditions, all measurements were in the ±7% range. Three of 14 phantom measurement exceeded the 6% discrepancy range. Clinical IVD measurements detected 5 true positive cases (12.2% of cohort) that required intervention due to rotations in the SAVI applicator. For a ±7% tolerance criteria, 90.2% of the patients tested passed IVD. Of the eight patients that failed at the 7% level, IVD detected 3 OSLD placement errors, 2 rotational discrepancy cases, and 1 large air-gap at the point of measurement. CONCLUSIONS: Accuracy and reproducibility are imperative tenets of HDR brachytherapy APBI. IVD utilizing OSLD is an effective method for detecting treatment set-up and delivery errors for patients receiving SAVI-based APBI with dose accuracy within ±3.32%. Errors requiring intervention due to SAVI device rotation were detected in 12.2% of our cohort, and these errors would have likely gone undetected without IVD. Using OSLD as IVD to measure skin Dmax doses that may increase the risk of breast cosmetic defects should be investigated further. Table 1. Brachytherapy treatment delivery and dosimetry data. *PTV-Eval is a uniform 10 mm expansion on the CTV with exclusion of PTV within 5 mm of skin or chest wall. +Percent dose discrepancy refers to difference in dose between APBI plan calculations and IVD measurements. Citation Format: Tyler Gutschenritter, Afua Yorke, Nayak Polissar, Nirnaya Miljacic, Janice Kim, Lori Young. Optical stimulated luminescence dosimeters for skin dose measurements during accelerated partial breast brachytherapy: In vivo dosimetric validation and clinical outcomes [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-11.

Abstract P6-04-13: Centralized adequacy assessment of ductal carcinoma in situ samples for the COMET study (AFT-25)

Abstract Introduction COMET (Comparing an Operation to Monitoring, with or without Endocrine Therapy) is a phase III clinical trial randomizing patients diagnosed with low-intermediate grade DCIS to either active monitoring or surgery. The study has a planned accrual goal of 1200 patients and is enrolling until 12/31/22. The protocol requires agreement between two pathologists (who do not need to be at the same institution) that a case fulfills COMET eligibility criteria. If there is disagreement, a third pathology review is required. As per protocol, tissue blocks or unstained slides of biopsies containing DCIS from enrolled patients are sent to a designated central location. While central pathology review is not a pre-requisite of the study, a retrospective review of received materials was performed to determine adequacy for correlative molecular and spatial profiling studies. Methods Sites submit either a tissue block or twenty (20) sequentially numbered, unstained, serial five-micron tissue sections from a diagnostic biopsy of DCIS to the Alliance Foundation Trials (AFT) central biorepository, a CAP-accredited biobank. All submitted biospecimens are de-identified (coded) and investigators are blinded to arm assignment and primary study outcomes. To evaluate the adequacy of specimens for subsequent correlative science studies, one unstained slide from each submitted slide set was stained with routine hematoxylin and eosin by the biobank, scanned at 40X magnification with an Aperio scanner, and provided to one of two expert breast pathologists for adequacy review. Slides were rated as “DCIS present”, “DCIS absent”, or “possible DCIS.” To conserve tissue, submitted tissue blocks are held in abeyance pending future correlative science planning. Results As of May 2022, tissue has been submitted from 789 of 856 eligible patients enrolled in the trial, demonstrating a very high level (92%) of case submission compliance. Despite the limiting size of such lesions and general clinical center hesitancy to release blocks for clinical trial research, tissue blocks were received from 376 of 789 (48%) of cases. Among 359 cases involving slide-only submissions that have been retrospectively reviewed to date, 294 were definite DCIS (82%), 25 (7%) were classified as possible DCIS, and 40 cases (11%) were classified as no DCIS present in the section reviewed. In no case was high grade DCIS or invasive breast cancer observed. Of the cases considered possible DCIS, atypical cells were present, but the lesions were too small or incomplete to confirm DCIS. The small percentage of cases that lacked DCIS or definite DCIS could be attributed to the receipt of a different block or subsequent (deeper) section from the same block used for the initial diagnosis. These cases were previously known to the submitting institutions. Conclusion Interim analysis at 71% accrual demonstrates both the feasibility of obtaining diagnostic biopsy material of limited size and the adequacy of these samples for subsequent correlative science studies that aim to improve pathology diagnostics and patient management. Citation Format: Rachel Factor, Stuart Schnitt, Robert West, Terry Hyslop, Thomas Lynch, Deborah Collyar, Desiree Basila, Lars Grimm, Lorraine King, Jeffrey Marks, Sunil Badve, Mark Watson, Marc Ryser, Anna Weiss, Anna Rapperport, Linda McCall, H. T. Carisa Le-Petross, Ann Partridge, E Shelley Hwang, Alastair M. Thompson. Centralized adequacy assessment of ductal carcinoma in situ samples for the COMET study (AFT-25) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-13.

Abstract P4-03-29: Impact of the COVID-19 pandemic on breast cancer incidence and tumor stage in the Netherlands and Norway

Abstract Introduction. The SARS-CoV-2 infection rate and the COVID-19 death rate were relatively high in the Netherlands during the first wave of the COVID-19 pandemic (2.7 and 7.2 times higher than in Norway, respectively). Moreover, social measures differed between the two countries. This study aimed to compare the effect of the pandemic on breast cancer incidence and stage between the Netherlands and Norway. Methods. Women diagnosed with DCIS or invasive breast cancer between January 2017 and December 2021 were selected from the Netherlands Cancer Registry and from the Cancer Registry of Norway. The COVID-19 period was divided in three approximately equal periods: March-September 2020 (first wave), October 2020-April 2021 (second wave), May-December 2021 (post-second wave). Breast cancer incidence during the COVID-19 periods was compared with averaged data of the corresponding reference period: March-September 2017, 2018, 2019 (first wave_ref), October-April 2017, 2018, 2019 (second wave_ref), May-December 2017, 2018, 2019 (post-second wave_ref). Incidences were compared by age group, clinical tumor stage, and method of detection. Results. The number of breast cancer diagnosis and the breast cancer incidence are shown in Table 1. Compared to the reference period, breast cancer incidence was lower during the first wave in the Netherlands and Norway (IRR: 0.72; 95%CI: 0.70-0.75; IRR: 0.83, 95%CI 0.78-0.88, respectively), and was higher post-second wave in Norway (IRR: 1.10, 95%CI: 1.04-1.16) (Table 1). During the first wave, breast cancer incidence was lower in all age groups in the Netherlands (age < 50 IRR: 0.85, 95%CI: 0.79-0.91; 50-69 IRR: 0.64, 95%CIL 0.61-0.67; 70-74 IRR: 0.61, 95%CI: 0.56-0.67; >74 IRR: 0.86, 95%CI: 0.80-0.93, respectively). During the first wave, incidence was lower in women aged 50-69 in Norway (i.e., women eligible for screening; IRR: 0.68, 95%CI: 0.62-0.74). Post-second wave incidence was higher in women aged 50-69 and >74 in Norway (IRR: 1.09, 95%CI: 1.01-1.17; IRR: 1.13, 95%CI: 1.00-1.28, respectively). In the first wave the incidence of DCIS, stage I tumors, and screen-detected tumors was lower in the Netherlands (IRR: 0.55, 95%CI: 0.50-0.61; IRR: 0.62, 95%CI: 0.59-0.65, IRR: 0.36, 95%CI: 0.33-0.38, respectively) as well as Norway (IRR: 0.66, 95%CI: 0.54-0.79; IRR: 0.73, 95%CI: 0.66-0.81, IRR: 0.46; 95%CI: 0.40-0.52, respectively). Conclusion. The current study showed that the incidence of early-stage tumors mainly decreased. Moreover, during the first wave of the pandemic breast cancer incidence decreased in all age groups in the Netherlands but only in women aged 50-69 in Norway. The relatively high infection and death rate in the Netherlands might have increased the fear of patients to visit the general practitioner (GP) and/or to overburden the healthcare system at the start-up of the pandemic. In addition, it might have reduced the capacity at the GP. As a result, appointments with the GP might have been postponed, resulting in a decrease in the number of breast cancer diagnoses in all age groups. A catch-up in breast cancer diagnoses was seen post-second wave in Norway, but not in the Netherlands. Incidence rates should therefore be monitored in the coming period. Table 1: Number of breast cancer diagnoses (breast cancer incidence) during the COVID-19 pandemic and during the corresponding reference period (incidence is expressed per 100.000 women living in the Netherlands or Norway during the period of interest) Citation Format: Anouk Eijkelboom, Linda de Munck, Marthe Larsen, Jan Nygård, Solveig Hofvind, Sabine Siesling. Impact of the COVID-19 pandemic on breast cancer incidence and tumor stage in the Netherlands and Norway [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-29.

Abstract PD14-09: PD14-09 The effect of timing of TP53 genetic testing on treatment and outcomes among women with Li-Fraumeni syndrome and breast cancer

Abstract Background: Li-Fraumeni syndrome (LFS) is a pan-cancer predisposition syndrome caused by pathogenic germline TP53 variants. Breast cancer (BC) is the most prevalent tumor in women with LFS. The risk of secondary malignancies, including multiple primary BCs, other LFS-related cancers, radiation-induced sarcomas, and local recurrences are important clinical concerns in the LFS setting. The diagnosis of LFS may influence treatment decisions and outcomes. Methods: In this international multicenter study, we analyzed women with pathogenic or likely pathogenic germline TP53 variants and BC (DCIS or invasive breast carcinoma) diagnosed 2002-2022 from three retrospective LFS cohorts (Dana Farber Cancer Institute, USA; Institut Gustave Roussy, France; Hospital Sírio-Libanês, Brazil). We excluded carriers of TP53 unconfirmed possibly mosaic variants, carriers of a 2nd pathogenic variant in another BC susceptibility gene, and those with missing data related to timing of genetic testing (TGT) or date of 1st BC diagnosis (dx). The overall cohort was divided in two groups: genetic testing before or at 1st BC dx (group A) and those with testing ≥1 year after 1st BC dx (group B). In cases with synchronous bilateral BC, we included the tumor of higher risk of recurrence (invasive, higher stage, more aggressive tumor biology) and excluded the other. The chi-square test was used to measure the association between TGT and other categorical variables. Results: 209 patients (pts) met criteria for this analysis. The median age of 1st BC dx was 35 years (IQR, 31-42). BC was the 1st cancer dx in 87.5% of the pts. Among 1st breast tumors, 38 were DCIS, 147 were early-stage BC (61 I, 49 II, 37 III) and 7 stage IV (17 missing). There were no differences between groups A and B regarding staging at dx. Missense TP53 variants were the most common type of germline mutation (n=154, 73.6%), with 60.4% (n=93) in the DNA-binding domain and 38.9% (n=60) in the tetramerization domain. Median follow-up from 1st BC dx was 6 years (IQR, 3-10). 53.1% of pts (n=111) underwent TP53 germline testing only after 1st BC dx. Family history of BC < 50 and non-BC malignancy prior to or synchronous with 1st BC dx were not associated with TGT (p=0.3 and p=0.2, respectively). 35.4% of pts developed a second primary BC (25 ipsilateral; 49 contralateral). Among pts without synchronous bilateral BC or metastatic BC at dx, 97 pts underwent contralateral risk reducing mastectomy (CRRM), 56.7% (55/97) as part of treatment surgery for the 1st BC. CRRM uptake was associated with TGT (A 70.3% vs B 41.6%, p=0.001). Of 194 pts with detailed data on surgical treatment (1st BC), 146 underwent mastectomies and 48 breast conserving surgery (BCS). Group A had more mastectomies (79.5% vs 61.2%, p=0.001) and less radiation therapy (10.2% vs 45.9%, p< 0.001). Among the irradiated pts, 9.8% (n=5) developed sarcomas in the irradiated field. Thirty-eight pts had BC recurrence: 21 loco-regional (A 6 vs B 15, p< 0.05), mostly in-breast, and 17 distant relapses. There was a significant statistical association between TGT and type of BC surgery (p=0.001), radiation-therapy (p< 0.001), CRRM uptake (p=0.001) and local relapses (p< 0.05). Conclusion: This analysis of BC in our sizable cohort of LFS patients with treatment data confirms that, timing of genetic testing affects some treatment options and outcomes, including surgical procedures and use or avoidance of radiation. These decisions appear to influence the risk of local recurrence or additional primary BC and radiation-induced sarcoma. Recognition of germline TP53 variants in breast cancer patients as part of genetic testing at diagnosis appears to have implications for treatment options and outcomes. Citation Format: Renata Sandoval, Michele Bottosso, Natalia Polidorio, Brittany Bychkovsky, Benjamin Verret, Alessandra Gennari, Sophie Hyman, Maria Isabel Achatz, Olivier Caron, Fabrice Andre, Judy Garber. PD14-09 The effect of timing of TP53 genetic testing on treatment and outcomes among women with Li-Fraumeni syndrome and breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD14-09.

Abstract B019: Discrete regulation of the collagen proteome among pathological features in DCIS and invasive breast cancer by mass spectrometry tissue imaging

Abstract Ductal carcinoma in situ (DCIS) is characterized by inter-tumor heterogeneity that poses a therapeutic challenge due to its unpredictable recurrence and progression to invasive breast cancer (IBC). In recent publications, collagen stromal differences have been reported between patients that progressed to IBC (progressors) and those that did not (non-progressors). However, details on the role spatial regulation of the collagen proteome might play in this progression have yet to be studied. Here, we investigated the pathological distribution of collagen post-translational modifications in a cohort of patients classified as progressors with ipsilateral IBC recurrence compared to non-progressors. Previously published methods for collagen proteomics by targeted tissue mass spectrometry imaging were used. The method reports collagen types and post-translational modifications within the collagen triple-helical region as well as approximately 40 other extracellular matrix (ECM) proteins involved in the regulation of collagen fibers. Initial studies investigated collagen variation in lumpectomies (n=7) with DCIS, DCIS plus invasive ductal carcinoma (IDC) or IDC only. Over 590 peptides were found to be linked to annotated pathologies. A preliminary comparison of DCIS (n=2392 spectra) to IBC (n=4696 spectra) using area under the receiver operating curve (AUROC) ≥0.85 demonstrated that 47 peptides could individually discriminate between DCIS and IBC in this limited cohort. Image segmentation of the 405,652 pixels demonstrated 11 high-level hierarchical groups designating unique spatially localized ECM proteomic groups; these groups overlaid with histopathological features and pathological annotations. A total of 87 samples from the Resource of Archival Breast Tissue (RAHBT) matched with clinical characteristics were also investigated. Cores were histologically diverse within the tissue microarrays, with cribriform, micropapillary, papillary, solid, and comedo necrosis architectural patterns. Initial results suggest certain peptides may differentiate between non-progressors and progressors with ipsilateral IBC recurrence. Our current work focuses on correlating collagen signatures to mixed pathologies and the cellular content of cores. Further investigation of the collagen proteome is warranted. Overall, the data suggest unique collagen signatures in DCIS that could be useful for understanding recurrence and progression to IBC. Citation Format: Taylor S. Hulahan, Elizabeth N. Wallace, Siri H. Strand, Robert Michael Angelo, Graham Colditz, Eun-Sil Shelley Hwang, Robert West, Laura Spruill, Jeffrey R. Marks, Richard R. Drake, Peggi M. Angel. Discrete regulation of the collagen proteome among pathological features in DCIS and invasive breast cancer by mass spectrometry tissue imaging [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B019.

Abstract IA030: Molecular subtypes and spatial heterogeneity in DCIS

Abstract The large heterogeneity of DCIS complicates the identification of markers for risk of progression to invasive breast cancer. Molecular and cellular heterogeneity is observed across DCIS, between multiple foci of DCIS within a lesion and within mixed lesions of invasive tumors with DCIS foci. The intrinsic breast cancer subtypes represent fundamental biological properties of the disease and are also found at the DCIS stage. However, their frequency and relevance as prognostic markers in pre-invasive stage is still not clear. Novel technologies for spatial characterization of tumors allow detailed mapping of DCIS and the microenvironment and may give us clues to which DCIS have the propensity to invade surrounding stroma. In the presentation, we will discuss results from our ongoing genomic characterization of DCIS and invasive breast carcinomas that illustrate the need for stratification when searching for prognostic markers. We have found disproportionate distribution and characteristics of the intrinsic subtypes in DCIS compared with invasive breast cancer and the dominance of Luminal A and HER2 subtypes. Bona-fide basal-like tumors may rarely be found at the DCIS stage and HER2-enriched DCIS are associated with specific immune cell profiles. Citation Format: Therese Sørlie. Molecular subtypes and spatial heterogeneity in DCIS [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA030.

Abstract PR005: Intraductal administration of a recombinant transferrin receptor-directed immunotoxin clears ductal carcinoma in situ in preclinical mammary in-duct (MIND) models of breast cancer

Abstract Background: For DCIS, a preneoplastic lesion with a 15-50% chance of recurrence or progression, there is a reappraisal of the necessity of aggressive treatment with its attendant toxicities. HB21(Fv)-PE40, a conjugate of an Fv fragment of the human transferrin-receptor (TFR) mAb and a 40 kDa fragment of bacterial Pseudomonas exotoxin (PE), has potent tumor cell killing activity. HB21(Fv)-PE40 binds to abundantly expressed TFR on cancer cells; the molecule is internalized, processed, and trafficked to the cytosol. Inside the cell, PE-toxin catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor 2 (EF2), inactivates EF2, and leads to an arrest in protein translation and cell death by apoptosis. However, due to its abundant expression in the liver, the recombinant immunotoxin (RIT) is potentially toxic. We hypothesized that RIT administration via the mammary ductal opening at the teat will destroy preneoplasias, both visible and occult, in the entire ductal tree, while systemic effects will be minimal. The intraductal approach could provide a direct, safe, and highly effective treatment for DCIS. Methods: We tested this concept in two models of DCIS using an ER/PR-, HER2+ cell line derived from a DCIS, SUM225-Luc, and in the ER/PR+, HER2- breast cancer cell line, MCF-7-Luc. In both cell lines, the IC50 of the toxin was in the nM range. DCIS developed within one week in the MIND models following i.duc injection of tumor cells in the 4th pair of mammary glands of female NSG mice. On day 7, the tumor-bearing mice received vehicle, TFR mAb alone, or the HB21(Fv)-PE40 conjugate by the i.duc or i.v route three times at weekly intervals and were observed for 1-6 months. Within two weeks of the treatment, IVIS imaging signals were undetectable in the mammary gland treated with RIT i.duc in both the models (P<0.0001). Mammary gland whole mount analysis, histopathology, and immunohistochemistry for Ki67, Ku80, TFR and CD31 showed that i.duc toxin rendered more than 90% of the mice tumor-free. Pharmacokinetics studies were conducted in mice with the RIT administered i.v. or i.duc. RIT was undetectable by TFR-ELISA in the blood of i.duc-treated mice. Conclusions. Overall, we have shown that HB21(Fv)-PE40 has remarkable antitumor activity by i.duc administration in two MIND models of DCIS. RIT was undetectable in blood after i.duc injection by ELISA, suggesting that the toxin remains inside the ductal system during its 30 min half-life. This preclinical study provides a solid foundation for a clinical study. Dose escalation studies of HB21(Fv)-PE40 by the i.duc route could be performed in patients with DCIS and early breast cancer who will undergo mastectomy as part of their treatment regimen. This study design will allow a detailed examination of the local (breast) and systemic effects of i.duc HB21(Fv)-PE40. It will introduce a potent agent for DCIS treatment and cancer interception in women at high risk of developing breast cancer. The contribution of the immune system remains to be explored. Citation Format: Saraswati Sukumar. Intraductal administration of a recombinant transferrin receptor-directed immunotoxin clears ductal carcinoma in situ in preclinical mammary in-duct (MIND) models of breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR005.

The initial experience of MRI-guided precision prone breast irradiation with daily adaptive planning in treating early stage breast cancer patients.

A major challenge in breast radiotherapy is accurately targeting the surgical cavity volume. Application of the emerging MRI-guided radiotherapy (MRgRT) technique in breast radiotherapy may enable more accurate targeting and potentially reduce side effects associated with treatment. To study the feasibility of delivering MRI-guided partial breast radiotherapy or Precision Prone Irradiation (PPI) to treat DCIS and early stage breast cancer patients. Eleven patients with diagnosed DCIS or early stage breast cancer treated with lumpectomy underwent CT-based and MRI-based simulations and treatment planning in the prone position. MRI-guided radiotherapy was utilized to deliver partial breast irradiation. A customized adaptive plan was created for each delivered radiotherapy fraction and the cumulative doses to the target volumes and nearby organs at risk were determined. The CT-based and the MRI-guided radiotherapy plans were compared with respect to target volumes, target volume coverage, and dose to nearby organs. All patients receiving PPI successfully completed their treatments as planned. Clinical target volume (CTV) and planning target volume (PTV) dose coverage and organs-at-risk (OAR) dose constraints were met in all fractions planned and delivered and the MRI-guided clinical target volumes were smaller when compared to those of the CT-based partial breast radiotherapy plans for these eleven patients. MRI-guided partial breast radiotherapy as a breast radiotherapy technology is feasible and is a potential high clinical impact application of MRgRT. PPI has the potential to improve the therapeutic index of breast radiotherapy by more accurately delivering radiation dose to the cavity target and decreasing toxicities associated with radiation to the surrounding normal tissues. Prospective clinical data and further technical refinements of this novel technology may broaden its clinical implementation.

20 (PB-020) Poster Spotlight - Contrast Enhanced Mammography in Breast Cancer Surveillance

Background: Women with a personal history of breast cancer or DCIS (PHBC) are at increased risk of either a local recurrence or a new primary breast cancer. Adjunctive screening ultrasound or MRI is often used to supplement mammography. Contrast enhanced mammography (CEM) is reported to have higher sensitivity than MG and ultrasound, and similar performance with better accessibility than MRI.

ASO Visual Abstract: The Presence of Non-classic LCIS is Not a Contraindication to Breast Conservation in Patients with Concomitant Invasive Breast Cancer or DCIS.

ASO Visual Abstract: The Presence of Non-classic LCIS is Not a Contraindication to Breast Conservation in Patients with Concomitant Invasive Breast Cancer or DCIS.

Acute dermatitis in adult female patients receiving hypofractionated radiotherapy for breast cancer: experience from a low- and middle-income country.

Radiotherapy (RT) is an important component of treatment in the management of breast cancer patients. The radiation treatment paradigm has been shifted towards hypofractionated RT. This study aims to determine the severity of acute dermatitis in patients receiving hypofractionated RT for breast cancer at a tertiary care university hospital in Pakistan. Patients with biopsy-proven invasive breast carcinoma or DCIS who were referred for radical radiotherapy after discussion in the breast tumour board were retrospectively reviewed. Physical assessment of the patients for evaluation of the severity of radiation dermatitis will be carried out in the first week, last week and on the first follow-up after 1 month of completion of RT, according to the Radiation Therapy Oncology Group/European Organisation For Research And Treatment Of Cancer (RTOG/EORTC) criteria. We identified 92 female patients in 6 months at Aga Khan University Hospital, with a mean age of 53.1 years. Most of the treated patients had clinical stage 3 (64%) cancer, while others were stage 2 (42%), stage 1 (2%) and stage 0 (2%). The surgeries performed were mastectomy in 59 patients and breast-conserving surgery in 33 patients. Histology was Intra Ductal Carcinoma (IDC) (95%), DCIS (3%) and Invasive Lobular Carcinoma (ILC) (2%). Most of the patients received chemotherapy (96%). Radiotherapy dose was 4256 cGy in 16 fractions, followed by a boost of 10 Gy. The radiation techniques used were intensity-modulated radiotherapy (47.8%) and three-dimensional conformal radiotherapy (52.2%). Most of the patients experienced no toxicity (59%), while grade I toxicity was observed in 29% of the patients and grade II toxicity was observed in 11%. Only 1% of the patients experienced grade III skin toxicity. Hypofractionated radiation therapy is beneficial because of the shorter overall treatment time which reduces the socio-economic burden, not only for patients but also for radiotherapeutic institutions. However, extended follow-up is to be reported for long-term toxicity and other consequences.

Depiction of breast cancers on digital mammograms by artificial intelligence-based computer-assisted diagnosis according to cancer characteristics.

To evaluate how breast cancers are depicted by artificial intelligence-based computer-assisted diagnosis (AI-CAD) according to clinical, radiological, and pathological factors. From January 2017 to December 2017, 896 patients diagnosed with 930 breast cancers were enrolled in this retrospective study. Commercial AI-CAD was applied to digital mammograms and abnormality scores were obtained. We evaluated the abnormality score according to clinical, radiological, and pathological characteristics. False-negative results were defined by abnormality scores less than 10. The median abnormality score of 930 breasts was 87.4 (range 0-99). The false-negative rate of AI-CAD was 19.4% (180/930). Cancers with an abnormality score of more than 90 showed a high proportion of palpable lesions, BI-RADS 4c and 5 lesions, cancers presenting as mass with or without microcalcifications and invasive cancers compared with low-scored cancers (all p < 0.001). False-negative cancers were more likely to develop in asymptomatic patients and extremely dense breasts and to be diagnosed as occult breast cancers and DCIS compared to detected cancers. Breast cancers depicted with high abnormality scores by AI-CAD are associated with higher BI-RADS category, invasive pathology, and higher cancer stage. • High-scored cancers by AI-CAD included a high proportion of BI-RADS 4c and 5 lesions, masses with or without microcalcifications, and cancers with invasive pathology. • Among invasive cancers, cancers with higher T and N stage and HER2-enriched subtype were depicted with higher abnormality scores by AI-CAD. • Cancers missed by AI-CAD tended to be in asymptomatic patients and extremely dense breasts and to be diagnosed as occult breast cancers by radiologists.

357 Treatment of breast cancer in elderly patients: A tailored approach

Introduction and aims of the study: Breast cancer is the most common cancer in women and its prevalence increases with age. However, treatment of elderly patients remains controversial. We conducted a review of all available data on breast cancer treatment for women over 80 years old. Methods: A literature search was performed (Google Scholar, PubMed, Cochrane) using the terms breast cancer, DCIS and/or, treatment, surgery, chemotherapy, radiation therapy, endocrine therapy, prognosis and elderly, age over 80.

Abstract P2-10-02: Random periareolar fine-needle aspiration (RPFNA) cell number, prior precancerous breast disease and subsequent uptake of a prevention intervention predict short-term breast cancer risk

Abstract Introduction: In 2000 we published initial observations from a high-risk cohort of 480 women that cytologic evidence of hyperplasia with atypia in benign breast tissue obtained by random periareolar fine-needle aspiration (RPFNA) was associated with a five-fold increased risk of developing DCIS or invasive breast cancer at a median follow-up of 45 months [Fabian, JNCI 2000]. Few women in the initial cohort had any exposure to prevention agents, as NSABP-P1 was not reported until 1998. We began a new high-risk cohort in 2002 as the tissue processing changed from a filter technique to Thin PrepTM. The superior nuclear detail permitted assessment of cytologic atypia in the absence of high cellularity. Women in the second cohort were told that RPFNA atypia was a risk factor for developing breast cancer and in addition to standard prevention options were offered participation in clinical trials, if applicable. The purpose of this subsequent analysis was to determine if the predictive value of RPFNA atypia was maintained with change in tissue processing and availability of prevention options. Methods: A total of 1,135 high-risk women, eligible on the basis of family history, BRCA1/2 mutation status, prior biopsy indicating LCIS or atypical hyperplasia (AH), prior contralateral breast cancer and/or high mammographic breast density, underwent baseline RPFNA and were enrolled in our second cohort between 2002 and 2015. As in the earlier study published in 2000, if women had 2 aspirations without an intervening intervention within 21 months the worse result was utilized as baseline. In addition to cytomorphology, breast tissue was also categorized by cellularity of the aspirate (10-100, 100-1000, 1000-5000, and &amp;gt;5000 cells per cytology slide). The primary aspirator (CJF) and cytopathologist (CMZ) were the same for both cohorts. Women were censored at the time of prophylactic mastectomy, development of other site cancer, or death. Kaplan-Meier hazard plots and Cox-regression analysis were used to analyze time to development of DCIS or invasive breast cancer and effect of joint variables, respectively. Results: At a median follow-up of 86 months, 79 cases of DCIS or invasive breast cancer had been diagnosed. By univariate analysis, RPFNA atypia at entry was not predictive of subsequent breast cancer (p=0.58; log-rank test). However, breast cancer risk was increased by a prior breast biopsy with LCIS or AH (HR 2.6, 95% CI 1.6-2.4, p&amp;lt;0.001) or by high RPFNA cellularity, defined as &amp;gt;5000 epithelial cells per RPFNA cytomorphology slide (HR 2.1, 95% CI 1.3-3.5, p=0.0034). Thirty-six percent of women subsequently chose to undergo a prevention intervention, including a standard drug, enrollment in a prevention clinical trial of 6-12 months duration, or a prophylactic bilateral salpingo-oophorectomy (BSO) prior to age 45. Prevention interventions were more prevalent in women with RPFNA atypia (49% vs 30%, p&amp;lt;0.001). Not only was uptake of a prevention intervention associated with reduced breast cancer risk on univariate analysis (p=0.043), it was retained on multivariate analysis. The final Cox Regression risk model included prior breast biopsy with LCIS or AH (HR 2.4, 95% CI 1.5-3.9; p&amp;lt;0.001), high RPFNA cellularity (HR 2.2, 95% CI 1.3-3.7; p=0.003) and prevention intervention (HR 0.54, 95% CI 0.33-0.89; p=0.015). Conclusions: In a second large cohort of high-risk women for whom RPFNA acquired cells were processed to slides via ThinPrep™, high RPFNA cellularity (&amp;gt;5000 epithelial cells/slide) but not cytologic atypia predicted short-term breast cancer risk. However, women with atypia were significantly more likely than women without atypia to participate in a prevention intervention, which in turn was associated with reduced breast cancer risk Citation Format: Whitney L Hensing, Carol J Fabian, Carola M Zalles, Priyanka Sharma, Amy L Kreutzjans, Kandy R Powers, Lynn Chollet-Hilton, Bruce F Kimler. Random periareolar fine-needle aspiration (RPFNA) cell number, prior precancerous breast disease and subsequent uptake of a prevention intervention predict short-term breast cancer risk [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 P2-10-02.

Abstract P2-15-03: Neoadjuvant endocrine therapy (NET) as bridge therapy for early stage breast cancer during COVID-19: A single institution experience

Abstract Background: Neoadjuvant endocrine therapy (NET) has long been limited to patients who were deemed medically unfit for immediate surgery or on clinical trials. Coronavirus disease 2019 (COVID-19) resulted in a global pandemic, which led to deferral of elective surgeries including breast surgeries for early stage breast cancer patients during March - June 2020. Institutional guidelines were developed based on societal recommendations, including NCCN, to use NET as a bridge to surgery. Objective: Primary objective was to establish a database of early stage HR+ Her2/neu- breast cancer patients diagnosed during COVID-19 who were treated with NET as a bridge to surgery. Secondary endpoints include correlation between duration of NET and changes in pathological variables. Method: This was a single institution, retrospective observational study from Perlmutter Cancer Center at NYU Langone Hospital and NYU Langone Hospital - Long Island of DCIS and early stage breast cancer patients diagnosed from March 15, 2020 - June 1, 2020 during COVID-19 pandemic. Inclusion criteria were males and females older than 18 years of age and initial diagnosis of DCIS or early stage HR+ Her2/neu- breast cancer who did not require neoadjuvant chemotherapy by established guidelines. Descriptive statistics were calculated separately by DCIS and invasive breast cancer using SAS version 9.4. Results: From March 15 - June 1, 2020, 13 patients who were diagnosed with DCIS and 41 patients with early stage HR+ Her2/neu- invasive breast cancer received NET (Table 1). Of the 41 patients with invasive breast cancer, 19 (46%) had Oncotype DX assay on biopsy specimens; 12/19 (63%) had scores 10-14 and 7/19 (37%) had scores 15-25. 38/41 (92.7%) had post-surgery Ki-67% and 16/38 (42.1%) demonstrated maturation arrest (Ki-67 &amp;lt;2.7%). 26/41 (63%) invasive breast cancer patients had pre and post Ki-67% checked while on aromatase inhibitors (AI); 21/26 (81%) had a decrease in Ki-67%, 2/26 (7.7%) patients had no change, and 3/26 (11.5%) had an increase. Of those 21 patients, the percent change of Ki-67% from baseline was mean 69.15% ± 22.58 and median 71.83%. No significant associations with changes (pre to post) in Ki-67%, T stage, ER% and PR% in NET for ≤4 weeks and &amp;gt;4 weeks (Table 2). Median duration of NET in invasive breast cancer was 6.85 weeks. 1 patient had a complete pathological response after NET and 2 patients were upstaged from DCIS to invasive carcinoma at the time of surgery. Conclusion: While the sample sizes are small, this is a unique cohort of early stage surgically resectable breast cancer patients who were treated with NET during the COVID-19 pandemic. This real-world data confirms pathological changes, especially decrease in Ki-67% even with short duration use of NET that has been reported in trials of neoadjuvant AI. Long term follow-up for survival outcome is planned. Table 1.Demographics of early stage breast cancer patients diagnosed during COVID-19.DCIS (n=13)Invasive Breast Cancer (n=41)Total (n=54)Menopause status (n, %)Pre-menopause7 (53.8)6 (14.6)13 (24.1)Post-menopause6 (46.2)35 (85.4)41 (75.9)Diagnosis (n, %)Self-Palpated08 (19.5)8 (14.8)Screening13 (100)33 (80.5)46 (85.2)Age (n, %)≤503 (23.1)5 (12.2)8 (14.8)50+10 (76.9)36 (87.8)46 (85.2)Clinical Stage (n, %)Tis13 (100)013 (24.1)I037 (90.2)37 (68.5)II04 (9.8)4 (7.4)NET in weeks (n, %)≤43 (23.1)11 (26.8)14 (25.9)4+10 (76.9)30 (73.2)40 (74.1)Genomic Testing (n, %)Oncotype DX019 (86.4)19 (86.4)ProSigna03 (13.6)3 (13.6)Mammaprint000 Table 2.No significant associations with changes in pre to post in T stage, ER%, PR% or Ki-67% in patients treated with NET for ≤4 weeks and &amp;gt;4 weeks.≤4 weeks&amp;gt;4 weeksp-valueChange in T stage0.5810Decrease2 (27.27%)8 (26.67%)No change7 (63.64%)15 (50%)Increase1 (9.09%)7 (23.33%)Change in ER%0.2444Decrease4 (36.36%)9 (30%)No change4 (36.36%)5 (16.67%)Increase3 (27.27%)16 (53.33%)Change in PR%1.0000Decrease7 (70%)21 (70%)No change2 (20%)5 (16.67%)Increase1 (10%)4 (13.33%)Change in Ki-67%0.3224Decrease4 (66.67%)17 (85%)No Change1 (16.67%)1 (5%)Increase1 (16.67%)2 (10%) Citation Format: Julie Huang, Joshua Feinberg, Bahram Dabiri, Jordan Baum, Meredith Akerman, Anthony Pasquarella, Abhinav Rohatgi, Shubhada Dhage, Amber Guth, Nina D'Abreo. Neoadjuvant endocrine therapy (NET) as bridge therapy for early stage breast cancer during COVID-19: A single institution experience [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 P2-15-03.