Impact of the COVID-19 Pandemic on Breast Cancer Patient Care: A Retrospective Study in a Tertiary Care Center in Lebanon

INTRODUCTION: The COVID-19 pandemic poses challenges to the healthcare systems including cancer treatment. We aim to evaluate the impact of lockdown during COVID-19 on breast cancer (BC) care in terms of BC stage at presentation, treatment compliance and delays, and follow-up in a tertiary care center in Lebanon. METHOD(S): This is a retrospective observational study comparing patients with BC who presented to a tertiary care center in Lebanon in the pre-COVID period (Sep 2019-Dec 2019) and during COVID (Sep 2020-Dec 2020). After receiving the IRB approval, we retrieved the charts of BC patients who had their initial presentation, were under treatment or were on follow-up during our period of interest. We extracted data from electronic medical records of patients related to demographic parameters, cause of visit, tumor description, and type of treatment received. Descriptive analysis, as well as multivariate analysis, were done using SPSS. RESULT(S): Out of the 497 patients included, 274 visited the hospital in the pre-COVID period (median age 52.5 years) and 223 patients during COVID (median age 54.7 years). More than half of patients presented for BC screening in the pre-COVID (52%), while 52% came symptomatic during COVID. Almost 54% had advanced BC at presentation in the COVID period compared to 48% pre-COVID but with no statistical significance (p=0.36). During the COVID period, almost 39% of patients had surgery, 79.7% received chemotherapy, and 21.2% received radiotherapy, but with no significant difference between the two periods. Also, no difference was found in the type of surgery done between the two periods. The mean time between the onset of symptoms and biopsy was significantly longer in the COVID period (4.8 +/- 3.5 months) than that in the pre-COVID (3.2 +/- 5.1 months). The mean time between the biopsy and first treatment was not significantly different between the two periods (1.5 +/- 2.2 months versus 2.1+/-3.8 months). For patients who received neoadjuvant chemotherapy, the mean time between the last chemotherapy and surgery was longer in the COVID period (1.9 +/- 1.4 months) than in the pre-COVID period (1.2 +/- 1.1 months). Multivariate analysis showed that age at diagnosis (p=0.014) and time to diagnosis (p=0.01) were significantly associated with the advanced stage of BC. CONCLUSION(S): This study showed that COVID pandemic has resulted in a delay in the initial presentation of patients resulting in more advanced stages at presentation. However, the management of breast cancer was not substantially impacted by the COVID-19 lockdown.

The Impact of the COVID-19 Pandemic on Breast Cancer Diagnoses in San Antonio, TX

Introduction: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in women in the United States. The significant advances in care over the last decades are largely attributable to early detection and treatment. The pre-COVID-19 pandemic 5year survival rate of breast cancer was in the range of 90%, however, there has been public concern that the pandemic has led to delayed diagnosis. The objective of this study was to determine if patients diagnosed during the pandemic had more advanced breast cancer at presentation compared to those diagnosed prior. Method(s): This is a retrospective study of patients with an ICD code for Breast Cancer seen within the University of Texas Health San Antonio MD Anderson Cancer Center between 1/1/2018 and 12/31/2021. Data abstractors collected information on gender, age, race, ethnicity, funding, screening mammogram dates, date of cancer diagnosis, stage at diagnosis, and treatment. Those diagnosed before 1/1/2018 or that received initial treatment outside our institution were excluded from the analysis. Pearson's Chi-squared and logistic regression tests were used to determine the relationship between time and stage at diagnosis. The timeline was divided into three periods: from 01/01/2018 to 03/31/2020 as the pre-COVID era, from 04/01/2020 to 12/31/2020 as the lockdown period, and from 01/01/2021 to the present as the post-vaccine era. Result(s): A total of 696 patients with breast cancer were included. There was a significant statistical difference between the cancer stage at diagnosis in the pre-COVID-19 era compared to the lockdown period and the post-vaccine era (p= 0.003, table 1). Therefore, patients diagnosed after the beginning of lockdown were more likely to have more advanced cancer as time progressed. The odds ratio for Tis stage was 0.38 (95% CI: 0.23-0.60;P < 0.001) in the post-vaccine era compared to the pre-COVID era. The OR for Tis stage was not statistically significant (OR, 0.68;95% CI: 0.421.10;P < 0.12) when comparing the lockdown period to the pre-COVID era. Conclusion(s): Patients diagnosed with breast cancer in the COVID-19 pandemic were more likely to present with more advanced disease at diagnosis compared to those diagnosed in the pre-COVID19 era confirming our hypothesis. The OR of presenting with Tis disease when diagnosed during the post-vaccine compared to the pre-COVID-19 era was 0.38, however, this was not seen when comparing the lockdown period to the pre-pandemic era. We believe this difference was not significant because delays in cancer care may take months to years to take full effect. (Table Presented).

Trastuzumab deruxtecan (T-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic hormone receptor-negative (HR-), HER2-low breast cancer: updated results from BEGONIA, a phase 1b/2 study

Background: Patients with HR- advanced/metastatic breast cancer (a/mBC) with a low level of HER2 (immunohistochemistry [IHC] score 1+ or IHC 2+ and negative in situ hybridization [ISH]) have poor prognosis. Combining 1L chemotherapy with immune checkpoint inhibitors can modestly improve outcomes vs chemotherapy alone, but treatment benefit is largely seen in patients with PD-L1+ disease. BEGONIA (NCT03742102) is an ongoing 2-part, open-label platform study, evaluating safety and efficacy of D, an anti-PD-L1 antibody, combined with other novel therapies in 1L triple-negative a/mBC, including HR-, HER2-low disease. T-DXd is a trastuzumab-topoisomerase I inhibitor antibody-drug conjugate that improves survival in patients with previously treated HR-, HER2-low mBC (NCT03734029;Modi NEJM 2022). Here, we report updated results of the T-DXd + D combination from BEGONIA. Method(s): Patients with unresectable HR-, HER2-low (per local testing, IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) a/mBC were enrolled in the T-DXd + D arm. Patients eligible for 1L treatment, regardless of PD-L1 status, received intravenous T-DXd 5.4 mg/kg + D 1120 mg every 3 weeks until progression or unacceptable toxicity. PD-L1, assessed using the VENTANA PD-L1 (SP263) Assay, was defined as high if >= 5% of the tumor area was populated by PDL1-expressing tumor or immune cells. Primary endpoints were safety and tolerability. Secondary endpoints included investigator-assessed objective response rate (ORR;RECIST v1.1);progressionfree survival [PFS];and response duration. Patients included in the efficacy analysis had >= 2 ontreatment disease assessments, progressed, died, or withdrew from the study. Result(s): As of April 8, 2022, 56 patients received T-DXd + D (34 ongoing) and 46 were included in the efficacy analysis. Median (range) follow-up was 10.1 (0-22) months. Median age was 53.5 years, 71% had received prior treatment for early stage BC, and 64% had visceral metastases at baseline. Confirmed ORR was 26/46 (57% 95% CI, 41-71) and unconfirmed ORR was 33/54 (61% 95% CI, 47-74);1/46 patients (2%) had complete and 25/46 (54%) had partial responses. Confirmed response occurred irrespective of PD-L1 expression (PD-L1 high ORR, 5/7 [71%];PD-L1 low, 13/21 [62%];PD-L1 missing, 8/18 [44%]). Median duration of response was not reached;however, 64% of patients remained in response at 12 month follow-up and 73% had an ongoing response at data cutoff. Median PFS was 12.6 months (95% CI, 8-not reached). Adverse events (AEs) were consistent with the agents' known safety, with treatment-related AEs occurring in 49 patients (88%), any Grade 3/4 AEs in 18 patients (32%), and any serious AEs in 10 patients (18%). The most common all-Grade AEs were nausea (41 [73%]), fatigue (26 [46%]), and vomiting (17 [30%]). Adjudicated treatment-related interstitial lung disease/pneumonitis occurred for 5 patients (9%), which were mostly Grade 1 or 2 and 1 case of Grade 5 associated with COVID pneumonia. Seven patients (13%) and 21 patients (38%) had T-DXd dose reduction and dose delay, respectively;22 (39%) had D dose delay. Seven patients (13%) discontinued treatment due to AEs. Conclusion(s): For patients with HR-, HER2-low a/mBC, T-DXd in combination with D in the 1L setting shows manageable safety and promising efficacy including durable responses and an encouraging PFS. Although subgroups were small, responses were observed irrespective of PD-L1 expression. Analysis of additional translational data is ongoing. Funding(s): AstraZeneca/Daiichi Sankyo.

SarsCov2 pandemic and patients with metastatic cancers in Germany-Data from four prospective cancer registries

Introduction: Patients (pts) with metastatic cancers undergoing treatment are considered a high risk group for infection and potentially inferior outcome during the SarsCov2 pandemic. Currently no data have been published on the test rate, infection rate, efects on treatment and potential outcome. Here we present data from four prospective cohort studies (cancer registries) addressing these questions. Method(s): MYRIAM (multiple myeloma (MM), NCT03308474), OPAL (advanced breast cancer (ABC), NCT03417115), CARAT (advanced or metastatic renal cell carcinoma (mRCC), NCT03374267) and SAPHIR (gastric/oesophageal cancer (ESCC, GAC or GEJAC), NCT04290806) are prospective, observational, open, multicentre, interdisciplinary and intersectional clinical registries that collect data on all (sequential) treatments, patient and tumour characteristics, clinical and patient-reported outcomes in about 200 hospitals and ofce-based practices in Germany. Pts are recruited at start of treatment. In April 2nd 2020 data collection was updated regarding testing for SarsCov2, test results, efects on cancer treatment and outcome for all patients newly recruited, under observation or deceased afer March 1st 2020. Interim results as by June 17th have been summarised here and will be updated regarding further details with a data cut on August 31st 2020. Result(s): Until data cut for this snapshot analysis the question regarding testing had been answered for a total of 239 pts in the four projects (94 ABC, 72 MM, 46 RCC, 27 GAC/ESCC/GEJAC). Of these a total of 56 pts (23%) had been tested for a SarsCov2 infection and 5 patients (2% and 9% of those tested) had been tested positive. Further results on the test rate, severity of symptoms at diagnosis, course of disease and consequences on the cancer treatment will be analysed and presented with an updated data cut when about 500 pts are expected to have been documented. Conclusion(s): First data on SarsCov2 testing in patients with advanced cancers in Germany reveals that this high risk group had access to testing and that positive cases were identifed in routine care. While these first interim data have to be interpreted with caution, they proof that quick implementation of relevant new variables into existing cohort studies is feasibly and important to address urgent questions regarding the care of cancer patients.

Optimizing Immunization Schedules for Therapeutic Vaccination

Background Most cancer vaccines will not generate high levels of T-cell immunity with only one immunization. Even vaccines against foreign antigens, such as COVID, may require three or four immunizations spaced some months apart to achieve protective levels of immunity in cancer patients. The use of cancer vaccines in the therapeutic setting, as single agents or as part of a combination regimen to treat established cancers, would require high levels of T-cells to be generated quickly. We evaluated immunization schedules with a 5-antigen, multiepitope plasmid DNA vaccine, STEMVAC, targeting cancer stem cell associated proteins. The vaccine is immunogenic in patients with advanced breast cancer (NCT02157051) and the majority of patients can develop high levels of STEMVAC specific type I T-cells after 3 priming and 2 booster immunizations. Using a murine model, we questioned whether we could more rapidly achieve high levels of antigen specific Type I T-cells with STEMVAC immunization. Methods Six-week-old FVB mice were used for experiments. A dose of 300ug of STEMVAC plasmid with 5ug of rm-GMCSF as an adjuvant was given in 4 immunizations using three different schedules;(1) every 3-4 days, (2) once a week, and (3) every 2 weeks (standard). Immunogenicity was evaluated two weeks after the last vaccine using IFN-gamma ELISPOT quantitating responses to each of the 5 antigens in the vaccine. Parameters studied included magnitude, incidence, and breadth of the T-cell response. Ten mice were included/group with empty plasmid and PBS as controls. Results All three immunization schedules could generate a significant IFN-gamma response to at least one of the antigens encoded in STEMVAC as compared to controls. Vaccines given every two weeks elicited the greatest magnitude immune response among the three schedules (vs. 3-4 days, p=0.001;vs. 1 week, p=0.01). Of note, although the total magnitude of immune response elicited was lower, the weekly immunization schedule resulted in a significantly greater number of mice responding to vaccination as well as a greater breadth of response with all mice responding to at least 2 antigens and 50% to 3-5 antigens. Conclusions Varying the time between immunizations can significantly impact the quality of the T-cell response to a mulitantigen plasmid-based vaccine. Further studies are ongoing to correlate these differences to anti-tumor activity.

ONE MORE FEATHER IN THE CAP (DECITABINE): YET ANOTHER CASE OF CHEMOTHERAPY-INDUCED LUNG INJURY

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Lung toxicity due to antineoplastic therapy is reported with both cytotoxic and molecularly targeted agents [1]. We present one such case of lung injury induced by capecitabine. CASE PRESENTATION: A 79-year-old female with history of triple negative infiltrating duct carcinoma of the right breast (status post mastectomy and adjuvant chemotherapy with docetaxel and cyclophosphamide 3 years prior) presented to the hospital with dyspnea on exertion following her fourth cycle of capecitabine therapy for breast cancer recurrence. Patient developed nausea, vomiting, and malaise with cycles 1, 2, and 3 of capecitabine therapy with onset of severe dyspnea on exertion, cough, and hypoxia following cycle 4. Computed tomography (CT) scan of the chest on admission showed consolidative opacities in the right upper, right middle, and anterior right lower lobe along with smaller opacities in the left lung apex and small subcentimeter nodules;no pulmonary embolism. Antibiotics were given for a short duration for suspected pneumonia without improvement. Capecitabine was held on discharge. She presented again to the emergency room with worsening shortness of breath, diarrhea, fatigue, and dizziness. COVID test was negative. Chest x-ray redemonstrated patchy airspace disease involving the right apical, lateral, mid lower lung field. Oral steroids were recommended for suspected organizing pneumonia, but the patient refused due to concerns about side effects. Her hospital course was complicated by Clostridium difficile infection (treated with oral vancomycin) and left lower extremity deep venous thrombosis (treated with anticoagulation). Subsequently she followed up with pulmonology outpatient. Repeat imaging showed evolving infiltrates in the same areas with elevated aspergillus IgG level (18.0 mcg/ml) and IgE (178 kU/L) but negative galactomannan and sputum bacterial/fungal/acid fast cultures. Oral steroids were initiated with clinical and symptomatic improvement. DISCUSSION: Capecitabine is a prodrug of fluorouracil (antimetabolite). It is used as a chemotherapy agent in multiple types of cancer including breast cancer. Respiratory side effects include cough (<7%) and bronchitis (<5%). Lung injury/pneumonitis is a rare complication with only a few cases reported to date [2,3]. The timing of symptoms with chemotherapy administration and the negative infectious work-up supports capecitabine as the inciting etiology of lung injury. Withholding chemotherapy and starting systemic steroids were effective treatments in this case of chemotherapy induced lung toxicity. CONCLUSIONS: Capecitabine induced lung injury is a rare but important entity and should always be kept in mind while evaluating dyspnea in cancer patients. Reference #1: Capri G, Chang J, et al. An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer. Ann Oncol. 2010;21(3):474. Epub 2009 Oct 8. DOI: 10.1093/annonc/mdp373 Reference #2: C. J. Benthin, G. Allada. Capecitabine-Induced Lung Injury. American Journal of Respiratory and Critical Care Medicine 2016;193:A1653. Reference #3: Andrew K Chan, Bok A Choo, John Glaholm. Pulmonary toxicity with oxaliplatin and capecitabine/5-Fluorouracil chemotherapy: a case report and review of the literature. Onkologie. 2011;34(8-9):443-6. doi: 10.1159/000331133. Epub 2011 Aug 19. DISCLOSURES: No relevant relationships by William Karkowsky No relevant relationships by Chahat Puri No relevant relationships by Sahib Singh

Clinical Outcome and Characteristics of Turkish Breast Cancer Patients who had SARS-Cov-2 Infection

OBJECTIVE COVID-19 pandemic has placed an unprecedented burden on health-care system. Patients with cancer are reported to have a higher risk of infection and a more complicated COVID-19 course. Breast cancer (BC) is the most common cancer in women in Turkey. We report clinical outcomes and characteristics of patients with COVID-19 who were on treatment for BC at our center. METHODS We reviewed medical records of BC patients who had COVID-19 between July 2020 and 2021 at our center. We recorded pathological, clinical, treatment characteristics, and the clinical outcome of COVID-19 infection. RESULTS A total 82 BC patients had COVID-19 between July 2020 and 2021. All patients were female, with a median age of 49 (43-64 years). 85% of all patients had early and 14.6% of them had advanced stage BC. COVID-19 had a mild clinical course in 73%, hospitalization was required in 27% of patients. Twenty-five patients who required hospitalization were discharged and three patients died due to COVID-19. All of the patients who died from COVID-19 had metastatic BC (p=0.002). Metastatic disease (p=0.002) and chemotherapy within 7 days of COVID-19 diagnosis (p=0.024) have been associated with increased mortality. CONCLUSION Majority of BC patients with COVID-19 have a mild course, patients with risk factors that increase mortality should be followed more carefully.

Niraparib plus aromatase inhibitors (AI) for germinal mutated BRCA1/2 (gBRCAm) or homologous recombination-deficient (HRd), hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC): LUZERN interim analysis

Background: The poly(ADP-ribose) polymerase inhibitor niraparib showed clinical activity in advanced gBRCAm ovarian and breast cancers. LUZERN aims to assess the effectiveness of niraparib plus AI in HR+/HER2–, AI-resistant ABC with a pathogenic variant in homologous recombination-related genes. Here we report findings from the stage 1 interim analysis. Methods: This open-label, single-arm, Simon’s 2-stage, phase II trial is enrolling HR+/HER2– ABC patients (pts) with gBRCAm (cohort A;n=6 in stage 1, n=7 in stage 2) and gBRCA wild-type/HRd (cohort B;n=9 in stage 2). Pts had to have received ≤1 prior line of chemotherapy for ABC, 1–2 prior lines of endocrine therapy for early or ABC with secondary endocrine resistance to the last AI regimen. Pts receive niraparib (200/300mg daily orally) plus AI (same agent given with the prior regimen) on each 28-day cycle. Primary endpoint: clinical benefit rate (CBR) as per RECIST 1.1. Secondary endpoints: overall response rate, progression-free survival (PFS), and safety per CTCAE 5.0. If ≥1/6 pts experienced clinical benefit, the trial should proceed to stage 2. Results: Six pts were enrolled in stage 1. Median age was 46 years (range 32–76), 66.7% of pts had visceral disease, and 83.3% had received prior CDK4/6 inhibitor-containing regimen for ABC. At data cut-off, 50.0% of pts were ongoing and median duration of treatment was 4.6 months (range 2.4–5.7). One patient achieved complete response, meeting the criterion to proceed to stage 2. Median investigator-assessed PFS was 5.3 months (95%CI 3.9–NA). The most frequent adverse events (AEs) of any grade (G) were nausea (3 [50.0%]), neutropenia (2 [33.3%];16.7% G3), constipation (2 [33.3%]), and vomiting (1 [16.7%]). Serious AEs occurred in 3 pts (50.0%;G3 COVID-19 pneumonia;G3 pseudomonal bacteriemia;G2 sacral pain). No treatment-related discontinuations/deaths were reported. Conclusions: Niraparib plus AI showed preliminary activity with a tolerable safety profile in gBRCAm HR+/HER2– AI-resistant ABC pts. Based on the steering committee recommendation, enrolment in cohorts A and B is ongoing. Clinical trial identification: ClinicalTrials.gov identifier: NCT04240106. Legal entity responsible for the study: MEDSIR. Funding: GlaxoSmithKline. Disclosure: J.Á. García Saenz: Financial Interests, Personal, Advisory Board: Seagen, Gilead;Financial Interests, Personal, Invited Speaker: Novartis, Celgene, Eli Lilly, Eisai, AstraZeneca, Daiichi Sankyo, MSD, Exact Sciences;Financial Interests, Institutional, Funding: AstraZeneca. J. De la Haba Rodriguez: Financial Interests, Personal, Other, Consultant and Advisory Role, Research Funding and Speaking: Pfizer, Novartis, Roche, Lilly;Financial Interests, Personal, Other, grant support: Pfizer. J.E. Ales Martínez: Financial Interests, Personal, Other, travel grant: Pfizer;Financial Interests, Personal, Research Grant: MEDSIR. E. Alba Conejo: Financial Interests, Personal, Advisory Role: Roche, Novartis, Pfizer, Lilly, BMS, Astrazeneca, Pierre Fabre, Daiichi, Exact Sciences;Financial Interests, Personal, Research Grant: Pfizer. J. Balmaña: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer;Financial Interests, Institutional, Other, Steering committee member: AstraZeneca;Financial Interests, Institutional, Principal Investigator: Medsir, Pfizer. J.M. Perez Garcia: Financial Interests, Personal, Advisory Role: Lilly,Roche, Eisai, Daichii Sankyo, AstraZeneca, Seattle Genetics, Medsir;Financial Interests, Personal, Other, travel expenses: Roche. M. Sampayo-Cordero: Financial Interests, Personal, Other, honoraria: Medsir, Syntax for Science, Optimapharm, and Ability pharma;Financial Interests, Personal, Research Grant: Medsir;Financial Interests, Personal, Other, travel expenses: Medsir, Syntax for Science, Optimapharm, and Roche;Financial Interests, Personal, Other, consultant: Medsir, Syntax for Science, and Optimapharm;Financial Interests, Personal, Speaker’s Bureau: Medsir;Financial Interests, Personal, Full or part-time Employment: Me sir. A. Malfettone: Non-Financial Interests, Personal, Full or part-time Employment: MEDSIR. J. Cortés: Financial Interests, Personal, Advisory Role: Roche, Celgene, Cellestia, Astrazeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks;Financial Interests, Personal, Other, honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo;Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London.;Financial Interests, Personal, Stocks/Shares: MEDSIR, Nektar Pharmaceuticals, Leuko (relative);Financial Interests, Personal, Other, travel, accomodation: Roche, Novartis, Eisai, pfizer, Daiichi Sankyo, Astrazeneca. A. Llombart Cussac: Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD;Financial Interests, Personal, Stocks/Shares: MEDSIR and Initia-Research;Financial Interests, Personal, Advisory Role: Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, GSK;Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, and MSD;Financial Interests, Personal, Research Grant: Roche, Foundation Medicine, Pierre-Fabre, and Agendia;Financial Interests, Personal, Other, travel compensation: Roche, Lilly, Novartis, Pfizer, and AstraZeneca. All other authors have declared no conflicts of interest.

Primary endpoint analysis of a randomized phase II of darolutamide or capecitabine in patients with triple-negative androgen receptor-positive advanced breast cancer (UCBG3-06 START trial)

Background: A subgroup of triple negative breast cancer (TNBC) expresses the androgen receptor (AR). In this trial we evaluated the efficacy and tolerability of the AR inhibitor darolutamide (D) or capecitabine (C) in patients (pts) with advanced AR-positive TNBC (NCT03383679). Methods: Pts with centrally reviewed AR-positive (≥ 10% by immunohistochemistry) TNBC treated with up to one line of chemotherapy for advanced disease were eligible. They were randomized in a 2:1 ratio to receive D 600 mg twice daily or C 1000 mg/m2 twice daily 2-weeks on/ 1-week off, until progression or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR) at 16 weeks and was assessed in the eligible population and in the sensitivity analysis population (pts with delayed tumour assessment performed in the context of COVID pandemic). Main secondary endpoints included objective response rate, overall survival, progression-free survival (PFS) and safety. Results: A total of 254 pts from 45 centres were screened;94 pts were randomized (61 in D arm, 33 in C arm) from April 2018 to July 2021. A clinical benefit was observed in D arm in 13 of 53 evaluable pts (CBR at 16 weeks 24.5%;95% CI: 12.9%-36.1%) including 2 PR and 1 CR and in C arm in 11 of 23 evaluable pts (CBR at 16 weeks 47.8%;95% CI: 27.4%-68.2%). In the sensitivity analysis, a clinical benefit was observed in D arm in 17 of 58 evaluable patients (CBR ≥ 16 weeks 29.3%;95% CI: 17.6%-41.0%) and in C arm in 19 of 32 evaluable patients (CBR ≥ 16 weeks 59.4%;95% CI: 42.3%-76.4%). 7 pts presented with drug-related serious adverse events: 3 in D arm and 4 in C arm. In D arm, asthenia (26.7%), nausea (25%) and ASAT increase (21.7%) were the most common adverse events, the majority being grade 1 or 2, similar to previous safety data. Median PFS were 1.8 months (CI 95% 1.7-3.1) and 3.6 months (1.8-9.1) in D arm and C arm respectively. Other secondary endpoints will be presented at the meeting. Conclusions: Despite not reaching the pre-specified CBR, darulotamide demonstrated clinical activity with significant benefit for a group of patients. A research program to identify predictive biomarkers of sensitivity is ongoing. Clinical trial identification: EudraCT: 2017-002284-18 NCT03383679. Legal entity responsible for the study: UNICANCER. Funding: BAYER. Disclosure: All authors have declared no conflicts of interest.

Adjusting the TMIST study design to accommodate slower than expected accrual: ECOG-ACRIN EA1151

Background: The ECOG-ACRIN Tomosynthesis Mammographic Imaging Screening Trial (TMIST), which opened in 2017, is a randomized trial designed to assess whether Tomosynthesis Mammography (TM) should replace Digital Mammography (DM) for breast cancer screening. It is hypothesized that women assigned to TM for 3-5 screening rounds will have fewer advanced breast cancers than the women assigned to DM. Advanced cancers are those that have distant metastases or positive nodes, are invasive tumors greater than or equal to 2.0 cm in size, or are invasive tumors greater than 1.0 cm in size that are triple negative or HER 2+. The initially planned enrollment of 164,946 women was due to be completed by the end of 2020, with follow-up concluded by 2025. There were substantial challenges in meeting this timeline, including the organizational and funding structure of the NCI National Clinical Trials Network which is dependent upon sites using their existing staffing resources (not always readily available at the time of study activation). This led to longer than anticipated start of enrollment for most interested sites and lower than anticipated annual enrollment per participating site based ultimately on the staffing support that could be allocated to manage TMIST. In addition, research staffing shortages and periodic research operations closures due to COVID-19 have also impacted enrolling TMIST sites, though unevenly, since the start of the pandemic. Enrollment plateaued at approximately 2,100 subjects per month by the end of 2020. With that accrual rate expected, the trial design was modified to reduce the sample size so that the study could be completed by 2027. Methods: With the approval of the NCI CIRB, we changed how the primary endpoint measure for TMIST is assessed from the number of advanced cancers that occur by 4.5 years after randomization to the time from randomization to occurrence of advanced cancers. All advanced cancers occurring within 7 years of randomization are now included and all participants followed for at least three years. In addition, the power of the study of the study was modified from 0.9 to 0.85, while the originally assumed effect size at 4.5 years was retained These changes allowed a reduction of sample size to 128,905, with subject recruitment projected to end in 2024. As of February 14, 2022, there are 125 sites open, 114 in the U.S. and 11 in other countries, with an additional 31 sites planning to open. As of February 14, 2022, a total of 63,845 women have been enrolled in the trial worldwide at 115 sites, with 20% of US participants self-identifying as belonging to minority racial and ethnic groups and 70% consenting to optional blood and/or buccal cell collection.

Covid-19 Pandemic Impact on Breast Cancer Detection-The Major Effects Over an Early Diagnosis.

The COVID-19 pandemic has disrupted medical care systems, by decreasing patient addressability to outpatient care. The main objective of this study was to compare the patient's addressability to breast imaging techniques for diagnosis, and follow-up in the Clinical Emergency County Hospital of Craiova, Romania. We selected the mammographies performed over a period of 4 years (2018-2021) in our clinic. We divided the patients into four groups, one for each year (2018, 2019, 2020, 2021). Furtherly, we merged the data into two groups, one group for the pre-pandemic years (2018 and 2019) and one for the pandemic years (2020 and 2021). In our clinic, the number of mammographies plummeted to 0 during the month of April 2020 due to the lockdown and closure of non-urgent outpatient services in hospitals treating COVID-19 patients, and slowly creeped to 11 in the month of May and peaked to 160 in July (for the rest of the year). There was a huge difference regarding the patient's addressability to mammography immediately after the lockdown, with a 95.2% less addressability compared to the pre-pandemic period (May 2020 compared to May 2018). As an overall, by comparing both pre-pandemic years included in the study with the pandemic years, we obtained an addressability reduced with 37.3% suggesting the possible future delays in diagnosing breast tumors.

Germline BRCA1/2 mutation testing in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC): A real-world study in the Syapse Learning Health Network (LHN)

Background: Germline (g)BRCA1/2 mutations represent approximately 5% of metastatic breast cancer. Poly ADP-ribose polymerase inhibitors (PARPi) have shown improved clinical outcomes, a manageable toxicity profile, and favorable patient (pt)-reported outcomes versus chemotherapy in pts with gBRCA1/2 mutated HER2-locally advanced or metastatic breast cancer. With the advent of PARPi, clinical guidelines have broadened eligibility criteria for gBRCA1/2 testing. However, limited information is available on the impact of the COVID-19 pandemic on gBRCA1/2 testing rates. We assessed trends and factors associated with gBRCA1/2 testing in pts with HER2-ABC before and during the COVID-19 pandemic. Methods: This retrospective study included pts from the Syapse LHN, a longitudinal database of pts with cancer cared for in community-based, integrated care delivery networks in 25 states in the United States. Pts were eligible for gBRCA1/2 testing from initial ABC diagnosis until death or date of last contact with the participating health system. Information on gBRCA1/2 testing was obtained from scaled sources and further curated by Certified Tumor Registrars. Logistic regression evaluated the associations between age at diagnosis, family Shistory of relevant cancer, race/ethnicity, median household income, health system, and diagnosis year with gBRCA1/2 testing among HER2-ABCs;models included hormone receptor status. Results: The study population included 1769 pts with HER2-ABC, including 577 pts with triple negative ABC initially diagnosed from 2010: 96% were women, 69% were non-Hispanic White, and 94% had an estimated median household income >$30, 000 USD;median age at initial diagnosis was 61 years. The percentage of pts ever gBRCA1/2-tested among those eligible increased over time: 26%, 28%, and 31% by end of 2018, 2019, and 2020, respectively. Similarly, the percentages of new testing among eligible but not previously tested pts increased from 2018-March 2020, decreased from April-September 2020, and trended upwards thereafter (Table 1). In logistic regression models combining data from pre-and post-COVID-19 periods, family history of relevant cancer (odds ratio [OR]=1.9;95% CI, 1.5-2.4), younger age at diagnosis (>65 reference;<45: OR=12.8, 95% CI, 8.9-18.3;45-54: OR=6.7, 95% CI, 4.9-9.3;55-64: OR=2.0, 95% CI, 1.5-2.8), and diagnosis year of 2013 or later (OR=1.9, 95% CI, 1.4-2.6) were significantly associated with increased odds of gBRCA1/2 testing. Positive hormone receptor status (OR=0.5;95% CI, 0.4-0.6) and Hispanic ethnicity (OR=0.5;95% CI, 0.3-0.9) were significantly associated with reduced odds;associations with non-Hispanic Black ethnicity did not reach statistical significance (OR=0.8;95% CI, 0.6-1.1). Conclusion: Following the expanded eligibility criteria for gBRCA1/2 testing, testing rates increased from 2018 to 2019 and decreased only slightly during the national COVID-19 lockdown. Age at diagnosis, family history, diagnosis year, ethnicity, and hormone receptor status impacted the odds of testing. Given that gBRCA1/2 mutations are actionable, focused efforts should be developed to resume the pre-pandemic trajectory of gBRCA1/2 mutation testing.

Neoadjuvant approach in patients with early breast cancer: evaluation of the breast cancer patient (patient assessment, staging, planning)

Neoadjuvant treatment (NAT) has become a standard treatment in locally advanced breast cancer and an option in early stage (stage I–II) breast cancer (EBC). It is known that patients who achieve a pathologic complete response (pCR) have better long-term out comes, especially Her2 positive and triple negative (TN) breast cancer. Selection of patients for NAT in early stage breast cancer rely in several factors, as patient characteristics (i.e., age and comorbid ities), tumor histology, stage at diagnosis and the potential changes in surgical or adjuvant treatments when NAT is administered. Early stage breast cancer patients that are not candidates for breast conservative surgery (BCS) at front, may benefit from NAT to reduce tumor size and facilitate surgery. In other cases, as young patients with TN tumors between 1–2 cm may benefit from NAT, even if BCS can be performed up front, as chemotherapy will be given anyway along the treatment and there is a high likelihood of pCR. Patients with a positive axilla at diagnosis, regardless of tumor size, may also benefit from less axillary surgery if axillary pCR is achieved. Rates of axillary pCR are especially high in TN and Her2 positive tumors. A distinct approach is suggested in luminal tumors subtypes. In these patients, besides the factors already mentioned, intensity of hormone receptor expression would help to decide on neoadjuvant hormone or chemotherapy treatment. Immunohistochemistry differentiation between luminal A and B by Ki67 assessment and in some cases, the use of genomic platforms may help defining type of NAT. Assessing breast cancer patients for NAT include incorporating all factors into the decision making process. In the COVID era, we have witnessed the use of NAT in patients who may be directed to surgery, unable to have it performed, as surgery has been reserved for emergency cases only. In this situation, it has been a great challenge managing breast cancer patients and tailoring individualized treatment decisions. Besides physical examination, breast imaging is performed to assess extent of disease and to determine BCS eligibility before NAT. Breast imaging should include mammogram with tomosynthesis, breast and axillary US and in most of cases MRI. MRI may be omitted in S12 Speakers’ s / The Breast 56S1 (2021) S1–S16 selected cases (i.e. fatty breasts, neoadjuvant hormone therapy). Contrast enhanced mammogram is an emerging technique, whether it will add accuracy to the MRI findings or replace it in selected cases is still to be defined. Shear wave elastography is under investigation for assessment of response to neoadjuvant therapy as well as for predicting response. Generally, in EBC no further body imaging (CT or bone scan) is needed unless metastatic disease is suspected. PET scan is reserved for patients with inconclusive metastatic dissemination or with more advanced disease. Pathology confirmation by core biopsy and evaluation of estrogen and progesterone receptor, Her2, and Ki67 must be obtained before treatment. Axillary US will characterize axillary lymph nodes and will guide biopsy of axillary nodes. If planning NAT, markers need to be placed in breast tumor/s and in biopsy proven positive axillary node. Same breast imaging should be repeated after NAT to assess response and to determine type of breast and axillary surgery. Sentinel lymph node biopsy after NAT is the preferred method. After NAT, surgical plan is delineated taking into account baseline characteristics, tumor response and patient desire. Conflict of Interest: Honoraria: Agendia. Advisory Board: Sirius medical.

ABC6 Consensus: Assessment by a Group of German Experts.

Background: The first International Consensus Conference for Advanced Breast Cancer (ABC1) took place 10 years ago in November 2011. The rationale was - and still is - to standardize treatment of advanced breast cancer (ABC) based on the available evidence and to ensure that worldwide all breast cancer patients receive adequate treatment and access to new therapies. Rationale for the Manuscript: The 6th International Consensus Conference for ABC (ABC6) took place from November 4 to 6, 2021 and was the first in a purely online format, due to the COVID-19 pandemic. In the present manuscript, a working group of German breast cancer experts comments on the voting results of the ABC6 panelists regarding their applicability for routine clinical practice in Germany. Method: The ABC6 votes mainly include modified or new statements. With regard to all statements not modified for the ABC6 consensus, the German experts refer to the published paper of the ABC5 consensus. The German experts base their comments on the current recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO Mamma). Topics: ABC6 focused on new treatment options and their implications for clinical practice. Optimal therapy sequencing for example was one of the issues. To solve the challenge of a more individualized treatment, precision medicine is fundamental. Oligometastatic disease, brain metastases and adequate supportive and palliative care were also addressed. Of special interest was the treatment of inoperable locally advanced breast cancer, which was discussed as a separate topic. As in previous years, patient advocates from around the world were an integral part of the ABC6 conference and had a major input into the consensus.

Extremely Advanced Breast Cancer Presentation: Possible Effect of Coronavirus Pandemic Anxiety.

BACKGROUND/AIM: Corona virus infection dramatically spread worldwide during 2020 and extraordinary restrictions have been implemented in order to reduce viral transmission. These measures compelled a complete restructuring of the health system, including temporary cancer screening suspension and a significant slow-down in cancer diagnoses and treatments. CASE REPORT: We report five cases of extremely advanced breast cancer referred to our Department amid the COVID-19 pandemic. These patients exhibited a poor prognosis or worse quality of life due to their oncological disease. CONCLUSION: In our opinion, both the slow-down of diagnosis and treatment of oncological disease and anxiety over COVID-19 influenced this presentation. Moreover, other patients were unable to receive palliative care. Hopefully, these cases will not develop into extremely advanced-stage disease, and we will be able to provide at least the necessary palliative care.