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Trastuzumab deruxtecan has been shown to have responses in heavily pretreated patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, the safety of this medication in patients with severe liver dysfunction and untreated or symptomatic central nervous system metastases is unknown. We describe a patient with metastatic HER2-positive breast cancer with liver failure and leptomeningeal metastases who was treated with dose-reduced trastuzumab deruxtecan. With treatment, the patient's hyperbilirubinemia resolved and she demonstrated a response on imaging. She was dose-escalated to full dose with minimal adverse events.

BACKGROUND: Inherited BRCA gene mutations (pathogenic variants) cause 10% of breast cancers. BRCA pathogenic variants predispose carriers to triple-negative breast cancer (TNBC); around 30% of patients with TNBC carry BRCA pathogenic variants. The 2018 NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian recommend genetic counseling referrals for patients with TNBC diagnosed at age ≤60 years. This study sought to describe genetic counseling referral patterns among long-term TNBC survivors at The University of Texas MD Anderson Cancer Center. METHODS: This single-institution retrospective analysis of female long-term (disease-free for ≥5 years) TNBC survivors sought to determine the rate of genetic counseling referral among patients diagnosed at age ≤60 years between 1992 and 2008. Patients who underwent treatment and surveillance visits at our institution and were followed until 2017 were included. We collected BRCA pathogenic variant status among tested patients. Descriptive statistical methods and a univariate analysis were used to identify patient characteristics associated with genetic counseling referral. RESULTS: We identified 646 female long-term TNBC survivors with a median age at diagnosis of 47 years. Of these, 245 (38%) received a recommendation for a genetic counseling referral. Among those referred, 156 (64%) underwent genetic testing, and 35% of those tested had BRCA pathogenic variants. Interestingly, among those referred, 20% declined genetic testing. The rate of genetic referrals improved over time, from 25% among TNBC survivors whose last surveillance visit was between 2011 and 2013 to 100% among those whose last surveillance visit was between 2014 or later. Younger age and premenopausal status at diagnosis and a family history of breast or ovarian cancer were associated with an increased rate of referral for genetic counseling. CONCLUSIONS: Among long-term TNBC survivors, the rate of referral to genetic counseling increased over time, and among those tested, 35% carried a BRCA pathogenic variant. Survivorship care provides an excellent opportunity to refer eligible patients for genetic counseling.

e13067 Background: Recently, next generation sequencing (NGS) has been used with increasing frequency to guide therapy decisions for patients with metastatic solid tumors. NGS is a DNA sequencing technology that detects somatically acquired mutations. If an actionable mutation is identified, it may affect prognosis and guide therapy. At our institution we serve a large proportion of minority and underserved patients and analyzed their NGS results to determine if there was a change in management. Methods: Patients with metastatic breast cancer treated at one of two sites at Baylor College of Medicine who underwent NGS via Tempus between 2018-2020 were included. Tempus provided access to the variant database for these patients. We analyzed the charts of 43 patients who underwent NGS via Tempus on tissue, blood or both. In those patients with clinically actionable mutations, we noted if there was a change in management. Utilizing Redcap, we extracted demographics, sites of metastasis, biomarker activity and site, genomic sequencing, and duration and sequencing of therapies given along with clinical trial information. Results: Of the 43 patients included in this analysis, the mean age was 55 years, 33% were African American, 30% were Hispanic, 21% were white/non-Hispanic, 12% were Asian, 4% were other. Two thirds of patients were treated in the Harris Health System (a safety net hospital with a unique and diverse population) while one third was treated at the Baylor St. Luke’s Medical Center (a private academically affiliated institution). Of the 43 patients, 14 had PIK3CA mutations and 3 had a change in management. 2 patients had microsatellite instability (MSI) and received immunotherapy, and 1 patient had a HER2 mutation and entered a clinical trial with Neratinib. Additionally, 2 patients were incidentally found to have MUTYH germline mutation which is associated with polyposis. Conclusions: With increasing frequency, patients with metastatic malignancy undergo NGS in order to determine if there is an actionable mutation that can guide their next line of treatment. However, this technology could be cost prohibitive for many underserved patients. Our study analyzes a unique and diverse population of patients, many of whom are underserved. We were able conduct this testing in our cohort, study the frequency of somatic mutations and monitor for change in treatment. Of the variants analyzed, PIK3CA mutations are actionable and patients can receive Alpelisib + Fulvestrant- however many did not. There was not a large shift in management based on the incorporation of this DNA sequencing technology which suggests that, unlike the case of other solid tumors, there aren’t yet as many actionable targets for patients with metastatic breast cancer. Shared decision making along with consideration of cost is paramount for these patients as we shift into an era of highly personalized medicine.

Purpose Resource limitations in low- and middle-income countries make the management of CNS tumors challenging, particularly in Brazil, a country with major disparities in socioeconomic status and access to health care. We aimed to evaluate cancer-related neurosurgical procedures in the public health care system. Methods On the basis of Brazil’s public health system database, we collected data for neurosurgical procedures related to CNS tumors performed between January 2008 and November 2013. Information about the number of procedures, costs, length of stay, and number of inpatient deaths were analyzed for each state and then correlated to the state-specific population, gross domestic product per capita, and number of procedures. Results In all, 57,361 procedures were performed, the majority of them in the Southeast region. The mean length of hospital stay was 14.4 days, but longer hospital stay was reported for patients treated in the North. The inpatient mortality rate was 7.11%. Mortality rates decreased as the number of procedures ( P < .001), gross domestic product per capita ( P < .001), or state population increased ( P < .001). On multivariate analysis, only the number of procedures (odds ratio, 0.93; 95% CI, 0.91 to 0.96; P < .001) and state population (odds ratio, 1.25; 95% CI, 1.13 to 1.38; P < .001) had an independent association with mortality. Conclusion To the best of our knowledge, this is the first study to evaluate disparities in CNS tumor surgery in a middle-income country, confirming that regional disparities exist and that clinical and economic outcomes correlate with income level, number of procedures, and state population.

Background: The third most populous county in the United States, the Harris Country, has some of the worst outcomes of breast cancer in the country. In this county, 27% of mammogram eligible women, ages 40-64 are uninsured, compared to about 11% the national average. Harris Health (HH) is a state funded network of SafetyNet hospitals and clinics that provide comprehensive care, including breast cancer screening to the uninsured and underinsured residents of the Harris county. The population who receives care at the HH sites is majority of racial and ethnic minorities and generally lower socioeconomic status than the county average. The number of screening mammograms abruptly dropped by 94% across the United States following the declaration of the COVID-19 national emergency. Currently there is no data on how breast cancer screening rates have been affected during the pandemic across Houston, and specifically in Harris County where health disparities gap already existed. We hypothesized that the population across HH sites have lower rates of screening mammograms following the COVID-19 pandemic declaration compared to the rest of the population across Houston who visit Baylor St. Luke’s Health- Texas (SLH) catchment area. Methods: We retrieved the monthly gross number of screening mammograms performed at all HH sites and SLH sites from February to October for both 2019 and 2020 on the PENRAD database. We then used the Independent-Samples Mann-Whitney U Test to assess differences in the distribution of percent change in mammogram between HH sites and SLH sites. First, we compared the total mammogram numbers for February to October (2020 vs. 2019). We then compared only the numbers for each month (e.g., May 2020 vs. May 2019). Beyond basic descriptive counts, statistical analysis was limited to mammogram among women ages 40 – 69. Statistical significance was set at p Citation Format: Maryam Nemati Shafaee, Luke Gilman, Abiodun Oluyomi, Melissa Bondy, Tamara Ortiz-Perez, Chris Amos, Mothaffar Rimawi. Disparities in breast cancer screening and the impact of COVID-19 in Houston, Texas [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr P33.

Fulvestrant is a steroidal selective estrogen receptor degrader that was approved by the US FDA in 2002 for treatment of ER-positive metastatic breast cancer (ER + MBC) post-progression on aromatase inhibitors. In 2017, the label was updated to include endocrine therapy naive ER + MBC. While initially fulvestrant was thought to be equivalent to aromatase inhibitors with monthly dose of 250 mg intramuscular injection, several postmarketing trials challenged this understanding. Subsequently, the recommended dose changed to 500 mg monthly plus loading dose, and this was proven to be superior to anastrozole in efficacy. Most recently the results of FALCON trial have further challenged the way fulvestrant is viewed and used. This report provides a historical perspective on this compound, its evolving role in management of ER + MBC and what the future may hold for this drug.

Background Patients with sarcomatoid renal-cell carcinomas (sRCC) have poor outcomes and limited treatment options. Preclinical and clinical data suggest susceptibility to cytotoxic agents and vascular endothelial growth factor–targeted therapies. We designed a phase 2 trial to evaluate the efficacy and safety of capecitabine, gemcitabine, and bevacizumab in sRCC. Patients and Methods Patients with metastatic or unresectable sRCC were eligible for inclusion. Patients received oral capecitabine 800 mg/m2 twice daily on days 1 to 21 of a 28-day cycle, intravenous gemcitabine 900 mg/m2 on days 1 and 15, and intravenous bevacizumab 10 mg/kg on days 1 and 15. Primary end points were progression-free survival and time to treatment failure (TTF). Secondary end points were safety, objective response rate, and overall survival. Results Thirty-four patients were enrolled onto the trial. One patient was excluded from survival analysis and 4 from response analysis as a result of missing data. Median progression-free survival was 5.5 months (95% confidence interval [CI], 3.4-7.7), median TTF was 4.2 months (95% CI, 2.4-6.0), and median overall survival was 12 months (95% CI, 10.6-13.4). Objective response rate was 20% (5 partial responses, 1 complete response), and disease control rate was 73%. Thirty-one (91%) of the 34 patients discontinued treatment. The most common reason for treatment discontinuation was progressive disease, which occurred in 24 patients (71%). The most common grade 3 toxicity was rash (including hand–foot syndrome) in 24% patients. Conclusion The combination of capecitabine, gemcitabine, and bevacizumab is an option for patients with sRCC; however, response rates are low. Novel therapies are needed to improve outcomes in patients with sRCC.

The estrogen receptor (ER) has been targeted for breast cancer treatment for over a century, but many challenges persist. ER-positivity identifies the largest breast cancer subgroup, and ER-directed therapies prolong survival and improve symptoms in the advanced setting with a very favorable side effect profile. Treatment strategies have included decreasing estrogen synthesis and modulating or degrading the ER. However, ER+ breast cancer once diagnosed in the advanced setting still represents an incurable condition. Many efforts are ongoing to circumvent resistance mechanisms with a few strategies already incorporated into clinical practice such as the combination of endocrine agents with drugs that interfere with other signaling pathways and cell-cycle progression. Important questions remain as how best to select each available strategy, how to sequence them and ultimately how to extend benefits to the largest number of patients in need.

e12065Background: While Oncotype-Dx testing has become the standard of care in early stage ER positive BC, its role in the management of BRCA associated breast cancer is not well defined. Inherited mutations in the BRCA gene are responsible for 5-10% of breast cancers. BRCA2 mutation predisposes to ER positive BC 50% of the time, while BRCA1 mutation is more commonly associated with ER negative tumors. In this report, we sought to evaluate the role of Oncotype Dx in a population of patients (pts) with known BRCA status. Methods: We performed an IRB approved single institution retrospective analysis of women with known BRCA status diagnosed with stage I-II BC (T0-T3, N0-N1). We included women diagnosed with ER and/or PR positive, Her2 neu normal BC between years 1974-2015. Tumor grade and Oncotype –Dx scores were retrieved. We evaluated the relationship between BRCA and Oncotype-Dx scores. Results: 691 pts were included in this study. 133 (19%) were BRCA1 or 2 positive and 558 (81%) were negative. 65 of th...

1095Background: Inherited mutations in the BRCA gene are responsible for 5-10% of breast cancers. These mutations, predominantly BRCA 1, predispose to TNBC. Around 20% of women with TNBC are BRCA m...

3 Background: Contralateral breast cancer (CBC) risk in BRCA1 & 2 mutations is up to 64%. Patients (pts) with estrogen receptor positive (ER+) breast cancer (BC) are offered tamoxifen (TAM) or Aromase inhibitors (AI) adjuvantly. Reports suggest that TAM may reduce the risk of CBC in BRCA mutation; however there is no such data on the effect of AIs. Here, we evaluate the effect of TAM and AI as potential CBC risk reducers in a cohort of women with known BRCA status. Methods: 1043 BC pts receiving genetic counseling and BRCA testing were included. 13 had metastasis, 168 had a variant BRCA, and 50 had synchronous BC, and were excluded. Of the 812 remaining pts, 153 had a deleterious BRCA 1 or 2 mutations. Pts were followed from the diagnosis of BC until CBC, death, or last follow-up. The study had IRB approval. Univariate analyses were performed to test the significance of each variable in relation to BRCA status using chi-square tests for categorical variables and t tests for continuous variables. Results: The median age at diagnosis of BC was 42.3 years (range: 21-84). Median follow up was 8.6 years. 86% (700) had ER+ tumors, 80% were diagnosed with T1-2, and 81% had N0-N1. 76% (622) received TAM, and 37% (304) received AI. A total of 68 (8.7%) CBCs occurred of which 14% (21/153) occurred in BRCA carriers vs 7% (47/659) in BRCA non-carriers. Multivariate analyses indicated that BRCA status and AI use were significantly associated with CBC. Specifically, compared with BRCA negative, pts with BRCA1+ or BRCA2+ had larger hazard of developing CBC, Hazard Ratio (HR) (95% confidence interval (CI)) = 2.49 (1.21, 5.10), p = 0.013 for BRCA1+ vs Negative. HR (95%CI) = 1.97 (1.05, 3.73), p = 0.036 for BRCA2+ vs Negative. Compared to pts who did not receive AI, those who received AI had smaller hazard of developing CBC, HR (95%CI) = 0.42 (0.22, 0.81), p = 0.01. The interaction between AI and BRCA status was not significant (p = 0.4), hence all pts benefited from AI use in terms of CBC risk reduction. TAM use did not show significant effect on the risk of CBC in univariate and multivariate analyses (p > 0.13). Conclusions: This is the first report showing that AIs can reduce risk of CBC in women with BC who have a BRCA mutation. This finding should be validated in larger independent cohorts.