Background: SG was approved in 2020 for the treatment of metastatic triple negative breast cancer (TNBC). The most common grade 3/4 adverse event in the ASCENT trial was neutropenia (51.2%) with a 6% incidence of febrile neutropenia. 1 Package insert recommendations do not endorse primary prophylactic growth factor support, rather only initiating if severe neutropenia occurs on treatment.2 Objective: This study retrospectively reviewed the utilization of growth factor support in patients (pts) with metastatic TNBC initiated on SG at each Mayo Clinic Enterprise site. Methods: We performed a multi-center, retrospective review of all pts with TNBC who received SG from January 2021 to December 2021 at Mayo Clinic sites in Minnesota, Florida, Arizona, and its community-based health system network. Data collected included history of neutropenia with previous cycles of SG resulting in a treatment delay, number of cycles, grade of neutropenia and cycle/day of treatment plan when growth factor added. Pts who received only one dose of SG were excluded. The Fisher’s exact test was utilized to compare the difference in the use of primary prophylaxis between sites. Results: 67 pts received at least two doses of SG. Within this cohort, 42 pts (63%) received growth factor support during treatment with SG. Growth factor support was most often added during the first two cycles (59.5%). A total of 12 patients initiated growth factor with no history of delays related to neutropenia and without neutropenia at the time of administration. Eleven of these pts had growth factor support added on Cycle 1 as primary prophylaxis. Primary prophylaxis was most common at Mayo Clinic – Rochester compared to the other sites (Table 1), however there was not a statistically significant difference (p=0.27). There were 26 pts (39%) with a treatment delay due to neutropenia while receiving SG, of which 21 (81%) were managed with the addition of growth factor (13 pegfilgrastim, 8 filgrastim). The median number of cycles for all pts was 5 (range: 1-25). Pts who received growth factor were treated with a median of 5 cycles (range: 1-25) and pts who did not receive growth factor were treated with a median of 4 cycles (range: 1-19) (p=0.10). Conclusions: We observed wide variability in the use of prophylactic growth factor between Mayo Clinic sites with SG. The optimal practice of growth factor use with SG warrants further exploration. References: 1. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529-1541 2. Immunomedics, Inc. Trodelvy (sacituzumab govitecan-hziy) [package insert]. Foster City, CA: Gilead Sciences; 2020. Table 1: Grade of neutropenia for patients receiving SG when growth factor initiated Citation Format: Kaylee Clark, Jamie L. Carroll, Alvaro Moreno-Aspitia, Brenda Ernst, Farah Raheem, Ashley Heil, Beth Boyer, Kristin Mara, Matthew P. Goetz, Roberto A. Leon-Ferre, Karthik V. Giridhar, Jodi Taraba. Mayo Clinic Enterprise patterns of growth-factor utilization for sacituzumab govitecan (SG)-induced neutropenia among patients with metastatic triple negative 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 P4-07-56.
Purpose: Blood-based candidate biomarkers of disease can be monitored by analyzing CTCs and/or circulating cfDNA isolated from the peripheral blood. Our primary objective is to understand the relative contributions of these circulating factors (i.e., CTCs and cfDNA) to the overall disease profile in MBC. Methods: Clinically archived FFPE tumor tissue and prospective blood samples are collected through a minimal risk protocol approved by the Mayo Clinic IRB (#16-001540) from patients with MBC and objective evidence of disease progression. Blood samples include 20 mL whole blood in Streck blood collection tubes (BCTs) for platelet poor plasma (PPP); 20 mL whole blood in AccuCyte BCTs for CTCs, WBCs, and PPP; and 10 mL whole blood in EDTA BCTs for PPP. Nucleated, EpCAM+/cytokeratin+/CD45- CTCs are identified, assessed for ER/HER2 status, and isolated using a centrifugation and direct imaging platform that allows for single cell retrieval (RareCyte). DNA is extracted from PPP, CTCs, WBCs, and FFPE tumor tissue using established methods. Targeted sequencing for SNVs/indels is performed on paired WBCs and CTC-DNA, AccuCyte-cfDNA, Streck-cfDNA, EDTA-cfDNA, and tumor tissue derived DNA using the same NGS panel and informatics pipeline (65 genes; CleanPlex OncoZoom; Paragon Genomics). Results: Tissue and blood samples were collected from 40 patients with metastatic breast cancer. 10 cases were selected for initial analyses on the basis of CTC yield (range 3-113 per 3.75 mL blood); up to 5 CTCs per subject were isolated and pooled for DNA extraction. Plasma cfDNA yields and variant allele frequencies were highly comparable between AccuCyte and Streck collected blood samples. Mutations (range 1-3) were identified in CTC-DNA and/or cfDNA in 9 of 10 cases for a total of 18 detected mutations: 10 in CTC-DNA and cfDNA (BRCA2 N372H, PIK3CA E542K, PIK3CA E545K (x3), PIK3CA H1047R, PTEN R130P, RET G691S, TP53 C135W, TP53 Q192*); 5 in CTC-DNA only (EGFR R521K, EGFR T790M, PIK3CA H1047R, SMAD4 C363Y, TP53 N263D); and 3 in cfDNA only (DNMT3A W893S, DNMT3A S714C, TP53 Q136E). Parallel analyses of samples from 10 more subjects are in progress. Analysis of tumor tissue for all 20 subjects and of EDTA-cfDNA and single CTCs for a subset of cases is ongoing. Updated results will be presented at the meeting. Conclusions: It is feasible to isolate high quality CTCs and cfDNA from the same blood collection tube to perform targeted sequencing; this streamlines specimen processing, decreases overall costs, and minimizes required blood volumes. Importantly, there is overlap in the majority of mutations identified in CTC-DNA and cfDNA, but actionable mutations (e.g., PIK3CA, EGFR) were detected in CTC-DNA only. The clinical and theranostic relevance of these findings is unclear and warrants further investigation. Citation Format: Minetta C. Liu, Karthik V. Giridhar, Roberto A. Leon Ferre, Jamie L. Carroll, Matthew P. Goetz, Tufia C. Haddad, Deanne R. Smith, Siddhartha Yadav, Vidushi Kapoor, Guoying Liu, Tad George, Nolan Ericson, Arturo B. Ramirez, Eric Kaldjian, Keegan E. Haselkorn. Comparison of circulating tumor cell (CTC) derived DNA and circulating cell-free DNA (cfDNA) from simultaneous blood sampling of patients with metastatic breast cancer (MBC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3119.
Background: Germline mutation screening of BRCA1 and BRCA2 genes is performed in suspected familial breast cancer cases, but a causative mutation is found in only 30% of patients. The development of additional methods to identify good candidates for BRCA1 and BRCA2 analysis would therefore increase the efficacy of diagnostic mutation screening. With this in mind, we developed a study to determine molecular signatures of BRCA1—or BRCA2—mutated breast cancers. Materials and Methods: Array-cgh (comparative genomic hybridization) and transcriptomic analysis were performed on a series of 103 familial breast cancers. The series included 7 breast cancers with a BRCA1 mutation and 5 breast cancers with a BRCA2 mutation. The remaining 91 cases were obtained from 73 families selected on the basis of at least 3 affected first-degree relatives or at least 2 affected first-degree relatives with breast cancer at an average age of 45 years. Array-cgh analyses were performed on a 4407 BAC-array (CIT-V8) manufactured by IntegraGen. Transcriptomic analyses were performed using an Affymetrix Human Genome U133 Plus 2.0 chip. Results: Using supervised clustering analyses we identified two transcriptomic signatures: one for BRCA1-mutated breast cancers consisting of 600 probe sets and another for BRCA2-mutated breast cancers also consisting of 600 probes sets. We also defined cgh-array signatures, based on the presence of specific genomic rearrangements, one for BRCA1-mutated breast cancers and one for BRCA2-mutated breast cancers. Conclusions: This study identified molecular signatures of breast cancers with BRCA1 or BRCA2 germline mutations. Genes present in these signatures could be exploited to find new markers for such breast cancers. We also identified specific genomic rearrangements in these breast cancers, which could be screened for in a diagnostic setting using fluorescence in situ hybridization, thus improving patient selection for BRCA1 and BRCA2 molecular genetic analysis.
48 Background: Improving new patient access to medical oncology clinics is a priority. Unlike external referrals which undergo a review process, internal referrals (from any Mayo department or community-based, affiliated health system) are scheduled directly. At times, these internal referrals lack necessary clinical information, or may be more appropriate for electronic consultation (e-consult). This impacts the patient experience, provider satisfaction, and access to new patient visits. A pilot program was implemented in the Medical Oncology breast clinic to review new internal referrals prior to scheduling. Methods: In 2018, all internally referred patients to Medical Oncology breast clinic were reviewed by an advanced practice provider in breast oncology. Electronic medical records were reviewed to collect diagnosis, pathology, radiology information and treatment to date. Internal referrals were either accepted directly to medical oncology breast clinic, triaged to an internal medicine clinic for workup of a new breast mass, converted to an e-consult, or declined as no medical oncology need was identified. Results: 52 patients were referred internally to Medical Oncology breast clinic. Of these, 29 (55.8%) were accepted directly as new consultations, 8 (15.4%) were triaged to the Internal Medicine clinic, 6 (11.5%) were converted to e-consults, and 6 (11.5%) were declined as not requiring breast medical oncology input. Of the 8 patients that started in the IM clinic, 6 eventually required Medical Oncology breast clinic consults for invasive breast cancers. The most common e-consult was for extending adjuvant endocrine therapy (3/6). 1/6 e-consults required a follow up consultation. The most common reason for declining a consult was no diagnosis of an invasive breast cancer (4/6). A total of 16/52 referrals (30.2%) did not require a breast oncology new consultation. Conclusions: Review of internal referrals improved the efficiency of new breast cancer medical oncology consultations. This review process has been implemented across the entire Medical Oncology practice.
Background: Earlier studies report a direct association between diseases of the skin—particularly those on the face—and depression. However, to our knowledge, such associations have not been examined in patients with non-squamous, non-basal call skin cancers. Methods: The primary goal was to assess whether malignant skin disease—specifically on the face as opposed to other sites—was associated with depression. The medical records of patients with cutaneous cancer (either primary or metastatic but non-squamous, non-basal cell) were reviewed for the relevant data. Results: One hundred and sixty-five patients were studied. Only 23 patients (14%) had metastases to the face, and 115 (70%) had a readily viewable skin cancer. Twenty-one patients (13%) developed depression after a diagnosis of cutaneous cancer (of note, the rate of missing data for depression was 37%). Only one patient with facial cutaneous cancer manifested depression, yielding an odds ratio for not developing depression (95% confidence interval (CI)) of 4.4 (0.5,35); p = 0.13. Depression appeared to occur more often in women (62% versus 43%), patients with a history of depression (52% versus 6%), and younger patients (median age with and without depression 55 years and 67 years, respectively). Conclusion: In contrast to other cutaneous diseases, no association was found between cutaneous cancer to the face and depression. Nonetheless, high rates of missing data underscore the need to focus on depression in patients with cutaneous cancers in the future.
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