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  • 1
    Online Resource
    Online Resource
    Elsevier BV ; 2023
    In:  Surgical Oncology Clinics of North America Vol. 32, No. 4 ( 2023-10), p. 663-673
    In: Surgical Oncology Clinics of North America, Elsevier BV, Vol. 32, No. 4 ( 2023-10), p. 663-673
    Type of Medium: Online Resource
    ISSN: 1055-3207
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e13096-e13096
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e13096-e13096
    Abstract: e13096 Background: Breast cancers remain the most lethal malignancies amongst women worldwide and the second leading cause of cancer-related mortalities in the US. Subtype heterogeneity and aggressive invasive potential are believed to be the major contributors of these outcomes. Triple-negative breast cancer (TNBC) are notoriously aggressive, difficult-to-treat, and metastatic. Inflammation-driven tumorigenesis has been shown to correlate with cell-free DNA (cfDNA) and other damage-associated molecular patterns (DAMPs) in cancer patient sera. We showed that nucleic-acid scavengers (NAS) can block pro-inflammatory signals elicited by DAMP-activation of innate immune sensors (e.g. toll-like receptors). Treatment with the NAS PAMAM-G3 drastically reduced liver metastatic burden in an immunocompetent murine model of pancreatic cancer. Methods: TNBC cells lines were treated with a cocktail of standard-of-care chemotherapeutic agents and the conditioned media (CM) from these cells served as an in vitro DAMP source. Downstream function of TLR activation was tested via a HEK293-TLR reporter cell line measuring absorbance at 655nm. The in vitro invasive phenotype was tested and quantified using a Transwell-Matrigel invasion assay. Cytokine secretion was measured using a BioLegend cytokine array. Results: TNBC CM greatly increased TNBC cell invasion in vitro and that treatment with the NAS PAMAM-G3 significantly inhibits this effect. Treatment of human monocytes (THP-1) with TNBC CM elicited a strong pro-inflammatory response with elevated levels of IL-8, IL-6, CCL2, and IL-1β. Other biologically immune responders including human PBMCs will be tested to determine the potential impact on the tumor immune microenvironment during tumorigenesis and treatment. Conclusions: To elucidate the mechanism by which this NAS works in these tumor settings, our lab has developed several PAMAM-G3 derivatives, including biotin, IR-, and near-IR fluorophore labeled molecules. These molecules will allow us to capture and characterize DAMPs and do in vivo live imaging experiments to gain insight into NAS PK/PD properties. This insight into NAS capabilities will enhance our understanding of metastatic progression and its interplay with the immune system. Moreover, these principles will aid in the development of novel of anti-metastatic therapies to improve TNBC patient outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS616-TPS616
    Abstract: TPS616 Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS) each year. Without treatment, it is estimated that only 20-30% of DCIS will lead to invasive breast cancer (IBC). However, over 97% of women are currently treated with surgery +/- radiation. An alternative to surgery is active monitoring (AM), a management approach in which mammograms/physical exams are used to monitor breast changes and determine when, or if, surgery is needed. The COMET Study will compare risks and benefits of AM versus surgery for low-risk DCIS in the setting of a Phase III multicenter prospective randomized trial. The study is funded by the Patient-Centered Outcomes Research Institute. The COMET trial opened in the U.S. in June 2017 (Clinicaltrials.gov reference: NCT02926911). In November 2021, the Data Safety Monitoring Board reviewed the trial and suggested that it continue as planned. Patient accrual will continue until 12/31/2022. Methods: The primary objective is to assess whether the 2-year ipsilateral IBC rate for AM is non-inferior to that for surgery. Secondary objectives include determining whether AM is non-inferior to surgery for 2-year mastectomy rate; breast conservation rate; contralateral breast cancer rate; overall and breast cancer-specific survival. Patient reported outcomes will enable comparison of health-related quality of life and psychosocial outcomes between surgery and AM groups at baseline, 6-months, and years 1-5. Eligibility criteria include: age 〉 40 at diagnosis; pathologic confirmation of grade I/II DCIS or atypia verging on DCIS without invasion by two pathologists; ER and/or PR ≥ 10%; no mass on physical exam or imaging. The accrual goal is 1200 randomized patients across 100 Alliance for Clinical Trials in Oncology sites. Sample size is estimated using a 2-group test of non-inferiority of proportions, with the 2-year IBC rate in the surgery group assumed to be 0.10 based on published studies and non-inferiority margin of 0.05. Based on a 1-sided un-pooled z-test, with alpha = 0.05, a sample size of n = 446 per group will have 80% power to detect the specified non-inferiority margin. Final analysis plan will include a per protocol component as well as a pragmatic component for patients who are randomized and decline participation in their assigned arm. Primary analyses will adjust for dropout, non-compliance and contamination by utilizing instrumental variable methods. Clinical trial information: NCT02926911.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 585-585
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 8_suppl ( 2019-03-10), p. 7-7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 8_suppl ( 2019-03-10), p. 7-7
    Abstract: 7 Background: Neoadjuvant chemotherapy (NAC) for breast cancer (BC) is being increasingly used in patients with stage I/II disease. Although previously reserved for patients with locally advanced disease, its use in patients with localized disease allows for higher rates of breast-conserving procedures and provides insight into tumor biology. A complete pathologic response (pCR) to NAC correlates with better clinical outcomes; sadly, many patients do not achieve pCR. The advent of immunotherapy has provided cancer patients with additional treatment options. To optimize immunotherapy in BC we must understand the peripheral cellular immunome (immune subsets and activation status) of patients as they undergo standard of care therapy (SOC). Methods: Our population includes patients with stages I-III BC undergoing SOC. Samples were collected pre- and post-NAC, post-surgery and at 2-month follow-up (FU). Results: Flow cytometry analysis for 11 patients was performed at each time-point to examine percentages of circulating immune cells (see Table). We grouped samples in 3 categories: human epidermal growth factor receptor 2 (HER2+) positive, HER2 negative (HER2-) and triple-negative (TN) tumors. 3 out of 11 patients had pCR (1 HER2+, 1 HER2-, 1 TN); they had highest percentage of circulating CD56+ NK cells during treatment course. Conclusions: We observed striking changes in the immunome of women with stage I-III BC undergoing NAC. Although our findings are preliminary, given our sample size, we observed distinct trends within each immune cell population in specific tumor receptor subtypes. These trends could serve to guide our therapies, allow for better patient selection and predict treatment response in patients. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 6512-6512
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 6512-6512
    Abstract: 6512 Background: National tumor registries, such as the NCDB (National Cancer Database) and SEER (Surveillance, Epidemiology, and End Results Program), have been used to explore numerous research questions related to trends in disease incidence, treatment patterns, and outcomes. However, some have criticized that they may not fully represent the general population. As such, we sought to compare the incident breast cancer cases in the NCDB and SEER to a national population cancer registry. Methods: All patients diagnosed with malignant or in situ breast cancer 2010-2019 were selected from the NCDB (Fall 2022 release) and SEER-22 (November 2021 release) and compared to breast cancer patient counts from the US Cancer Statistics Public Use Database (USCS, 2021 submission). Patient frequencies were summarized by age, sex, race/ethnicity, and year of diagnosis. Percent case coverage was estimated as the number of patients in the NCDB or SEER divided by the number of patients in the USCS. Chi-square tests were used to compare patient counts across data sources. Results: In total, the USCS database reported 3,047,509 patients diagnosed with breast cancer between 2010-2019, of which, 77.5% (N=2,362,477) were included in the NCDB and 46.0% (N=1,403,272) in SEER. Over time, case coverage steadily improved for the NCDB (72.8% in 2010 to 81.5% in 2019), while only a minor increase was observed in SEER (46.0% in 2010 to 46.6% in 2019). When compared to the USCS, case ascertainment was notably lower for individuals age ≥50 in both the NCDB and SEER (both p 〈 0.001). The overwhelming majority of patients were captured by the NCDB (age 〈 50: 81.7%; age ≥50: 76.6%) while SEER identified approximately half (age 〈 50: 49.4%; age ≥50: 45.3%). Case ascertainment also varied significantly by patient sex across registries (both p 〈 0.001). For male breast cancers, 84.1% were captured in the NCDB, only 77.5% of female patients were included. In contrast, case coverage in SEER was better for females than males (46.1% vs 43.5%). Notably, registries varied significantly by race/ethnicity (both p 〈 0.001). Case coverage in the NCDB was highest for non-Hispanic White (78.2%), non-Hispanic Black (77.7%), and non-Hispanic Asian or Pacific Islander (72.5%) patients, and it was lowest for Hispanic (56.4%) and non-Hispanic American Indian/Alaska Native (41.1%). In SEER, case coverage was highest for non-Hispanic Asian or Pacific Islander (78.1%) and Hispanic (69.6%) patients, and it was considerably lower for all other subgroups (non-Hispanic Black 44.8%, non-Hispanic White 42.4%, and non-Hispanic American Indian/Alaska Native 36.6%). Conclusions: National US tumor registries provide data for a large sampling of breast cancer patients, and case coverage has improved over time. However, significant differences in case coverage were observed based on age, sex, and race/ethnicity, suggesting that analyses using these data sets should be interpreted with caution.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 30_suppl ( 2018-10-20), p. 207-207
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 30_suppl ( 2018-10-20), p. 207-207
    Abstract: 207 Background: Despite the recognized side effect of financial toxicity after cancer, treatment decisions for breast cancer rarely include the costs of care. We sought to determine women’s experiences with breast cancer treatment costs, and their preferences for cost transparency at diagnosis. Methods: Women ≥18 years old with a history of breast cancer completed an 88-question electronic survey based on validated or published items. Descriptive statistics and regression analysis were used. Results: In total, 607 women with stage 0-III breast cancer participated. Median age at diagnosis was 49.6 years. Median time from diagnosis was 6.7 years (range 0.1-37.1). The majority had private (70%) insurance or Medicare (25%), and reported an annual household income ≥$74,000. 43% reported considering costs in treatment decisions. Median reported out-of-pocket (OOP) costs were $3,500; 25% reported OOP costs ≥$8,000, 10% reported OOP costs ≥$18,000 and 5% reported OOP costs ≥$30,000. 15.5% reported significant to catastrophic financial burden. Bilateral mastectomy +/- reconstruction vs lumpectomy (OR 1.9, p 0.03), greater stage at diagnosis (stage 3 vs 0, OR 3.9, p 〈 0.01), and discussion of costs during the clinical encounter (OR 2.3, p 〈 0.01) were associated with a higher risk of financial harm. Women who reported discussing costs were more likely to be stage 2 or 3 (56% vs 40%, p = 0.02), less likely to be depressed (24% vs 30%, p = 0.03), and had less insurance coverage (trend p = 0.02) compared to those who did not. Older age (OR 0.95, p 〈 0.01), increasing household income (overall p 〈 0.001), better insurance coverage (OR 0.5, p 〈 0.001), and longer time since diagnosis (OR 0.65, p 〈 0.001) was associated with a decreased risk of financial harm. 78% of participants never discussed costs with their cancer team. 79% preferred cost transparency prior to embarking on care, and 40% preferred that doctors consider costs when making recommendations. Conclusions: Many women with breast cancer reported significant financial burden related to their care, and the vast majority preferred knowing costs at diagnosis. Cost transparency may improve the quality of preference-sensitive treatment decisions and reduce the risk of financial harm.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e13083-e13083
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 1006-1006
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e17607-e17607
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e17607-e17607
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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