Publications by authors named "Kim Hirshfield"

Introduction: Recent trial-level meta-analyses have established disease-free survival (DFS) as a valid surrogate for overall survival (OS) in human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), irrespective of disease stage, and in early-stage hormone receptor-positive (HR+)/HER2- BC. To advance the understanding of the association between additional DFS endpoints and OS, this study assessed the patient-level correlations between DFS and OS, invasive DFS (IDFS) and OS, and distant DFS (DDFS) and OS in Medicare beneficiaries with early-stage HER2- BC, overall and in subgroups of patients with HR+/HER2- BC and triple-negative BC (TNBC).

Methods: Patients with stages I-III HER2- BC aged ≥ 66 years were identified from SEER-Medicare data (2010-2019).

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Aim: This study aimed to describe treatment patterns and quantify the economic impact of recurrence in early-stage human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC).

Materials & Methods: Medicare beneficiaries with stages I-III HER2-negative BC and lumpectomy or partial/total mastectomy were identified from SEER-Medicare data (2010-2019). Perioperative therapies were reported in the neoadjuvant and adjuvant setting.

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Additional therapies are needed to improve outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. Research on the potential role of immunotherapy, particularly programmed cell death protein 1/programmed cell death ligand 1 inhibitors, is rapidly expanding in both the early and metastatic settings with some preliminary evidence suggesting benefit when used as part of combination therapy. Several ongoing phase 3 studies should help define their future role in treating these patients.

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Introduction: Triple-negative breast cancer (TNBC) is associated with a high recurrence risk. However, the magnitude of direct and indirect costs associated with recurrence is lacking in the literature.

Methods: Adults 18-65 years old diagnosed with TNBC were identified from the OptumHealth Reporting and Insights claims database (1999-2017) and stratified by recurrence.

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Background: Prostate cancer (PCa) phenotypes vary from indolent to aggressive. Molecular subtyping may be useful in predicting aggressive cancers and directing therapy. One such subtype involving deletions of chromodomain helicase DNA binding protein 1 (), a tumor suppressor gene, are found in 10-26% of PCa tumors.

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Metaplastic breast cancer (MBC) is a rare and aggressive subtype of breast cancer. Tumor characteristics typically feature estrogen receptor, progesterone receptor, and HER2-negative, triple-negative breast cancer (TNBC), with a poorer prognosis relative to pure invasive ductal or lobular disease. Resistance to chemotherapy often leads to local recurrence and distant metastasis.

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To analyze therapy for metastatic triple-negative breast cancer (mTNBC), factors contributing to survival and costs. Using 2010-2016 SEER-Medicare data, we identified women (≥65 years) with mTNBC. Of 302 eligible patients, 152 (50%) received systemic therapy.

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Background: Invasive pleomorphic lobular carcinoma (PLC) of the breast is a subtype of invasive lobular cancer which compromises approximately 1% of all epithelial breast malignancies and is characterized by higher nuclear pleomorphism and poorer prognosis than classic invasive lobular cancer (ILC). Since PLC is more aggressive than classical ILC, we examined the underlying molecular alterations in this subtype of breast cancer to understand the possible benefit from targeted therapies.

Methods: In this study, we investigate the clinical characteristics and molecular alterations in 16 PLC from our institution.

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To examine real-world treatment patterns and outcomes in neoadjuvant and adjuvant settings for early-stage triple-negative breast cancer (TNBC). Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients (≥65 years) with newly diagnosed stage II/III TNBC in 2010-2015 who had surgery plus neoadjuvant and/or adjuvant (systemic and/or radiation) therapy. Treatment, survival, healthcare resource use and costs were assessed through 2016.

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Mammogram-detected breast cancers have a better prognosis than those identified through clinical breast exam (CBE) or through self-detection, primarily because tumors detected by mammography are more likely to be smaller and do not involve regional nodes. In a sample of 1,322 Black women, aged 40-75 years, diagnosed with breast cancer between 2002 and 2016, we evaluated factors associated with CBE and self-detection versus screening mammogram as the initial mode of breast cancer detection, using multivariable logistic regression models. Compared with screening mammogram, history of routine screening mammogram (OR 0.

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Introduction: CHD1 has been identified as a tumor suppressor gene in prostate cancer. Previous studies have shown strong associations between CHD1 deletion, prostate specific antigen [PSA] recurrence, and absence of ERG fusion. In this preliminary study we seek to find whether there is an independent correlation between CHD1 status and response to androgen deprivation therapy[ADT].

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Fusions involving the oncogenic gene RET have been observed in thyroid and lung cancers. Here we report RET gene alterations, including amplification, missense mutations, known fusions, novel fusions, and rearrangements in breast cancer. Their frequency, oncogenic potential, and actionability in breast cancer are described.

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Purpose: Inherited germline defects are implicated in up to 10% of human tumors, with particularly well-known roles in breast and ovarian cancers that harbor -mutated genes. There is also increasing evidence for the role of germline alterations in other malignancies such as colon and pancreatic cancers. Mutations in familial cancer genes can be detected by high throughput sequencing (HTS), when applied to formalin-fixed paraffin-embedded (FFPE) tumor specimens.

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The antitumor effects of a novel antibody drug conjugate (ADC) was tested against human solid tumor cell lines and against human triple negative breast cancer (TNBC) xenografts in immunosuppressed mice. The ADC targeting activated matriptase of tumor cells was synthesized by using the potent anti-tubulin toxin, monomethyl auristatin-E linked to the activated matriptase-specific monoclonal antibody (M69) via a lysosomal protease-cleavable dipeptide linker. This ADC was found to be cytotoxic against multiple activated matriptase-positive epithelial carcinoma cell lines and markedly inhibited growth of triple negative breast cancer xenografts and a primary human TNBC (PDX) .

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- fusions, including -, have been identified as potential oncogenic drivers and actionable alterations in a number of different cancer types. The clinical relevance of fusions in endometrial cancer has not yet been described. Formalin-fixed, paraffin-embedded metastatic endometrial carcinoma from the spleen and peritoneum were sent for comprehensive genomic profiling (CGP) using the FoundationOne platform as part of a prospective tumor genomic profiling protocol.

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Response to immune checkpoint therapy can be associated with a high mutation burden, but other mechanisms are also likely to be important. We identified a patient with metastatic gastric cancer with meaningful clinical benefit from treatment with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab. This tumor showed no evidence of high mutation burden or mismatch repair defect but was strongly positive for presence of Epstein-Barr virus (EBV) encoded RNA.

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Purpose Limited data are available on the survival of patients with breast cancer with preexisting mental illness, and elderly women are of special interest because they experience the highest incidence of breast cancer. Therefore, we compared all-cause and breast cancer-specific mortality for elderly patients with breast cancer with and without mental illness. Methods A retrospective cohort study was conducted by using SEER-Medicare data, including 19,028 women ≥ 68 years of age who were diagnosed with stage I to IIIa breast cancer in the United States from 2005 to 2007.

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Purpose: This study aimed to compare diagnosis and treatment delays in elderly breast cancer patients with and without pre-existing mental illness.

Methods: A retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results-Medicare data including 16,636 women 68+ years, who were diagnosed with stage I-IIIa breast cancer in the United States from 2005 to 2007. Mental illness was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes recorded on inpatient and outpatient claims during the 3 years prior to breast cancer diagnosis.

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A coding region polymorphism exists in the gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia.

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Purpose: In an effort to explain racial disparities in breast cancer survival, this study aimed to investigate how comorbidity affects breast cancer-specific mortality by race.

Methods: A retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results-Medicare linked data including 68,090 women 66+ years, who were diagnosed with stage I-III breast cancer in the United States from 1994 to 2004. Hospital and outpatient claims from the year prior to breast cancer diagnosis were used to identify comorbid conditions and patients were followed for survival through 2010.

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Recent evidence suggests that glutamate signaling plays an important role in cancer. Riluzole is a glutamate release inhibitor and FDA-approved drug for the treatment of amyotrophic lateral sclerosis. It has been investigated as an inhibitor of cancer cell growth and tumorigenesis with the intention of repurposing it for the treatment of cancer.

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Article Synopsis
  • Many melanoma patients with BRAF mutations initially respond well to BRAF inhibitors like vemurafenib but often develop resistance over time.
  • A study on a patient who developed resistance revealed a new fusion gene that contributed to this resistance while still allowing sensitivity to MEK inhibitors.
  • The patient benefitted from a treatment combining BRAF and MEK inhibitors, and later biopsies showed the fusion gene was lost after discontinuing the inhibitors, highlighting the dynamic nature of melanoma cell evolution.
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Article Synopsis
  • * At Rutgers Cancer Institute of New Jersey, a multidisciplinary team has developed a Clinical Data Warehouse using diverse data sources like Electronic Medical Records and tumor registries.
  • * The Warehouse allows for the analysis of various clinical and molecular data to help physicians make informed treatment decisions by identifying trends in patient tumors.
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