Longitudinal monitoring of circulating tumor DNA to detect relapse early and predict outcome in early breast cancer.

Purpose: Detection of molecular residual disease (MRD) allows for the identification of breast cancer patients at high-risk of recurrence, with the potential that early initiation of treatment at early stages of relapse could improve patient outcomes. The Invitae Personalized Cancer Monitoring™ assay (PCM) is a newly developed next-generation sequencing approach that utilizes up to 50 patient-specific, tumor-informed DNA variants, to detect circulating tumor DNA (ctDNA). The ability of the PCM assay to detect MRD before clinical relapse was evaluated.

Clinician-Reported Management Recommendations in Response to Universal Germline Genetic Testing in Patients With Prostate Cancer.

Purpose: Identification of pathogenic germline variants in patients with prostate cancer can help inform treatment selection, screening for secondary malignancies, and cascade testing. Limited real-world data are available on clinician recommendations following germline genetic testing in patients with prostate cancer.

Materials And Methods: Patient data and clinician recommendations were collected from unselected patients with prostate cancer who underwent germline testing through the PROCLAIM trial.

Disparate Rates of Germline Variants in Cancer Predisposition Genes in African American/Black Compared With Non-Hispanic White Individuals Between 2015 and 2022.

Purpose: African American/Black (AA/B) individuals are under-represented in genomic databases and thus less likely to receive definitive information from germline genetic testing (GGT) than non-Hispanic White (NHW) individuals. With nearly 500,000 AA/B and NHW individuals having undergone multigene panel testing (MGPT) for hereditary cancer risk at a single commercial laboratory, to our knowledge, we present the largest study to date investigating cancer GGT results in AA/B and NHW individuals.

Methods: MGPT results from a retrospective cohort of AA/B (n = 48,684) and NHW (n = 444,831) patients were evaluated.

Universal Germline-Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision-Making.

Background: Whereas the National Comprehensive Cancer Network (NCCN) criteria restrict germline-genetic testing (GGT) to a subset of breast cancer (BC) patients, the American Society of Breast Surgeons recommends universal GGT. Although the yield of pathogenic germline variants (PGV) in unselected BC patients has been studied, the practicality and utility of incorporating universal GGT into routine cancer care in community and rural settings is understudied. This study reports real-world implementation of universal GGT for patients with breast cancer and genetics-informed, treatment decision-making in a rural, community practice with limited resources.

Cascade testing for hereditary cancer: comprehensive multigene panels identify unexpected actionable findings in relatives.

Current guidelines recommend single variant testing in relatives of patients with known pathogenic or likely pathogenic germline variants in cancer predisposition genes. This approach may preclude the use of risk-reducing strategies in family members who have pathogenic or likely pathogenic germline variants in other cancer predisposition genes. Cascade testing using multigene panels was performed in 3696 relatives of 7433 probands.

Discovery of Gamma Rays from the Quiescent Sun with HAWC.

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory.

Nondisparate Survival of Non-Hispanic Black Women With Breast Cancer Despite Less Favorable Pathology: Effect of Access to and Provision of Care Within a Military Health Care System.

Introduction: Breast cancer mortality rates are 40% higher in non-Hispanic Blacks (NHBs) than in non-Hispanic White (NHWs) in the United States. All women treated within the Murtha Cancer Center at Walter Reed National Military Medical Center (MCC/WRNMMC) have health insurance and are provided multidisciplinary health care. Pathological factors and outcomes of NHBs and NHWs treated within the MCC/WRNMMC were evaluated to determine whether equal-access health care reduces disparate phenotypes and survival between the racial groups.

Survival Disparities in US Black Compared to White Women with Hormone Receptor Positive-HER2 Negative Breast Cancer.

Black women in the US have significantly higher breast cancer mortality than White women. Within biomarker-defined tumor subtypes, disparate outcomes seem to be limited to women with hormone receptor positive and HER2 negative (HR+/HER2-) breast cancer, a subtype usually associated with favorable prognosis. In this review, we present data from an array of studies that demonstrate significantly higher mortality in Black compared to White women with HR+/HER2-breast cancer and contrast these data to studies from integrated healthcare systems that failed to find survival differences.

Effect of Differences in Access to Screening, Healthcare, and Treatment on Cancer Disparities.

Cancer is a heterogeneous disease with over 100 recognized types that differ by organ site and cellular origins [...

Cancer Incidence and Etiology in the Active Duty Population of U.S. Military.

Introduction: As members of the military, all active duty service members (ADS) must meet physical fitness requirements and are provided with equal-access healthcare through the DoD. In addition, 92% of ADS are ≤40 years of age. Together, these characteristics suggest that ADS represent a healthy population that may have a low risk of cancer.

Eligibility, uptake and response to germline genetic testing in women with DCIS.

Background: Ductal carcinoma (DCIS) is a malignant, yet pre-invasive disease of the breast. While the majority of DCIS have low risk of recurrence, a subset of women with germline pathogenic variants (PV) in cancer predisposition genes are at increased risk for recurrence. Uptake of genetic testing and subsequent surgical intervention in women with DCIS has not been well-studied.

Influence of germline test results on surgical decision making in women with invasive breast cancer.

Background: While therapeutic mastectomy with contralateral prophylactic mastectomy (TM+CPM) and/or bilateral salpingo-oophorectomy (BSO) are recommended for women with pathogenic variants (PV) in some cancer predisposition genes, evidence for the utility of these surgeries for women with PV in other genes currently is insufficient. In conjunction, current guidelines recommend that clinical management should not be influenced by a return of a variant of uncertain significance (VUS). Return of germline test results may, however, influence surgical decision making regardless of current guidelines.

Relationship between Cigarette Smoking and Cancer Characteristics and Survival among Breast Cancer Patients.

Carcinogenic effects of tobacco smoke may affect breast tumorigenesis. To assess whether cigarette smoking is associated with breast cancer characteristics, we investigated the relationships between smoking, pathological characteristics, and outcomes in 2153 women diagnosed with breast cancer 2001-2016. Patients were classified as never, former, or current smokers at the time of diagnosis.

The DNA damage repair landscape in Black women with breast cancer.

Background: Estrogen receptor positive (ER+) breast cancer is one of the most commonly diagnosed malignancies in women irrespective of their race or ethnicity. While Black women with ER+ breast cancer are 42% more likely to die of their disease than White women, molecular mechanisms underlying this disparate outcome are understudied. Recent studies identify DNA damage repair (DDR) genes as a new class of endocrine therapy resistance driver that contributes to poor survival among ER+ breast cancer patients.

Effector Genes in as Potential Targets for Incorporating Blast Resistance in Wheat.

Wheat blast (WB), caused by pathotype, recently emerged as a destructive disease that threatens global wheat production. Because few sources of genetic resistance have been identified in wheat, genetic transformation of wheat with rice blast resistance genes could expand resistance to WB. We evaluated the presence/absence of homologs of rice blast effector genes in isolates with the aim of identifying avirulence genes in field populations whose cognate rice resistance genes could potentially confer resistance to WB.

Genetic testing in Non-Hispanic Black women with breast cancer treated within an equal-access healthcare system.

Purpose: Identification of women with hereditary forms of cancer allows for precision medicine approaches to improve survival. Non-Hispanic Black (NHB) women in the US general population are less likely to undergo genetic testing or utilize risk-reducing strategies. Whether these disparities exist within the equal-access US military healthcare system is not known.

Heritability of Low ER Staining/HER2-Breast Tumors: Are We Missing an Opportunity for Germline Testing?

In 2010, the genetic testing criteria was changed to allow women diagnosed ≤ 60 years old with triple negative breast cancer (TNBC) to undergo germline testing. In the same year, estrogen receptor (ER) positivity was defined as having ≥1% ER staining cells. While tumors with 1-10% ER staining cells and HER2 negative (HER2-) status share characteristics with TNBC, the utility of germline testing in women with ER low positive/HER2- (ERLP/HER2-) tumors is not well-understood.

Cancer Previvors in an Active Duty Service Women Population: An Opportunity for Prevention and Increased Force Readiness.

Background: The majority of active duty service women (ADS) are young, have access to healthcare, and meet fitness standards set by the U.S. military, suggesting that ADS represent a healthy population at low risk of cancer.

Frequency and spectrum of mutations across 94 cancer predisposition genes in African American women with invasive breast cancer.

African American women are at increased risk of being diagnosed at a young age and/or with triple negative breast cancer, both factors which are included in current guidelines for identifying women who may benefit from genetic testing. Commercial breast cancer predisposition genetic panels, based largely on data derived from women of European ancestry, may not capture the full spectrum of cancer predisposition genes associated with breast cancer in African American women. Between 2001 and 2018, 488 unselected African American women with invasive breast cancer enrolled in the Clinical Breast Care Project.

Constraints on Lorentz Invariance Violation from HAWC Observations of Gamma Rays above 100 TeV.

Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV.

Multiple Galactic Sources with Emission Above 56 TeV Detected by HAWC.

We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date.

Should Genetic Testing for Cancer Predisposition Be Standard-of-Care for Women with Invasive Breast Cancer? The Murtha Cancer Center Experience.

Currently, genetic testing is offered only to women diagnosed with breast cancer who meet a defined set of criteria and is not included as standard-of-care treatment at the time of diagnosis. Thus, a significant number of women diagnosed with breast cancer may miss the opportunity for precision medical treatment and risk management. The effects of eligibility, timing, and uptake of genetic testing were evaluated in a cohort of women with invasive breast cancer diagnosed between 2001-2018.