Faculty Bibliography

In this response to the editorial by J. J. Amon in Health and Human Rights (Amon, 2025), we reply to Dr. Amon's claims alleging methodological problems and "politicalization" associated with our peer-reviewed work, which was published in the Journal of Religion and Health (Schwartz et al., 2025) and in the Rambam Maimonides Medical Journal (Roth & Wald, 2025). Here, we offer our response, in which we provide additional details related to our informatics and statistical methodologies to refute claims raised in Amon's editorial, that our analyses were conducted in a non-standardized manner. We also explain the distinctions between the critique of Israeli governmental policies and anti-Zionism, which is a form of antisemitism, as clearly defined by the consensus-driven International Holocaust Remembrance Alliance (2016). Finally, we once again highlight the presence of the anti-Zionist form of antisemitism within medical communities and associated discourse.

PURPOSE/OBJECTIVE:The functional composition and diversity of the gut microbiome may affect breast cancer risk by modulation of systemic sex hormones. Gut bacteria with β-glucuronidase enzymatic activity may deconjugate estrogens, leading to increased estrogen reabsorption into the circulation thereby increasing breast cancer risk. We investigated the relationship between the gut bacterial microbiome and endogenous estrogens and related sex hormones in women with hormone receptor-positive breast cancer compared to healthy control women. The goal was to determine if the estrobolome (i.e., bacteria capable of modulating the body's circulated estrogen levels) was altered in those with breast cancer compared with controls. METHODS:In this prospective case-control study, postmenopausal women (n = 46) with newly diagnosed stage I-III estrogen and/or progesterone receptor-positive breast cancer were compared with healthy postmenopausal female controls (n = 22). Bacterial composition of the gut microbiome was analyzed by 16S rRNA gene sequencing from fecal specimens. Plasma and urine sex hormones were quantified using high-performance liquid chromatography/mass spectrometry. RESULTS:We found evidence that some β-glucuronidase positive bacteria were enriched in the breast cancer patients compared to healthy controls, whereas abundances of some β-glucuronidase negative bacteria were reduced. There was also a wide distribution of prevalence of β-glucuronidase positive taxa in both breast cancer subjects and healthy controls, as well as higher probability of breast cancer subjects having higher average β-glucuronidase levels. Significant differences were found in endogenous progesterone levels between the breast cancer patients and healthy controls. CONCLUSION/CONCLUSIONS:This pilot study showed differences in the gut microbiome and endogenous progesterone levels among postmenopausal women with hormone receptor-positive breast cancer compared with healthy controls. These interesting findings may have implications for breast cancer risk and prevention and warrant further exploration.

BACKGROUND:Toll-like receptor (TLR) agonists and radiation therapy hold promise for cancer immunotherapy. We conducted a phase I/II trial combining topical imiquimod (IMQ, a TLR-7 agonist) and local radiotherapy (RT) in patients with metastatic breast cancer accompanied by longitudinal transcriptional analysis of tumor biopsies. METHODS:The primary objective of the trial (NCT01421017) was to assess systemic responses by immune-related response criteria (irRC) after an 8-week cycle of topical IMQ and concurrent local RT (cohort 1). An amendment to the trial added two cohorts, both received one dose of cyclophosphamide (CTX) administered 1 week before study treatment initiation, IMQ/RT/CTX (cohort 2) and RT/CTX control (cohort 3). Cutaneous metastases were prospectively assigned to treatment with IMQ and RT (area A) or IMQ alone (area B). Secondary objectives were safety (Common Terminology Criteria for Adverse Events criteria) and local response in skin metastases. In all IMQ cohorts, tumors were biopsied before treatment and at 2 and 3 weeks. RESULTS:31 patients were enrolled (n=12, n=12, and n=7, in cohort 1, 2, and 3, respectively), with 4 out of 24 patients in the IMQ cohorts showing systemic tumor responses (two complete responses (CR) and two partial responses (PR)). No objective responses were observed in the seven patients enrolled in the control arm (RT alone). The treatment was well-tolerated, no grade 4-5 treatment-related adverse events occurred and grade 3 AEs were manageable (anemia, local pain, and local ulceration, n=1 each). Local objective responses were observed in 19/24 (9 CR and 10 PR) and 5/24 (5 PR) in areas treated with combined IMQ-RT and IMQ alone, respectively (p<0.001). All 24 patients treated with IMQ underwent serial biopsies, and 84 samples yielded sufficient material for transcriptional analyses. These revealed that the presence of a T-helper 1 functional orientation of the tumor microenvironment paralleled by the downregulation of DNA-repair genes was associated with CR after IMQ+RT, but not after IMQ alone. No post-treatment activation of immune-effector functions was observed in stable and progressing lesions. CONCLUSIONS:Our findings support the safety and clinical efficacy of combining topical IMQ with local RT for recurrent breast cancer, with evidence of local and occasional systemic antitumor activity. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT01421017.

Antisemitism has been rising for decades and worsened following the events of Oct 7, 2023. Although anecdotal evidence suggests that these trends extend into the US medical community, quantitative data have been lacking. To address this gap, we quantitated publications about antisemitism, analyzed social media posts from the accounts of 220,405 healthcare professionals, and disseminated a survey to members of Jewish medical associations. Publications and social media posts about antisemitism rose > fivefold, while posts promoting antisemitic stereotypes increased 2-fourfold. Most Jewish-identifying medical students and professionals (75.4%) reported exposure to antisemitism. Together, our results suggest that antisemitism is escalating within the US healthcare community.

Throughout history, Jewish people have long been recognized for their achievements in the world of medical science. For example, prior to the Holocaust, many outstanding physicians in Germany were Jewish. However, even in the 1930s, refugee European Jewish doctors faced significant barriers when they tried to escape and practice elsewhere because of long-standing prejudices and anti-Jewish quotas in medical schools and hospitals around the world. Eventually quotas fell, and the period after World War II once again saw a tremendous growth in numbers of Jews excelling in medicine internationally. Since the Hamas attack on Israel on October 7, 2023, there has been a resurgence of antisemitism worldwide. It is especially noticeable in the world of healthcare. This article evaluates and highlights examples of antisemitism in four countries by authors from each of these jurisdictions.

PURPOSE/OBJECTIVE:Although ongoing studies are assessing the efficacy of new systemic therapies for patients with triple negative breast cancer (TNBC), the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival. METHODS:We used our prospective patient registry to evaluate data from 2012 to 2023. We included patients who received SRS for TNBC-BM. A competing risk analysis was conducted to assess local and distant control. RESULTS:Forty-three patients with 262 tumors were included. The median overall survival (OS) was 16 months (95% CI 13-19 months). Predictors of increased OS after initial SRS include Breast GPA score > 1 (p < 0.001) and use of immunotherapy such as pembrolizumab (p = 0.011). The median time on immunotherapy was 8 months (IQR 4.4, 11.2). The median time to new CNS lesions after the first SRS treatment was 17 months (95% CI 12-22). The cumulative rate for development of new CNS metastases after initial SRS at 6 months, 1 year, and 2 years was 23%, 40%, and 70%, respectively. Thirty patients (70%) underwent multiple SRS treatments, with a median time of 5 months (95% CI 0.59-9.4 months) for the appearance of new CNS metastases after second SRS treatment. CONCLUSIONS:TNBC patients with BM can achieve longer survival than might have been previously anticipated with median survival now surpassing one year. The use of immunotherapy is associated with increased median OS of 23 months.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Median survival for all patients with breast cancer with brain metastases (BCBMs) has increased in the era of targeted therapy (TT) and with improved local control of intracranial tumors using stereotactic radiosurgery (SRS) and surgical resection. However, detailed characterization of the patients with long-term survival in the past 5 years remains sparse. The aim of this article is to characterize patients with BCBM who achieved long-term survival and identify factors associated with the uniquely better outcomes and to find predictors of mortality for patients with BCBM. METHODS:We reviewed 190 patients with breast cancer with 931 brain tumors receiving SRS who were followed at our institution with prospective data collection between 2012 and 2022. We analyzed clinical, molecular, and imaging data to assess relationship to outcomes and tumor control. RESULTS:The median overall survival from initial SRS and from breast cancer diagnosis was 25 months (95% CI 19-31 months) and 130 months (95% CI 100-160 months), respectively. Sixteen patients (17%) achieved long-term survival (survival ≥5 years from SRS), 9 of whom are still alive. Predictors of long-term survival included HER2+ status ( P = .041) and treatment with TT ( P = .046). A limited number of patients (11%) died of central nervous system (CNS) causes. A predictor of CNS-related death was the development of leptomeningeal disease after SRS ( P = .025), whereas predictors of non-CNS death included extracranial metastases at first SRS ( P = .017), triple-negative breast cancer ( P = .002), a Karnofsky Performance Status of <80 at first SRS ( P = .002), and active systemic disease at last follow-up ( P = .001). Only 13% of patients eventually needed whole brain radiotherapy. Among the long-term survivors, none died of CNS progression. CONCLUSION/CONCLUSIONS:Patients with BCBM can achieve long-term survival. The use of TT and HER2+ disease are associated with long-term survival. The primary cause of death was extracranial disease progression, and none of the patients living ≥5 years died of CNS-related disease.