Estrogen and Estrogen Receptor Modulators: Potential Therapeutic Strategies for COVID-19 and Breast Cancer

Hu, Shuying; Yin, Feiying; Nie, Litao; Qin, Jian; Chen, Jian

doi:10.3389/fendo.2022.829879

Cited by 6 publications

(6 citation statements)

References 83 publications

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“…21,22 Sex-related differences in susceptibility to SARS-CoV-2 infection have also been hypothesized because of the possible immune-enhancing effects of estrogens, as documented by the correlation between immune-cell infiltration and estrogen receptor level in normal and SARS-CoV-2-infected human tissues, alongside the estrogen-inducted decline in angiotensin-converting enzyme 2 activity. 23,24 Nevertheless, despite 60% of the patients in our study having a hormone receptorpositive tumor, only approximately 30% of those on active oncologic treatment at COVID-19 diagnosis were receiving endocrine therapy with or without CDK 4/6 inhibitors. In addition, 31.5% of the patients had $ 2 comorbidities known to negatively influence COVID-19 outcomes, particularly hypertension, cardiovascular diseases, and pulmonary diseases.…”

Section: Discussionmentioning

confidence: 73%

Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer

Tagliamento

Gennari

Lambertini

et al. 2023

JCO

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PURPOSE Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. METHODS We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974 ). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis. RESULTS By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor–positive, 25.2% (n = 131) human epidermal growth factor receptor 2–positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19–specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls. CONCLUSION Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

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Section: Discussionmentioning

confidence: 73%

Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer

Tagliamento

Gennari

Lambertini

et al. 2023

JCO

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“…Moreover, some research suggests that estrogen may play a role in regulating immune responses because it enhances antiviral immunity. 43 These findings have the potential to guide the development of gender-specific treatments and aid future studies aimed at understanding the pathogenesis of COVID-19. However, the study has some limitations, such as a small sample size, that may restrict the generalizability of the findings.…”

Section: Discussionmentioning

confidence: 96%

Association between COVID-19 Severity and Expression of Viral Nucleic Acid Sensor Genes in Peripheral Blood Mononuclear Cells and Nasopharyngeal Epithelial Cells

Ghoreshi,

Behboudi,

Askarpour

et al. 2024

The American Journal of Tropical Medicine and Hygiene

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This study examined expression of key viral nucleic acid sensor genes MDA5, ZBP1, and AIM2 in nasopharyngeal epithelial cells and peripheral blood mononuclear cells (PBMCs) obtained from 153 COVID-19 patients across a spectrum of disease severity (mild, severe, and critical) and 42 healthy controls. Quantitative reverse transcription polymerase chain reaction was used to quantify and compare sensor transcript levels. The COVID-19 cohort had a mean age of 53.6 years. All three sensor genes including MDA5 (3.2-fold), ZBP1 (5.1-fold), and AIM2 (4.7-fold) exhibited significantly higher messenger RNA expression in both nasopharyngeal and PBMC samples from infected patients compared with healthy controls. Furthermore, sensor transcript upregulation positively correlated with escalating disease severity. During early stages, ZBP1 and AIM2 transcripts were selectively elevated within the nasopharyngeal compartment, suggesting a localized antiviral response. Whereas later during critical disease stages, ZBP1 and AIM2 levels became preferentially heightened within circulating PBMCs, indicating systemic immune cell activation. By comparison, MDA5 elevation manifested within nasopharyngeal epithelial cells during both early- and late-phase infection. Intriguingly, males displayed higher ZBP1 and AIM2 expression compared with females, whereas MDA5 transcript levels were conversely higher among females. Overall, escalation of these key viral sensor genes appears closely linked to COVID-19 progression, with initial nasal mucosal upregulation transitioning to widespread blood cell activation in severe systemic disease. These patterns of sensor expression suggest frontline immunological efforts to constrain early viral invasion and combat severe late-stage COVID-19 illness through innate detection of replicating SARS-CoV-2.

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“…Breast and ovarian cancers showed a similar pattern of relative risk reduction especially with later waves, which was more pronounced for BC patients. One cannot exclude the possibility that long-term usage of selective estrogen receptors (SERMs) has played a protective role in BC survivors suffering from COVID-19 [ 26 , 27 , 28 ]. On the other hand, endometrial and cervical cancers did not show a reduced RR of death during waves.…”

Section: Discussionmentioning

confidence: 99%

Relative Risk of Death in Bulgarian Cancer Patients during the Initial Waves of the COVID-19 Pandemic

Shivarov,

Grigorova,

Yordanov

2023

Healthcare

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Background: The COVID-19 pandemic has led to millions of documented deaths worldwide, with diverse distribution among countries. Surprisingly, Bulgaria, a middle-income European Union member state, ranked highest in COVID-19 mortality. This study aims to assess whether Bulgarian cancer patients experienced a higher relative risk (RR) of death compared to the general Bulgarian population during the pandemic. Materials and Methods: Data from the Bulgarian National Statistical Institute and the Bulgarian National Cancer Registry were analyzed to estimate monthly RR of death in cancer patients compared to the general population before and during the first two years of the pandemic. The impact of the COVID-19 waves and predominant SARS-CoV-2 variants on RR was evaluated on various cancer types and age groups using a multiple linear regression approach. Results: During the COVID-19 waves, both the general population and cancer patients experienced a significant increase in mortality rates. Surprisingly, the RR of death in cancer patients was lower during pandemic waves. The results from the statistical modeling revealed a significant association between the COVID-19 waves and reduced RR for all cancer patients. Notably, the effect was more pronounced during waves associated with the Alpha and Delta variants. The results also showed varying impacts of the COVID-19 waves on RR when we analyzed subsamples of data grouped depending on the cancer type, age and sex. Conclusions: Despite increased overall mortality in Bulgarian cancer patients during the pandemic, the RR of death was lower compared to the Bulgarian general population, indicating that protective measures were relatively effective in this vulnerable group. This study underscores the importance of implementing and encouraging preventive measures, especially in cancer patients, to mitigate the impact of future viral pandemics and reduce excess mortality.

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Estrogen and Estrogen Receptor Modulators: Potential Therapeutic Strategies for COVID-19 and Breast Cancer

Cited by 6 publications

References 83 publications

Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer

Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer

Association between COVID-19 Severity and Expression of Viral Nucleic Acid Sensor Genes in Peripheral Blood Mononuclear Cells and Nasopharyngeal Epithelial Cells

Relative Risk of Death in Bulgarian Cancer Patients during the Initial Waves of the COVID-19 Pandemic

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