Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics.

Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer-associated MDSCs using the widely studied mouse model based on the mouse mammary tumor virus (MMTV) promoter-driven expression of the polyomavirus middle T oncoprotein (MMTV-PyMT). To identify MDSCs in an unbiased manner, we used single-cell RNA sequencing to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice with wild-type controls. Our computational analysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturation trajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.

Therapeutic vaccines for breast cancer: Has the time finally come?

The ability to exploit the immune system as a weapon against cancer has revolutionised the treatment of cancer patients, especially through immune checkpoint inhibitors (ICIs). However, ICIs demonstrated a modest benefit in treating breast cancer (BC), with the exception of certain subsets of triple-negative BCs. An immune-suppressive tumour microenvironment (TME), typically present in BC, is an important factor in the poor response to immunotherapy. After almost two decades of poor clinical trial results, cancer vaccines (CVs), an active immunotherapy, have come back in the spotlight because of some technological advancements, ultimately boosted by coronavirus disease 2019 pandemic. In particular, neoantigens are emerging as the preferred targets for CVs, with gene-based and viral vector-based platforms in development. Moreover, lipid nanoparticles proved to be immunogenic and efficient delivery vehicles. Past clinical trials investigating CVs focused especially on the metastatic disease, where the TME is more likely compromised by inhibitory mechanisms. In this sense, favouring the use of CVs as monotherapy in premalignant or in the adjuvant setting and establishing combination treatments (i.e. CV plus ICI) in late-stage disease are promising strategies. This review provides a full overview of the past and current breast cancer vaccine landscape.

The potential role of abnormal angiotensin-converting enzyme 2 expression correlated with immune infiltration after SARS-CoV-2 infection in the prognosis of breast cancer.

The potential role of abnormal ACE2 expression after SARS-CoV-2 infection in the prognosis of breast cancer is still ambiguous. In this study, we analyzed ACE2 changes in breast cancer and studied the correlation between ACE2 and the prognosis and further analyzed the relationship between immune infiltration and the prognosis of different breast cancer subtypes. Finally, we inferred the prognosis of breast cancer patients after SARS-CoV-2 infection. We found that ACE2 expression decreased significantly in breast cancer, except for basal-like subtype. Decreased ACE2 expression level was correlated with abnormal immune infiltration and poorer prognosis of luminal B breast cancer (RFS: HR 0.76, 95%CI=0.63-0.92, p=0.005; DMFS: HR 0.70, 95%CI=0.49-1.00, p=0.046). The expression of ACE2 was strongly positively correlated with the immune infiltration level of CD8+ T cell (r=0.184, p<0.001), CD4+ T cell (r=0.104, p=0.02) and neutrophils (r=0.101, p=0.02). ACE2 expression level in the luminal subtype was positively correlated with CD8A and CD8B markers in CD8+ T cells, and CEACAM3, S100A12 in neutrophils. In conclusion, breast tumor tissues might undergo a further decrease in the expression level of ACE2 after SARS-CoV-2 infection, which could contribute to further deterioration of immune infiltration and worsen the prognosis of luminal B breast cancer after SARS-CoV-2 infection.

Prognostic and immunological value of ATP6AP1 in breast cancer: implications for SARS-CoV-2.

Abnormal ATPase H+ Transporting Accessory Protein 1 (ATP6AP1) expression may promote carcinogenesis. We investigated the association of ATP6AP1 with breast cancer (BC) and COVID-19. The Oncomine, Gene Expression Profiling Interactive Analysis, Human Protein Atlas and Kaplan-Meier plotter databases were used to evaluate the expression and prognostic value of ATP6AP1 in BC. ATP6AP1 was upregulated in BC tissues, and higher ATP6AP1 expression was associated with poorer outcomes. Data from the Tumor Immune Estimation Resource, Tumor-Immune System Interaction Database and Kaplan-Meier plotter indicated that ATP6AP1 expression correlated with immune infiltration, and that its prognostic effects in BC depended on tumor-infiltrating immune cell subtype levels. Multiple databases were used to evaluate the association of ATP6AP1 with clinicopathological factors, assess the mutation and methylation of ATP6AP1, and analyze gene co-expression and enrichment. The ATP6AP1 promoter was hypomethylated in BC tissues and differentially methylated between different disease stages and subtypes. Data from the Gene Expression Omnibus indicated that ATP6AP1 levels in certain cell types were reduced after SARS-CoV-2 infections. Ultimately, higher ATP6AP1 expression was associated with a poorer prognosis and with higher or lower infiltration of particular immune cells in BC. BC patients may be particularly susceptible to SARS-CoV-2 infections, which may alter their prognoses.

Impact of the COVID-19 pandemic on health care activities at a Uruguayan mastology unit.

PURPOSE: Health emergency due to COVID-19 started in Uruguay on March 13, 2020; our mastology unit tried to ensure adequate oncological care, and protect patients from the virus infection and complications. OBJECTIVE: To assess the health care activities in the "peak" of the pandemic during 3 months. MATERIALS AND METHODS: we collected data from the electronic health record. RESULTS: There were a total of 293 medical appointments from 131 patients (221 face-to-face), that decreased by 16.7% compared to the same period in 2019 (352 appointments). The medical appointments were scheduled to evaluate the continuity of systemic treatment or modifications (95 patients; 72.5%), follow-up (17; 12.9%), first-time consultation (12; 9.1%), and assess paraclinical studies (7; 5.3%). The patients were on hormone therapy (81 patients; 74%), chemotherapy (CT) (21; 19%), and anti-HER2 therapies (9; 8%). New twenty treatments were initiated. Of the 14 patients that were on adjuvant/neoadjuvant CT, 9 (64.3%) continued with the same regimen with the addition of prophylactic granulocyte-colony-stimulating factors (G-CSF), and 5 (35.7%), who were receiving weekly paclitaxel, continued the treatment with no changes. Of the seven patients that were on palliative CT, 2 (28.5%) continued the treatment with the addition of G-CSF, 3 (42.8%) continued with weekly capecitabine or paclitaxel with no treatment changes, and 2 (28.5%) changed their treatment regimen (a less myelosuppressive regimen was selected for one and due to progression of the disease in the other patient). The ninety patients who were receiving adjuvant, neoadjuvant, or palliative criteria hormone therapy and/or anti-HER2 therapies, continued the treatment with no changes. CONCLUSIONS: The evidence suggests that, although medical appointments decreased by approximately 17%, we could maintain healthcare activities, continued most of the treatments while the most modified was CT with G-CSF to avoid myelosuppression.

Emerging Immunotherapies against Novel Molecular Targets in Breast Cancer.

Immunotherapy is a highly emerging form of breast cancer therapy that enables clinicians to target cancers with specific receptor expression profiles. Two popular immunotherapeutic approaches involve chimeric antigen receptor-T cells (CAR-T) and bispecific antibodies (BsAb). Briefly mentioned in this review as well is the mRNA vaccine technology recently popularized by the COVID-19 vaccine. These forms of immunotherapy can highly select for the tumor target of interest to generate specific tumor lysis. Along with improvements in CAR-T, bispecific antibody engineering, and therapeutic administration, much research has been done on novel molecular targets that can especially be useful for triple-negative breast cancer (TNBC) immunotherapy. Combining emerging immunotherapeutics with tumor marker discovery sets the stage for highly targeted immunotherapy to be the future of cancer treatments. This review highlights the principles of CAR-T and BsAb therapy, improvements in CAR and BsAb engineering, and recently identified human breast cancer markers in the context of in vitro or in vivo CAR-T or BsAb treatment.

COVID-19 Pandemic Stressors and Psychological Symptoms in Breast Cancer Patients.

BACKGROUND: The current Coronavirus disease 2019 (COVID-19) pandemic is a highly stressful event that may lead to significant psychological symptoms, particularly in cancer patients who are at a greater risk of contracting viruses. This study examined the frequency of stressors experienced in relation to the ongoing coronavirus pandemic and its relationship with psychological symptoms (i.e., anxiety, depression, insomnia, fear of cancer recurrence) in breast cancer patients. METHODS: Thirty-six women diagnosed with a non-metastatic breast cancer completed the Insomnia Severity Index, the Hospital Anxiety and Depression Scale, the severity subscale of the Fear of Cancer Recurrence Inventory, and the COVID-19 Stressors Questionnaire developed by our research team. Participants either completed the questionnaires during (30.6%) or after (69.4%) their chemotherapy treatment. RESULTS: Results revealed that most of the participants (63.9%) have experienced at least one stressor related to the COVID-19 pandemic (one: 27.8%, two: 22.2%, three: 11.1%). The most frequently reported stressor was increased responsibilities at home (33.3%). Higher levels of concerns related to the experienced stressors were significantly correlated with higher levels of anxiety, depressive symptoms, insomnia, and fear of cancer recurrence, rs(32) = 0.36 to 0.59, all ps < 0.05. CONCLUSIONS: Cancer patients experience a significant number of stressors related to the COVID-19 pandemic, which are associated with increased psychological symptoms. These results contribute to a better understanding of the psychological consequences of a global pandemic in the context of cancer and they highlight the need to better support patients during such a challenging time.

COVID-19: a potential driver of immune-mediated breast cancer recurrence?

Severe coronavirus disease 2019 (COVID-19) causes a hyperactivation of immune cells, resulting in lung inflammation. Recent studies showed that COVID-19 induces the production of factors previously implicated in the reawakening of dormant breast cancer cells such as neutrophil extracellular traps (NETs). The presence of NETs and of a pro-inflammatory microenvironment may therefore promote breast cancer reactivation, increasing the risk of pulmonary metastasis. Further studies will be required to confirm the link between COVID-19 and cancer recurrence. However, an increased awareness on the potential risks for breast cancer patients with COVID-19 may lead to improved treatment strategies to prevent metastatic relapse.

Patient-reported Outcomes of Patients With Breast Cancer During the COVID-19 Outbreak in the Epicenter of China: A Cross-sectional Survey Study.

INTRODUCTION: We aimed to analyze the psychological status in patients with breast cancer (BC) in the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. PATIENTS AND METHODS: A total of 658 individuals were recruited from multiple BC centers in Hubei Province. Online questionnaires were conducted, and these included demographic information, clinical features, and 4 patient-reported outcome scales (Generalized Anxiety Disorder Questionnaire [GAD-7], Patient Health Questionnaire [PHQ-9], Insomnia Severity Index [ISI], and Impact of Events Scale-Revised [IES-R]). Multivariable logistic regression analysis was designed to identify potential factors on mental health outcomes. RESULTS: Questionnaires were collected from February 16, 2020 to February 19, 2020, the peak time point of the COVID-19 outbreak in China. Of patients with BC, 46.2% had to modify planned necessary anti-cancer treatment during the outbreak. Severe anxiety and severe depression were reported by 8.9% and 9.3% of patients, respectively. Severe distress and insomnia were reported by 20.8% and 4.0% of patients, respectively. Multivariable logistic regression analysis demonstrated poor general condition, shorter duration after BC diagnosis, aggressive BC molecular subtypes, and close contact with patients with COVID-19 as independent factors associated with anxiety. Poor general condition and central venous catheter flushing delay were factors that were independently associated with depression. In terms of insomnia, poor generation condition was the only associated independent factor. Poor physical condition and treatment discontinuation were underlying risk factors for distress based on multivariable analysis. CONCLUSION: High rates of anxiety, depression, distress, and insomnia were observed in patients with BC during the COVID-19 outbreak. Special attention should be paid to the psychological status of patients with BC, especially those with poor general condition, treatment discontinuation, aggressive molecular subtypes, and metastatic BC.