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1.
Essays Biochem ; 65(6): 1025-1038, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1334002

ABSTRACT

COVID-19 symptoms and mortality are largely due to its devastating effects in the lungs. The disease is caused by the SARS (Severe Acute Respiratory Syndrome)-CoV-2 coronavirus, which requires host cell proteins such as ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) for infection of lung epithelia. The expression and function of the steroid hormone receptor family is important in many aspects that impact on COVID-19 effects in the lung - notably lung development and function, the immune system, and expression of TMPRSS2 and ACE2. This review provides a brief summary of current knowledge on the roles of the steroid hormone receptors [androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), mineralocorticoid receptor (MR) and oestrogen receptor (ER)] in the lung, their effects on host cell proteins that facilitate SARS-CoV-2 uptake, and provides a snapshot of current clinical trials investigating the use of steroid receptor (SR) ligands to treat COVID-19.


Subject(s)
COVID-19/metabolism , Lung/metabolism , Lung/virology , Receptors, Steroid/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Female , Hormone Antagonists/therapeutic use , Humans , Immunomodulation , Male , Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Receptors, Glucocorticoid/metabolism , Receptors, Mineralocorticoid/metabolism , Receptors, Progesterone/metabolism , SARS-CoV-2 , Serine Endopeptidases/metabolism , Sex Factors , COVID-19 Drug Treatment
2.
Curr Opin Obstet Gynecol ; 33(1): 53-58, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1066445

ABSTRACT

PURPOSE OF REVIEW: The present review summarizes recent original publications addressing the topic of risk-adapted adjuvant therapy in early breast cancer (EBC). As neoadjuvant therapy has become a standard for triple negative and HER2+ EBC, it focusses on luminal EBC. RECENT FINDINGS: Gene expression assays have become standard of care in luminal EBC, at least for patients with node negative disease. Two prospective randomized clinical trials, TAILORx (Oncotype DX) and MINDACT (MammaPrint) have presented additional analyses underlining the clinical utility of the tests. In times of COVID-19, immunohistochemically determined ER, PR, and Ki67 and early Ki67 response to endocrine therapy can be used to safely allocate patients for preoperative endocrine therapy and delay surgeries if resources are scarce. In patients with luminal high-risk disease, adding a CDK 4/6 inhibitor (abemaciclib) improves patient outcome already after short-term follow-up. SUMMARY: Determination of recurrence risk will remain important in luminal EBC for optimal therapy decisions. In the future, risk-adapted treatment concepts will include decision making for chemotherapy but also for endocrine-based approaches.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , COVID-19/epidemiology , Protein Kinase Inhibitors/therapeutic use , Aminopyridines/therapeutic use , Benzimidazoles/therapeutic use , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Gene Expression Profiling , Humans , Ki-67 Antigen/metabolism , Neoadjuvant Therapy , Piperazines/therapeutic use , Pyridines/therapeutic use , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Risk Assessment , SARS-CoV-2
3.
J Exp Clin Cancer Res ; 39(1): 171, 2020 Aug 27.
Article in English | MEDLINE | ID: covidwho-733038

ABSTRACT

The Covid-19 pandemic has challenged hard the national health systems worldwide. According to the national policy issued in March 2020 in response to the evolving Covid-19 pandemic, several hospitals were re-configured as Covid-19 centers and elective surgery procedures were rescheduled according to the most recent recommendations. In addition, Covid-19 protected cancer hubs were established, including the Regina Elena National Cancer Institute of Rome, Central Italy. At our Institute, the Breast Surgery Department continued working under the sign of a multidisciplinary approach. The number of professional figures involved in case evaluation was reduced to a minimum and interactions took place in the full respect of the required safety measures. Treatments for benign disease, pure prophylactic surgery and elective reconstructive procedures were all postponed and priority was assigned to the histologically-proven malignant breast tumors and highly suspicious lesions. From March 15th though April 30th 2020, we treated a total of 79 patients. This number is fully consistent with the average quantitative standards reached by our Department under ordinary circumstances. Patients were mostly discharged the day after surgery and none was readmitted due to surgery-related late complications. More generally, post-operative complications rates were unexpectedly low, particularly in light of the relatively high number of reconstructive procedures performed in this emergency situation. A strict follow up was performed based on the close contact with the surgical staff by telephone, messaging apps and telemedicine.Patients ascertainment for their Covid-19 status prior to hospital admission and hospital discharge allowed to maintain the "no-Covid-19" status at our Institution. In addition, during the aforementioned time window, none of the care providers developed SARS-CoV-2 infection or disease, as shown by the results of anti-SARS-CoV-2 immunoglobulin M and G profiling. In conclusions, elective breast cancer surgery procedures were successfully performed in a lockdown situation due to a novel viral pandemic. The well-coordinated regional and hospital efforts in terms of medical resource re-allocation and definition of clinical priorities allowed to maintain high quality standards of breast cancer care while ensuring safety to the cancer patients and care providers involved.


Subject(s)
Betacoronavirus/isolation & purification , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/surgery , Coronavirus Infections/prevention & control , Mastectomy/statistics & numerical data , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Practice Patterns, Physicians'/standards , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Breast Neoplasms/virology , COVID-19 , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/virology , Carcinoma, Lobular/pathology , Carcinoma, Lobular/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , Follow-Up Studies , Humans , Italy/epidemiology , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , SARS-CoV-2
4.
Breast Cancer Res Treat ; 184(2): 637-647, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-716322

ABSTRACT

PURPOSE: The COVID-19 pandemic has impacted early breast cancer (EBC) treatment worldwide. This study analyzed how Brazilian breast specialists are managing EBC. METHODS: An electronic survey was conducted with members of the Brazilian Society of Breast Cancer Specialists (SBM) between April 30 and May 11, 2020. Bivariate analysis was used to describe changes in how specialists managed EBC at the beginning and during the pandemic, according to breast cancer subtype and oncoplastic surgery. RESULTS: The response rate was 34.4% (503/1462 specialists). Most of the respondents (324; 64.4%) lived in a state capital city, were board-certified as breast specialists (395; 78.5%) and either worked in an academic institute or one associated with breast cancer treatment (390; 77.5%). The best response rate was from the southeast of the country (240; 47.7%) followed by the northeast (128; 25.4%). At the beginning of the pandemic, 43% changed their management approach. As the outbreak progressed, this proportion increased to 69.8% (p < 0.001). The southeast of the country (p = 0.005) and the state capital cities (p < 0.001) were associated with changes at the beginning of the pandemic, while being female (p = 0.001) was associated with changes during the pandemic. For hormone receptor-positive tumors with the best prognosis (Ki-67 < 20%), 47.9% and 17.7% of specialists would recommend neoadjuvant endocrine therapy for postmenopausal and premenopausal women, respectively. For tumors with poorer prognosis (Ki-67 > 30%), 34% and 10.9% would recommend it for postmenopausal and premenopausal women, respectively. Menopausal status significantly affected whether the specialists changed their approach (p < 0.00001). For tumors ≥ 1.0 cm, 42.9% of respondents would recommend neoadjuvant systemic therapy for triple-negative tumors and 39.6% for HER2 + tumors. Overall, 63.4% would recommend immediate total breast reconstruction, while only 3.4% would recommend autologous reconstruction. In breast-conserving surgery, 75% would recommend partial breast reconstruction; however, 54.1% would contraindicate mammoplasty. Furthermore, 84.9% of respondents would not recommend prophylactic mastectomy in cases of BRCA mutation. CONCLUSIONS: Important changes occurred in EBC treatment, particularly for hormone receptor-positive tumors, as the outbreak progressed in each region. Systematic monitoring could assure appropriate breast cancer treatment, mitigating the impact of the pandemic.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/therapy , Coronavirus Infections , Mammaplasty , Mastectomy , Neoadjuvant Therapy , Pandemics , Pneumonia, Viral , Adult , Betacoronavirus , Brazil , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , COVID-19 , Delivery of Health Care , Disease Management , Female , Genes, BRCA1 , Genes, BRCA2 , Humans , Male , Mastectomy, Segmental , Middle Aged , Patient Selection , Postmenopause , Premenopause , Prophylactic Mastectomy , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , SARS-CoV-2 , Societies, Medical , Surveys and Questionnaires , Tumor Burden
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