Validation of liquid biopsy for ESR1-mutation analysis in hormone-sensitive breast cancer: a pooled meta-analysis.

Several retrospective and prospective studies have shown that genomic alterations in Estrogen-receptor one (ESR1) can be characterized not only in tissue samples but also by sequencing circulating tumor DNA (ctDNA) in liquid biopsy. Therefore, liquid biopsy is a potential noninvasive surrogate for tissue biopsy. This meta-analysis was designed to compare the prevalence of ESR 1 mutation detected with liquid biopsy and tissue biopsy. A pooled meta-analysis of studies published between 1 January 2007 and 1 March 2021 was conducted regarding the methodologies used for ESR1 mutation analysis. Liquid biopsy is a valid, inexpensive, and attractive noninvasive alternative to tumor biopsies for the identification of ESR1 mutations. Liquid biopsy for ESR 1 analysis would facilitate regular testing, allowing monitoring of the sensitivity to ET and guiding treatment strategies.

Impact of the Sinopharm's BBIBP-CorV vaccine in preventing hospital admissions and death in infected vaccinees: Results from a retrospective study in the emirate of Abu Dhabi, United Arab Emirates (UAE).

BACKGROUND: This is a community-based, retrospective, observational study conducted to determine effectiveness of the BBIBP-CorV inactivated vaccine in the real-world setting against hospital admissions and death. STUDY DESIGN: Study participants were selected from 214,940 PCR-positive cases of COVID-19 reported to the Department of Health, Abu Dhabi Emirate, United Arab Emirates (UAE) between September 01, 2020 and May 1, 2021. Of these, 176,640 individuals were included in the study who were aged ≥ 15 years with confirmed COVID-19 positive status who had records linked to their vaccination status. Those with incomplete or missing records were excluded (n = 38,300). Study participants were divided into three groups depending upon their vaccination status: fully vaccinated (two doses), partially vaccinated (single dose), and non-vaccinated. Study outcomes included COVID-19-related admissions to hospital general and critical care wards and death. Vaccine effectiveness for each outcome was based on the incidence density per 1000 person-years. RESULTS: The fully-, partially- and non-vaccinated groups included 62,931, 21,768 and 91,941 individuals, respectively. Based on the incidence rate ratios, the vaccine effectiveness in fully vaccinated individuals was 80%, 92%, and 97% in preventing COVID-19-related hospital admissions, critical care admissions, and death, respectively, when compared to the non-vaccinated group. No protection was observed for critical and non-critical care hospital admissions for the partially vaccinated group, while some protection against death was apparent, although statistically insignificant. CONCLUSIONS: In a COVID-19 pandemic, use of the Sinopharm BBIBP-CorV inactivated vaccine is effective in preventing severe disease and death in a two-dose regimen. Lack of protection with the single dose may be explained by insufficient seroconversion and/or neutralizing antibody responses, behavioral factors (i.e., false sense of protection), and/or other biological factors (emergence of variants, possibility of reinfection, duration of vaccine protection, etc.).

Model-based evaluation of the COVID-19 epidemiological impact on international visitors during Expo 2020.

The impact of the COVID-19 pandemic on large events has been substantial. In this work, an evaluation of the potential impact of international arrivals due to Expo 2020 in terms of potential COVID-19 infections from October 1st, 2021, until the end of April 2022 in the United Arab Emirates is presented. Our simulation results indicate that: (i) the vaccination status of the visitors appears to have a small impact on cases, this is expected as the small numbers of temporary visitors with respect to the total population contribute little to the herd immunity status; and (ii) the number of infected arrivals is the major factor of impact potentially causing a surge in cases countrywide with the subsequent hospitalisations and fatalities. These results indicate that the prevention of infected arrivals should take all precedence priority to mitigate the impact of international visitors with their vaccination status being of less relevance.

Mycosis fungoides of the vulva.

Mycosis fungoides (MF) is an indolent form of non-Hodgkin lymphoma and the most common type of primary cutaneous T-cell lymphoma. The overall incidence of MF is approximately 4 per 1 million. Involvement of the vulva by MF is extremely rare, with only seven reported cases in the literature. At the vulva, it is mainly a metastatic lesion and rarely a primary malignancy. We describe a case of vulvar MF and discuss the previous cases. The presentation can easily be confused with benign skin disorders. A vulvar lesion can reflect a systemic disease. When a patient consults for a vulvar lesion it is therefore important not only to look at the vulva but also to examine her in and ask general questions. In a patient with a vulvar mass and cutaneous lesions on other locations MF should be considered in the differential diagnosis.

The association between type of endocrine therapy and development of estrogen receptor-1 mutation(s) in patients with hormone-sensitive advanced breast cancer: A systematic review and meta-analysis of randomized and non-randomized trials.

BACKGROUND: Breast cancer has, due to its high incidence, the highest mortality of cancer in women. The most common molecular type of breast cancer is the luminal subtype, which expresses estrogen and progesterone receptors and is typically treated with surgery and adjuvant endocrine therapy (ET). Estrogen receptor alpha (ERα), encoded by the estrogen receptor-1 (ESR1) gene, is expressed in approximately 70% of all breast cancers, and ET represents a major treatment modality in ERα-positive cancers. However, resistance to different ET evolves frequently, leading to disease progression or recurrence in ER+ breast cancer. Acquired mutations in the Ligand Binding Domain (LBD) of the ERα referred as ESR1 mutations; could be selected by ET itself leading to resistance over the course of ET therapy. OBJECTIVE: The goal of this review is to estimate the effect of Aromatase Inhibitors (AIs), Tamoxifen (TAM) and Fulvestrant (FUL) on the development of ESR1 mutations in hormone-sensitive advanced breast cancer. METHODS: A systematic review of qualitative studies published between January 1st, 2007 and March 1st, 2019 was conducted using the PubMed and Thomas Reuters Web of Science databases. Search terms included ESR1 mutations, estrogen receptor, breast cancer, recurrent, metastatic disease, aromatase inhibitors, fulvestrant and tamoxifen. Only full-text studies in English concerning the development of ESR1 mutations and their outcomes on disease progression were included. Selection of studies was performed using predefined data fields, taking study quality indicators into consideration. Inclusion criteria of the study populations were: Ghoncheh et al. (2016) [1] female patients above 18 years; Nielsen et al. (2011) [2] Estrogen-receptor positive (ER+) breast cancer in the advanced setting; Reinert et al. (2017) [3] previous exposure to endocrine therapy including SERDs (preferably Fulvestrant), SERMs (preferably Tamoxifen) or Aromatase Inhibitors. RESULTS: The current review enrolled 16 articles, including 4 multicentre double blinded RCTs and 12 cohorts and comprising a total of 2632 patients. The overall incidence rate of the ESR1 mutation was 24% (95% CI: 18%-31%). We observed that D538G was the most frequent ESR1 mutation. Several studies showed that prior endocrine therapy (AIs, TAM, FUL) could result in an ESR1 mutation and therapy resistance leading to disease progression or recurrence. Different mechanisms had been implied to explain the underlying ET resistance. One of the key findings of this work is the significant difference in ESR1 mutation incidence between patients with and without AI therapy (OR: 9.34, 95% CI: 3.28-26.62, P ≤.001). CONCLUSION: ESR1 mutations are not uncommon phenomenon in patients with hormone-sensitive advanced breast cancer. There is a significant higher incidence rate of ESR1 mutations in patients with previous AI-containing therapeutic regimens, compared to those who received non-AI containing regimes. These ESR1 mutations could lead to the development of complete endocrine resistance to AI, whereas only partial resistance is seen in case of TAM or FUL.

The prevalence of estrogen receptor-1 mutation in advanced breast cancer: The estrogen receptor one study (EROS1).

BACKGROUND: Breast cancer has, due its high incidence, the highest mortality of cancer in women. The most common molecular variety of breast cancer is luminal subtype that expresses estrogen and progesterone receptors. Estrogen receptor alpha (ERα), encoded by the estrogen receptor1 (ESR1) gene, is expressed in approximately 70% of all breast cancers, and hormonal therapy represents a major treatment modality in all stages of ER positive breast cancers. Acquired mutations in the ligand-binding domain (LBD) of ERα, referred as ESR1 mutation, result in resistance to different endocrine therapies leading to disease progression or recurrence. Recent studies reviled that these ESR1 mutations lead to constitutive activity of the estrogen receptor ER, meaning that the receptor is active in absence of its ligand conferring resistance against endocrine therapy and tumor growth. Published studies have not yet been able to determine the exact prevalence rate of ESR1 mutations, but set the outer boundaries between 11-55%. PURPOSE: The goal of the present study is to determine the frequency rate of ESR1 mutations in ER positive recurrent breast cancer by using digital droplet PCR (ddPCR) technique. MATERIALS AND METHODS: This retrospective study was conducted in the Multidisciplinary Breast Clinic of Antwerp University Hospital. The seven most common ESR1mutations (c.1138G>C (p. (E380Q)), c.1610A>G (p.(Y537C)), c.1613A>G (p.(p.D538G)), c.1607T>G (p.(L536R)), c.1387T>C (p.S463R)), c.16410A>C (p.(Y537S)), c.609T>A (p.(Y537N)) were assessed in available baseline plasma samples of 21 patients with ER positive recurrent breast cancer. Inclusion criteria for study participation were: female, age above 18 years, ER positive breast cancer, 5years adjuvant hormonal therapy of primary disease, and disease recurrence or metastasis during or after stop of endocrine therapy. ESR1 mutations were analyzed in cell-free DNA (cfDNA) by using digital droplet PCR (ddPCR). RESULTS: cfDNA was obtained from 21 patients with recurrent breast cancer. ESR1 mutations were found in 4/21 (19%; 95% CI, 5%-42%). The test sensitivity was lower than the targeted value <0.1% in 29% of patients (6/21). No significant statistical difference in baseline clinical characteristics was observed in patients with wild-type and mutant ER (p>0.05). Adjuvant endocrine therapy for primary disease was Tamoxifen (TAM) for 57% of patients (12 of 21) of whom 8 patients had received aromatase inhibitor (AI) after two years, while 43% of patients (9 of 21) had received AI as first line adjuvant hormonal therapy. All the patients had received aromatase inhibitor AI therapy in first or second line therapy with initially a variable period of good response. CONCLUSION: ESR1 mutation analysis could be determined in archived plasma samples using simple non-invasive methods. In the future, screening for mutation status could improve the therapeutic strategies in controlling ER signaling before the occurrence of wide spread disease metastasis.

The predictive value of sentinel node biopsy in early breast cancer after neo-adjuvant chemotherapy: A prospective study.

OBJECTIVE: A sentinel Node (SN) has replaced axillary lymph node dissection (ALND) in patients with clinically node negative axilla (cN0). SN after Neo-adjuvant chemotherapy (NACT) is feasible but not accurate in clinically node positive (cN1-3) patients. The goal of this study is to determine the negative predictive value (NPV) of SN in cN0 breast cancer after NACT. A secondary endpoint is to determine if ALND can be avoided after NACT regardless of the pre-treatment clinical staging of the axilla, in case of a normalization of the 18F-fluoro-2-deoxy-glucose positron emission tomography scan (PET-CT scan). DESIGN: A single institution prospective study regarding the negative predictive value of the SN in breast cancer after NACT was conducted in the Multidisciplinary Breast Clinic of the Antwerp University Hospital from 29/03/2010 until 01/12/2015 (Study number: B30020108368). Inclusion criteria for study participation were: breast cancer, age above 18 years, female, tumor stages T2-T4 N0-3 or T1N1-N3. All patients were staged by a mammography, ultrasound of the axilla, MRI of the breast, PET-CT scan and bone scintigraphy. They received NACT consisting of 12 cycles of paclitaxel or 4 cycles of docetaxel followed by dose dense doxorubicin or epirubicin/cyclofosfamide or vice versa as a standard initial treatment. After 6 weeks, a PET-CT scan was performed for early tumour response evaluation. At the day of operation, a 99mTC-labelled nanocolloid was used to identify the SN. During the surgery the SN were removed separately together with a complete ALND. RESULTS: A total of 150 patients were enrolled in our study of which 129 were eligible for analysis. 53 patients had a positive SN of which 32 have a positive axillary lymph nodes (ALN), positive predictive value (PPV) was 60%; 76 patients had a negative SN of which 6 had a positive ALN (NPV 92%). The sensitivity is 84% and the specificity 76% with a false omission rate (FOR) of 8%. In total 45 patients ALN were clinical negative and no suspect lymph nodes were seen on ultrasound, MRI and PET-CT scan) and 45 patients had negative a SN, with no ALN and 2 patients had a positive SN of which 1 patients had axillary involvement (NPV 100%). The FOR of cN1: 5%, cN2: 37%, cN3 33%. A total of 22 patients out of 84 patients (26%) of which 15/49 cN1 (30%), 6/23 (26%) cN2, 1/12 (8%) have after 6 weeks of chemotherapy and normalization on PET-CT scan. A total of 17 patients had a negative SN and ALN. The FOR was in this group was 0%. CONCLUSION: A SNB should become the standard after NACT if case of a cN0. If after NACT the PET CT has normalized, no ALND should be performed if the SN is negative.

Microlaryngoscopic repair of iatrogenic pharyngeal pouch perforations: treatment of choice?

BACKGROUND: Endoscopic stapled diverticulostomy (ESD) has become the preferred technique for managing pharyngeal pouches. Iatrogenic perforation, created during stapling, is a rare but serious complication with significant morbidity and mortality. The conventional management in these instances is to convert it to an external procedure and excise the pouch. METHODS: Iatrogenic perforations were noticed after stapling in 3 cases in our series of 73 patients who underwent ESD. They were repaired using microlaryngoscopic techniques. RESULTS: All patients had an unremarkable postoperative course. CONCLUSIONS: Selected cases with iatrogenic perforations can be repaired primarily and observed with excellent outcome, obviating the need for an external pouch excision.