Implementation of Universal Pan-Cancer Germline Genetic Testing in an Arab Population: The Jordanian Exploratory Cancer Genetics Study.

PURPOSE: Germline genetic testing (GGT) significantly affects cancer care. While universal testing has been studied in Western societies, less is known about adoption elsewhere. MATERIALS AND METHODS: In this study, 3,319 unselected, pan-cancer Jordanian patients diagnosed between April 2021 and September 2022 received GGT. Pathogenic germline variant (PGV) frequency among patients who were in-criteria (IC) or out-of-criteria (OOC; 2020 National Comprehensive Cancer Network criteria) and changes in clinical management in response to GGT results were evaluated. Statistical analysis was performed using two-tailed Fisher's exact test with significance level P < .05. RESULTS: The cohort was predominantly female (69.9%), with a mean age of 53.7 years at testing, and 53.1% were IC. While patients who were IC were more likely than patients who were OOC to have a PGV (15.8% v 9.6%; P < .0001), 149 (34.8%) patients with PGVs were OOC. Clinical management recommendations in response to GGT, including changes to treatment and/or follow-up, were made for 57.3% (161 of 281) of patients with high- or moderate-risk PGVs, including 26.1% (42 of 161) of patients who were OOC. CONCLUSION: Universal GGT of patients with newly diagnosed cancer was successfully implemented in Jordan and led to identification of actionable PGVs that would have been missed with guidelines-based testing.

Clinical Characteristics and Outcomes of CML in Adolescents and Young Adults.

BACKGROUND: While Chronic Myeloid Leukemia (CML) is a disease of older adults, there is a growing population of adolescent and young adults (AYAs) with CML. This study evaluated the clinical characteristics and outcomes of CML in AYAs. PATIENTS AND METHODS: Data from medical records of adults with chronic phase CML diagnosed and treated at our center from 2011until 2021were retrospectively analyzed. Age between 18 and 29 years was used to define AYAs. Response to tyrosine kinase inhibitors (TKIs), progression to accelerated phase (AP) or blast crisis (BC), event-free survival (EFS) and overall survival (OS) were compared between AYAs and older adults. RESULTS: Among 163 patients included, 41 (25.1%) were AYAs. AYAs were more likely to be males (P = .02), to present with symptoms (P = .004), had a higher median white blood cell count (P = .007), neutrophil count (P = .029), eosinophil count (P = 0.01), low-risk Sokal (P = .033) and Hasford (P = .005) groups. TKI-sensitivity as well as median times for achievement of complete cytogenetic and major molecular response were comparable between both groups. After a median follow-up of 76 (range: 11-235) months, there was no difference in OS (P = .528), or cumulative incidence of transformation to accelerated phase or blast crisis (P = .11). On the other hand, AYA had an inferior EFS (P = .034). CONCLUSION: A quarter of the patients diagnosed with CML in our population were AYAs. Despite being characterized as "lower-risk," they presented with a greater disease burden, had a shorter EFS but comparable OS. Further studies are needed to better understand the disease biology of this group.

Genetic counseling and genetic testing for pathogenic germline mutations among high-risk patients previously diagnosed with breast cancer: a traceback approach.

Genetic counseling and testing are more accessible than ever due to reduced costs, expanding indications and public awareness. Nonetheless, many patients missed the opportunity of genetic counseling and testing due to barriers that existed at that time of their cancer diagnoses. Given the identified implications of pathogenic mutations on patients' treatment and familial outcomes, an opportunity exists to utilize a 'traceback' approach to retrospectively examine their genetic makeup and provide consequent insights to their disease and treatment. In this study, we identified living patients diagnosed with breast cancer (BC) between July 2007 and January 2022 who would have been eligible for testing, but not tested. Overall, 422 patients met the eligibility criteria, 282 were reached and invited to participate, and germline testing was performed for 238, accounting for 84.4% of those invited. The median age (range) was 39.5 (24-64) years at BC diagnosis and 49 (31-75) years at the date of testing. Genetic testing revealed that 25 (10.5%) patients had pathogenic/likely pathogenic (P/LP) variants; mostly in BRCA2 and BRCA1. We concluded that long overdue genetic referral through a traceback approach is feasible and effective to diagnose P/LP variants in patients with history of BC who had missed the opportunity of genetic testing, with potential clinical implications for patients and their relatives.

From Despair to Hope: First Arabic Experience of 177Lu-PSMA and 161Tb-PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer.

The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [177Lu]Lu and [161Tb]Tb, in heavily treated patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 148 cycles of beta-emitting PSMA radioligand therapy were given to 53 patients at a specialized cancer care center in Amman, Jordan. This treatment was offered following the exhaustion of all prior treatment modalities. Approximately half of the cases (n = 26) demonstrated an initial partial response to PSMA radioligand therapy. Moreover, roughly one-fourth of the patients (n = 13) exhibited a sustained satisfactory biochemical response, which qualified them to receive a total of six PSMA radioligand therapy cycles and maintain continued follow-up for additional treatment cycles. This was reflected by an adequate prostate-specific antigen (PSA) decline and a concomitant partial response evident on [68Ga]Ga-PSMA positron emission tomography/computed tomography imaging. A minority of patients (n= 18; 34%) experienced side effects. Generally, these were low-grade and self-limiting toxicities. This study endorses previous research evidence about PSMA radioligand therapy's safety and efficacy. It also provides the first clinical insight from patients of Arab ethnicity. This should facilitate and promote further evidence, both regionally and internationally.

Impact of COVID-19 on Management and Outcomes of Oncology Patients: Results of MENA COVID-19 and Cancer Registry (MCCR).

Introduction: Despite extensive studies of the impact of COVID-19 on patients with cancer, there is a dearth of information from the Middle East and North Africa (MENA) region. Our study aimed to report pertinent MENA COVID-19 and Cancer Registry (MCCR) findings on patient management and outcomes. Methods: MCCR was adapted from the American Society of Clinical Oncology COVID-19 Registry to collect data specifically from patients with cancer and SARS-CoV-2 infection from 12 centers in eight countries including Saudi Arabia, Jordan, Lebanon, Turkey, Egypt, Algeria, United Arab Emirates, and Morocco. The Registry included data on patients and disease characteristics, treatment, and patient outcomes. Logistic regression was used to assess associations with mortality. Results: Between November 29, 2020, and June 8, 2021, data were captured on 2008 patients diagnosed with COVID-19 from the beginning of the pandemic. Median age was 56 years (16-98), 56.4% were females, and 26% were current or ex-smokers. Breast cancer (28.5%) was the leading diagnosis and 50.5% had metastatic disease. Delays of planned treatment (>14 days) occurred in 80.3% for surgery, 48.8% for radiation therapy, and 32.9% for systemic therapy. Significant reduction in the delays of all three treatment modalities occurred after June 1, 2020. All-cause mortality rates at 30 and 90 days were 17.1% and 23.4%, respectively. All-cause mortality rates at 30 days did not change significantly after June 1, 2020; however, 90-day mortality increased from 33.4% to 42.9% before and after that date (p = 0.015). Multivariable regression analysis showed the following predictors of higher 30- and 90-day mortality: age older than 70 years, having metastatic disease, disease progression, and being off chemotherapy. Conclusion: Patients with cancer in the MENA region experienced similar risks and outcome of COVID-19 as reported in other populations. Although there were fewer treatment delays after June 1, 2020, 90-day mortality increased, which may be attributed to other risk factors such as disease progression or new patients who presented with more advanced disease.

Next generation selective estrogen receptor degraders in postmenopausal women with advanced-stage hormone receptors-positive, HER2-negative breast cancer.

Breast cancer is the most prevalent malignancy in women, and is characterized by its heterogeneity; exhibiting various subgroups identifiable through molecular biomarkers that also serve as predictive indicators. More than two thirds of breast tumors are classified as luminal with positive hormone receptors (HR), indicating that cancer cells proliferation is promoted by hormones. Endocrine therapies play a vital role in the effective treatment of breast cancer by manipulating the signaling of estrogen receptors (ER), leading to a reduction in cell proliferation and growth rate. Selective estrogen receptor modulators (SERMs), such as tamoxifen and toremifene, function by blocking estrogen's effects. Aromatase inhibitors (AI), including anastrozole, letrozole and exemestane, suppress estrogen production. On the other hand, selective estrogen receptor degraders (SERDs), like fulvestrant, act by blocking and damaging estrogen receptors. Tamoxifen and AI are widely used both in early- and advanced-stage disease, while fulvestrant is used as a single agent or in combination with other agents like the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors (palbociclib, abemaciclib, ribociclib) or alpelisib for advanced-stage disease. Currently, SERDs are recognized as an effective therapeutic approach for the treatment of ER-positive breast cancer, showing proficiency in reducing and blocking ER signaling. This review aims to outline the ongoing development of novel oral SERDs from a practical therapeutic perspective, enhancing our understanding of the mechanisms of action underlying these compounds.

Germline Genetic Mutations in Adult Patients with Sarcoma: Insight into the Middle East Genetic Landscape.

Data on germline mutations in soft tissue and bone sarcomas are scarce. We sought to identify the prevalence of germline mutations in adult sarcoma patients treated at a tertiary cancer center. Newly diagnosed patients were offered germline genetic testing via an 84-gene panel. The prevalence of pathogenic germline variants (PGVs) and their association with disease-, and patient- related factors are reported. A total of 87 patients were enrolled, the median age was 48 (19-78) years, and 47 (54%) were females. Gastrointestinal stromal tumors (n = 12, 13.8%), liposarcoma (n = 10, 11.5%), and Ewing sarcoma (n = 10, 11.5%) were the main subtypes. A total of 20 PGVs were detected in 18 (20.7%) patients. Variants of uncertain significance, in the absence of PGVs, were detected in 40 (45.9%) patients. Young age (p = 0.031), presence of a second primary cancer (p = 0.019), and female gender (p = 0.042) were correlated with the presence of PGVs. All identified PGVs have potential clinical actionability and cascade testing, and eight (44.44%) suggested eligibility for a targeted therapy. Almost one in five adult patients with soft tissue and bone sarcomas harbor pathogenic or likely pathogenic variants. Many of these variants are potentially actionable, and almost all have implications on cancer screening and family counselling. In this cohort from the Middle East, younger age, presence of a second primary tumor, and female gender were significantly associated with higher PGVs rates. Larger studies able to correlate treatment outcomes with genetic variants are highly needed.

Challenges and Opportunities in Breast Cancer Care in Low-Resourced Countries, Jordan as An Example.

Jordan is a relatively small country with a rapidly growing population and a challenged economy. Breast cancer is the most diagnosed cancer among women worldwide and also in Jordan. Though the age-standardized rate (ASR) of breast cancer incidence is still lower than that in Western societies, the number of newly diagnosed cases continues to increase, involving younger women, and new cases are usually detected at more advanced stages. Improvements in breast cancer care across the health care continuum, including early detection, prevention, treatment, and survivorship and palliative care, have become very visible, but may not match the magnitude of the problem. More organized, goal-oriented work is urgently needed to downstage the disease and improve awareness of, access to, and participation in early detection programs. The cost of recently introduced anti-cancer therapies poses a great challenge, but the impact of these therapies on treatment outcomes, including overall survival, is becoming very noticeable. Though the concept of a multidisciplinary approach to breast cancer treatment is often used at most health care facilities, its implementation in real practice varies significantly. The availability of breast reconstruction procedures, survivorship programs, germline genetic testing, counselling, and palliative care is improving, but these are not widely practiced. In this manuscript, we review the status of breast cancer in Jordan and highlight some of the existing challenges and opportunities.

Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome.

BACKGROUND: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients. METHODS: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed. RESULTS: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis. CONCLUSIONS: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis.

Primary Thromboprophylaxis for the Prevention of Venous Thromboembolism in Cancer Patients with Central Venous Catheters: A Literature Review.

Cancer is a known risk factor for venous thromboembolism (VTE). The wider adoption of immunotherapy and anti-angiogenic drugs in recent years have increased this risk further. Central venous catheters (CVCs) are widely used access devices utilized to deliver infusion therapy, mostly in ambulatory settings. The endothelial injury associated with the use of these catheters adds to the risk of VTE to already high-risk patients. The introduction of direct oral anticoagulants (DOACs), with its proven efficacy and safety in multiple clinical indications, have renewed the attention to VTE prophylaxis in cancer patients with CVC. Several clinical trials and meta-analyses had shown that both apixaban and rivaroxaban are effective in lowering the risk of VTE, without increasing the risk of bleeding. Several risk assessment models (RAM) have utilized patient-related, tumor-related, and treatment-related factors, in addition to widely available biomarkers, like Hemoglobin (Hb) level, white blood cell (WBC) and platelets counts to stratify patients into two or three VTE risk levels. In this manuscript, we review the published clinical trials and meta-analyses that attempted to study the efficacy and safety of anticoagulants, mostly the DOACs, in cancer patients with CVCs. We will also propose a practical risk-directed approach to enhance VTE prophylaxis rate.

Systemic Barriers to Optimal Cancer Care in Resource-Limited Countries: Jordanian Healthcare as an Example.

This narrative review explores the multifaceted barriers hindering access to quality cancer care in Jordan. A literature-based narrative review was undertaken to explore the current identified barriers to cancer care in Jordan. Four databases were searched using relevant keywords to identify key insights on barriers and proposed solutions. Key challenges and potential solutions were identified based on evidence from studies, reports, and initiatives. Medical services and infrastructure exhibit centralized disparities, impacting rural and underserved areas. Human resources shortages, geopolitical instability, and quality management issues pose significant challenges. Public awareness campaigns face hurdles in addressing the tobacco epidemic and late-stage diagnosis. Socioeconomic disparities, particularly in health insurance and urban-rural divides, further compound barriers. Refugees encounter distinct challenges, including late-stage diagnosis, financial barriers, and psychological distress. Despite multiple challenges, Jordan presents a model for regional development and health equity. This study not only contributes to improving cancer care in Jordan but also offers a roadmap for policymakers, healthcare practitioners, and researchers in similar contexts globally. Government initiatives, financial aspects, and proposed policy measures are examined as potential solutions. Recommendations include coordinated prevention strategies, enhanced screening uptake, training programs, the equitable distribution of facilities, and policy directives aligned with global commitments. The role of digital technologies, telemedicine, and community engagement models is emphasized.

Cerebral venous sinus thrombosis in a patient treated with ribociclib for metastatic breast cancer. Case reports and literature review.

Breast cancer is the most diagnosed cancer among women worldwide. Cyclin dependent kinase 4/6 inhibitors (ribociclib, palbociclib, and abemaciclib) modulate endocrine resistance and are widely used treatment for patients with advanced-stage hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Reports of both venous and arterial thromboembolic events, as a complication of cyclin dependent kinase 4/6 inhibitors, are increasingly recognized, but none involved cerebral venous sinus. We herein report on a 44-year-old female patient who initially presented with an early-stage breast cancer treated with surgery, chemotherapy, radiation therapy and finished 5 years of tamoxifen uneventfully. Eight years after her initial diagnosis, she relapsed with a solitary brain lesion which was resected and treated with radiation therapy, and was then started on aromatase inhibitors. Few months later, she progressed with biopsy-proven cervical and mediastinal lymph node metastasis. She was then switched to fulvestrant and ribociclib; both were well-tolerated. However, few weeks later she presented with increasing headache and mild dizziness. Imaging studies showed right lateral sinus acute non-occlusive thrombosis with no parenchymal changes. Patient was anticoagulated with low molecular weight heparin and follow-up visits showed stable disease with no bleeding.

Survival Trends in Pediatric Differentiated Thyroid Cancer: A Middle Eastern Perspective.

Pediatric Differentiated Thyroid Cancer (pedDTC) is a rare pediatric malignancy with an increasing incidence over time. To date, there is a paucity of literature specifically addressing pedDTC within the context of Middle Eastern ethnicity. This retrospective study aimed to assess the risk-stratifying factors for overall survival (OS) and event-free survival (EFS) in pediatric DTC patients from Iraq and Jordan. The medical records of 81 patients from two tertiary cancer institutes were retrieved. Kaplan-Meier analysis was employed to investigate OS and EFS, and the Cox proportional hazards model was employed to estimate hazard ratios. All patients underwent surgery and radioactive iodine therapy, with a median age of 14 and an interquartile range of 12-15. Lymph node involvement was observed in 55% of cases, while distant metastases were present in 13.5%. After a median follow-up period of 68 months, the 10-year survival rate was determined to be 94%, while the 10-year EFS rate was 58%. EFS was negatively impacted by cervical lymph node metastases and early age of diagnosis (p ≤ 0.01, each). Therefore, pediatrics with initial cervical lymph node metastases and those diagnosed before puberty tend to experience poorer EFS, which may justify the need for more aggressive management plans.

Modifiable risk factors for cancer in the middle East and North Africa: a scoping review.

PURPOSE: This scoping review examines controllable predisposing factors attributable to cancer in the Middle East and North Africa (MENA) region's adult population, highlighting opportunities to enhance cancer prevention programs. DESIGN: We systematically searched the PubMed, Science Direct, and CINAHL, EMBASE, and Cochrane Library databases from 1997 to 2022 for articles reporting on the impact of modifiable risk factors on adult patients with cancer in the MENA region. RESULTS: The review identified 42 relevant articles, revealing that tobacco consumption, obesity, physical inactivity, and diet are significant modifiable risk factors for cancer in the region. Tobacco smoking is a leading cause of lung, bladder, squamous cell carcinoma, and colorectal cancer. A shift towards a westernized, calorie-dense diet has been observed, with some evidence suggesting that a Mediterranean diet may be protective against cancer. Obesity is a known risk factor for cancer, particularly breast malignancy, but further research is needed to determine its impact in the MENA region. Physical inactivity has been linked to colorectal cancer, but more studies are required to establish this relationship conclusively. Alcohol consumption, infections, and exposure to environmental carcinogens are additional risk factors, although the literature on these topics is limited. CONCLUSION: The review emphasizes the need for further research and the development of targeted cancer prevention strategies in the MENA region.

The Application of Existing Risk Assessment Models (RAMS) to Predict the Occurrence of Venous Thromboembolic Events among Patients with Classic Hodgkin Lymphoma.

Background: A majority of patients included in risk assessment models (RAMs) developed to predict venous thromboembolic events (VTE) in lymphoma were non-Hodgkin lymphoma. Our study aims to evaluate the incidence and predictors of VTE, utilizing different RAMs, in patients with classic Hodgkin lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). Methods: Adult patients with cHL, treated and followed at our center, were included. Correlations between different variables, Khorana score, and thrombosis in lymphoma (ThroLy) RAMs with VTE were examined using Fisher's exact test and logistic regression analysis. Results: A total of 321 patients were included, with a median age of 29 (range: 18-83) years. Of them, 169 (52.6%) had advanced-stage disease. Combined modality treatment was given to 169 (52.6%) patients. A total of 52 (16.2%) patients had relapsed or refractory disease. VTE were reported in 15 (4.7%) patients and were mostly during the administration of first-line (n = 8, 53.3%), or salvage chemotherapy (n = 6, 40.0%). There was no correlation between a Khorana score > 2 (p = 0.689) or ThroLy score > 3 (p = 0.335) and VTE. Older age (p = 0.014) and relapsed or refractory disease (p = 0.003) significantly correlated with VTE. Conclusions: VTE are uncommon in cHL. The commonly used RAMs failed to predict VTE. However, older age and relapsed or refractory disease significantly increased this risk.

Survival Outcomes after Placement of Inferior Vena Cava Filters in Cancer Patients: Insights from a Comprehensive Cancer Center's Experience.

BACKGROUND: Inferior vena cava (IVC) filters serve as a vital intervention when systemic anticoagulation proves ineffective or contraindicated, particularly in the context of cancer patients. This study aimed to provide real-world insights into the outcomes of cancer patients following IVC filter placement. PATIENTS AND METHODS: Cancer patients with IVC filters were retrospectively reviewed. The indications and survival outcomes following IVC filter insertion have been reported. RESULTS: A total of 176 cancer patients with IVC filters were included in the study. The median patient age was 56 years (range: 18-88 years). Solid tumors were the most common primary cancers (n = 125, 71.0%), and the majority (n = 99, 79.2%) had the advanced-stage disease at the time of IVC insertion. The filters were inserted because of contraindications to anticoagulation (n = 99, 56.3%) or the failure of anticoagulation (n = 56, 31.8%). The median survival (range) following filter placement was only 2 (1.45-2.55) months for patients with advanced-stage solid tumors, 5 (0.62-9.38) months for patients with brain tumors, and 44 (8.59-79.41) months for those with early-stage solid tumors, p < 0.001. CONCLUSIONS: Our findings suggest that IVC filter placement offers limited benefits to patients with advanced-stage disease. The underlying tumor, stage, and life expectancy are crucial factors in the decision-making process before IVC filter insertion.

Management of breast cancer patients with BRCA gene mutations in Jordan: perspectives and challenges.

BACKGROUND: This paper explores and discusses local challenges oncologists face for diagnosing and managing breast cancer patients with BRCA gene mutations in Jordan. METHODS: A task force involving key opinion leaders, experts in the management of breast cancer, and stakeholders in healthcare systems where genetic testing is available in Jordan discussed current evidence and local real-life practice. The task force then formulated recommendations to achieve better patient outcomes and satisfaction based on evidence-based medicine and their clinical experience in BRCA-mutated breast cancer management. RESULTS AND CONCLUSION: Eligibility of patients for genetic testing, physician acceptance and willingness to integrate genetic testing into routine practice is encouraging but remains restricted by testing availability and financial coverage. Until more data is available, genetic testing should be targeted for breast cancer patients based on tumor subtypes, as well as family and personal history of cancer, as per international guidelines. Whenever possible, genetic testing should aim to detect all actionable genes through a multigene panel including BRCA1/2. Major challenges faced in clinical practice in Jordan include fear of genetic discrimination and social stigmatization, as well as hesitancy toward risk-reducing surgery. Pre-testing counseling is therefore critical to promote acceptance of genetic testing. Since geneticists are in short supply in Jordan, genetic counseling can be offered through a specially trained genetic counselor or through a hybrid system that includes oncologist-based counselling. In addition to cancer prevention, germline genetic testing may assist in the selection of specific anti-cancer therapy, such as PARP inhibitors, in patients with BRCA1/2 mutation. Nationwide initiatives are also needed to ensure access to PARP inhibition therapy and provide financial coverage for genetic screening, mastectomies and reconstructive surgery across Jordan.

Pathogenic germline variants in patients with breast cancer: conversations across generations, practices and patients' attitude.

Background: Breast cancer susceptibility genes such as BRCA1, BRCA2, PALB2, CHEK2 and many others are increasingly recognized among our patient population. In addition to their impact on treatment decisions of tested patients themselves, identifying at-risk family members offer opportunities for cancer preventive measures. Methods: This is an observational cross-sectional study of adult breast cancer patients with positive breast-cancer-susceptibility germline variants who received treatment at our institution. Patients with variants of uncertain significance (VUS), or who refused to give consent, were excluded. The data was collected from an eligible sample of breast cancer patients using a structured questionnaire developed by the study team and tested for validity and reliability, as well as a clinical chart review form. Patients were invited to participate in the study during their scheduled oncology clinics visit. Results: 169 patients were enrolled, including 42 (24.9%) with pathogenic/likely pathogenic (P/LP) BRCA1 variants, 84 (49.7%) with BRCA2 and 43 (25.4%) with non-BRCA variants. All patients were female and the mean age was 45 ± 9.9 years. Among 140 eligible patients, 104 (74.3%) underwent prophylactic mastectomy, while 79 (59.0%) of 134 eligible patients had prophylactic bilateral salpingo-oophorectomy (BSO). Results were communicated with family members by majority (n = 160, 94.7%), including 642 first degree female relatives, and 286 (44.5%) of them have taken no action. Fear of positive test results, cost of testing, unwillingness to undergo preventive measures, and social stigma were cited as barriers to genetic testing in 54%, 50%, 34% and 15%, respectively. Conclusion: Risk-reducing interventions including mastectomy and BSO were carried by majority of patients with P/LP variants. However, though the rate of communication of genetic testing results with family members was high, proper preventive measures were relatively low. Cost and fear of cancer diagnosis, were the leading causes that prevented cascade testing in our cohort.

COVID-19 Antibody Seroconversion in Cancer Patients: Impact of Therapy Cessation-A Single-Center Study.

BACKGROUND: The effective development of COVID-19 vaccination has mitigated its harm. Using two laboratory methods, we investigated the efficacy of the BNT162b2 mRNA and BBIBP-CorV COVID-19 vaccines on seroconversion rates in cancer patients undergoing active cancer treatment. METHODS: SARS-CoV-2 vaccines were scheduled for 134 individuals. The consenting participants submitted three venous blood samples. Three samples: T0, T1, and T2. The ABBOTT-SARS-CoV-2 IgG II Quant and Elecsys® Anti-SARS-CoV-2 assays were used to evaluate the samples and convert the antibody titers to WHO (BAU)/mL units. RESULTS: Cancer patients exhibited a higher seroconversion rate at T2, regardless of vaccination type, and the mean antibody titers at T1 and T2 were higher than those at T0. BBIBP-CorV patients required a booster because BNT162b2 showed a higher seroconversion rate between T0 and T1. Statistics indicate that comparing Abbott and Roche quantitative antibody results without considering the sample collection time is inaccurate. CONCLUSIONS: COVID-19 vaccines can still induce a humoral immune response in patients undergoing cancer-targeted therapy. The strength of this study is the long-term monitoring of antibody levels after vaccination in cancer patients on active therapy using two different immunoassays. Further multicenter studies with a larger number of patients are required to validate these findings.

Treatment options for patients with hormone receptor-positive, HER2-negative advanced-stage breast cancer: maintaining cyclin-dependent kinase 4/6 inhibitors beyond progression.

Breast cancer is the most commonly diagnosed cancer in women worldwide. Over the past decade, the treatment paradigm for patients with metastatic breast cancer (MBC) has taken an important shift towards better survival and improved quality of life (QOL), especially for those with hormone receptor (HR)-positive diseases which represent the majority of breast cancer subtypes. The introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in the upfront therapy of such patients has resulted in dramatic improvement in progression-free survival (PFS) and overall survival (OS), too. However, almost all patients would, sooner or later, develop disease progression and necessitate transition to different lines of treatment that may include chemotherapy. The idea of maintaining CDK4/6 inhibitors beyond disease progression seems attractive, as this approach has the potential to improve outcome in this setting despite the fact that the true benefit, in terms of survival, might not carry the same weight as it initially does. Researchers have been investigating potential mechanisms of resistance and identify possible biological markers for response after disease progression. Much of the available data is retrospective; however, few randomized clinical trials were recently published and few more are ongoing, addressing this point. In this paper, we intend to review the available published studies investigating the potential role for keeping CDK4/6 inhibitors in play beyond disease progression.