Systemic Treatment of Patients With Metastatic Breast Cancer: ASCO Resource-Stratified Guideline.

PURPOSE: To guide clinicians and policymakers in three global resource-constrained settings on treating patients with metastatic breast cancer (MBC) when Maximal setting-guideline recommended treatment is unavailable. METHODS: A multidisciplinary, multinational panel reviewed existing ASCO guidelines and conducted modified ADAPTE and formal consensus processes. RESULTS: Four published resource-agnostic guidelines were adapted for resource-constrained settings; informing two rounds of formal consensus; recommendations received ≥75% agreement. RECOMMENDATIONS: Clinicians should recommend treatment according to menopausal status, pathological and biomarker features when quality results are available. In first-line, for hormone receptor (HR)-positive MBC, when a non-steroidal aromatase inhibitor and CDK 4/6 inhibitor combination is unavailable, use hormonal therapy alone. For life-threatening disease, use single-agent chemotherapy or surgery for local control. For premenopausal patients, use ovarian suppression or ablation plus hormone therapy in Basic settings. For human epidermal growth factor receptor 2 (HER2)-positive MBC, if trastuzumab, pertuzumab, and chemotherapy are unavailable, use trastuzumab and chemotherapy; if unavailable, use chemotherapy. For HER2-positive, HR-positive MBC, use standard first-line therapy, or endocrine therapy if contraindications. For triple-negative MBC with unknown PD-L1 status, or if PD-L1-positive and immunotherapy unavailable, use single-agent chemotherapy. For germline BRCA1/2 mutation-positive MBC, if poly(ADP-ribose) polymerase inhibitor is unavailable, use hormonal therapy (HR-positive MBC) and chemotherapy (HR-negative MBC). In second-line, for HR-positive MBC, Enhanced setting recommendations depend on prior treatment; for Limited, use tamoxifen or chemotherapy. For HER2-positive MBC, if trastuzumab deruxtecan is unavailable, use trastuzumab emtansine; if unavailable, capecitabine and lapatinib; if unavailable, trastuzumab and/or chemotherapy (hormonal therapy alone for HR-positive MBC).Additional information is available at www.asco.org/resource-stratified-guidelines. It is ASCO's view that healthcare providers and system decision-makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Improved Survival of Young Patients With Breast Cancer 40 Years and Younger at Diagnosis.

PURPOSE: Around 50% of patients with breast cancer in low- or middle-income countries are younger than 50 years, a poor prognostic variable. We report the outcome of patients with breast cancer 40 years and younger. METHODS: We reviewed 386 patients with breast cancer 40 years and younger and retrieved demographic, clinicopathologic, treatment-related, disease progression, and survival data from electronic medical records. RESULTS: The median age at diagnosis was 36 years, and infiltrating ductal carcinoma was present in 94.3% of patients, infiltrating lobular carcinoma in 1.3%, and ductal carcinoma in situ in 4.4%. Grade 1 disease was present in 8.5% of patients, grade 2 in 35.5%, and grade 3 in 53.4%; 25.1% had human epidermal growth factor receptor 2 (HER2)-positive, 74.6% had hormone receptor (HR)+, and 16.6% had triple-negative breast cancer. Early breast cancer (EBC) constituted 63.6% (stage I, 22.4%; stage II, 41.2%) of patients, whereas 23.2% had stage III, and 13.2% had metastatic disease at diagnosis. Of patients with EBC, 51% had partial mastectomy and 49.0% had total mastectomy. And 77.1% had chemotherapy with or without anti-HER2 therapy. All HR+ patients received adjuvant hormonal therapy. The disease-free survival at 5 years was 72.5% and 55.9% at 10 years. The overall survival (OS) was 89.4% at 5 years and 76% at 10 years. Patients with stages I/II had an OS of 96.0% at 5 years and 87.1% at 10 years. Patients with stage III had an OS of 88.3% at 5 years and 68.7% at 10 years. The OS of patients with stage IV was 64.5% at 5 years and 48.4% at 10 years. CONCLUSION: We report survival rates of 89% at 5 years and 76% at 10 years with modern multidisciplinary management. Best results were seen in EBC: OS rates of 96% and 87% at 5 years and 10 years.

Genetic Counseling, Screening and Risk-Reducing Surgery in Patients with Primary Breast Cancer and Germline BRCA Mutations: Unmet Needs in Low- and Middle-Income Countries.

OBJECTIVE: Worldwide genetic counseling practices are variable and often not reported in low- and middle-income countries (LMICs). We present the follow-up genetic counseling, breast screening, risk-reducing salpingo-oophorectomy (RRSO) and contralateral prophylactic mastectomy (CPM) in a cohort of study patients with either BRCA pathogenic mutations or BRCA variant of unknown significance (VUS). MATERIALS AND METHODS: Chart review and phone calls for the collection of information. Out of a cohort of 250 patients, 14 had deleterious mutations and 31 had a VUS, of whom 19 had primary early breast cancer. We collected information about genetic counseling, screening, CPM and RRSO. RESULTS: Fourteen patients with deleterious mutations (7 BRCA1 and 7 BRCA2) and 19 patients with VUS mutations (20 VUS, 4 BRCA1, 16 BRCA2; 1 patient had both) were surveyed. Of 14 patients with deleterious BRCA mutations, 57.14% (8/14 patients) received genetic counseling from their oncologist. Subsequently 85.71% (12/14) are undergoing mammography screening and 35.71% (5/14) breast screening magnetic resonance imaging (MRI). Furthermore, 50% of them underwent CPM and 57.14% underwent RRSO. Of 19 patients with VUS mutations, 10.5% received genetic counseling from their oncologist; 78.9% were undergoing regular screening mammogram and 31.5% were undergoing breast MRI; one patient underwent CPM and two patients RRSO. CONCLUSION: Within three years from knowing they have a mutation, 50% of patients with germline BRCA mutations had undergone CPM and 60% RRSO, the majority of them had screening mammography surveillance but only 50% had screening MRI. Follow-up of patients with VUS with mammography was 78% but MRI was only 31%. Lack of MRI surveillance reflects both limited resources and insufficient counseling. Genetic counseling was done by medical oncologists, which reflects a trend in LMIC. Our Data shows the importance of the need for professional genetic counselors and optimal surveillance in Lebanon and other LMICs.

Management of breast cancer patients with BRCA gene mutations in Lebanon of the Middle East: perspectives and challenges.

BACKGROUND: This commentary explores and discusses the challenges oncologists face in diagnosing and managing breast cancer patients with BRCA gene mutations in Lebanon and the Middle East. METHODS: Key opinion leaders shared their recommendations to achieve better patient outcomes and satisfaction based on evidence-based medicine and their clinical experience in BRCA management. RESULTS: Challenges associated with BRCA management can be divided into four main levels: physicians, patients, test, and treatment factors. More genetic counselors are to be identified given their important role in the management of individuals with BRCA gene mutations. CONCLUSION: Genetic counseling, continuing education, infrastructure, testing, expertise, and financial support are needed to fulfill the unmet needs in the management of BRCA mutation carriers.

Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer.

Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.

Metronomic chemotherapy for patients with metastatic breast cancer: Review of effectiveness and potential use during pandemics.

Metronomic chemotherapy (M-CT) is defined as dose dense administration of chemotherapy at lower doses than maximum tolerated dose but at shorter free intervals, to obtain a near continuous exposure of cancer cells to those potentially effective drugs. M-CT is a useful strategy to obtain response, overcome resistance and reduce side effects, with low costs. This review will focus on the use of M-CT in advanced breast cancer (ABC). Cytostatic and cytotoxic effect on cancer cells, the anti-angiogenic and the immunomodulatory effects are its main mechanisms of actions. Many clinical trials proved the efficacy and tolerability of different monotherapies and combinations of chemotherapeutic agents administered in metronomic doses and frequencies in ABC. M-CT is a reasonable option for second and later lines of chemotherapy in metastatic breast cancer including those with prior anthracycline or taxane exposure, older patients and patients with comorbidities, and even as first-line in certain groups of patients. The acceptable efficacy and low toxicity of oral metronomic chemotherapy makes it a reasonable option during COVID-19 pandemic as well as in the post-COVID era which is projected to last for some time.

Breast cancer treatment: A phased approach to implementation.

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana.

Enhancing global access to cancer medicines.

Globally, cancer is the second leading cause of death, with numbers greatly exceeding those for human immunodeficiency virus/acquired immunodeficiency syndrome, tuberculosis, and malaria combined. Limited access to timely diagnosis, to affordable, effective treatment, and to high-quality care are just some of the factors that lead to disparities in cancer survival between countries and within countries. In this article, the authors consider various factors that prevent access to cancer medicines (particularly access to essential cancer medicines). Even if an essential cancer medicine is included on a national medicines list, cost might preclude its use, it might be prescribed or used inappropriately, weak infrastructure might prevent it being accessed by those who could benefit, or quality might not be guaranteed. Potential strategies to address the access problems are discussed, including universal health coverage for essential cancer medicines, fairer methods for pricing cancer medicines, reducing development costs, optimizing regulation, and improving reliability in the global supply chain. Optimizing schedules for cancer therapy could reduce not only costs, but also adverse events, and improve access. More and better biomarkers are required to target patients who are most likely to benefit from cancer medicines. The optimum use of cancer medicines depends on the effective delivery of several services allied to oncology (including laboratory, imaging, surgery, and radiotherapy). Investment is necessary in all aspects of cancer care, from these supportive services to technologies, and the training of health care workers and other staff.

Impact of Merit-Based Immigration Policies on Brain Drain From Low- and Middle-Income Countries.

PURPOSE: Brain drain is the migration of educated and skilled individuals from a less developed region or country to a more economically established one. The Trump administration proposed a merit-based immigration plan. This article addresses its potential impact on health care delivery in low- and middle-income countries (LMICs) and their preparedness to deal with it. MATERIALS AND METHODS: Data on immigration policies, numbers of international medical graduates practicing in high-income countries (HICs), various scientific exchange methods, and efforts for capacity building in LMICs. RESULTS: Talented individuals seek to advance their knowledge and skills, and may stay in HICs because of greater rewards and opportunities. HICs also rely on immigrant international medical graduates to supplement their physician workforces. CONCLUSION: Ambitious individuals from LMICs need and should have opportunities to advance their education and training in more advanced countries. LMICs should increase their educational efforts, research capabilities, infrastructures, and living conditions to better serve their own populations and reduce their brain drain phenomenon.

Trends in Breast Cancer Staging at Diagnosis Associated with Screening Campaigns in Lebanon.

Introduction: Mammography screening has been shown to improve early breast cancer (BC) detection, by shifting the disease at diagnosis to locally confined stages, offering lighter treatments and better prognoses. BC awareness campaigns calling for annual mammography screenings have been ongoing in Lebanon since 2002. Changes in BC staging at diagnosis as a consequence of documented improvements in mammography uptake remain to be described. Materials and Methods: We reviewed 2,822 BC cases identified by pathology reports in the American University of Beirut Medical Center between the years 1990 and 2015. After age stratification, we have trended the extracted stages versus time. Results were compared between the prescreening (1990-2001) and the postscreening period (2002-2015). Results: During the postscreening period, stage I represented 31%, stage II 47%, stage III 14%, and stage IV 8% of the cases. Stage I cases had more than doubled whereas stage III cases showed a mirror decrease compared with the years before the implementation of awareness campaigns. The increase in stage I was significantly more prominent in women aged 40 years and older (from 14% to 32%), compared with the younger group. Shifts in staging happened in parallel with a concurrent rise in reported uptake of mammography screening. Conclusions: Our findings demonstrate significant trends in earlier detection, which are likely associated with an increase in screening uptake and an awareness of BC as a public health issue. Staging data from hospitals all over Lebanon should be available for building national evidence. The Ministry of Public Health should require reporting of BC stage at diagnosis to the National Cancer Registry, as part of the annual cancer incidence reporting in Lebanon.

American Society of Clinical Oncology's Global Oncology Leadership Task Force: Findings and Actions.

In response to rising cancer incidence and mortality rates in low- and middle-income countries and the increasingly global profile of ASCO's membership, the ASCO Board of Directors appointed the Global Oncology Leadership Task Force (Task Force) to provide recommendations on ASCO's engagement in global oncology. To accomplish its work, the Task Force convened meetings of global oncology experts, conducted focus group discussions with member groups, did site visits to South America and India, and met regularly to analyze the findings and develop recommendations. Task Force findings included global concerns, such as access to care, and specific concerns of middle- and low-resource settings. The need to strengthen health systems and the importance of alliances with a range of international cancer stakeholders were emphasized. Task Force recommendations to the ASCO Board of Directors were based on a three-part global oncology strategy of professional development, improvement of access to quality care, and acceleration of global oncology research. Specific areas of focus within each of these strategic pillars are provided along with an update on areas of ASCO activity as these recommendations are implemented.

Cancer Care for Refugees and Displaced Populations: Middle East Conflicts and Global Natural Disasters.

Conflicts and natural disasters can cause major disruptions to people's lives. Media and news agencies usually focus on immediate consequences of these events, including loss of life and injuries, environmental and property destruction, and relief efforts. In this article, we will examine the effects of conflicts (focusing on in the Middle East) and global natural disasters on patients already diagnosed with cancer and on those who are diagnosed with cancer during and in the immediate aftermath of these events. We will review the limited literature, provide situational analysis, and discuss medical relief efforts, governmental readiness, and the role of United Nations agencies and international nongovernmental organizations. We will also discuss treatment of patients with cancer in the context of prolonged displacements and limited resources.

Prevalence and Severity of Sleep Disturbances among Patients with Early Breast Cancer.

CONTEXT: Data regarding health-related quality of life in breast cancer patients in the Middle East are limited with fatigue and sleep disturbance being the most distressing symptoms reported by patients treated for early breast cancer. AIMS: The aim of this study was to examine the prevalence and incidence of insomnia among patients with early-stage breast cancer patients treated with chemotherapy. SUBJECTS AND METHODS: This was a prospective cohort study. We enrolled patients with stage I-III breast cancer patients treated with chemotherapy at the American University of Beirut Medical Center. At three different time points (prior to, during, and following chemotherapy), we assessed the severity of sleep disturbances using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. The Institution Review Board approved the study. RESULTS: Fifty-two patients were recruited. There was a significant increase in sleep disturbances during chemotherapy which improved to below baseline levels on completion of therapy. Prior to chemotherapy, 36% of patients reported poor sleep versus 58% during chemotherapy. The percentage of patients reporting clinical insomnia rose from 11% pretreatment to 36% during chemotherapy reflecting a significant symptomatic burden that is poorly documented and managed in routine clinical practice. CONCLUSIONS: Patients with nonmetastatic breast cancer experience an increase in sleep disturbances during the treatment phase. Physicians should be aware of the need to routinely screen for sleep disturbance in breast cancer patients undergoing chemotherapy.

microRNA Expression in Ethnic Specific Early Stage Breast Cancer: an Integration and Comparative Analysis.

Breast cancer (BC) has a higher incidence in young Lebanese woman as compared to the West. We assessed the microRNA (miRNA) microarray profile of tissues derived from Lebanese patients with early BC and performed mRNA-miRNA integration analysis. 173 miRNAs were significantly dysregulated in 45 BC versus 17 normal adjacent breast tissues, including 74 with a fold change more than two of which 17 were never reported before in cancer. Integration analysis of mRNA-miRNA microarray data revealed a potential role of 51 dysregulated miRNA regulating 719 tumor suppressive or oncogenic mRNA associated with increased proliferation and decreased migration and invasion. We then performed a comparative miRNA microarray profile analysis of BC tissue between these 45 Lebanese and 197 matched American BC patients. Notably, Lebanese BC patients had 21 exclusively dysregulated miRNA (e.g. miR-31, 362-3p, and 663) and 4 miRNA with different expression manner compared to American patients (e.g. miR-1288-star and 324-3p). Some of these differences could reflect variation in patient age at diagnosis or ethnic variation affecting miRNA epigenetic regulation or sequence of miRNA precursors. Our data provide a basis for genetic/epigenetic investigations to explore the role of miRNA in early stage BC in young women, including ethnic specific differences.

Practice and Impact of Multidisciplinary Tumor Boards on Patient Management: A Prospective Study.

PURPOSE: Multidisciplinary tumor boards (MTBs) have become commonplace. The use, attendance, and function of MTBs need continued assessment and improvement. METHODS: We prospectively recorded and assessed all cases presented at MTBs between October 2013 and December 2014. Data were collected before and during each MTB. Data were analyzed using SPSS for Windows version 23 (SPSS, Chicago, IL). RESULTS: Five hundred three cases were presented: 234 cases (46%) at GI cancer MTBs, 149 cases (29.6%) at breast cancer MTBs, 69 cases (13.7%) at thoracic/head and neck cancer MTBs, and 51 cases (10.7%) at neuro-oncology MTBs. A total of 86.7% of MTB cases were presented to make plans for management. Plans for upfront management were made in 67% of the breast cancer cases, 63% of GI cases, 59% of thoracic/head and neck cases, and 49% of neuro-oncology cases. Three hundred ninety-four cases (78.3%) were presented by medical oncologists, whereas only 74 cases (14.7%) were presented by surgeons, and 10 cases (2%) were presented by radiation oncologists. The majority of MTBs, with the exception of the neurosurgery MTBs, were led by medical oncologists. Surgeons presented the least number of cases but attended the most, and their contributions to discussions and decision making were essential. CONCLUSION: MTBs enhance the multidisciplinary management of patients with cancer. Upfront multidisciplinary decision making should be considered as an indicator of benefit from MTBs, in addition to changes in management plans made at MTBs. Increasing the contributions of surgeons to MTBs should include bringing more of their own cases for discussion.