Programmed death-ligand 1 (PD-L1) expression predicts response to neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis.

BACKGROUND: In patients with metastatic triple-negative breast cancer (TNBC), programmed death-ligand 1 (PD-L1) expression has been demonstrated to predict response to immunotherapy. It is unclear whether PD-L1 expression measured with currently available validated assays can predict chemotherapy response in patients with non-metastatic TNBC. METHODS: We conducted a systematic review and meta-analysis of clinical studies to assess the PD-L1 expression as a predictor of response to chemotherapy in non-metastatic TNBC using validated assays. The primary endpoint was pathological complete response (pCR) rate to neoadjuvant chemotherapy. Secondary endpoints included the prevalence of PD-L1 expression in non-metastatic TNBC and its impact on disease-free survival (DFS) and overall survival (OS). Moreover, RNA sequence data from the TCGA breast cancer cohort was used to define the relationship between PDCD1 expression and response to chemotherapy and prognosis. RESULTS: Nineteen studies were eligible for the meta-analysis with a total of 2403 patients with non-metastatic TNBC disease. The PD-L1-positive cohort had a significantly higher likelihood of achieving pCR with neoadjuvant chemotherapy (pooled odds ratio = 1.95; 95% CI = 1.39-2.73, p < 0.0001). In studies which reported long-term outcomes, PD-L1 positivity was associated with significantly better DFS and OS compared to PD-L1 negative patients (pooled hazard ratio = 0.51; 95% CI = 0.35-0.74, p < 0.0001 and 0.51; 95% CI = 0.27-0.94, p = 0.031, respectively). Transcriptomic data suggested that PD-L1 expression is a surrogate marker for the upregulation of key immune-related genes that mediate response to chemotherapy in TNBC. CONCLUSION: This analysis clearly shows that patients with PD-L1 positive TNBC respond better to neoadjuvant chemotherapy and are associated with better survival outcomes compared to patients with PD-L1 negative tumours. The newly distinct quadruple negative breast cancer (QNBC) subtype should be defined as the BC subtype with the poorest outcome in the non-metastatic setting, highlighting the need for more aggressive therapy approaches.

A systematic review and meta-analysis of the impact of radiation-related lymphopenia on outcomes in pancreatic cancer.

Background: Pancreatic cancer is a devastating disease with a 5-year survival rate of 5-10%. Radiation is commonly used in neoadjuvant and adjuvant settings to improve local control. Studies have shown that circulating lymphocyte count depletion after radiation has been associated with poor tumor control and inferior overall survival (OS) outcomes. Method: To better understand the impact of radiation-associated lymphopenia in pancreatic cancer, the authors undertook this systematic review and meta-analysis of clinical studies that have reported radiation-related lymphopenia in pancreatic cancer. Results: A systematic methodology search of PubMed, Embase and the Cochrane Library resulted in 2969 abstracts. Nine studies fulfilled the inclusion criteria. Six studies reported on outcomes in patients undergoing definitive chemoradiation and three studies comparing outcomes in stereotactic body radiotherapy versus definitive chemoradiation. The patients with severe lymphopenia were at increased risk of death with a pooled hazard ratio of 2.33 (95% CI: 1.79, 3.03; I2: 36%; p < 0.001) compared with patients with no severe lymphopenia. The odds of developing severe lymphopenia were 1.12 (95% CI: 0.45, 2.79; I2: 95%; p < 0.81). The pooled mean difference for OS was -6.80 months (95% CI: -10.35, -3.24; I2: 99%; p < 0.002), suggesting that patients who develop grade 3 or 4 lymphopenia have inferior median OS outcomes. Limiting the mean splenic dose to less than 9 Gy as well as various spleen dosimetric parameters such as visit (V)10 <32%, V15 <23% and V20 <15.4% can reduce the incidence of severe lymphopenia. Conclusion: Radiation-related lymphopenia is associated with an increased hazard of death and inferior median OS. Spleen dosimetric parameters correlate with the incidence of severe lymphopenia and with sub-optimal survival outcomes. There is a need to validate these findings in prospective studies.

The first BGICC consensus and recommendations for breast cancer awareness, early detection and risk reduction in low- and middle-income countries and the MENA region.

In low-middle income countries (LMICs) and the Middle East and North Africa (MENA) region, there is an unmet need to establish and improve breast cancer (BC) awareness, early diagnosis and risk reduction programs. During the 12th Breast, Gynecological & Immuno-oncology International Cancer Conference - Egypt 2020, 26 experts from 7 countries worldwide voted to establish the first consensus for BC awareness, early detection and risk reduction in LMICs/MENA region. The panel advised that there is an extreme necessity for a well-developed BC data registries and prospective clinical studies that address alternative modalities/modified BC screening programs in areas of limited resources. The most important recommendations of the panel were: (a) BC awareness campaigns should be promoted to public and all adult age groups; (b) early detection programs should combine geographically distributed mammographic facilities with clinical breast examination (CBE); (c) breast awareness should be encouraged; and (d) intensive surveillance and chemoprevention strategies should be fostered for high-risk women. The panel defined some areas for future clinical research, which included the role of CBE and breast self-examination as an alternative to radiological screening in areas of limited resources, the interval and methodology of BC surveillance in women with increased risk of BC and the use of low dose tamoxifen in BC risk reduction. In LMICs/MENA region, BC awareness and early detection campaigns should take into consideration the specific disease criteria and the socioeconomic status of the target population. The statements with no consensus reached should serve as potential catalyst for future clinical research.

A Systematic Review of Radiation-Related Lymphopenia in Genito-urinary Malignancies.

BACKGROUND: The impact of radiation-related lymphopenia on clinical outcomes has been reported in various solid malignancies such as high grade gliomas, head and neck cancers, thoracic malignancies and gastro-intestinal malignancies but its impact is not clearly known in the context of common genito-urinary (GU) malignancies. METHODOLOGY: To better understand the effect of radiation-associated lymphopenia in prostate and bladder cancer, we undertook this systematic review of clinical studies that have studied radiation-related lymphopenia in GU malignancies. A systematic methodology search of PubMed, Embase, and Cochrane library resulted in 2125 abstracts. Ten studies fulfilled the inclusion criteria which included any prospective, retrospective study or cohort study of prostate, urinary bladder, kidney, ureter, urethra, penile cancer in humans, and radiation should be part of treatment and intent has to be in definitive or adjuvant settings. Finally the study should have data on radiation-related lymphopenia. RESULTS: Four studies reported on the cancer-specific outcomes related to the lymphopenia. The incidence of low lymphocyte counts were documented in all the studies. Three studies analyzed the factors associated with the Lymphocyte depletion. Pooled incidence of severe lymphopenia was 29.25% and mild to moderate lymphopenia was 60.75%. Bone marrow volume receiving 40 Gy was associated with the incidence of lymphopenia. CONCLUSION: One-third of the patients suffer from severe lymphopenia after radiation in prostate and bladder cancer. There are no clear data to support the correlation between severe lymphopenia and disease outcomes. Bone marrow dosimetry can affect the incidence and severity of lymphopenia. There is need of prospective datasets to identify the impact of radiation-related lymphopenia in GU malignancies focusing on long-term side effects, recurrence rates, and overall survival.

Whole lung irradiation for completely responding pulmonary metastases in pediatric Ewing sarcoma.

Aim: Scarce data assessing the real value of whole lung irradiation (WLI) in Ewing's sarcoma (ES) with lung-only metastasis, with published conflicting results. We studied the impact of WLI in a homogenous pediatric population. Materials & methods: Retrospective study evaluating the survival outcomes of WLI in these patients. Results: Out of 163 metastatic ES; 41 patients were eligible for WLI. 30 patients (73.1%) received WLI (+ve) while 11 patients (26.8%) did not receive WLI (-ve). Five-year event-free survival was statistically significant in WLI (+ve). Five-year pulmonary relapse-free survival showed trend for improvement with WLI (+ve), while 5-year overall survival was not statistically significant between the two arms. Conclusion: WLI added significantly to the long term clinical outcome of metastatic ES patients, with no irreversible toxicity.

Implementation of breast cancer continuum of care in low- and middle-income countries during the COVID-19 pandemic.

Breast cancer is the most common malignancy among women worldwide. The current COVID-19 pandemic represents an unprecedented challenge leading to care disruption, which is more severe in low- and middle-income countries (LMIC) due to existing economic obstacles. This review presents the global perspective and preparedness plans for breast cancer continuum of care amid the COVID-19 outbreak and discusses challenges faced by LMIC in implementing these strategies. Prioritization and triage of breast cancer patients in a multidisciplinary team setting are of paramount importance. Deescalation of systemic and radiation therapy can be utilized safely in selected clinical scenarios. The presence of a framework and resource-adapted recommendations exploiting available evidence-based data with judicious personalized use of current resources is essential for breast cancer care in LMIC during the COVID-19 pandemic.

Clinicopathologic Features of Breast Cancer in Egypt-Contemporary Profile and Future Needs: A Systematic Review and Meta-Analysis.

PURPOSE: Breast cancer (BC) is the most common cancer among Egyptian females. No current national cancer database is available in Egypt to provide reliable data on the specific clinicopathologic features of BC in this population. Herein, we investigated the clinical profile of BC among Egyptian women. METHODS: A systematic review of studies on BC published from inception until December 2021 was performed. We explored pooled estimated proportions of different stages of BC at presentation in Egypt and other clinicopathologic features including age, menopausal status, tumor (T) and lymph node (N) stages, and biological subtypes. Data analysis was performed using meta package (R). RESULTS: Twenty-six studies were eligible for our systematic review and meta-analysis, including 31,172 BC cases. In 12 studies, including 15,067 patients with BC, the estimated mean age was 50.46 years (95% CI, 48.7 to 52.1; I2, 99%), with a pooled proportion of premenopausal/perimenopausal women of 57% (95% CI, 50 to 63; I2, 98%). Among 9,738 patients with BC, pooled proportions of stage I, II, III, and IV were 6% (95% CI, 4 to 8; I2, 90%), 37% (95% CI, 31 to 43; I2, 93%), 45% (95% CI, 42 to 49; I2, 78%), and 11% (95% CI, 9 to 15; I2, 87%), respectively. The pooled proportions of patients with T3 and T4 tumors were 21% (95% CI, 14 to 31; I2, 99%) and 8% (95% CI, 5 to 12; I2, 96%), respectively, while those with positive lymph nodes were 70% (95% CI, 59 to 79; I2, 99%). CONCLUSION: Dominance of advanced stage and young age at diagnosis represented the two main features of BC among Egyptian women. Our data may serve to guide the policymakers in Egypt as well as other countries with lower resources to prioritize the diagnostic and therapeutic needs in this context.

A Systematic Review and Meta-analysis of the Impact of Radiation-Related Lymphopenia on Outcomes in High-Grade Gliomas.

Supriya MallickIntroduction Malignant gliomas are the most common primary malignant brain tumors and are typically treated with maximal safe surgical resection followed by chemoradiation. One of the unintended effects of radiation is depletion of circulating lymphocyte pool, which has been correlated with inferior overall survival outcomes. Methods A comprehensive and systematic searches of the PubMed, Cochrane Central, and Embase databases were done to assess the studies that have reported radiation-related lymphopenia in high-grade gliomas. Hazard ratios (HRs), odds ratios (OR), and mean differences were represented with Forest plots comparing patients with severe lymphopenia and no severe lymphopenia. Review Manager Version 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for the analysis. Results Nineteen studies were included in the final systematic review and 12 studies were included in the meta-analysis. The odds of developing severe lymphopenia were 0.39 (95% CI:0.19, 0.81, I 2 = 94%, p = 0.01). Patients with severe lymphopenia were at increased risk of death with a pooled HR = 2.19 (95% CI: 1.70, 2.83, I 2 = 0%, p <0.00001) compared to patients with no severe lymphopenia. The mean difference in survival between patients with severe lymphopenia and no severe lymphopenia was -6.72 months (95% CI: -8.95, -4.49, I 2 = 99%, p <0.00001), with a better mean survival in the no severe lymphopenia group. Conclusion Radiation-induced severe lymphopenia was associated with poor overall survival and increased risk of death. Photon therapy, larger planning target volume, higher brain dose, higher hypothalamus dose, and female gender were associated with increased risk of severe lymphopenia.

Current overview and special considerations for second breast cancer in Hodgkin lymphoma survivors.

Second breast cancer (SBC) is the most common solid cancer among Hodgkin Lymphoma (HL) female survivors. We reviewed the related modifying risk factors, radiation-induced carcinogenesis, tumors characteristics, management specificities, prevention and surveillance modalities based on current evidence. The risk of developing SBC may be influenced essentially by the age at HL treatment, follow-up latency, dose of irradiation received and the extent of irradiated field. SBCs generally develop at younger age, they are often bilateral, and exhibit more aggressive biological features and worse prognosis. No firm answer about the benefits of breast surveillance is provided by literature, but compelling evidence tends toward a clinical benefit in early detection. Increasing awareness among health providers' care and current survivors as well as the implementation of screening measures is crucial. Great efforts are ongoing in individualizing treatment strategies for future HL patients and response-adapted approaches are holding promise in prevention of these second malignancies.

Virtual educational meetings and activities during the COVID-19 pandemic and beyond: Egyptian oncologists' experience.

The COVID-19 pandemic has had ramifications for most healthcare activities, including medical education and communication aspects. Virtual educational meetings and activities (VEMAs) have been utilised tremendously in the pandemic era, reflecting a transition to new horizons of cyberspace. This creates the need to explore possible challenges for the implementation of such services in the rapidly evolving field of oncology. The aim of our study is to explore the impact of the COVID-19 pandemic on VEMAs in the oncology community in Egypt. It focused on the evaluation of current attitudes, satisfaction and expectations of Egyptian oncologists during and beyond the COVID-19 era. The study is a cross-sectional study using a survey that was distributed through social media. It targeted Egyptian oncologists during the months of May and June 2020. A total of 118 participants completed the survey and most of them were younger than 35 years (71%). Most participants (93.2%) agreed that COVID-19 affected the stream of live medical educational meetings. About three-quarters of them attended VEMAs during the COVID-19 period compared to 50% prior to the pandemic. The majority reported that evening hours after 8 PM was the best time to attend VEMAs and 1 hour is the optimal duration for a virtual meeting. Although the COVID-19 pandemic appeared as an unprecedented challenge for medical education, it can be a catalyst for VEMAs, especially in a rapidly evolving field such as oncology. Further research is needed to assess whether learners are ready and willing to make greater use of online educational platforms and investigate the possible barriers and strategies to enhance their use.

Risk and impact of radiation related lymphopenia in lung cancer: A systematic review and meta-analysis.

BACKGROUND: Despite the modern advances in treatment techniques, the survival of locally advanced lung cancer patients continues to remain poor. Circulating lymphocytes have an important role to play in local immune response to RT as well as immune checkpoint inhibitors, and radiation related lymphopenia has been associated with inferior survival in various tumors. METHODS: We undertook this systematic review and meta-analysis to evaluate the literature on risk and impact of lymphopenia in thoracic tumors. A systematic methodology search of the PubMed, Embase and Cochrane library was performed and eligible studies selected based on pre-defined inclusion and exclusion criteria. Review Manager Version 5.4.1 was used for the meta-analysis. RESULTS: Fourteen studies were included in the final systematic review and 10 in the quantitative analysis. Overall mean incidence of severe lymphopenia (absolute lymphocyte count < 500) was 64.24%. The patients with severe lymphopenia were at increased risk of death with a pooled HR of 1.59 (95% CI: 1.40, 1.81, I2 = 17%, P < 0.001) and progression with a pooled HR of 2.1 (95% CI: 1.57, 2.81, I2 = 59%, P < 0.001) compared to patients with no severe lymphopenia. Dosimetric parameters including gross tumor volume, lung V5 and heart V5 were predictive of lymphopenia, while advanced age, lower baseline lymphocyte counts, higher stage and large tumor size were other risk factors. Models predicting estimated radiation dose to lymphocytes were a good surrogate for treatment outcomes. CONCLUSION: Radiation related lymphopenia is associated with increased hazard of progression and death in lung cancer. Minimizing the lung and heart dose, especially in patients with concurrent other risk factors can reduce lymphopenia and potentially improve treatment outcomes in these patients.

A Systematic Review and Meta-Analysis of Cancer Patients Affected by a Novel Coronavirus.

BACKGROUND: Cancer patients with coronavirus disease 2019 (COVID-19) have been reported to have double the case fatality rate of the general population. METHODS: A systematic search of PubMed, Embase, and Cochrane Central was done for studies on cancer patients with COVID-19. Pooled proportions were calculated for categorical variables. Odds ratio (OR) and forest plots (random-effects model) were constructed for both primary and secondary outcomes. RESULTS: This systematic review of 38 studies and meta-analysis of 181 323 patients from 26 studies included 23 736 cancer patients. Our meta-analysis shows that cancer patients with COVID-19 have a higher likelihood of death (n = 165 980, OR = 2.54, 95% confidence interval [CI] = 1.47 to 4.42), which was largely driven by mortality among patients in China. Cancer patients were more likely to be intubated. Among cancer subtypes, the mortality was highest in hematological malignancies (n = 878, OR = 2.39, 95% CI = 1.17 to 4.87) followed by lung cancer (n = 646, OR = 1.83, 95% CI = 1.00 to 3.37). There was no association between receipt of a particular type of oncologic therapy and mortality. Our study showed that cancer patients affected by COVID-19 are a decade older than the normal population and have a higher proportion of comorbidities. There was insufficient data to assess the association of COVID-19-directed therapy and survival outcomes in cancer patients. CONCLUSION: Cancer patients with COVID-19 disease are at increased risk of mortality and morbidity. A more nuanced understanding of the interaction between cancer-directed therapies and COVID-19-directed therapies is needed. This will require uniform prospective recording of data, possibly in multi-institutional registry databases.

Clinico-pathological relationship between androgen receptor and tumour infiltrating lymphocytes in triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with ill-defined therapeutic targets. Androgen receptor (AR) and tumour-infiltrating lymphocytes (TILs) had a prognostic and predictive value in TNBC. The relationship between AR, TILs and clinical behaviour is still not fully understood. METHODS: Thirty-six TNBC patients were evaluated for AR (positive if ≥1% expression), CD3, CD4, CD8 and CD20 by immunohistochemistry. Stromal TILs were quantified following TILs Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) was defined as stromal TILs ≥ 50%, whereas lymphocyte-deficient breast cancer (LDBC) was defined as <50%. RESULTS: The mean age was 52.5 years and 27.8% were ≥60 years. Seven patients (21.2%) were AR+. All AR+ cases were postmenopausal (≥50 years old). LPBC was 32.2% of the whole cohort. Median TILs were 37.5% and 10% (p = 0.1) and median CD20 was 20% and 7.5% (p = 0.008) in AR- and AR+, respectively. Mean CD3 was 80.7% and 93.3% (p = 0.007) and CD8 was 75% and 80.8% (p= 0.41) in AR- and AR+, respectively. All patients who were ≥60 years old expressed CD20. LDBC was found to be significantly higher in N+ versus N- patients (p = 0.03) with median TILs of 20% versus 50% in N+ versus N-, respectively (p = 0.03). LDBC was associated with higher risk of lymph node (LN) involvement (odds ratio = 6; 95% CI = 1.05-34.21; p = 0.04). CONCLUSIONS: AR expression was evident in older age (≥50 years). Median CD20 was higher in AR- TNBC, while mean CD3 was higher in AR+ tumours. LDBC was associated with higher risk of LN involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.

The radiotherapy utilization rate in pediatric tumors: An analysis of 13,305 patients.

PURPOSE: Although the radiotherapy utilization rate (RUR) is determined for most adult cancers, it is seldom reported in childhood tumors, particularly in low- and middle-income countries (LMIC) where the majority of pediatric cancer patients reside. This study aims to investigate the real-life RUR for pediatric tumors in a large LMIC center. MATERIALS AND METHODS: The electronic files of patients treated at a single institution during 2010-2017 were reviewed and the RUR was defined as the percentage of patients who received at least one radiotherapy (RT) course from the total number of patients. RESULTS: A total of 4390 out of 13,305 pediatric cancer patients received at least one RT course with a RUR of 33%. The curative, salvage, and palliative RURs were 27.8%, 2%, and 5.7%, respectively. There was a considerable variation in the RUR between various tumors, ranging from 0% in choroid plexus papilloma and other rare tumors to 100% in intracranial germinoma. Moreover, the RUR varied among different stages within each tumor type. Overall, 753 patients received 920 palliative RT courses (range 1-9) at a median dose of 30 Gy. The most commonly irradiated metastatic sites were the bone (34%) and the brain (9.8%). CONCLUSION: This is the first analysis to provide valuable insights into the RUR for childhood tumors. Together with population-based pediatric cancer registries, this will help decipher pediatric RT needs and deficits. Additionally, the underutilization of palliative RT calls for multidisciplinary palliative care provision for pediatric cancer patients.

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.

The role of cardio-protective agents in cardio-preservation in breast cancer patients receiving Anthracyclines ± Trastuzumab: a Meta-analysis of clinical studies.

BACKGROUND: Breast cancer patients often receive cardiotoxic drugs such as anthracyclines (ANT) and Trastuzumab. Numerous trials have tested angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and beta-blockers (BB) as monotherapy or in combination to reprogram cardiac function dynamics in these patients, but no clear conclusions have been reached thus far, due to evident heterogeneity in the design of clinical studies. METHODS: This PRISMA-guided systematic review and meta-analysis assessed a pooled effect estimate of the potential benefit/harm of ACEi/ARB/BB in breast cancer patients treated with ANT ±â€¯Trastuzumab. The protocol was registered on the PROSPERO database. Electronic databases (PubMed, Cochrane Central, Scopus, Web of Science) were searched from inception until February 2019. RESULTS: Twenty-two prospective studies comprising of 2,302 participants were included in the meta-analysis. The 16 studies testing the protective effects of ACEi/ARB/BB after immediate completion of chemotherapy showed a significant lower difference in the mean change of left ventricular ejection fraction (LVEF) in patiens receiving cardio-protective drugs as compared to controls, with a standardized mean difference [SMD = -2.36 (95% CI: -3.23 to -1.49), p < 0.00001] favoring the protective role of these drugs. LVEF was evaluated after 6 months after completion of chemotherapy in 3 studies, where ACEi/ARB/BB persistently showed cardio-protective effects as compared to controls [SMD = -6.54 (95% CI: -10.74 to -2.34), p = 0.002]. After 1 year from completion of chemotherapy, ACEi/ARB/BB preserved beneficial effects on LVEF vs control [SMD = -5.37 (95% CI: -9.31 to -1.43), p = 0.008]. The effect of ACEi/ARB/BB on end-systolic volume (ESV) and end-diastolic volume (EDV) were evaluated immediately after chemotherapy completion and after 1 year. No significant protective effect was apparent. On the other hand, end-diastolic diameter (EDD) was significantly spared in the ACEi/ARB/BB group vs control after chemotherapy completion [SMD = -1.11 (95% CI: -1.88 to -0.35), p = 0.004]. Heart failure as a clinical endpoint was assessed in 11 trials. The incidence of heart failure was significantly lower in the ACEi/ARB/BB group as compared to control [Odds ratio = 0.12 (95% CI: 0.03 to 0.45), p = 0.002]. CONCLUSION: ACEi/ARB/BB may act as cardioprotective agents in breast cancer patients who undergo ANT ±â€¯Trastuzumab. More studies are required to better assess the magnitude of the cardiotoxicity hazards of ANT ±â€¯Trastuzumab, with more precise assessment of the effect of ACEi/ARB/BB on cardio-protection.