INTRODUCTION:Biosimilars have the potential to offer cost savings with comparable efficacy and safety to innovator products and, thus, increase access to treatment for more patients. However, there were significant challenges in the acceptance of oncology biosimilars in our organization in the beginning which we addressed by implementing practical strategies described in the paper. AREAS COVERED:While much of the published literature places an emphasis on the pharmacoeconomic impact of biosimilars, this paper is a novel addition to the literature because it provides practical experience and detailed processes for the formulary adoption and implementation of oncology biosimilars along with a focus on their pharmacoeconomic impact, education of oncology healthcare professionals, pharmacovigilance, and integration into the electronic health record. A narrative literature review was conducted to identify the existing evidence on biosimilar adoption and implementation in the oncology setting. EXPERT OPINION:Healthcare organizations must establish a consistent method for assessing and adopting oncology biosimilars to increase efficiency and coordination among the many team members responsible for their introduction into clinical practice. Conducting medication use evaluations and real-world evidence studies of biosimilars can help in building trust among healthcare professionals and patients in biosimilars.

PURPOSE:Oncotype Dx Recurrence Score (RS) is prognostic and predictive of chemotherapy benefit in women with node-negative and node-positive in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer. Nevertheless, its direct cost may be inhibitive. This study assesses the correlation between the RS and the free online PREDICT tools' estimations of adjuvant chemotherapy benefit. PATIENTS AND METHODS:A retrospective review of the electronic medical records of 112 patients with tumors tested for the RS and the PREDICT tool was used to estimate survival benefits. The correlation between RS and PREDICT estimations was analyzed using Spearman rank and McNemar tests. RESULTS:The median age of patients was 53 (95% CI, 50 to 55) years, with most patients having negative axillary lymph nodes (78%). While the absolute value for RS showed significant positive correlations with adjuvant chemotherapy's benefit as estimated by PREDICT, no significant correlations were found between the two methods in the percentage of chemotherapy gain. Notably, discordance rates between 48% and 67% between RS-based risk assignments and those based on PREDICT estimates were significant across the study population and subgroups. Only one disease recurrence and one breast cancer-related death were documented over a median follow-up of 23.5 (95% CI, 19.8 to 27.2) months. CONCLUSION:Our findings highlight a significant discordance between RS and PREDICT tools in predicting the benefits of adjuvant chemotherapy in patients with HR+, HER2- early breast cancer. While both tools aim to personalize cancer treatment, their discordance varies, suggesting that PREDICT could not substitute RS to predict adjuvant chemotherapy benefits regardless of patient risk classification. Further studies are needed to explore these relationships and optimize precision medicine approaches in breast cancer management.

Breast cancer is the most prevalent type of cancer among women worldwide. Many recently diagnosed and treated breast cancer patients complain about sleep disorders, depression, anxiety, stress, and fatigue. This study aimed to evaluate sleep quality among breast cancer patients and to assess its association with psychological disorders, and socio-demographic and clinical characteristics of patients. This cross-sectional study was conducted among women who received radiotherapy for breast cancer (stage 1–3) at King Abdul-Aziz Medical City-Jeddah from January to August 2021. Each participant completed a personal information form, the Pittsburgh Sleep Quality Index (PSQI), the Depression, Anxiety, and Stress Scale-21 (DASS-21), and the International Physical Activity Questionnaire (IPAQ). Clinical data were collected from the medical records to evaluate certain risk factors. Descriptive statistics were used for participant characteristics, and analyses of variance were used to assess associations between the qualitative variables. Fifty-six women with a mean age of 50.1 years and an average of 10 months after cancer diagnosis were included. Poor sleep quality was present in 58

Background: HER2-targeting therapies may increase the risk of decreased left ventricular ejection fraction (LVEF), potentially leading to heart failure. The growing number of breast cancer survivors due to HER2-targeted treatments necessitates long-term cardiotoxicity management. Method: This retrospective study included HER2-positive breast cancer patients aged 18 or older who received at least 1 dose of HER2-targeting treatment between 2016 and 2020. The primary endpoint was the incidence of cardiotoxicity, defined as LVEF <50% with a 10% decline, LVEF drop by >15%, or onset of symptomatic heart failure. Secondary endpoints included the proportion of patients with baseline LVEF 50% to 55% developing cardiotoxicity, those discontinuing HER2 therapy due to heart failure, those treated with heart failure medications, and those continuing HER2 therapy while on heart failure medications. Another secondary outcome was the development of a hospital protocol for monitoring cardiotoxicity in these patients. Results: A total of 212 patients were included, with a median age of 56.5 years (interquartile range: 43-58 years). Twenty-two patients (10.37%) experienced cardiotoxicity from HER2-targeted treatment. Thirteen patients (6.13%) had asymptomatic heart failure with LVEF decrease of more than 10% to less than 50%. Five patients (2.35%) with LVEF less than 40% had asymptomatic heart failure, while 4 patients (1.88%) had symptomatic heart failure regardless of LVEF decline. HER2-targeted treatment was temporarily discontinued in 3 (13.63%) patients and permanently in 4 (18.18%) patients due to cardiotoxicity. The remaining 15 patients resumed treatment without interruption. Only 13 out of 22 patients were referred to cardiologists and prescribed heart failure medications. Conclusion: Close monitoring of LVEF in patients receiving HER2-targeting therapy can help health care providers initiate anti-heart failure medications to prevent LVEF deterioration and maintain HER2-targeting therapy.

Aims This study estimated, for Saudi Arabia, the cost-efficiency of converting patients from reference Neupogen and Neulastim to one of two filgrastim biosimilars (Nivestim, Zarzio); the budget-neutral expanded access to supportive care with biosimilar filgrastim and therapeutic care to ado-trastuzumab emtansine thus afforded; and the number-needed-to-convert (NNC) to provide supportive or therapeutic treatment to one patient. Materials and methods Replicating prior studies, we modeled the cost-efficiencies gained from converting varying proportions of a hypothetical panel of 4,000 patients undergoing six cycles of cancer treatment from Neupogen or Neulastim to one of the two biosimilar G-CSF formulations, using national cost inputs. Cost-savings in USD were used to estimate the additional doses of biosimilar G-CSF and expanded access to ado-trastuzumab emtansine on a budget-neutral basis, and NNC to purchase one additional dose of supportive or therapeutic treatment. Results Savings from conversion from reference to a biosimilar filgrastim were $3,086,400 (Nivestim) and $3,460,800 (Zarzio). With reference pegfilgrastim, savings from conversion were $11,712,240 (Nivestim) and $12,086,640 (Zarzio). Biosimilar conversion from reference to biosimilar filgrastim enabled expanded access to ado-trastuzumab emtansine ranging from 61 patients (5 days, Nivestim) to 191 patients (14 days, Zarzio). For supportive care, biosimilar conversion enabled expanded access ranging from 8,244 patients (5 days, Nivestim) to 25,882 patients (14 days, Zarzio). For biosimilar conversion from daily filgrastim, the NNC for treatment with ado-trastuzumab emtansine decreased as days of injections increased [5 days: 395 (Nivestim), 352 (Zarzio); 14 days: 141(Nivestim), 126 (Zarzio)]. Alternately, for biosimilar conversion from single-injection pegfilgrastim to daily biosimilar filgrastim, the NNC for treatment with ado-trastuzumab emtansine rose as days of injections increased, being highest under the 14-day scenario (146, Nivestim; 130, Zarzio). Conclusion This simulation study demonstrated significant potential cost-savings from biosimilar conversion. These savings provide budget-neutral increased access to supportive and therapeutic cancer care.

The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study’s main outcome, while the secondary endpoint was a clinical benefit. Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7

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.

PURPOSELuminal, human epidermal growth factor receptor 2–negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT).MATERIALS AND METHODSThe SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2–negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31.RESULTSAt the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate (P = .05).CONCLUSIONThe upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

Aim: In this study, we aimed to investigate the incidence rate, risk factors, and mortality rates in patients with early-stage breast cancer using anti-HER2 (Human epidermal growth factor receptor-2) treatment. Patients and Methods: A total of 106 patients diagnosed with human epidermal growth factor 2 (HER2)-positive early-stage breast cancer and receiving anti-HER2 treatment at King Abdulaziz Medical City (KAMC) from 2015 to 2019 were included in the analysis to assess the incidence of cardiotoxicity was collected as a retrospective study. Univariate and multivariate analyses as well as multiple exact logistic regression analysis were conducted to understand the relationships between the left ventricular ejection fraction (LVEF) and treatment combinations and comorbidities Results: The LVEF measurements using an echocardiography method at the baseline (before any treatment) and during the anti-HER2 therapy were assessed. The results suggest that the higher the drug combination, the higher the odds ratio for the declined ejection fraction (EF) patient group. Further, patients treated with the pertuzumab and trastuzumab combination were four times more likely to have a decline in their EF than those who did not use the pertuzumab and trastuzumab drug combination (OR 4.28, 95% CI [1.68–10.91]). Conclusion: This study demonstrated that the drug combination considered here is associated with reduced LVEF and, similarly, comorbidities were also related to EF. However, a larger study in a global patient population will confirm the present observations.

Introduction: Oncotype DX assay recurrence score (ODX-RS) cut-off values have recently changed after the publication of the TAILOR-X trial results. We aim to explore decisions for adjuvant chemotherapy (ACT) based on physicians’ clinical assessment and the evolving ODX-RS. Methodology: Patients who underwent ODX testing after curative surgical resection of estrogen receptor positive (ER+), Her2 non-overexpressed (Her2–) and lymph node-negative (LN–) breast cancer (BC) were eligible. Management of these patients was guided by the results of the old ODX-RS-1 (<18, 18–30, and ≥31) risk grouping. For the purpose of this study, treatment decisions were also assumed according to TAILOR-X results (ODX-RS-2). Decisions of 3 medical oncologists on ACT were solicited by blinding them to the RS to investigate concordance with ODXA RS-1 and 2 recommendations. Results: Sixty-six consecutive patients were included. Median age was 50.5 (range: 21–73) years. There was 1 male patient, and 37/65 females (56.9%) were premenopausal. Among the 3 oncologists, recommendations for ACT based on clinical assessment were discrepant in 29 (43.9%) patients. Based on majority consensus (≥2 oncologists), ACT would have been recommended to 22/41 (53.7%) and 22/46 (47.82%) patients with low-risk tumors according to ODX-RS-1 and ODX-RS-2, respectively. Compared to ODX-RS-1, ODX-RS-2 identifies 12% (46 vs. 41) more low-risk patients and 66% (20 vs. 12 patients) more high-risk patients. Conclusion: Overtreatment and discrepancies in the management of patients with ER+/Her2–/LN– early BC can be minimized by the implementation of ODX genomic assay. Some differences in ACT recommendations exist between ODX-RS-1 and ODX-RS-2.

PURPOSE:To investigate the association between mammographic density (MD) phenotypes and both clinicopathologic features of breast cancer (BC) and tumor location. METHODS:MD was measured for 297 BC-affected females using qualitative (visual method) and quantitative (fully automated area-based method) approaches. Radiologists' description, visible external markers, and surgical scar were used to establish the location of tumors. Binary logistic regression models were used to assess the association between MD phenotypes and BC clinicopathologic features. RESULTS:Categorical and numerical MD measures showed no association with clinicopathologic features of BC (p > 0.05). Participants with higher BI-RADS scores [(51-75% glandular) and (> 75% glandular)] (p < 0.001), and percent density (PD) categories [PD (21-49%) and PD ≥ 50%] (p = 0.01) were more likely to have tumors emanating from dense areas. Additionally, tumors were commonly found in dense regions of the breast among patients with higher medians of PD (p = 0.001), dense area (DA) (p = 0.02), and lower medians of non-dense area (NDA) (p < 0.001). Adjusted logistic regression models showed that high BI-RADS density (> 75% glandular) has an almost fivefold increased odds of tumors developing within dense areas (OR 4.99, 95% CI 0.93-25.9; p = 0.05. PD (OR 1.02, 95% CI 1-1.03, p = 0.002) and NDA (OR 0.99, 95% CI 0.991-0.997, p < 0.001) had very small effect on tumor location. Compared to tumors within non-dense areas, tumors in dense areas tended to exhibit human epidermal growth factor receptor 2 positive (p = 0.05) and carcinoma in situ (p = 0.01) characteristics. CONCLUSION:MD shows no significant association with clinicopathologic features of BC. However, BC was more likely to originate from dense tissue, with tumors in dense regions having human epidermal growth receptor 2 positive and carcinoma in situ characteristics.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma (NHL), representing 30% of all lymphoma cases. Within the first 2-3 years following immunochemotherapy, 30-40% of patients will experience a relapse or a refractory disease, thereby exhibiting a poor prognosis. High-dose immunotherapy followed by autologous stem cell transplantation is the standard care for relapsed/refractory (RR) patients with DLBCL. However, >60% of patients are ineligible for a transplant, presenting a therapeutic challenge. Chimeric antigen receptor (CAR) T-cell therapy has shown promising efficacy in patients with DLBCL, including those with R/R disease. The present study conducted a meta-analysis that showed highly favorable outcomes [objective response rate (ORR): 69%; complete remission (CR): 49%] in B-cell NHL patients (n=419) who were treated with second-generation CAR T cells. The response rate varied in different types of B-cell NHL. In 306 patients with R/R DLBCL eligible for rate evaluation, the ORR and CR rate mean estimates were 68% [95% confidence interval (CI), 55-79%] and 46% (95% CI, 38-54%), respectively. Thus, the findings indicated that immunotherapy with CAR T cells has improved outcomes for patients with R/R DLBCL and other subtypes of B-cell NHL compared with standard chemotherapy regimens. The study revealed that grade ≥3 anemia (34%) and thrombocytopenia (30%) were the most common adverse effects of CAR T-cell therapy. Incidence of grade ≥3 cytokine release syndrome and neurotoxicity associated with CAR T-cell therapy was effectively managed.

594 Background: While hormonal therapy (HT) is a fundamental treatment in breast cancer therapy, neoadjuvant NAHT is not considered standard. The SAFIA trial is a prospective international neoadjuvant Phase III investigating the potential role of the addition of palbociclib (P) in patients (pts) sensitive to HT. We report the results of induction Faslodex (+/- zoladex) in pts initially selected by RS < 31, in order to assess their individual HT sensitivity before double-blind randomization HT vs HT + P followed by surgery. Materials and Methods: A total of 308 pts (stages II and IIIA Luminal A/B HER2 negative) in 24 centers and 6 countries (Middle-East/Maghreb) underwent upfront RS to select pts for induction HT. Pts with RS < 31 received induction neoadjuvant fulvestrant (500 mg i.m Day 1, 14, 28 then q.4 weeks) + goseriline (3.6 mg s.c q.4 w for pre and peri-menopausal pts) for 4 months, followed by clinical and radiological assessment of the disease response before randomization. Response was defined as no progression: Complete Response-CR/ Partial Response-PR: > 50% and Minor Response-MR: < 50% to > 0%/ No Response-NR: progression > 0%. Results: A total of 70 pts (22%) with RS > 31 were excluded, leaving 238 eligible pts for NAHT, age (25-84); pre-peri/ post menopause: 135 (57%)/103 (43%); Luminal A/B: 112 (49%)/114 (51%); Stage II/IIIA: 196 (87%) / 29 (13%). One hundred and seventy-seven pts (177) have validated responses to induction NAHT: CR: 9 pts (5%) / MR: 105 pts (59%) for major response rate: 64% / MR: 56 pts (32%) / NR: 7 pts (4%); available RS 0-10: 23 pts (16%) / RS 11-18: 67 pts (47%) / RS 19-25: 34 pts (24%) / RS 26-30: 18 pts (13%). Correlations between Response to NAHT and RS are shown in the table below (not statistically significant). Conclusions: In our population, upfront Oncotype DX RS < 31 allowed to select pts for induction NAHT without loss of chances with a no-progression rate (CR+PR = MR) of 96%. No significant correlation was found between RS and response to NAHT. Upfront RS > 31 (22%) is selecting pts candidates for neoadjuvant chemotherapy with a potential high risk of endocrine resistance. Clinical trial information: ICRG1201 .

Introduction. Granulocyte colony-stimulating factor (G-CSF) is commonly used for prevention and treatment of febrile neutropenia among solid tumor patients. It is considered an effective and relatively safe supportive care medication; however, it can cause rare and serious side effects such as spleen rupture or infarction. Case Presentation. We are reporting a case of a 27-year-old female with breast cancer who has been treated with dose-dense chemotherapy and received colony-stimulating factor as primary prevention of febrile neutropenia that was complicated halfway through with splenic infarction. This finding was confirmed by computed tomography (CT) scan and splenic biopsy. Management was conservative without the need of surgical intervention. Conclusion. Although splenic infarction is an extremely rare side effect of G-CSF, it can be a serious complication that should be recognized, monitored, and managed carefully.

Introduction: A meeting was organized by the Generics and Biosimilars Initiative (GaBI) in collaboration with Saudi Pharmaceutical Society (SPS), to discuss the regulation, approval process, interchangeability/substitution, and post-marketing surveillance of biosimilars in Gulf Cooperation Council (GCC) countries. This 'First GCC Stakeholder Meeting on Approval Process, Interchangeability/Substitution and Safety of Biosimilars', took place on 20 November 2017, in Riyadh, Saudi Arabia and gave relevant stakeholders an opportunity to discuss these concepts between themselves and with experts from Saudi Arabia and abroad. Methods: The meeting brought regulators from GCC countries and academics, medical specialists, and pharmacologists and pharmacists from Saudi Arabia together with experts from Italy, Norway, Saudi Arabia and the US, to share knowledge and exchange information. There were a number of expert speaker presentations with an interactive panel discussion. Following this, the audience was presented with data for two semi-fictional similar biotherapeutic products. The participants were divided into two discussion groups where they evaluated the fictional data supplied. Results: The presentations were successful in conveying information about the current state of biosimilar regulation, approval, interchangeability/substitution, and post-marketing surveillance of effectiveness and safety. This resulted in a useful interactive discussion from which clearly defined action points could be extracted. Conclusion: Biosimilar medicines are becoming increasingly available and used across GCC countries. The First GCC biosimilars stakeholder meeting was successful in bringing representatives from GCC nations together with those from Europe and the US, to discuss the best routes forward for successful biosimilar approval and regulation and enabled action points to facilitate biosimilar uptake with appropriate pharmacovigilance to be outlined.

Background: Hodgkin lymphoma (HL) exhibits considerable clinicopathological variations in different parts of the world. This study was prompted by the limited availability of HL data in developing countries (particularly long-term outcomes). Methods: We performed a retrospective review of eligible adult HL patients treated at 3 tertiary centers in Saudi Arabia between January 1997 and December 2012. Results: The review included 340 patients with a median age of 26 years (range 15-82 years); 53% were male, 74% had an advanced stage, 22% had bulky disease, and 70% had low-to-intermediate risk according to the International Prognostic Score. Nodular sclerosis was the most common histological subtype (59%). Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) was offered to 92% and radiotherapy to 43%. Initial therapy outcomes were complete response, partial response, and progressive disease in 91%, 5%, and 2% of patients, respectively. At a median follow-up of 39 months, the actuarial freedom from treatment failure at 5 years was 74%, with a 5-year overall survival of 91%. Multivariate analysis showed that advanced disease stage and high-risk international prognostic index independently predicted an adverse outcome. Conclusion: Our Saudi patient population exhibited outcomes that were comparable to those reported in developed countries.

BACKGROUND Bleomycin pulmonary toxicity (BPT) has been described in Hodgkin's lymphoma (HL) patients treated with bleomycin-containing chemotherapy regimens. METHODOLOGY We reviewed the records of 164 consecutive HL patients. RESULTS BPT was observed in 24 of 164 patients (15%). Older age and history of concomitant lung disease were significantly associated with approximately threefold (odds ratio: 3.38; 95% CI: 1.25-9.13; p = 0.02) and sevenfold (odds ratio: 7.19; 95% CI: 2.64-19.54; p < 0.0001) increase in BPT risk, respectively. The actuarial 5-year progression-free and overall survival for BPT and non-BPT groups, were not significantly different. CONCLUSION In Saudi Arabian HL patients, the risk of BPT and its effect on survival outcome were comparable to that reported from developed countries.

The association between PIK3CA mutation and resistance to anti-HER2 therapy (AHT) is not precisely defined. This meta-analysis intended to explore the clinical utility of PIK3CA mutation in HER2-positive breast cancer treated with AHT. Literature search identified 19 eligible studies. There were 1720 patients with advanced, 828 with early and 1290 patients treated in the neoadjuvant setting. In metastatic breast cancer, AHT showed no differential objective response benefit between the wild type (WT) and the mutated type (MT) PIK3CA subgroups (odds ratio [OR] = 1.09; 95 % CI 0.60-2.00; P = 0.78). AHT favorable affected progression-free survival (PFS) irrespective of PIK3CA mutation. There was no PFS difference between WT and MT regardless of the offered therapy. In early breast cancer, trastuzumab combined with the same chemotherapy conferred consistent relapse-free survival benefit in WT and MT subgroups (WT: HR = 0.59; 95 % CI 0.44-0.80; P < 0.001 vs. MT: HR = 0.42; 95 % CI 0.24-0.74; P < 0.001). In the neoadjuvant setting, AHT-based therapy produced a 72 % higher pathologic complete response (pCR) rate in WT as compared with that in MT PIK3CA tumors (OR = 1.72; 95 % CI 1.29-2.13; P < 0.001). In that setting, there was no disease-free or overall survival difference based on PIK3CA mutational status. In this meta-analysis, AHT did not achieve differential benefit according to PIK3CA mutation in HER2-positive metastatic or early breast cancer; however, in the neoadjuvant setting, patients harboring WT PIK3CA tumors attained a higher pCR rate.

Background: The relationship between lymphocyte infiltrates (LIs) and breast cancer outcome remains controversial.We performed this meta-analysis to elucidate the relationship.Methods: A literature search identified 21 eligible studies.Results: 16,097 patients were included.Multivariate analyses data for patients with unspecified receptors status showed that rich LIs expression was associated with 52% (hazard ratio [HR] = 0.48; 95% confidence interval [CI], 0.30-0.77),and 29% (HR = 0.71; 95% CI, 0.63-0.80)reduction in the risk of relapse and death, respectively.In the neoadjuvant setting, rich LIs predicted a 28% increase in complete pathological response rate.The prognostic and predictive utility of rich LIs was restricted to patients with estrogen receptor negative (ER-) or triple negative disease.Only rich CD8+ T cells tumors demonstrated clinical utility. Conclusion:LIs significantly correlated to outcome predominantly in ER-tumors.Integrating immunotherapy with conventional therapy may warrant future research in breast cancer.