Breast Cancer Treatment Guidelines Research Articles

Characteristics of Chemotherapy Treatments for Breast Cancer Patients at Bhayangkara Tk.1 Pudsdokkes Polri Hospital, Jakarta

Background: Breast cancer is a malignant breast tumor that develops in the ductal or lobular epithelium and usually attacks women. Chemotherapy is a cornerstone of breast cancer treatment, particularly for patients with advanced disease or those who are not candidates for surgery or radiation therapy. This research aims to observe the use of chemotherapy drugs for breast cancer patients in terms of chemotherapy regimens and cycles at Bhayangkara Tk.1 Pudsdokkes Polri Hospital. Methods: This study employs descriptive quantitative approaches. Data were gathered retrospectively from medical records of breast cancer patients receiving chemotherapy at Bhayangkara Tk.1 Pudsdokkes Polri Hospital Jakarta from July to December 2021. Results: From 110 patients, 86 (78.18%) patients used the CAF regimen, 18 (16.36%) patients used the AC regimen, and 3 (2.73%) patients used the TAC regimen, while the regimen that did not comply with the guidelines was 2 (1.82%) patients using the combination of paclitaxel and epirubicin, 1 patient utilizing the combination of paclitaxel and doxorubicin. Forty-six (41.82%) patients with the CAF regimen had completed six cycles of chemotherapy with intervals of 3 weeks or 21 days, while only 5 patients (3.63%) completed four cycles of the AC regimen at 3-week or 21-day intervals. At the time of data collection, 11 patients, and 1 patient utilizing the AC regimen. This was because 59 patients had not yet finished the chemotherapy cycle, specifically in the advanced stage. Conclusions: The CAF regimen was the most commonly used chemotherapy regimen, followed by the AC and TAC regimens. This finding aligns with current clinical guidelines for breast cancer treatment. A significant number of patients had not yet completed their chemotherapy cycles, particularly those with advanced-stage breast cancer. This highlights the challenges associated with treating advanced disease and the need for more effective and less toxic treatment options.

Methodology for Using Real-World Data From Electronic Health Records to Assess Chemotherapy Administration in Women With Breast Cancer.

Identification of patients' intended chemotherapy regimens is critical to most research questions conducted in the real-world setting of cancer care. Yet, these data are not routinely available in electronic health records (EHRs) at the specificity required to address these questions. We developed a methodology to identify patients' intended regimens from EHR data in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study. In women older than 18 years, diagnosed with primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019), we categorized participants into 24 drug combinations described in National Comprehensive Cancer Network guidelines for breast cancer treatment. Participants were categorized into 50 guideline chemotherapy administration schedules within these combinations using an iterative algorithm process, followed by chart abstraction where necessary. We also identified patients intended to receive nonguideline administration schedules within guideline drug combinations and nonguideline drug combinations. This process was adapted at Kaiser Permanente Washington using abstracted data (2004-2015). In the OBCD cohort, 13,231 women received adjuvant or neoadjuvant chemotherapy, of whom 10,213 (77%) had their intended regimen identified via the algorithm, 2,416 (18%) had their intended regimen identified via abstraction, and 602 (4.5%) could not be identified. Across guideline drug combinations, 111 nonguideline dosing schedules were used, alongside 61 nonguideline drug combinations. A number of factors were associated with requiring abstraction for regimen determination, including: decreasing neighborhood household income, earlier diagnosis year, later stage, nodal status, and human epidermal growth factor receptor 2 (HER2)+ status. We describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens in large, observational studies. This methodology can improve efficiency of use of large-scale clinical data in real-world populations, helping answer critical questions to improve care delivery and patient outcomes.

Breast cancer treatment guidelines(2022 edition)

Breast cancer treatment guidelines(2022 edition)

Construction of a knowledge graph for breast cancer diagnosis based on Chinese electronic medical records: development and usability study

BackgroundElectronic medical records (EMRs) contain a wealth of information related to breast cancer diagnosis and treatment. Extracting relevant features from these medical records and constructing a knowledge graph can significantly contribute to an efficient data analysis and decision support system for breast cancer diagnosis.MethodsAn approach was proposed to develop a workflow for effectively extracting breast cancer-related features from Chinese breast cancer mammography reports and constructing a knowledge graph for breast cancer diagnosis. Firstly, the concept layer of the knowledge graph for breast cancer diagnosis was constructed based on breast cancer diagnosis and treatment guidelines, along with insights from clinical experts. .Next, a BiLSTM-Highway-CRF model was designed to extract the mammography features, which formed the data layer of the knowledge graph. Finally, the knowledge graph was constructed by combining the concept layer and the data layer in a Neo4j graph data platform, and then applied in visualization analysis, semantic query and computer assisted diagnosis.ResultsMammographic features were extracted from a total of 1171 mammography examination reports. The overall extraction performance of the model achieved an accuracy rate of 97.16%, a recall rate of 98.06%, and a F1 score of 97.61%. Additionally, 47,660 relationships between entities were identified based on the four different types of relationships defined in the concept layer. The knowledge graph for breast cancer diagnosis was constructed after inputting mammographic features and relationships into the Neo4j graph data platform. The model was assessed from the concept layer, data layer, and application layer perspectives, and showed promising results.ConclusionsThe proposed workflow is applicable for constructing knowledge graphs for breast cancer diagnosis based on Chinese EMRs. This study serves as a reference for the rapid design, construction, and application of knowledge graphs for diagnosis and treatment of other diseases. Furthermore, it offers a potential solution to address the issues of limited data sharing and format inconsistencies present in Chinese EMR data.

Abstract P3-03-16: A methodology for using real-world data from electronic health records to assess chemotherapy administration in women with breast cancer

Abstract Introduction Chemotherapy administration in real-world cancer care can differ extensively from clinical trials. It is important to understand real-world practice to identify dose reductions, delays, regimen changes and early discontinuations that impact cancer outcomes. Such variables require knowledge of intended regimens, which may not be well-documented in structured data in electronic health records (EHRs). We examined EHR data from the Kaiser Permanente Northern California (KPNC) site of the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study to develop a process to identify each patient’s intended regimen. Methods In this study of women diagnosed and treated with primary stage I-IIIA breast cancer at KPNC from 2006-2019, and ages 18+y at diagnosis, we analyzed treatment patterns using structured EHR data on the drugs, dosages, and dates at which they were administered (from which intervals and total length can be derived). Chemotherapy agents were identified using the NCI’s CANMED database augmented with other sources. We used these data to categorize patients into the 22 drug combinations described in the National Cancer Care Network (NCCN) guidelines for breast cancer treatment. Within these 22 drug combinations, women were then subcategorized into 45 distinct chemotherapy administration schedules, defined as NCCN guideline regimens (NGRs). For this step, algorithms were developed that categorized patients into NGRs if they received the exact regimen described in the guidelines. For the second step, we conducted a manual review of the EHR data for patients who were unable to be categorized. This enabled us to gradually loosen the criteria (in terms of cycle intervals or number of cycles) so patients whose chemotherapy administration aligned closely with NGRs were categorized into each of the 45 NGRs. Clear patterns emerged of regimens that were administered to multiple patients, despite being outside of the NCCN guidelines, which we have defined as non-standard NGRs. For example, in the drug combination TC (cyclophosphamide and docetaxel) the NGR was TC every 21 days for 4 cycles. We found approximately 1 in 10 patients received 6 cycles, which we defined as a non-NGR. For the remaining uncategorized patients, medical chart abstraction was undertaken as a third step, at which point patients were categorized into either existing regimens or new non-NGRs if their intended regimen had not been previously described in the guidelines. Results Among 31,418 women with breast cancer, 12,427 (39.6%) received chemotherapy. We determined the intended chemotherapy regimens for 6,559 (52.8%) receiving the 45 NGRs using EHR data. We further expanded the algorithms through a manual review of the EHR data, which enabled us to categorize 2,977 (24.0%) additional women into their intended regimens. Abstracted medical notes were reviewed for the remaining patients for whom we had not been able to identify the intended regimen. Across both the manual review and abstraction processes, we were able to identify additional non-standard NGR regimens. In total, 9,536 (76.7%) of women were categorized into their intended regimen through the algorithm/manual review process, while 2891 (23.3%) of women underwent medical chart abstraction to identify the intended regimen. Conclusion Here, we describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens at a granularity and scale not seen previously. We are adapting this method at a second OBCD study site, Kaiser Permanente Washington, where all women have undergone medical chart abstraction. We hope this methodology leads to increased feasibility and efficiency of use of large-scale clinical data, in turn improving cancer care delivery, patient outcome evaluation, and other real-world questions. Citation Format: Jenna Bhimani, Kelli O’Connell, Rachael P. Burganowski, Isaac J. Ergas, Marilyn J. Foley, Grace B. Gallagher, Jennifer J. Griggs, Narre Heon, Tatjana Kolevska, Yuriy Kotsurovskyy, Candyce H. Kroenke, Kanichi G. Nakata, Sonia Persaud, Donna R. Rivera, Janise M. Roh, Sara Tabatabai, Emily Valice, Erin J. Bowles, Elisa V. Bandera, Lawrence H. Kushi, Elizabeth D. Kantor. A methodology for using real-world data from electronic health records to assess chemotherapy administration in women with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-16.

Development and validation of a novel endoplasmic reticulum stress-related lncRNA prognostic signature and candidate drugs in breast cancer.

Breast cancer (BC), the most common malignancy in women, has a high cancer-related mortality. Endoplasmic reticulum stress (ERS), a response to the accumulation of unfolded proteins, has emerging roles in tumorigenesis, including invasion, metastasis, immune escape, etc. However, few studies have focused on the correlation between ERS with long non-coding RNAs (lncRNAs) in BC. We attempted to construct an ERS-related lncRNA prognostic signature and study its value in BC from tumor mutational burden (TMB), tumor immune microenvironment (TIME), cluster, clinical treatment, and so on. In the present study, transcriptomic and clinical data of BC patients were extracted from The Cancer Genome Atlas (TCGA) database. Correlation test, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) method were performed to determine an ERS-related lncRNA prognostic signature. Survival and predictive performance were analyzed according to Kaplan–Meier curves and receiver operating characteristic (ROC) curves, while nomograms and calibration curves were established. Then, an enrichment analysis was performed to study the functions and biological processes of ERS-related lncRNAs. TMB and TIME were also analyzed to assess the mutational status and immune status. Additionally, by using consensus cluster analysis, we compared differences among tumor subtypes. Drug sensitivity analysis and immunologic efficacy evaluations were performed together for further exploration. We identified a novel prognostic signature consisting of 9 ERS-related lncRNAs. High-risk patients had worse prognoses. The signature had a good predictive performance as an independent prognostic indicator and was significantly associated with clinicopathological characteristics. Enrichment analysis showed that metabolic pathways were enriched in high-risk patients, while immune pathways were more active in low-risk patients. Low-risk patients had lower TMB, higher immune scores, and stronger immune functions. Cluster analysis clarified that cluster 2 had the most active immune functions and was sensitive to more drugs, which may have the best clinical immunological efficacy. A clinical efficacy evaluation revealed that patients in the low-risk group may benefit more from chemotherapy, targeted therapy, and immunotherapy. The novel signature has significant clinical implications in prognosis prediction for BC. Our study clarifies that there is a potential connection between the ERS-related lncRNAs and BC, which may provide new treatment guidelines for BC.

Public procurement of antineoplastic agents used for treating breast cancer in Brazil between 2013 and 2019

BackgroundBreast cancer is the most common cancer among women in Brazil and the country’s public health care system is the main care provider. Timely treatment can increase the chance of cure, prevent metastasis and improve quality of life. Effective public procurement of antineoplastic agents can therefore improve access to drug therapy. This study investigates patterns in the procurement of selected antineoplastic agents used for treating breast cancer by public bodies and avoidable expenditure on these drugs between January 2013 and December 2019.MethodsWe selected antineoplastic agents used for adjuvant or preoperative chemotherapy listed in the 2018 Breast Cancer Diagnosis and Treatment Guidelines and included in category L of the WHO Anatomical Therapeutic Chemical classification system. We analyzed regular purchases of antineoplastic agents registered in the Integrated General Services Administration System (SIASG), considering purchased quantity, unit price, date of purchase and procuring entity. Prices were inflation-adjusted to July 2019 based on the National Consumer Price Index.ResultsA total of 10 antineoplastic agents were selected. Trastuzumab and tamoxifen accounted for the largest share of total spending and largest volume of purchases, respectively. The Ministry of Education was the largest purchaser in volume terms of all the drugs studied, except trastuzumab 440 mg, where the category “Other Institutions” accounted for most purchases, and vinorelbine 20 mg, where the Ministry of Health made most purchases. The category “Other Institutions” accounted for the largest share of total spending. Total avoidable expenditure was R$99,130,645. Prices paid for medicines and avoidable expenditure were highest in the Ministry of Defense.ConclusionsThe differences observed in the performance of different categories of buyers as to amounts purchased and prices practiced for antineoplastic agents could be reduced by employing strategies to expand the centralization of purchases, resulting in expanded access to breast cancer medicines in the public sector.

Barriers and challenges in providing standard breast cancer care in low resource settings.

In this study, we investigated the barriers to the delivery of internationally accepted breast cancer care in low resource settings (LRS) as compared to well-endowed resource settings (WRS) via an online survey. The survey was completed by 199 surgeons from eleven countries: 51 from WRS and 148 from LRS, based on our definition. The two most common facilities lacking in LRS were sentinel lymph node biopsy and immune-histochemistry (67% and 60% respectively). Only 22% respondents from LRS confirmed that all their eligible patients received hormonal therapy and only 8% radiotherapy as compared to 98% and 75% from WRS. Widespread limitations exist in most LRS, making internationally accepted breast cancer treatment guidelines impossible to follow, and thus resulting in suboptimal cancer care.

Predictive biomarkers of benefit from chemotherapy in invasive lobular carcinoma of the breast.

e12552 Background: Treatment guidelines for breast cancer do not differ by histology. This study explores whether systemic therapy with chemotherapy followed by endocrine therapy (CET) confers an overall survival (OS) benefit vs. endocrine therapy alone (ET) in hormone receptor-positive and HER2-negative (HR+/HER2-) invasive lobular carcinoma (ILC) of the breast, and investigates various potential predictive biomarkers. Methods: Data on female patients with pathologic stage I-III, HR+/HER2- ILC diagnosed between 2010-2017 were extracted from the National Cancer Database (NCDB). A ten-percent year-stratified sample was randomly selected for this study. Potential differences in OS between ET and CET were explored using multivariate Cox Proportional-Hazards with considerations of socio-demographics, histologic subtype (pure lobular vs. mixed ductal-lobular), stage, nodal status, and OncotypeDX score (ODX). Results: N = 17,653 cases of HR+/HER2-, stage I-III ILC were randomly selected. This analysis focused on the 86.5% patients who received ET or CET (n = 15,271). 50.6% had AJCC stage I disease at diagnosis (of which 4.7% were node-positive, or ‘N+’), 35.7% had stage II (of which 45.5% were N+), and 13.6% had stage III (of which 97.8% were N+). 3.2% of cases had high-risk scoring per ODX (≥ 26), 33.2% had low-risk, while for 63.6% ODX data was unknown. CET administration was significantly associated with younger age (47.5% in age < 55, 34.0% in 55-64, 26.1% in 65-71 and 9.7% in ≥72), advanced staging (10.6% stage I, 38.6% stage II and 80.2% in stage III used CET), ODX (13.3% low ODX, 66.6% high ODX and 36.6% unknown ODX) and insurance (37.8% in private and 21.5% in non-private). OS was similar between ET and CET (adjusted 5-year cum hazard: 4.3% vs 4.5%, p = 0.57) in cohort overall. A benefit of CET was not observed in stratified analyses by age, histologic subtype, and ODX (high vs. low vs. unknown). However, stage-stratified analysis revealed an OS benefit with CET in stages II-III ILC. In nodal status-stratified analyses: CET had worse OS vs. ET with N- ILC (adjusted 5-year OS: 95.1% vs 96.4%, p = 0.02), but better OS in N+ (91.6% vs 88.9%, p = 0.008) disease. In further stratified models, the CET benefit was also observed in stage II with N+ (96.1% vs 92.0%, p = 0.02), unknown ODX with N+ (89.6% vs 85.4%, p = 0.001), pure lobular with N+ (95.8% vs 92.7%, p = 0.02) and mixed ductal-lobular with N+ (96.6% vs 91.2%, p = 0.0007), without differences in their N- counterparts. Although benefit of CET was observed in N+, the use of CET in N+ disease varied by overall AJCC staging: 33.1% vs. 57.1% vs. 80.8% in stages I, II and III respectively (p < 0.001). Conclusions: Benefit of CET over ET was observed in stages II and III ILC, particularly in N+ disease. No significant difference was observed in high ODX group. While treatment approach is associated with overall staging, it appears that nodal positivity specifically is most predictive of a benefit of CET over ET.

Abstract GS4-03: Patient-reported outcomes (PROs) for the intergroup sentinel mamma study (INSEMA, GBG75, ABCSG43): Persistent impact of axillary surgery on arm and breast symptoms in early breast cancer

Abstract Background: Despite increasing evidence disfavoring axillary lymph node dissection (ALND) for locoregional control, it remains part of guidelines for breast cancer (BC) treatment. In an attempt to re-evaluate standard local therapy, the INSEMA trial was designed to assess non-inferiority of avoiding sentinel lymph node biopsy (SLNB) or completion ALND (cALND) in early-stage clinically node-negative BC patients. Here we present PROs from the INSEMA trial. Methods: INSEMA (NCT02466737) investigates non-inferiority of invasive disease-free survival (iDFS) after no axillary surgical staging versus SLNB (first randomization 1:4) in patients with clinically node-negative BC (tumor size ≤5 cm) and primary breast-conserving surgery (BCS). In case of pN1a(sn) in the SLNB arm, patients underwent a second randomization to either SLNB alone or cALND (1:1). PROs were assessed at baseline (pre-surgery) and at 1, 3, 6, 12, and 18 months after final axillary surgery using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) and its breast cancer (BR23) module. Higher scores of C30 and BR23 (range 0-100) indicate better functioning and global health status (GHS)/quality of life (QoL) or worse symptom severity, respectively. The QoL scores were compared using the Mann-Whitney U test based on the safety set. Results: Between September 2015 and April 2019, 5,502 patients were recruited for the 1st randomization and 5,173 of them were included in the intent-to-treat set (4,138 SLNB vs 1,035 no SLNB). Patient and tumor characteristics were well-balanced between treatment arms. Median age at diagnosis was 62.0 years (range 24.0 - 89.0). Overall, recruited patients presented with low-risk BC marked by 85.6% clinically stage T1, 98.5% hormone-receptor positivity, 2.4% HER2-positivity, and 3.7% G3 tumors. The majority (73.5%) had an invasive carcinoma of no special type (72.8% in SLNB vs 76.0% in no SLNB arm) and 87.0% had Ki-67 ≤ 20%. Questionnaire completion response remained high throughout the trial: n=3,915 (75.7%) returned questionnaires at 1 month after final axillary surgery, n=3,938 (76.1%) at 3 months, n=4,024 (77.8%) at 6 months, n=3,907 (75.5%) at 12 months, and n=3,637 (70.3%) at 18 months. All QoL baseline parameters regarding GHS, functional scales, and symptom scales/items were well-balanced between arms (total 4,117 SLNB vs 1,056 no SLNB as treated; 270 of 4,117 received cALND). There were significant differences for the BRBS (breast symptoms) and BRAS (arm symptoms) scores favoring the no SLNB group in all post-baseline assessments Patients in the SLNB group showed persistent higher scores for BRAS (differences in mean values ≥5.0 points at all times of assessment) including pain, arm swelling, and impaired mobility in all postoperative visits with the highest difference at 1 month after final surgery (mean scores, 23.6 vs. 12.8, p<0.001). Differences between treatment arms regarding BRBS including pain, breast swelling, hypersensitivity, and other skin problems showed a smaller range, but still a continuous trend for improved QoL in the no SLNB arm. Scoring of the QLQ-C30 questionnaire revealed no relevant differences between the treatment groups postoperatively. Conclusions: This is one of the first randomized trials investigating the omission of SLNB in clinically node-negative patients and the first to report QoL data. Patients with no SLNB benefitted regarding arm symptoms/functioning while no relevant differences in other QoL scales were seen. Data for the primary outcome of the study (iDFS) are expected for the end of 2024. Citation Format: Bernd Gerber, Angrit Stachs, Kristina Veselinovic, Silke Polata, Thomas Müller, Thorsten Kühn, Jörg Heil, Beyhan Ataseven, Roland Reitsamer, Guido Hildebrandt, Michael Knauer, Michael Golatta, Andrea Stefek, Dirk-Michael Zahm, Marc Thill, Valentina Nekljudova, David Krug, Fenja Seither, Sibylle Loibl, Toralf Reimer. Patient-reported outcomes (PROs) for the intergroup sentinel mamma study (INSEMA, GBG75, ABCSG43): Persistent impact of axillary surgery on arm and breast symptoms in early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-03.

Abstract ES6-4: Parp inhibitors for brca1/2mutation associated breast cancer

Abstract More than 15 years ago we and others showed the use of potent PARP1 inhibitors (PARPi), that both inhibit the catalytic activity of the PARP1 enzyme and trap PARP1 onto DNA, generate a “synthetic lethal” interaction with the malignant cell specific loss of function of genes crucial for homologous recombination (HR) gene function. This phenomenon has now been exploited with therapeutic intent in several contexts leading to approved single agent PARPi treatments for advanced forms of ovarian, prostate, pancreatic and breast cancers. These approvals have in large part been associated a biomarker requirement for evidence of loss of function of HR. Recently a number of trials have investigated PARPi in a (neo)adjuvant breast cancer treatment (NACT) setting in patients with (or enriched for) HR deficiency. These have included phase II neoadjuvant PARPi studies such as the NeoTALA study using single agent talazoparib in germline BRCA1 and BRCA2 mutation carriers and the combination chemotherapy and olaparib therapy studies GeparOLA and PARTNER, enriched for HR deficient breast cancer, that have reported important signals with regard efficacy and tolerability. Two recent phase III trials have influenced recent early breast cancer treatment guidelines. These are the BrighTNess trial in the neoadjuvant setting and OlympiA in the post-(neo)adjuvant setting. BrighTNess recruited patients with biologically heterogeneous triple negative breast cancer (TNBC) and used the weak PARP1 trapping PARPi veliparib and OlympiA restricted eligibility to patients with the germline “pathogenic” or “likely pathogenic” mutation in BRCA1 or BRCA2 but included patients with hormone receptor positive breast cancer. BrighTNess did not show convincing evidence of benefit to the addition of veliparib to standard of care in TNBC NACT but has shown the benefit to the addition of carboplatin to sequential paclitaxel-AC NACT with significant improvements in event free survival (HR 0.57 ) compared to sequential paclitaxel-AC alone. OlympiA has reported following an interim analysis showing 12 months of olaparib in the post-(neo)adjuvant chemotherapy setting improves both invasive disease free and distant disease free survival by approximately 40% with highly statistically significant hazard ratios of 0.58 and 0.57 respectively that met pre-specified early stopping boundaries. The publication of results for OlympiA has led to rapid updates of both genetic testing and treatment international guidelines for BRCA1 and BRCA2 mutation associated breast cancer to include use of olaparib in patients meeting the eligibility criteria for the trial. The lecture will both explore the data and the implications for practice of the adoption of these guidelines and some of the ongoing questions to be addressed by ongoing clinical trial and translational research initiatives. Citation Format: ANJ Tutt. Parp inhibitors for brca1/2mutation associated breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES6-4.

Assessment of guideline adherence in breast cancer management among oncologists in Nigeria.

BackgroundBreast cancer management is evolving by the day and new discoveries is shifting the scale to more positive result mostly in developed countries and this is being reported and updated in the treatment guidelines to bridge the knowledge gaps and allow for global standardised management protocol. This study assessed the adherence to the breast cancer guideline use among oncologists in Nigeria, reviewing the commonly used guidelines, factors for the choice, effects on treatment and barriers to usage.MethodologyA proforma was sent by mail to the oncologist in Nigeria assessing their socio-demographic characteristics, knowledge of guidelines, use of guidelines, barriers to use of guidelines and benefits of guideline use and all the those that completed the survey within 1-month period were included in the study.ResultsA total of 109 oncologist responded to the survey with mean age of 42 years, mean year of oncology practice was 10 years. Sixty-four percent were consultants and 38% residents-in-training. All respondents were aware of breast cancer guidelines and 92.2% had used it in treatment decision making. The commonest used being National Comprehensive Cancer Network guideline in 87.4% and 82.6% had a choice guideline/institution adopted. The major reason for referring to a choice guideline by 66% of respondents was to gain access to evidence-based results and the major barrier to guideline use in 56% of cases was non compatibility with available resources.ConclusionThe study revealed high level of adherence to breast cancer guideline use among oncologists in Nigeria but there is need for more awareness about the locally developed ones like sub-Saharan adapted version and institutional based breast cancer treatment guidelines so as to address the barrier of disparities in target population and resources availability.

Provider Barriers and Facilitators of Breast Cancer Guideline-Concordant Therapy Delivery in Botswana: A Consolidated Framework for Implementation Research Analysis.

IntroductionSystemic treatment for breast cancer in sub‐Saharan Africa (SSA) is cost effective. However, there are limited real‐world data on the translation of breast cancer treatment guidelines into clinical practice in SSA. The study aimed to identify provider factors associated with adherence to breast cancer guideline‐concordant care at Princess Marina Hospital (PMH) in Botswana.Materials and MethodsThe Consolidated Framework for Implementation Research was used to conduct one‐on‐one semistructured interviews with breast cancer providers at PMH. Purposive sampling was used, and sample size was determined by thematic saturation. Transcribed interviews were double‐coded and analyzed in NVivo using an integrated analysis approach.ResultsForty‐one providers across eight departments were interviewed. There were variations in breast cancer guidelines used. Facilitators included a strong tension for change and a government‐funded comprehensive cancer care plan. Common provider and health system barriers were lack of available resources, staff shortages and poor skills retention, lack of relative priority compared with HIV/AIDS, suboptimal interdepartmental communication, and lack of a clearly defined national cancer control policy. Community‐level barriers included accessibility and associated transportation costs. Participants recommended the formal implementation of future guidelines that involved key stakeholders in all phases of planning and implementation, strategic government buy‐in, expansion of multidisciplinary tumor boards, leveraging nongovernmental and academic partnerships, and setting up monitoring, evaluation, and feedback processes.DiscussionThe study identified complex, multilevel factors affecting breast cancer treatment delivery in Botswana. These results and recommendations will inform strategies to overcome specific barriers in order to promote standardized breast cancer care delivery and improve survival outcomes.Implications for PracticeTo address the increasing cancer burden in low‐ and middle‐income countries, resource‐stratified guidelines have been developed by multiple international organizations to promote high‐quality guideline‐concordant care. However, these guidelines still require adaptation in order to be successfully translated into clinical practice in the countries where they are intended to be used. This study highlights a systematic approach of evaluating important contextual factors associated with the successful adaptation and implementation of resource‐stratified guidelines in sub‐Saharan Africa. In Botswana, there is a critical need for local stakeholder input to inform country‐level and facility‐level resources, cancer care accessibility, and community‐level barriers and facilitators.

Outcome of patients with an ultralow risk 70-gene signature in the MINDACT trial.

500 Background: Gene signatures have proven successful in identifying patients with a low risk of distant recurrence who could forego chemotherapy (CT) and are currently included in international treatment guidelines for breast cancer. For the 70-gene signature (MammaPrint) an additional threshold was established within the low risk category to identify patients with an ultralow risk of distant recurrence. In independent cohorts, these patients had excellent breast cancer specific survival at 15 years, suggesting that ultralow risk cancers represent indolent disease (Esserman, JAMA Oncol 2017, Delahaye, BC Res Treat 2017). Here we evaluate survival of patients with an ultralow risk 70-gene signature who participated in the randomized phase 3 MINDACT trial (Piccart, Lancet Oncol 2021). Methods: Of the 6,693 patients enrolled in the MINDACT trial (EORTC 10041/BIG 3-04) between 2007-2011, profiling revealed an ultralow risk 70-gene signature in 1,000 patients (15%). We assessed 5- and 8-year distant metastasis free interval (DMFI) and breast cancer specific survival (BCSS) in patients stratified by 70-gene signature result (high, low, ultralow), and within the ultralow risk group stratified by clinical risk. For these exploratory analyses, we used Kaplan-Meier estimates for time to event endpoints and Cox-regression models to calculate hazard ratio’s (HR). Results: Median follow-up was 8.7 years. Among the ultralow risk patients (n = 1,000), 67% were ≥50 years, 81% had tumors < 2cm, 80% were lymph node negative, 96% had grade 1 or 2 tumors and 99% were ER-positive. Systemic therapy was received by 83% of patients (69% endocrine therapy (ET), 14% ET + CT) and 16% received no adjuvant systemic treatment (AST). Survival estimates for all endpoints are shown in the table; 8-year DMFI was 97.0% (95% CI 95.8-98.1) for ultralow risk. The 8-year DMFI in ultralow risk patients who received no AST or ET only was 97.8% (95% CI 95.3-100) and 97.4% (95% CI 96.1-98.7), respectively. The HR for DMFI was 0.66 (95% CI 0.46-0.95) for ultralow vs low risk, after adjusting for tumor and treatment characteristics (preliminary results). Conclusions: In this prospective study, patients with an ultralow risk 70-gene signature have an excellent prognosis with 8-year BCSS above 99% regardless of clinical risk status, and with an 8-year DMFI of 95-98%.[Table: see text]

Effectiveness of a 6-Month 22.5-mg Leuprolide Acetate Depot Formulation With Tamoxifen for Postoperative Premenopausal Estrogen Suppression in Hormone Receptor-Positive Breast Cancer.

BackgroundIn patients with hormone receptor-positive (HR+)/premenopausal breast cancer, luteinizing hormone-releasing hormone analogs (LHRHas) are used as standard endocrine treatment. Based on previous clinical studies, 1-month formulations are recommended in most breast cancer treatment guidelines, but long-acting formulations facilitate reductions in side effects and patient discomfort caused by frequent administration. However, few efficacy studies have been conducted on 6-month formulations. Therefore, this study aimed to evaluate the efficacy of 6-month formulations of LHRHas.MethodsThis retrospective study was conducted from January 2018 to December 2019 and involved premenopausal patients with HR+ breast cancer administered 6-month LHRHas as adjuvant treatment after surgery, and those previously administered chemotherapy or other LHRHa types were excluded. Patients’ estradiol (E2) and follicle-stimulating hormone (FSH) levels were measured before surgery, and their E2 levels were also measured at 3, 6, 12, 18, and 24 months at periodic postsurgical examinations.ResultsA total of 228 patients were included, and the median patient age was 44 (range, 25–54) years. The mean serum E2 and FSH levels before surgery were 69.7 (range, 4–683) pg/mL and 7.3 (range, 0.4–88.9) mIU/mL, respectively, whereas the mean serum E2 level monitored at intervals during the 6-month LHRHa administration was 5.5 (range, 4.0–52) pg/mL. No women menstruated during the follow-up period after the LHRHas administration, and the E2 levels were less than 30 pg/mL in all patients except one.ConclusionsThe 6-month LHRHa formulation adequately suppressed ovarian function in premenopausal patients with HR+ breast cancer. This indicates that long-acting LHRHas can be effectively used for patient convenience and that there is high compliance with long-term use.

The Novel Coronavirus (COVID-19) Pandemic and the Response in Low-to-Middle Income Countries.

Purpose of ReviewThe COVID-19 pandemic has posed an unprecedented challenge to healthcare, particularly in resource-constrained low and middle-income countries (LMICs). We aim to summarize the challenges faced by LMICs in providing breast cancer care during the pandemic and their response during this crisis.Recent FindingsConversion of oncology centers into COVID-19 isolation centers and lack of LMIC applicable guidelines for breast cancer treatment worsened the challenge for providers. Few LMICs changed their management framework, taking steps like triaging patients, prioritizing care, therapeutic spacing, and a shift to telehealth.SummaryModified protocols where available have served LMICs well for resource allocation; however, effectiveness of these cannot be determined due to lack of outcomes reporting. This pandemic has underscored the importance of flexibility, prompt intervention, good communication, and reassessment to address unexpected healthcare challenges and has been a learning lesson to help tailor guidelines early in the future.

Abstract PS14-03: Ribociclib + letrozole in male patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC): Subgroup analysis of the phase IIIb CompLEEment-1 trial

Abstract Background: While the incidence of breast cancer in men is up to 100-fold less than in women, it is estimated that in 2020, 2,620 men in the United States will be diagnosed with breast cancer, and 520 will die from this disease. However, male patients are rarely included in breast cancer clinical trials and treatment guidelines for this population are often proposed based on data from female patients. Ribociclib (RIB), an oral, selective cyclin-dependent kinase 4/6 inhibitor, is approved for use in combination with endocrine therapy (ET) in women with HR+, HER2- ABC. Here, we present a subgroup analysis of male patients from the Core Phase of CompLEEment-1 (NCT02941926), a Phase IIIb trial of RIB in combination with letrozole (LET) in patients with HR+, HER2- ABC. In order to reflect a more typical real-world clinical setting, the eligibility criteria for this study allowed for a more diverse and broader patient population than those of previous Phase III trials of RIB + LET. Methods: CompLEEment-1 included women of any menopausal status and men with HR+, HER2- ABC treated with ≤1 line of prior chemotherapy and no prior hormonal therapy for advanced disease. Pts received RIB (600 mg QD, 3 weeks on/1 week off) in combination with LET (2.5 mg QD, continuous). Men and premenopausal women received a luteinizing hormone-releasing hormone agonist (3.6 mg goserelin or 7.5 mg leuprolide, Q28D). This subgroup analysis assessed the primary outcomes (safety and tolerability) and secondary outcomes of time to progression (TTP), overall response rate (ORR), and clinical benefit rate (CBR) in male patients. Results: At the data cutoff date (November 8, 2019), 39 male patients (1.2%; N = 3,246) had been evaluated, with a median duration of exposure to RIB of 19.2 months. Adverse events (AEs) were reported in 38 (97.4%) patients; with all but two experiencing a treatment-related AE. Grade ≥ 3 AEs were reported in 26 (66.7%) patients; serious AEs were reported in 6 patients. There were no treatment-related fatal AEs. The most common all-grade AEs were neutropenia (53.8%), hot flush (33.3%), and diarrhea (25.6%), with the most common grade ≥ 3 AE being neutropenia (41.0%). Overall, 7 patients (17.9%) had ≥ 1 dose reduction of RIB, all of whom had at least 1 due to an AE, and 18 patients (46.2%) permanently discontinued treatment, 4 (10.3%) due to AEs. Median TTP was not estimable (95% CI, 16.8-NE); event-free probability was 61.4% (95% CI, 38.4-77.9) at 30 months. For the 32 patients with measurable disease, ORR was 46.9% (95% CI, 29.1-65.3%) and CBR was 71.9% (95% CI, 53.3-86.3). Conclusions: In this subgroup analysis of male patients - a rare population who are often excluded from clinical trials - efficacy results support the use of RIB + LET in HR+, HER2- ABC in a close to real-world setting. The safety profile associated with RIB + LET was manageable, with very few patients discontinuing treatment due to AEs, consistent with previous Phase III trials of RIB + LET. Citation Format: Mario Campone, Michelino De Laurentiis, Claudio Zamagni, Igor Kudryavcev, Mariëtte Agterof, Ursa Brown-Glaberman, Markéta Pálácova, Sanjoy Chatterjee, Lakshmi Menon-Singh, Jiwen Wu, Katie Zhou, Miguel Martín. Ribociclib + letrozole in male patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC): Subgroup analysis of the phase IIIb CompLEEment-1 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-03.

Determinants of Guideline-Discordant Breast Cancer Care

Evidence-based breast cancer treatment guidelines recommend the most appropriate course of therapy based on tumor characteristics and extent of disease. Evaluating the multilevel factors associated with guideline discordance is critical to identifying strategies to eliminate breast cancer survival disparities. We identified females diagnosed with a first primary, stage I-III breast cancer between the ages of 20-69 years of age from the population-based Seattle-Puget Sound Surveillance, Epidemiology, and End Results registry. Participants completed a survey about social support, utilization of patient support services, hypothesized barriers to care, and initiation of breast cancer treatment. We used logistic regression to estimate odds ratios and 95% confidence intervals (CI). Among 1,390 participants, 10% reported guideline-discordant care. In analyses adjusted for patient-level sociodemographic factors, individuals who did not have someone to go with them to appointments or drive them home (OR 1.96; 95% CI, 1.09-3.59) and those who had problems talking to their doctors or their staff (OR 2.03; 95% CI, 1.13-3.64) were more likely to be guideline discordant than those with social support or without such problems, respectively. Use of patient support services was associated with a 43% lower odds of guideline discordance (OR 0.57; 95% CI, 0.36-0.88). Although guideline discordance in this cohort of early-stage breast cancer survivors diagnosed <70 years of age was low, instrumental social support, patient support services, and communication with doctors and their staff emerged as potential multilevel intervention targets for improving breast cancer care delivery. This study supports extending the reach of interventions designed to improve guideline concordance.

Guidelines for clinical diagnosis and treatment of advanced breast cancer in China (2020 Edition)

Breast cancer is the most common malignant tumor among women all over the world. In 2015, there were about 304, 000 new cases of breast cancer in Chinese female, with more than 70, 000 deaths. Of the new cases of breast cancer each year, about 3% to 10% of patients have distant metastasis at the time of diagnosis. Of the early-stage patients, about 30% developed into advanced breast cancer. The 5-years survival rate of advanced breast cancer was only 20%, and the median overall survival time was 2-3 years. Although advanced breast cancer is difficult to cure at present, we can alleviate the clinical symptoms of patients, improve their quality of life and further prolong their survival time by developing new therapeutic drugs and optimizing treatment models, to achieve the purpose of long-term survival with tumor. It is very important for patients with advanced breast cancer to choose the reasonable treatment plan. Since there is lack of standard recommendation for the treatment of advanced breast cancer after the first and second line chemotherapy, according to the research progress of breast cancer at home and abroad and the update of real-world clinical research data, the Chinese expert group analyzed, summarized and discussed the relevant research data, updated the diagnosis, treatment and prognosis of inoperable locally advanced and recurrent or metastatic breast cancer on the basis of version 2018, and formulated the "Guidelines for clinical diagnosis and treatment of advanced breast cancer in China (2020 Edition)" (ABCC 2020) for clinicians' reference.

The Role of Radiation Therapy in Addition to Lumpectomy and Hormone Therapy in Men 70 Years of Age and Older with Early Breast Cancer: A NCDB Analysis

Current treatment guidelines for male breast cancer are guided by female-only trials despite data suggesting distinct clinicopathologic differences between sexes. We sought to evaluate whether radiation therapy (RT) after lumpectomy was associated with equivalent survival among men > 70 years of age with stage I, estrogen receptor (ER) positive tumors, as seen in women from the Cancer and Leukemia Group B (CALGB) 9343 trial. We performed a retrospective analysis of 752 stage I, ER-positive male breast cancer patients ≥70 years who were treated with hormone therapy and surgery, with or without RT, from the National Cancer Database between 2004 and 2014. Patients were categorized based on surgery and RT (lumpectomy alone, lumpectomy with RT, and mastectomy alone). Multivariable Cox proportional hazards regression analysis was used to compare overall survival between treatment groups. Most patients underwent total mastectomy, with only 32.6% treated with lumpectomy. Of those who underwent lumpectomy, 72.7% received adjuvant RT. In multivariate analysis, there was no statistical difference in overall survival when comparing lumpectomy alone and lumpectomy with RT (aHR 0.72 [95% CI 0.38-1.37], p=0.31) or when comparing lumpectomy (alone or with RT) and mastectomy (aHR 1.28 [95% CI 0.88-1.87], p=0.20). In this national sample of elderly men with ER-positive early-stage disease treated with endocrine therapy, there were no significant differences in overall survival when comparing lumpectomy alone and lumpectomy with RT, or lumpectomy (alone or with RT) and mastectomy. These results suggest that less aggressive treatment may be appropriate for a subset of male breast cancer patients.