Breast Cancer Treatment Decisions Research Articles

Impact of race and age on intrinsic subtype distribution and treatment decisions in metastatic breast cancer: Preliminary analysis of HARMONY (LCCC1829).

1055 Background: Gene expression profiling (GEP) is used to classify breast cancer (BC) into four intrinsic subtypes: Luminal A (LumA), Luminal B (LumB), HER2-Enriched, and Basal-like. Non-LumA subtypes are associated with poorer outcomes. Studies in early BC show that hormone receptor-positive (HR+)/HER2-negative (HER2-) tumors have a higher frequency of non-LumA subtypes in Black and younger (<50) women. Similarly, triple negative BC, which carries the poorest prognosis and is mostly Basal-like, are overrepresented in Black and younger women. These variations in intrinsic subtype contribute to outcomes disparities. The extent to which these racial and age differences in subtypes and mortality occur in metastatic breast cancer (MBC) is unknown. Methods: HARMONY (NCT03769415) is a prospective clinical trial in patients with newly diagnosed MBC. Bulk tumor GEP (PAM50 intrinsic subtyping) is performed on primary and metastatic tumors. A primary objective is to determine the extent and treatment implications of molecular discordance (defined a priori as treatment differences by intrinsic subtype compared to clinical subtype); other endpoints to be reported later include GEP comparisons between primary and metastatic samples. Here we examine differences in a) intrinsic subtype and b) treatment patterns in MBC by race and age. Results: At the time of analysis, the study had accrued 220 participants. Mean age was 58, 24% were Black women. Sixty-five percent had HR+/HER2- MBC, 14% HER2-positive, and 21% triple negative. Unlike in early BC, LumB exceeded LumA (LumA 27%, LumB 35%, HER2-Enriched 12%, Basal-like 25%). Similar to early BC, subtype varied by race and age with more non-LumA subtypes in young and Black women. Discordance between intrinsic and clinical subtype was seen in 24% of Black, 20% of White women, in 29% of younger and 18% of older women. Treatment patterns also differed by race and age, where a higher percentage of younger Black women received first-line chemotherapy compared to younger White women overall (45% vs. 10%, p=0.0025), and in HR+/HER2- disease (33% vs 8.7%, p=>0.05). No difference was seen in older women (24% vs 17%, p=0.44). Median progression free survival was worst in younger Black women compared to all other participants (5.4 vs 19.5 months, p=0.027), which may be driven by clinical subtype. Conclusions: Intrinsic subtype of tumors in a metastatic population has a different distribution by race and age than early BC, with more poor-prognosis non-LumA subtypes, and approximately 1 in 5 have discordance between clinical and molecular subtype, which may be therapeutically relevant. Clinical trial information: NCT03769415 . [Table: see text]

Assessment of risk of overall and late distant recurrence by Breast Cancer Index in postmenopausal women with early-stage, HR+ breast cancer in the TEAM trial.

509 Background: Individual risk assessment of distant recurrence (DR) is particularly relevant for early-stage HR+ breast cancer patients, as they face a prolonged risk of recurrence even after adjuvant endocrine therapy. Previously, we have shown that the Breast Cancer Index (BCI) and BCIN+ risk groups are significantly prognostic for risk of overall (0-10y) and late (5-10y) distant recurrence in N0 and N1 breast cancer patients, respectively, enrolled in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial. Here, the prognostic performance of BCI and BCIN+ as a continuous risk score for overall and late distant recurrence was evaluated in the TEAM trial. Methods: BCI testing was performed blinded to clinical outcome with BCI/BCIN+ risk scores calculated as previously described. Cox proportional hazard models adjusted for age, tumor size, grade and treatments were used to estimate hazard ratios (HRs) and the associated 95% confidence intervals (CIs) for BCI/ BCIN+ continuous risk scores. The 10y risk of overall and late DR were estimated as a function of risk scores from the Cox models using Breslow estimates. Results: Continuous risk curves for overall and late DR were obtained in patients who did not receive adjuvant chemotherapy and those who remained DR-free at 5 years regardless of chemotherapy, respectively, to reflect the two key time points for breast cancer treatment decision-making. InN0 patients not treated with chemotherapy (N = 1197), BCI was significantly prognostic for overall DR with a HR of 1.39 (95% CI 1.25-1.54; p < 0.001), while BCIN+ was significantly prognostic in N1 patients who did not receive chemotherapy (N = 1319) with a HR of 4.29 (95% CI 2.93-6.28; p < 0.001). Among patients who remained DR-free at 5 years, in the N0 subset (N = 1285), BCI was significantly prognostic for late DR with a HR of 1.23 (95% CI 1.07-1.42; p < 0.001), while BCIN+ remained to be significantly prognostic in the N1 subset (N = 1762) with a HR of 2.78 (95% CI 1.75-4.43; p < 0.001). Similar results were observed in the HER2- subset for both overall and late DR. Continuous risk curves for BCI and BCIN+ for overall and late DR showed an increasing risk of DR with higher BCI/BCIN+ scores. Conclusions: Results from this largest BCI study to date further support the use of BCI to provide individualized risk estimates for both overall and late DR in women with HR+ breast cancer to aid in personalized decision-making for adjuvant therapy. [Table: see text]

Lost in translation? Information exchange during breast cancer care and implications for technology design.

1558 Background: Almost 4 million women in the US have had breast cancer, with 300,000 women diagnosed each year. Treatment decision-making following breast cancer diagnosis can be challenging as there are often several clinically appropriate treatment options, each with differing impacts on patient short- and long-term quality of life. Further, patients must manage this information during a time of high emotional burden, which can hinder decision-making. Not surprisingly, studies have found that less than 50% of patients believe their treatment plan aligns with their preferences. Numerous decision aids have been developed to support patient decision-making. However, sustained use of decision aids is limited due to poor integration in clinical workflow. We need to better understand the complex workflows and needs of decision aid users - patients and breast cancer clinicians. In this study, we investigate the information exchange between patients and clinicians when making breast cancer treatment decisions and identify design requirements for patient-centered decision support tools. Methods: This study is part of a larger research project to design a COMputerized PAtient-centered Collaborative Technology (COMPACT) to support personalized breast cancer decision-making. We observed clinicians at one academic medical center’s breast center from February-August 2022. Participating clinicians were followed throughout their clinical shift. Using a tablet computer and smart pencil, we recorded all aspects of clinician workflow. Written notes were transcribed and uploaded into Dedoose. Two human factors researchers inductively coded each observation in a consensus-based process. Results: We observed 79 hours of clinical care and 119 patient encounters across 20 observations of various clinical roles. Overall, we found that patients with breast cancer must manage an enormous amount of highly complex information that includes technical medical terms, mathematical concepts (e.g., risk), and uncertainty. We identified over 20 distinct decisions that patients face during their cancer journey, which were interdependent and evolved over time. We identified numerous patient-specific factors that influenced treatment decision-making, such as the patient’s work and family circumstances. For instance, one patient was organizing a conference and needed to plan her surgery around this event. Patients were frequently asked to remember and relay information across members of the care team, indicating inadequate system support of information transfer within the large cancer team. Based on these findings, we identified design requirements for interventions to support care coordination and patient-centered decision-making. Conclusions: These findings can inform the design of interventions to support breast cancer decision-making and improve patient-centered cancer care.

Abstract P4-02-20: Utility of the 70-gene signature and 10 year follow up in patients with early-stage breast cancer in a single institution study

Abstract Introduction: Genomic tests are routinely used by clinicians to guide treatment decisions in early-stage breast cancer (EBC). The 70-gene MammaPrint assay (MP) assesses the risk of distant recurrence in untreated patients with EBC and categorizes the tumors as High Risk (HR, MP index: -1 to ≤0) or Low Risk (LR, >0 to +1). The LR category is further divided into Low but non-UltraLow (LNUL; >0 to ≤0.355) and UltraLow Risk (UL; >0.355 to 1). Here, we report the risk of distant recurrence by MP and 10-year outcomes in patients with EBC diagnosed at Magee Women’s Hospital of the University of Pittsburgh Medical Center. Methods: In this retrospective analysis, 259 women diagnosed with EBC between 2005 and 2008, who received a MP result, were included. Patient clinical and tumor characteristics were collected. The median FU was 13.1 year among patients with clinical data. Treatment received, 10-year Distant Metastasis Free Interval (DMFI) and 10-year Breast Cancer Specific Survival (BCSS) are reported according to the MP groups. Differences in DMFI and BCSS between MP risk groups were assessed by log-rank. Patients were treated at the physician’s discretion. Treatment was started prior to obtaining MammaPrint results. Results: Among the 259 patients, 69% were post-menopausal women (mean [range] age: 58 [31-81] years) and diagnosed with hormone receptor-positive HER2-negative tumors (90%), grade 1 or 2 (64%), and without lymph node invasion (93%). In this cohort, 69% (n = 159) had a MP LR result and 31% (n = 100) had a MP HR result. Overall, 14% (n = 35) of patients had a MP UL risk of recurrence of whom 74% (n = 26/35) were post-menopausal women. Substantially more patients received chemotherapy in the HR group (57%, n = 57) compared with the LR group (15%, n = 24) (table). Considering that treatment was initiated before MammaPrint results were known, MP results might have allowed chemotherapy de-escalation in in 15% (n = 24) of patients with a MP LR. Similarly, in the 39% (n = 39) of women with a MP HR treated with endocrine therapy only, knowledge of MP results could have provided important information to add chemotherapy to the treatment plan.. In the MP UL group, 74 % (n = 26) of patients were treated with endocrine therapy only compared with those who received chemotherapy (9%, n = 3) and no adjuvant treatment (9%, n = 3). The 10-year DMFI and 10-year BCSS were higher in the LR compared with the HR group (table). When further stratifying the MP LR group in LNUL and UL, the 10y DMFI was 0.97 (95% CI; 0.94 – 1.00) and 1.00 for the MP LNUL and UL groups, respectively. Within the first 10 years, 8 of the 10 distant recurrences observed were in the MP HR group, and 2 were in the MP LNUL group. Among the 18 recorded deaths, 5 were breast cancer-related, 4 in the MP HR and 1 in the MP LR (LNUL) groups. Discussion: In this single-institution retrospective analysis, all patients showed excellent BCSS and DMFI outcomes confirming the ability of MP to correctly predict the good prognosis (LR) and poor prognosis (HR) in patients with EBC. In this analysis, as observed in other cohorts, women with a MP UL risk result had an excellent prognosis at 10 years while being treated mostly with endocrine therapy only. Taken together, with the low endocrine therapy adherence reported in the literature, these data suggest that patients with a MP UL result may be candidates for further treatment de-escalation to optimize the risk/benefit ratio of endocrine therapy in future studies. Table 1. Clinical outcomes and treatment received in patients stratified by MammaPrint results * Patients were treated at the physician’s discretion a p = 0.011, MP LR vs MP HR. b p = 0.032, MP UL vs LNUL vs HR. c p = 0.061 MP LR vs MP HR. d p = 0.170, MP UL vs LNUL vs HR. Citation Format: Azadeh Nasrazadani, Juan L. Gomez Marti, Margaret Q. Rosenzweig, Meghan McGuire, Katie Quinn, Josien Haan, Alexandre Houzelle, Rohit Bhargava, William Audeh, Adam M. Brufsky. Utility of the 70-gene signature and 10 year follow up in patients with early-stage breast cancer in a single institution study [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 P4-02-20.

Abstract P4-06-04: Clinical outcomes of loco-regional HER2-positive invasive lobular carcinoma of the breast

Abstract Background: HER2-positive invasive lobular carcinoma (ILC) of the breast is a rare entity. Treatment decisions for HER2-positive lobular breast cancer are often extrapolated from the HER2-positive ductal subtype of breast cancer but the clinical outcomes and prognostic factors are not well defined. Methodology: Women with a diagnosis of stage I to III HER2-positive ILC or invasive ductal carcinoma (IDC) of the breast between 2010 and 2018 were identified from the National Cancer Database. Baseline characteristics were compared between ILC and IDC using Chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. Five-year overall survival (OS) was estimated by the Kaplan Meir method. Multivariate cox proportional hazards regression model including age, race, ethnicity, Charleston Deyo score, grade, TNM stage, and treatment modalities such as type of surgery, chemotherapy, and radiation was used to identify factors associated with OS in HER2-positive ILC. In a subset of patients receiving neoadjuvant chemotherapy, the odds of achieving a complete pathological response were compared between women with ILC and IDC in a multivariate logistic regression model adjusting for age, race, ethnicity, Charleston Deyo score, grade, and clinical stage. Results: A total of 4,197 women with HER2-positive ILC and 116,984 women with HER2-positive IDC were included in the final analysis. The median age at diagnosis was 63 years for women with HER2-positive ILC and 56 years for women with HER2-positive IDC (p< 0.001). The five-year OS among women with HER2-positive ILC was 93.1%, 90.8%,and 78.8% in TNM stages I, II, and III respectively. In multivariate analysis, a significant difference in difference in overall survival was not observed between women with HER2 positive ILC and IDC (Hazard Ratio [HR]: 1.0, 95% Confidence Interval [CI]: 0.9 - 1.1, p=0.55). Among women receiving neoadjuvant chemotherapy, a complete pathological response was observed in 31.7% of women with HER2-positive ILC and 42.7% of HER2-positive IDC. In multivariate analysis, there was no difference in odds of achieving a complete pathological response to neoadjuvant chemotherapy between HER2-positive ILC and IDC (Odds Ratio [OR]: 0.8, 95%CI: 0.7 - 1.0, p=0.12). Higher odds of complete pathological response in HER2-positive ILC were observed for women with estrogen-receptor negative (OR: 2.0, 95% CI: 1.1- 3.8), p= 0.02) and progesterone-receptor negative (OR 2.4, 95%CI: 1.5- 3.7), p< 0.001) tumors. The five-year OS for women with a complete pathological response, partial response, and no response after neoadjuvant chemotherapy in HER2-positive ILC were 89.6%, 84.9%, and 77.3% respectively (p=0.01). Conclusion: This study demonstrates that HER2-positive ILC has comparable clinical outcomes to HER2-positive IDC and response to neoadjuvant chemotherapy correlates with OS in HER2-positive ILC. These findings lend support to the current practice of treating HER2-positive ILC and IDC in a similar manner. Citation Format: Suman Gaire, Pravash Budhathoki, Utsav Joshi, Anish Shah, Grace M. Choong, Siddhartha Yadav. Clinical outcomes of loco-regional HER2-positive invasive lobular carcinoma of the breast [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 P4-06-04.

Abstract P5-06-03: Analyzing the results of liquid biopsy in the identification of ERBB2 amplified and HER2 expressing metastatic breast cancer: comparison and combination of cell and cell-free platforms

Abstract Background Liquid biopsies are a non-invasive diagnostic approach for detecting circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) that may provide clinically actionable information for treatment decisions for metastatic breast cancer (MBC) patients when a conventional biopsy is otherwise infeasible. In addition, the development of quantitative, reproducible, and more sensitive HER2 assays is expected to enable the identification of patients with HER2-low MBC that may benefit from novel HER2-targeted therapies. Here we report a comprehensive liquid biopsy platform including immunofluorescent HER2 and ER quantitative protein expression in CTCs (ctcIF) coupled with the determination of ERBB2 amplification and the number of Large-scale State Transitions (LST) by single-cell CTC genomics (ctcDNA), and ctDNA alterations in plasma. Methods Blood samples were collected for cell-based and cell-free analysis from 62 patients with documented MBC and from 24 blood donors (HD) with no known cancer history. After isolation, nucleated cells were plated, and slides and plasma were bio-banked. CTCs were identified using Epic Sciences digital imaging and machine learning algorithms, and ctcIF enables quantitation of HER2 and ER protein expression. ctcDNA was analyzed by low-pass whole-genome sequencing (WGS), allowing detection of ERBB2 amplification (ERBB2amp) and quantification of large-scale state transitions (LST+) in individual CTCs. cfDNA from plasma was analyzed using a validated NGS panel (56 genes of interest) to detect ctDNA alterations. Results Within this cohort of 62 MBC patients, the presence of CTCs, ctcDNA (LST+) and ctDNA alterations were detected in 87%, 70%, and 59%, respectively, while no CTCs and no ctDNA alterations were detected in the HD cohort, suggesting high specificity. ctcDNA genomics was more sensitive than ctDNA in detecting ERBB2amp in MBC patients (11%, and 2%, respectively). A variant allele frequency (VAF) of > 40%, which is required for detecting a two-fold ERBB2 amplification by ctDNA, was not present among 86% and 0% of MBC detected by the ctcDNA and ctDNA platforms, respectively, suggesting that the ctcDNA platform can identify ERBB2amp among patients with a low ctDNA fraction. HER2+ or ER+ expression by ctcIF were detected in 37% and 58% of MBC patients, respectively. At the cellular level, across 62 patients, CTC with detectable ERBB2amp by ctcDNA had a higher median expression of HER2 protein by ctcIF compared to CTC with ERBB2nonamp (1772 MFI vs 122.5 MFI, respectively; p< 0.001). Similarly, at the patient level, among patients with circulating ERBB2amp, HER2 protein was detected by ctcIF in 100% of MBC patients (p< 0.001), suggesting a very high positive correlation between the presence of ctcDNA genomic ERBB2amp and ctcIF HER2 protein expression. A liquid biopsy classification of HER2 status by combining the three platforms (ctcIF, ctcDNA, and ctDNA) identified that among MBC, 11% were ERBB2amp, 26% were HER2 expressing (HER2+ and ERBB2nonamp), and 60% were HER2neg (HER2- and ERBB2nonamp). Combination models of the three individual platforms (ctcIF, ctcDNA, and ctDNA) were able to provide potentially clinically actionable biomarker data (LST+ CTC, ERBB2amp CTC, HER2+ CTC, ER+ CTC and 1A+ SNVs) to 79% of MBC patients while retaining 100% specificity. Conclusions Here we reported a comprehensive liquid biopsy profile combining ctcIF, ctcDNA, and ctDNA platforms with high sensitivity and specificity in determining clinically actionable HER2 and ER biomarker status that may impact therapeutic decision-making in late MBC patients. The comprehensive liquid biopsy platform’s combined utility can aid biomarker profiling of MBC among often biologically heterogeneous tumor sites of metastatic disease and those inaccessible by conventional tissue biopsy. Citation Format: Giuseppe Di Caro, Ernest T. Lam, Megan M. Slade, Anna Lundberg, Martin Blankfard, Nilesh Dharajiya, Alisa Tubbs, Rick Wenstrup, Lee Schwartzberg. Analyzing the results of liquid biopsy in the identification of ERBB2 amplified and HER2 expressing metastatic breast cancer: comparison and combination of cell and cell-free platforms [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 P5-06-03.

Clinical Utility of Genomic Tests Evaluating Homologous Recombination Repair Deficiency (HRD) for Treatment Decisions in Early and Metastatic Breast Cancer

Breast cancer is the most frequently occurring cancer worldwide. With its increasing incidence, it is a major public health problem, with many therapeutic challenges such as precision medicine for personalized treatment. Thanks to next-generation sequencing (NGS), progress in biomedical technologies, and the use of bioinformatics, it is now possible to identify specific molecular alterations in tumor cells-such as homologous recombination deficiencies (HRD)-enabling us to consider using DNA-damaging agents such as platinum salts or PARP inhibitors. Different approaches currently exist to analyze impairment of the homologous recombination pathway, e.g., the search for specific mutations in homologous recombination repair (HRR) genes, such as BRCA1/2; the use of genomic scars or mutational signatures; or the development of functional tests. Nevertheless, the role and value of these different tests in breast cancer treatment decisions remains to be clarified. In this review, we summarize current knowledge on the clinical utility of genomic tests, evaluating HRR deficiency for treatment decisions in early and metastatic breast cancer.

Improving patient-centered communication in breast cancer: a study protocol for a multilevel intervention of a shared treatment deliberation system (SharES) within the NCI community oncology research program (NCORP) (Alliance A231901CD)

BackgroundAdvances in precision medicine have given oncologists new evaluative tools to better individualize treatments for patients with curable breast cancer. These innovations have revealed a need to improve patient understanding of novel, often complex information related to breast cancer treatment decisions. Ensuring patients have the emotional support to face consequential treatment decisions, as well as the opportunity to engage and discuss with their clinicians, is key to improving patient-centered communication and patient understanding.Methods/designThis study will implement a multilevel intervention with patient and clinician components as a NCORP Cancer Care Delivery Research (CCDR) trial within the Alliance for Clinical Trials in Oncology Research Base (Alliance). The two interventions in this study, the Shared Decision Engagement System (SharES), include (1) two versions of an evidence-based patient-facing breast cancer treatment decision tool (iCanDecide +/− an emotional support module) and (2) a clinician-facing dashboard (Clinician Dashboard) that is reviewed by surgeons/clinicians and summarizes ongoing patient needs. The design is a near minimax, hybrid stepped wedge trial of SharES where both interventions are being evaluated in a crossed design over six 12-week time periods. The primary outcome (knowledge) and key secondary outcomes (i.e., self-efficacy and cancer worry) are assessed via patient report at 5 weeks after surgery. Secondary outcomes are also assessed at 5 weeks after surgery, as well as in a second survey 9 months after registration. We anticipate recruiting a total of 700 breast cancer patients (600 evaluable after attrition) from 25 surgical practices affiliated with Alliance.DiscussionUpon study completion, we will have better understanding of the impact of a multilevel intervention on patient-centered communication in breast cancer with a specific focus on whether the intervention components improve knowledge and self-efficacy and reduce cancer worry.Trial registrationClinicalTrials.govNCT04549571. Registered on 16 September 2020.

Survey on Distributed AI-Enhanced Deep Learning for Predicting Chemo Response in Non-Hormone Receptor Breast Cancer

This study offers a novel method for forecasting the response to chemotherapy in non-hormone receptor breast cancer, a difficult and complicated condition. TensorFlow-powered Spatial Temporal Integration (CNN-RNN) Architecture is used in the methods to integrate clinical data and histological images. Heuristic-driven deep learning techniques use domain-specific knowledge to build models and choose features. Using clinical knowledge, Hybrid Differential Evolution and Particle Swarm Optimization (DE-PSO) optimizes the model's parameters. Because Lime offers comprehensible justifications for the model's predictions, its adoption guarantees transparency and interpretability. Furthermore, federated learning is used in a distributed training approach to preserve scalability and safeguard patient data privacy. This method offers precision and empathy for better treatment decisions for non-hormone receptor breast cancer by fusing AI with clinical expertise.

Genetic testing women with newly diagnosed breast cancer: What criteria are the most predictive of a positive test?

Knowledge of pathogenic variants in cancer-predisposing genes is important when making breast cancer treatment decisions, but genetic testing is not universal and criteria must be met to qualify for genetic testing. The objective of this study was to evaluate the pathogenic variant yield for nine cancer predisposition genes by testing criteria, singly and in combination. Women diagnosed with breast cancer between June 2013 and May 2018 were recruited from four centers in Toronto, Canada. Participants completed a demographics and family history questionnaire and clinical characteristics were collected from medical charts. Genetic testing was done for BRCA1, BRCA2, PALB2, ATM, CHEK2, BRIP1, RAD51D, RECQL, and TP53. Pathogenic variant frequencies were calculated according to five criteria (age ≤ 50, triple-negative breast cancer, family history, bilateral breast cancer, or Jewish ethnicity). Of the 1006 women studied, 100 women (9.9%) were found to have a pathogenic variant in one of the nine genes tested. The highest prevalence of pathogenic variants was found in women with triple-negative breast cancer (23%). Of the 100 pathogenic variants detected, 78 were detected in women diagnosed at age 50 or less. A total of 96% of the mutations were identified with three criteria (age of diagnosis, family history, and triple-negative status). Genetic testing criteria for women with breast cancer should include women with triple-negative breast cancer, regardless of age. All women aged 50 years or below at time of breast cancer diagnosis should be offered genetic testing.

Multiparametric MR Imaging Radiomics Signatures for Assessing the Recurrence Risk of ER+/HER2- Breast Cancer Quantified With 21-Gene Recurrence Score.

While the Oncotype DX 21-gene recurrence score (RS) has been recommended for guiding ER+/HER2- breast cancer treatment decisions, it is limited by cost and availability. To develop a multiparametric MRI-based radiomics model for assessing ER+/HER2- breast cancer patients' 21-gene RS. Retrospective. A total of 151 patients with pathologically confirmed ER+/HER2- breast cancers, who underwent preoperative breast MR examinations and 21-gene expression assays, divided into training (n=106) and validation (n=45) cohorts. T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhancement (DCE) sequence at 1.5T or 3T. A total of 1046 radiomics features were extracted from each MRI sequence with a manual lesion segmentation method. After feature dimension reduction by the recursive feature elimination method and dataset balance by the synthetic minority oversampling technique, linear support vector machine classifier models were built to distinguish high RS (RS ≥ 26) from low RS (RS < 26) from T2WI, DWI apparent diffusion coefficient (ADC) maps, DCE and their combination (multiparametric). A model based on clinical characteristics and a fusion model combining clinical characteristics and multiparametric MRI were also built. Receiver operating characteristic (ROC) curve analysis and De Long's test with Bonferroni correction were used. A P value <0.01 was considered statistically significant. The area under the ROC curve (AUC) value of multiparametric radiomics model was 0.92, significantly higher than DCE (0.83), T2WI (0.78), and ADC (0.77) models in the training cohort. The radiomics model also achieved good performance in the validation cohort (AUC=0.77). The fusion model had significantly higher performance than the clinical model in both the training (AUC=0.92 and 0.64, respectively) and validation cohorts (AUC=0.78 and 0.62, respectively). The proposed multiparametric MRI-based radiomics models may have potential to help distinguish ER+/HER2- breast cancer patients' recurrence risk. 3. Stage 2.

Patient Preference and Demographic Factors Influencing Treatment Decisions in Early-Stage Breast Cancer

<h3>Purpose/Objective(s)</h3> To evaluate the treatment option preference for women with early-stage breast cancer undergoing radiotherapy. <h3>Materials/Methods</h3> Women were considered candidates for this study if they were eligible for accelerated partial breast irradiation (APBI) according to American Society for Radiation Oncology (ASTRO) guidelines. The ethics approved study protocol (HREBA.CC-19-0485) was designed to enroll 250 patients. Participants completed a demographic survey and selected between treatment options of 42.5 Gy in 16 fractions to the whole breast (Canadian hypofractionation), 26 Gy in 5 fractions to the whole breast (FAST-Forward), and 27 Gy in 5 fractions APBI (ACCEL). After radiotherapy, patients were surveyed at 3, 6, 12, and 24 months using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire BR-23 and self-rated breast appearance and symptom scoring criteria used in the RAPID and ACCEL trials. In this analysis of nominal demographic data, two cohorts of participants were defined: (i) short commute: patients traveling less than 30 minutes to the treating institution, and (ii) long commute: patients traveling more than 30 minutes. The chi-squared test of independence was used to measure statistical significance (alpha = 0.05). <h3>Results</h3> As of March 2022, 27 patients participated in the study. Fifteen patients selected 5-fraction partial breast, seven selected 5-fraction whole breast, and five selected 16-fraction whole breast. Of these, 15 had a short commute and 12 had a long commute. For participants with a short commute, 5 selected the 16-fraction option and 10 selected a 5-fraction option. For participants with a long commute, all selected a 5-fraction treatment option. The chi-squared test yielded a significant difference (p = 0.03), indicating that travel time for treatment is a factor in the treatment selection process. <h3>Conclusion</h3> At this early phase of patient accrual, the patient preference study indicates that travel time for treatment is a factor in selecting the preferred treatment option when fraction number as well as whole and partial breast options are available. The final study analysis is intended to address the participants' satisfaction in their treatment selection at follow-up time points.

The impact of standardized structured reporting of pathology reports for breast cancer care

PurposeWith the increasing complexity of modern oncological patient management and the growing amount of information needed from the pathologist, traditional narrative pathology reports (NR) do not suffice. Standardized synoptic reporting (SR) increases both completeness and readability. In the Netherlands SR for breast cancer was introduced in 2009. We explore the impact of synoptic reporting on breast cancer care. MethodsUsing data from the Netherlands Cancer Registry and Dutch Nationwide Pathology Databank, a retrospective population-based cohort study was performed. Data of breast cancer resections from 2007 to 2014 were collected to compare NR and SR for all outcome measures. Kaplan-Meier analyses and log-rank testing were used to estimate overall survival. ResultsOver time there was an increase from 12% to 78.9% in the use of SR. SR resulted in higher completeness of pathology reports, particularly for hormone and HER2/neu receptor status. Although there was no difference in the administration of antihormonal therapy, anti-HER2 treatment was more frequently administered to eligible patients in the SR group. An effect on overall survival could not yet be confirmed on multivariate analysis. ConclusionsWe demonstrate that SR has led to more complete pathology reports, which meets the needs for precision of information in breast cancer care. This is expected to improve communication and discussions between specialists regarding parameters important for adjuvant breast cancer treatment decisions. SR thereby improves breast cancer care and leads to improved allocation of treatment based on pathologic parameters and more personalized treatment regimens.

Watson for oncology decision system for treatment consistency study in breast cancer.

The Watson for Oncology (WFO) decision system has been rolled out in many cancers. However, the consistency of treatment for breast cancer is still unclear in relatively economically disadvantaged areas. Patients with postoperative adjuvant stage (January 2017 to December 2017) and advanced-stage breast cancer (January 2014 to December 2018) in northwest of China were included in this study. Patient information was imported to make treatment decisions using Watson version 19.20 analysis and subsequently compared with clinician decisions and analyzed for influencing factors. A total of 263 patients with postoperative adjuvant breast cancer and 200 with advanced breast cancer were included in this study. The overall treatment modality for WFO was in 80.2% and 50.5% agreement with clinicians in the adjuvant and advanced-stage population, respectively. In adjuvant treatment after breast cancer surgery, menopausal status (odds ratio (OR) = 2.89, P = 0.012, 95% CI, 1.260-6.630), histological grade (OR = 0.22, P = 0.019, 95% CI, 0.061-0.781) and tumor stage (OR = 0.22, P = 0.042, 95% CI, 0.050-0.943) were independent factors affecting the concordance between the two stages. In the first-line treatment of advanced breast cancer, hormone receptor status was a factor influencing the consistency of treatment (χ2 = 14.728, P < 0.001). There was good agreement between the WFOs and clinicians' treatment decisions in postoperative adjuvant breast cancer, but poor agreement was observed in patients with advanced breast cancer.

Shallow WGS of individual CTCs identifies actionable targets for informing treatment decisions in metastatic breast cancer

BackgroundWe report copy-number profiling by low-pass WGS (LP-WGS) in individual circulating tumour cells (CTCs) for guiding treatment in patients with metastatic breast cancer (MBC), comparing CTC results with mutations detected in circulating tumour DNA (ctDNA) in the same blood samples.MethodsAcross 10 patients with MBC who were progressing at the time of blood sampling and that had >20 CTCs detected by CellSearch®, 63 single cells (50 CTCs and 13 WBCs) and 16 cell pools (8 CTC pools and 8 WBC pools) were recovered from peripheral blood by CellSearch®/DEPArray™ and sequenced with Ampli1 LowPass technology (Menarini Silicon Biosystems). Copy-number aberrations were identified using the MSBiosuite software platform, and results were compared with mutations detected in matched plasma cfDNA analysed by targeted next-generation sequencing using the Oncomine™ Breast cfDNA Assay (Thermo Fisher).ResultsLP-WGS data demonstrated copy-number gains/losses in individual CTCs in regions including FGFR1, JAK2 and CDK6 in five patients, ERBB2 amplification in two HER2-negative patients and BRCA loss in two patients. Seven of eight matched plasmas also had mutations in ctDNA in PIK3CA, TP53, ESR1 and KRAS genes with mutant allele frequencies (MAF) ranging from 0.05 to 33.11%. Combining results from paired CTCs and ctDNA, clinically actionable targets were identified in all ten patients.ConclusionThis combined analysis of CTCs and ctDNA may offer a new approach for monitoring of disease progression and to direct therapy in patients with advanced MBC, at a time when they are coming towards the end of other treatment options.

EPH109 A Scoping Review of Interactive Online Decision Tools to Guide Surgery and Adjuvant Treatment Decisions in Breast Cancer

To evaluate the interactive, currently available, web-based tools to support treatment and surgery decisions in clinical practice and inform the future directions in clinical tool development to support breast cancer care.

Concordance of breast cancer biomarker testing in core needle biopsy and surgical specimens: A single institution experience.

Accurate diagnostic biomarker testing is crucial to treatment decisions in breast cancer. Biomarker testing is performed on core needle biopsies (CNB) and is often repeated in the surgical specimen (SS) after resection. As differences between CNB and SS testing may alter treatment decisions, we evaluated concordance between CNB and SS as well as associated changes in treatment and clinical outcomes. We performed a retrospective analysis of breast cancer patients at our institution between January 2010 and May 2020. Concordance between CNB and SS was assessed for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Survival in patients, including recurrence, metastatic recurrence, and death, were assessed using chi-squared likelihood ratio. In total, 961 patients met eligibility criteria. Concordance, minor discordance, total concordance (concordance plus minor discordance), and major discordance between CNB and SS were reported for ER (87.7%, 9.2%, 90.8%, and 2.9%), PR (58.1%, 29.1%, 87.2%, and 12.8%), and HER2 IHC (52.5%, 20.9%, 73.4%, 26.6%), respectively. HER2 FISH concordance and major discordance were 58.5% and 1.2%, respectively. Of major discordance, ER (48.2%, p< 0.001) and HER2 FISH (50.0%) led to more management changes than HER2 IHC (2.4%, p= 0.04) and PR (1.6%, p= 0.10). Patients with ER major discordance had increased risk of death (6.7% concordance vs. 22.2% major discordance, p= 0.004). Overall, retesting ER and HER2 was more clinically beneficial than retesting PR. To aid decision-making and minimize healthcare costs, we propose patient-centered guidelines on retesting biomarker profiles.

Does the addition of whole-body MRI to routine imaging influence real-world treatment decisions in metastatic breast cancer?

BackgroundThe assessment of metastatic breast cancer (MBC) can be limited with routine imaging such as computed tomography (CT) especially in bone-only or bone-predominant disease. This analysis investigates the effects of the use of WBMRI in addition to the use of routine CT, bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) on influencing systemic anti-cancer treatment (SACT) decisions in patients with known MBC.MethodsMBC patients undergoing SACT who had WBMRI undertaken within 8 weeks of either a routine CT, BS or FDG-PET/CT were reviewed retrospectively. The clinical indications for undertaking the WBMRI examinations were recorded. Data on the extent and distribution of the disease were collected and discordance/concordance of disease status across the imaging modalities were compared. SACT decisions at each time point were also evaluated.ResultsThere were 105 MBC patients with 148 WBMRI studies paired with CT, BS or FDG-PET/CT. 50 pairs (33.8%) showed differences in the extent of disease, with 44 pairs due to additional sites (AS) reported on WBMRI alone.81 patients (Group 1) had one WBMRI paired with routine imaging due to a variety of indications, with clinical symptoms (such as bone pain) being the most common (24.7%).24 patients (Group 2) had more than one WBMRI study paired with routine imaging comprising 67 pairs. 13/67 pairs (19.4%) showed discordance in assessments. 10/13 pairs had progressive disease (PD) reported on WBMRI alone.SACT change due to AS reported on WBMRI alone occurred in 21/23 pairs (91.3%) in Group 1. SACT change due to PD reported on WBMRI alone in Group 2 occurred in 6/14 pairs (42.9%). SACT change due to AS/PD in both groups occurred in 11/102 pairs (10.8%) with known invasive ductal carcinoma (IDC) and 13/28 pairs (46.4%) with invasive lobular carcinoma (ILC).ConclusionsThe use of WBMRI in MBC led to earlier recognition of PD and SACT change compared with the other imaging modalities. A higher proportion of discordant response assessments and SACT changes were observed in ILC compared with IDC in our patient group, although larger-scale studies are required to investigate this further.

Influence of decision support persons on breast cancer treatment decisions among Latinas.

12025 Background: Prior studies suggest that decision support persons (DSPs) involvement in breast cancer promotes greater deliberation and decision quality. Despite having the highest level of involvement, Latinx DSPs report the lowest satisfaction with their involvement. The reasons for this remain unknown. We examined the treatment decision-making experiences of Latinx DSPs, their influence on treatment deliberation, subjective decision quality (SDQ), and treatment received. Methods: Women with newly diagnosed early-stage breast cancer as reported to the Surveillance, Epidemiology, and End Results (SEER) registries of Georgia and Los Angeles County in 2014-2015 were surveyed. Participants identified the DSPs who played a key role in treatment decisions, who were also surveyed. We examined: (1) bivariate associations of DSP characteristics (e.g type, age, race/ethnicity, education, acculturation level) with DSP-reported level of engagement (informed about decisions, involvement (extent and satisfaction), and aware of patient preferences), (2) DSP engagement with patient-reported SDQ and treatment deliberation using multivariable linear regression with standardized scales (3), and treatment received by DSPs preferred treatment. Results: 2502 patients (68%) and 1203 eligible DSPs (70%) responded, resulting in 1,173 dyads, 292 where the patient identified as Latina, and 881 as non-Latina. Among Latina dyads, 78%, 17%, and 5% DSPs identified as Latinx, White, and Asian/Black/Other, respectively. Latinx DSPs within Latina/Latinx dyads were younger, had lower educational attainment and acculturation when compared to other dyads. The proportion of married/partnered status was not different across dyads, but the key DSP for the Latina-Latinx dyads was more often a daughter (37%), over a husband/partner (21%), compared to the other dyads. Latinx DSPs reported being more informed (adjusted mean 4.26, p = 0.058) compared to the other dyads, and being more informed was positively associated with higher patient SDQ (adjusted mean difference 0.176, p = 0.034), despite no difference in treatment deliberation. Overall, Latinx DSP had a higher preference for mastectomy, especially with reconstruction when compared to non-Latinx (40% vs 28%). Overall, 27% of Latinas (vs 13% non-Latina) underwent lumpectomy despite their DSP’s preference for mastectomy. Conclusions: These findings reveal that the key DSP for many married Latinas is often a daughter over spouse/partner. Our results suggest that including daughter/DSPs in treatment decisions and tailoring strategies to meet their information needs may positively impact Latina SDQ. Potential areas of improvement include surgical options preferences, where notable discrepancy was seen between Latinas and non-Latinas. Awareness of these differences can minimize treatment regret, improve decision quality, and ultimately outcomes in Latinas.

70P Factors influencing patient treatment decisions in early breast cancer (eBC): Discrete choice experiment (DCE) findings

The emerging treatment paradigm in eBC, with new systemic therapies varying in efficacy, safety and conditions of use, creates a complex patient journey involving many inflection points with respect to treatment sequence, duration and response to initial therapy. We quantified patient preferences for attributes of different treatment pathways in eBC in Germany, Italy and Japan.