HER2-negative Invasive Breast Cancer Research Articles

Performance evaluation of ML models for preoperative prediction of HER2-low BC based on CE-CBBCT radiomic features: A prospective study.

To explore the value of machine learning (ML) models based on contrast-enhanced cone-beam breast computed tomography (CE-CBBCT) radiomics features for the preoperative prediction of human epidermal growth factor receptor 2 (HER2)-low expression breast cancer (BC). Fifty-six patients with HER2-negative invasive BC who underwent preoperative CE-CBBCT were prospectively analyzed. Patients were randomly divided into training and validation cohorts at approximately 7:3. A total of 1046 quantitative radiomic features were extracted from CE-CBBCT images and normalized using z-scores. The Pearson correlation coefficient and recursive feature elimination were used to identify the optimal features. Six ML models were constructed based on the selected features: linear discriminant analysis (LDA), random forest (RF), support vector machine (SVM), logistic regression (LR), AdaBoost (AB), and decision tree (DT). To evaluate the performance of these models, receiver operating characteristic curves and area under the curve (AUC) were used. Seven features were selected as the optimal features for constructing the ML models. In the training cohort, the AUC values for SVM, LDA, RF, LR, AB, and DT were 0.984, 0.981, 1.000, 0.970, 1.000, and 1.000, respectively. In the validation cohort, the AUC values for the SVM, LDA, RF, LR, AB, and DT were 0.859, 0.880, 0.781, 0.880, 0.750, and 0.713, respectively. Among all ML models, the LDA and LR models demonstrated the best performance. The DeLong test showed that there were no significant differences among the receiver operating characteristic curves in all ML models in the training cohort (P > .05); however, in the validation cohort, the DeLong test showed that the differences between the AUCs of LDA and RF, AB, and DT were statistically significant (P = .037, .003, .046). The AUCs of LR and RF, AB, and DT were statistically significant (P = .023, .005, .030). Nevertheless, no statistically significant differences were observed when compared to the other ML models. ML models based on CE-CBBCT radiomics features achieved excellent performance in the preoperative prediction of HER2-low BC and could potentially serve as an effective tool to assist in precise and personalized targeted therapy.

The correlation between Ki 67 and Oncotype Dx on HR+, HER2- early breast cancer management: Insights of molecular testing.

e12546 Background: Elevated Ki-67 expression serves as an indicator of tumoral proliferation in breast cancer (BC) and is used in Ecuador for survival estimation, recurrence risk assessment, and guiding chemotherapy decisions. The Oncotype DX Breast Recurrence Score (ODX RS) is a validated 21-gene assay for hormone receptor-positive, HER2-negative invasive BC. It predicts chemotherapy benefits and the risk of distant recurrence over 10 years and is a mortality indicator. ODX RS has the potential to reduce the need for chemotherapy, alleviate financial burdens, and enhance clinical outcomes. Despite conflicting evidence on the significance of Ki-67 in the ODX RS, there is a lack of exploration within Latin populations. This study aims to compare the correlation of immunohistochemical (IHC) measured Ki-67 to the ODX RS in the Ecuadorian population. Methods: A retrospective analysis included women with early BC who underwent ODX RS testing in Ecuador from May 2020 to January 2023. Inclusion criteria: early BC (T1-T3/N0-N1a); IHC estrogen receptor (ER) positive; HER2 negative; and availability of tumor size, grade, lymph node status, and Ki67 proliferation index data. Exclusion criteria: patients with recurrent BC, incomplete pathology, or lacking IHC data. Patients were categorized into low (≤5%), intermediate (6%–29%), and high Ki67 expression groups (≥30%). Using the statistical software SPSS, the correlation between ODX scores and Ki-67 expression was analyzed using Pearson’s correlation coefficient. For risk stratification groups, Spearman's correlation was employed. Results: Among 77 patients undergoing Oncotype DX testing, 64 (with a mean age of 55) met the inclusion criteria. Eighty-six percent of cases were invasive ductal carcinomas (IDC). Seventeen percent exhibited low Ki-67 expression, 61% intermediate, and 20% high. No statistically significant correlation was found between IHC Ki-67 expression and ODX RS (r=0.051; p=0.69), neither when stratified by categories (r=0.086; p=0.50). A subanalysis based on risk categories showed 82% correspondence in the low Ki-67 group, 18% in the intermediate group, and 31% in the high Ki-67 group. No significant correlation was observed when stratified by histological types (invasive ductal carcinoma and invasive lobular carcinoma), nor by sample origin (core biopsy, excisional biopsy). Conclusions: There was no correlation between IHC Ki-67 expression and ODX risk scores in this study involving Ecuadorian patients. Our findings emphasize that IHC Ki-67 expression should not be the sole determinant for guiding therapeutic decisions and predicting recurrence in early breast cancer.[Table: see text]

Abstract PO1-01-07: Cryoablation and endocrine therapy for clinical stage I/II, ER+ breast cancer in patients with omission of surgical axillary staging. A retrospective study

Abstract OBJECTIVE To evaluate the efficacy of combined treatment with ultrasound-guided cryoablation and endocrine therapy (ET) in hormone receptor-positive (ER+), HER2-negative (HER-) invasive breast cancer (BC) patients with clinical stage I/II who are not candidates for axillary surgery. PATIENTS AND METHODS Patients with ER+, HER- invasive BC in clinical stage I/II who did not undergo sentinel lymph node biopsy (SLNB) or target axillary dissection (TAD) were included. They received treatment consisting of ultrasound-guided cryoablation combined with daily letrozole 2.5 mg orally. Cryoablation was performed as the initial treatment for BC < 15mm, followed by adjuvant ET, while neoadjuvant ET was administered for 6-12 months before cryoablation for BC ≥ 15mm. Cryoablation was performed using the ICEfx Galil argon gas system (Boston Scientific, USA) and the ProSense liquid nitrogen system (IceCure Medical Ltd, Caesarea, Israel). Follow-up breast ultrasound examinations were conducted every six months. Patients with a minimum follow-up of 12 months after cryoablation were included in the study. Core needle biopsies were performed if recurrence was suspected, and rescue cryoablation was considered for confirmed relapse. The tolerance and safety of the procedures were recorded. RESULTS From March 2019 to July 2023, a total of 96 patients with 105 ER+, HER2- invasive BC in clinical stage I/II who did not undergo SLNB or TAD were treated with ultrasound-guided cryoablation and ET. Among them, 58 patients (aged 58-96 years, mean 83, SD ±7.64) with 64 BC lesions (ranging from 5 to 60mm, mean 17, SD ±13.75) were followed up for a minimum of 12 months, with a mean follow-up period of 24 months (ranging from 12 to 50 months). The invasive carcinomas included 40 ductal, 16 lobular, 5 colloid, and 3 papillary cases. The ipsilateral breast tumor recurrence rate was 1,72% (1/58 patients). One patient with lobular carcinoma experienced a relapse at 17 months. Rescue cryoablation was performed, and after 25 months, she remains free of recurrence. Therefore, local control was achieved in all patients. Six patients died from causes unrelated to BC during the follow-up period. All procedures were well-tolerated with local anesthesia, and no serious complications were reported. CONCLUSION Ultrasound-guided cryoablation with ET constitutes an effective combined treatment for the local control of ER+, HER2- BC in patients with clinical stage I/II and omission for surgical axillary staging. Cryoablation is a very well tolerated procedure without morbidity. Citation Format: José María Oliver Goldaracena, Pilar Zamora, Covadonga Marti, Vicenta Córdoba Chicote, Maria José Roca Navarro, Diego Garrido Alonso, Ylenia Navarro Monforte, Teresa Diaz de Bustamante Durban, Fernando García Martínez, Jose Ignacio Sanchez-Mendez, Elisa York Pineda, Laura Yebenes Gregorio, Adolfo Loayza, Laura Frías Aldeguer, Elisa Moreno Palacios, Marcos Melendez Gisper, Joaquin Gomez Ramirez, Luis Asensio Gómez, Virginia Martínez Marín, David Hardisson Hernáez, Alberto Berjón García. Cryoablation and endocrine therapy for clinical stage I/II, ER+ breast cancer in patients with omission of surgical axillary staging. A retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-07.

Abstract PO2-02-05: CDK4/6 inhibitor dalpiciclib combined with letrozole as neoadjuvant therapy in postmenopausal patients with hormone receptor-positive, HER2-negative stage II-III breast cancer: a single-arm exploratory trial

Abstract Background: Patients with HR-positive, HER2-negative breast cancer respond poorly to neoadjuvant chemotherapy. The phase 3 DAWNA-1 and DAWNA-2 studies have proved that adding dalpiciclib (a CDK4/6 inhibitor) to endocrine therapy can significantly improve progression-free survival in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer. However, the evidence of dalpiciclib in the neoadjuvant setting is limited. This study aimed to explore the efficacy and safety of dalpiciclib plus letrozole as neoadjuvant therapy in in patients with HR-positive, HER2-negative stage II-III breast cancer. Methods: In this multicenter, single-arm exploratory trial (NCT05512780), adult postmenopausal women with HR-positive (estrogen receptor >10%), HER2-negative stage II-III invasive breast cancer were enrolled. Patients received oral dalpiciclib (150 mg on days 1-21 of each 28-day cycle) and oral letrozole (2.5 mg once daily) for 4 cycles, followed by surgery. The primary endpoint was objective response rate (ORR), assessed by investigator according to the Response Evaluation Criteria In Solid Tumors version 1.1. Secondary endpoints included complete cell cycle arrest (CCCA, defined as Ki-67 < 2.7% on day 15 of the first cycle) rate, total pathological complete response (tpCR; ypT0/is ypN0) rate, residual cancer burden (RCB) 0-I rate, and safety. Results: Between June 2022 and January 2023, 41 patients were screened at 9 sites, and 35 patients were enrolled and received at least one dose of study drug. The median age was 66 years (range, 52-83), and the median baseline Ki-67 level was 20% (range, 4%-40%). The majority of patients had T2 disease (65.7%), lymph node-positive disease (88.6%), and stage II disease (IIA: 45.7%; IIB: 40.0%). The ORR was 35.5% (11/31) at 8 weeks and 51.7% (15/29) at 16 weeks in patients with evaluable response. The CCCA rate was 70.0% (21/30) in patients with available data. Four patients refused surgery and chose to continue the drug therapy. Of 27 patients who had undergone surgery, one (3.7%) patient had tpCR and RCB 0. Of 35 patients, the most common adverse events were neutrophil count decreased (74.3%), white blood cell decreased (68.6%), anemia (34.3%), and fatigue (31.4%). The most common grade 3 or higher adverse event was neutrophil count decreased (45.7%). No febrile neutropenia or treatment-related deaths occurred. Conclusions: This is the first prospective study of neoadjuvant dalpiciclib in patients with HR-positive, HER2-negative breast cancer. The findings suggest the promising tumor response to neoadjuvant dalpiciclib plus letrozole in postmenopausal patients with HR-positive, HER2-negative breast cancer, with a manageable safety profile. This combination can effectively suppress the tumor cell proliferation, as reflected by change in Ki-67 level. Citation Format: Lina Zhang, Chao Yang, Jie Ma, Yuntao Li, Ruizhen Luo, Jianjun Han, Xiaochun Wang, Zhisheng Zhang, Li Ma, Haifeng Cai, Xiangshun Kong, Zunyi Wang, Xinping Zhou, Yueping Liu, JiaJie Shi, Yanshou Zhang, Meiqi Wang, Jiaxing Wang, Cuizhi Geng. CDK4/6 inhibitor dalpiciclib combined with letrozole as neoadjuvant therapy in postmenopausal patients with hormone receptor-positive, HER2-negative stage II-III breast cancer: a single-arm exploratory trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-05.

Abstract PO5-08-07: Ki-67 Expression in Breast Cancer associated with ATM, BRCA1, BRCA2, CHEK2 and PALB2 Pathogenic Variants

Abstract Background: Germline Pathogenic Variants (PVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are known to increase breast cancer (BCa) risk, but the effect of these PVs on tumor biology is not well-understood. Ki-67 is an established prognostic marker in hormone receptor (HR) positive breast cancer but the distribution of Ki-67 in breast cancer associated with germline PVs is not known. Methods: The study included patients with loco-regional (Stage I-III) HR-positive (ER+ or PR+), HER2-negative invasive ductal or lobular breast cancer evaluated at Mayo Clinic for curative intent treatment between 2012 and 2021. PV carrier status was ascertained in more than two-thirds of cases from germline whole exome sequencing (Regeneron) of patients who participated in a prospective registry at Mayo Clinic. Additional PV carriers were identified through a review of the results of clinical germline genetic testing in electronic medical records aided by natural language processing. Clinically performed Ki-67 values were abstracted from electronic medical records and analyzed as continuous and categorical variables (low: < 20% vs. high: ≥20%). Throughout the timeline of the study, a consistent method for assessment of Ki-67 was utilized at Mayo Clinic, Rochester: Immunohistochemical staining of the Ki-67 antigen in formalin-fixed paraffin-embedded tissue was performed using MIB-1 clone, the scanned slides were reviewed by a technologist and traced areas further analyzed for Ki-67 using Aperio Software. Patients who received neoadjuvant therapy prior to the assessment of Ki-67, with metastatic disease at diagnosis, with PVs in two or more genes of interest, or unknown germline PV or Ki-67 status were excluded from the analysis. Multiple primary tumors in the same patient diagnosed within one year of each other were analyzed independently. The control (non-carrier) group included randomly selected patients from the prospective registry who tested negative for PVs in the five genes over the same time period. Ki-67 values were compared between germline PV carriers and non-carriers in a multivariable logistic regression analysis adjusting for sex, race, age at diagnosis, stage at presentation, and histology of the tumor. Results: A total of 113 HR+/HER2- tumors from 111 PV carriers (ATM: 27, BRCA1: 24, BRCA2: 28, CHEK2: 22, and PALB2:12) along with 431 HR+/HER2- tumors from 422 randomly selected non-carriers were evaluated. The majority (>95%) of patients were non-Hispanic White. Germline PV carriers in each gene were diagnosed at a significantly younger age (P< 0.05) compared to non-carriers. The median Ki-67 value was 12 (Range: 1 to 93) for non-carriers, 16 (Range: 0 to 79) for ATM, 31 (Range: 4 to 86) for BRCA1, 30 (Range: 6 to 80) for BRCA2, 13 (Range: 1 to 38) for CHEK2, and 20 (Range: 3 to 46) for PALB2 PV carriers. In multivariable analysis, compared to non-carriers, we observed significantly higher odds of a high Ki67 value (≥20%) for tumors arising from germline PV carriers in BRCA1 (Odds Ratio (OR): 7.3, 95%CI: 2.3 – 23.3, p< 0.001), BRCA2 (OR: 3.0, 95%CI: 1.2 – 7.4, p=0.02) and PALB2 (OR: 3.9, 95%CI: 1.1 – 14.5, p=0.04). No such relationship was observed with either ATM (OR: 1.1, 95%CI: 0.4 – 2.9, p=0.81) or CHEK2 (OR: 0.8, 95%CI: 0.3 – 2.2, p=0.63). Conclusion: This study reveals that HR+/HER2- tumors in BRCA1, BRCA2, and PALB2 PV carriers have a significantly higher Ki-67 expression compared to non-carriers. These findings have implications for understanding prognosis and endocrine response PV with HR+ breast cancer. Further exploration of the relationships between Ki67 and germline PV status is necessary to personalize systemic therapy options in germline PV carriers. Acknowledgments: Thank you to Regeneron Genetics Center. The study was funded in part by the NIH Specialized Program of Research Excellence in Breast Cancer [P50CA116201] to Mayo Clinic, Mayo Clinic Department of Oncology Small Grants Program, and the Paul Calabresi Program at Mayo Clinic Citation Format: Robert Scheel, Grace Choong, Tara Rao, Nicholas Boddicker, Chunling Hu, Jie Na, Vinod Kaggal, Sean Murphy, Karthik Giridhar, Saba Yasir, Matthew Goetz, Fergus Couch, Siddhartha Yadav. Ki-67 Expression in Breast Cancer associated with ATM, BRCA1, BRCA2, CHEK2 and PALB2 Pathogenic Variants [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-07.

Efficacy of Single-Agent Chemotherapy in Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma.

Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC. Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic setting. We compared outcomes between 173 CAP-treated and 96 TAX-treated patients. CAP-treated patients had significantly better median progression-free survival (PFS) than TAX-treated patients (8.8 vs 5.0 months, HR 0.63, P < .001). Overall survival (OS) did not differ significantly between the groups (42.7 vs 36.6 months for CAP vs TAX, respectively, HR 0.84, P = .241). Multivariate analyses for PFS and OS revealed better outcomes in subjects with fewer metastatic sites and those exposed to more lines of ET. Additionally, Black patients showed worse OS outcomes compared to White patients (HR 2.46; P = .001). In ET-refractory HR+ HER2-negative mILC, single-agent CAP demonstrated superior PFS compared to TAX. Our findings highlight the potential benefit of CAP in this patient subset, warranting further investigation through prospective trials.

Risk factors for late recurrence and postrelapse survival in estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER) 2-negative breast cancer after 5 years of endocrine therapy

It is unclear which patients with ER-positive, HER2-negative breast cancer benefit from extended endocrine therapy beyond 5 years. Prognostic factors for late-recurring breast cancer postrelapse survival have been reported. We retrospectively analyzed data from 892 patients with ER-positive and HER2-negative invasive breast cancer who were disease-free after completing a 5-year adjuvant endocrine therapy. Patients were then classified as high-risk (positive lymph nodes, large tumor size, high tumor grade) or low-risk. High-risk patients were divided into extended endocrine therapy and stop groups. Comparisons were made using propensity score matching, and the benefits of extended endocrine therapy for high-risk patients and prognostic factors for postrelapse survival were assessed. The high- and low-risk groups comprised 444 and 448 patients, respectively. The 10-year distant disease-free survival (DDFS) rates were 96.3 % (95 % confidence interval [CI] 0.912–0.985) and 86.5 % (95 % CI 0.798–0911) in the extended and stop groups, respectively (P = 0.00382). Cox proportional hazards model revealed that extended endocrine therapy promoted greater reduction in distant metastasis risk than 5-year endocrine therapy in high-risk populations (hazard ratio [HR] 0.27; 95 % CI 0.11–0.68; P = 0.0054). Postrelapse survival was significantly different in patients with DDFS ≥7 years (HR 0.24; 95 % CI 0.072–0.81; P = 0.021) and those with better response to first-line treatment (HR 0.072; 95 % CI, 0.058–0.90; P = 0.041). Patients with risk factors for late recurrence should be considered for extended endocrine therapy. Longer DDFS and response to first-line treatment may be a prognostic factor for postrelapse survival after late recurrence.

Clinical Behavior, Management, and Treatment Response of Estrogen Receptor Low (1-10%) Breast Cancer.

Estrogen receptor (ER) and progesterone receptor (PR) guide management and impact outcomes of breast cancer (BC). This study compares ER-low (1-10%) with ER-negative (< 1%) and ER-positive (>10%) BCand investigates the significance of PR expression within ER-low disease. All patients with HER2-negative invasive BC were identified from the National Cancer Database 2018-2019. Treatment and outcomes were compared using chi-squared tests and multivariable logistic regression. Of 232,762 patients, ER expression was: negative (13.8%), low (2.0%), and > 10% (84.2%). Chemotherapy was given in 83.9% of ER- disease, 82.4% of ER-low/PR- disease, 58.9% of ER-low/PR+ disease, and only in 22.9% of ER+ disease. Within the ER-low subgroup, adjuvant endocrine therapy, recurrence score, and Ki67 varied by PR status (all < 0.01). Patients with ER-low disease selected for neoadjuvant chemotherapy (NAC) were younger and had higher T and N category, tumor grade, and Ki67. With NAC, pathological complete response (pCR) rates were similar between ER-low/PR- and ER-low/PR+ (39.5% and 38.1%, respectively, p = 0.67), and were closer to the ER- group (39.7%) than the ER+ group (8.4%). On multivariable analysis, the adjusted effect of ER status (1-10% versus > 10%) on chemotherapy administration was odds ratio (OR) 8.2 (95% CI 7.3-9.2, p < 0.001) for PR-negative, and OR 3.3 (95% CI 7.3-9.2, p < 0.001) for PR-positive. This study suggests that the tumor features and clinical management of ER-low tumors vary significantly by PR expression. Within ER-low tumors, PR- tumors more closely resemble ER- BC, while PR+ tumors exhibit less aggressive characteristics. In ER-low disease selected for treatment with NAC, response is similar to ER- regardless of PR status.

Percutaneous microwave ablation combined with endocrine therapy versus standard therapy for elderly patients with HR-positive and HER2-negative invasive breast cancer: a propensity score-matched analysis of a multi-center, prospective cohort study.

There is a growing trend to apply minimally invasive local treatments for elderly patients with early-stage breast cancer. As a minimally invasive thermal therapy, microwave ablation (MWA) has been attempted to treat breast cancer of small lesions, but its long-term local efficacy on elderly patients has seldom been reported. In this study, we aimed to compare outcomes of MWA combined with endocrine therapy to standard surgery combined with adjuvant therapy in the treatment of hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer for elderly patients. This prospective multi-center cohort study enrolled patients over 70 years old diagnosed with HR-positive and HER2-negative early-stage invasive breast cancer between January 2016 and July 2021. Patients chose either non-randomized to undergo MWA combined with endocrine therapy (MWA group) or standard surgery combined with adjuvant therapy (surgery group). Endpoints for the comparisons were disease-free survival (DFS), overall survival (OS) and length of hospital stay (LOS) after adjusting for previously reported risk factors using propensity score matching (1:3). Of the enrolled 132 patients, 33 were in the MWA group and 99 were in the surgery group. MWA was successfully performed in all cases, and technical effectiveness was achieved in all cases. With a median follow-up of 31 months, only one case had local recurrence 23 months after MWA. MWA combined with endocrine therapy and standard surgery combined adjuvant therapy for elderly patients with breast cancer achieved similar DFS [hazard ratio, 0.536; 95% confidence interval (CI): 0.128-2.249] and OS (hazard ratio, 0.537; 95% CI: 0.089-3.235). Besides, MWA had much shorter LOS than standard surgery (7.1 versus 13.0 days, P<0.001). MWA combined with endocrine therapy and standard surgery combined with adjuvant therapy for elderly breast cancer patients achieved similar outcomes. MWA combined with endocrine may be a feasible treatment strategy for elderly patients with HR-positive and HER2-negative invasive breast cancer.

Correlation between Oncotype DX, Predict, and Nottingham Prognostic Index on HR+, HER2- early breast cancer treatment: The current value of molecular testing.

1601 Background: The Oncotype DX Breast Recurrence Score (ODX) assay is a 21-gene assay validated in hormone receptor-positive, HER2 negative invasive breast cancer (BC) to predict chemotherapy benefit and risk of distant recurrence at 10 years regardless of node status and is also a strong predictor of mortality. ODX can minimize the misuse of chemotherapy, financial burden, and improve clinical outcomes. ODX is not widely used in Ecuador due to socioeconomic and healthcare access disparities; instead, many physicians stratify patients' risk according to clinicopathological and immunohistochemical features. We aim to compare the differences between ODX and two of the most common stratification clinical tools: Predict Score (PS) and Nottingham prognostic index (NPI). Methods: Retrospective analysis of women with early BC who underwent ODX testing in Ecuador from May 2020 to January 2023. Inclusion criteria: early BC (T1-T3 / N0-N1a); estrogen receptor (ER) positive; HER2 negative by immunohistochemistry; and available data of tumor size, grade, lymph node status, and Ki67 proliferation index. Exclusion criteria: patients with recurrent BC, incomplete pathology, or immunohistochemistry data. PS and NPI were calculated using online tools. The correlation between PS, NPI, and ODX scores was analyzed using Spearman's correlation coefficient in SPSS. Results: 77 patients underwent ODX testing, of which 58 patients (mean age 55 years old) met the inclusion criteria. Invasive breast carcinoma not otherwise specified was the most common type (48 patients (82%). Risk scores generated by PS correlated strongly with NPI for all patients (r=0.47; p ≤ 0.001). A strong correlation was also found between ODX and NPI (0.79, p&lt;0.027). Risk scores were then stratified by patient risk category. For low-risk patients, 68% of correspondence between ODX and PS was found, and 98% between ODX and NPI. Intermediate-risk patients showed a correspondence between ODX and PS of 5% and 9% for ODX and NPI. High-risk patients showed a correspondence of 50% between ODX and PS and 17% between ODX and NPI. Conclusions: ODX risk recurrence for low-risk patients is highly correlated with PS and NPI. For Intermediate and high-risk patients determined by PS and NPI, ODX testing provided valuable and prognostic information and should be considered to guide adjuvant treatment. [Table: see text]

Abstract OT3-32-01: OPTIMA, a prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early breast cancer

Abstract Background: Multi-parameter tumor gene expression assays (MPAs) are used to estimate individual patient risk and guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence for MPA use in postmenopausal node-positive breast cancer has been provided by the RxPONDER trial interim analysis but this relies on the absence of superiority in an analysis where &amp;gt;50% of events were unrelated to breast cancer. There is much uncertainty about MPA use for premenopausal patients. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) is a prospective international randomized controlled trial designed to validate MPAs as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population. Methods: OPTIMA is a partially blinded study with an adaptive two-stage design. The trial recruits women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumor Score (ROR_PT) &amp;gt;60 receive standard management whilst those with a low score (≤60) tumor are treated with endocrine therapy alone. Endocrine therapy for pre-menopausal women includes ovarian suppression for all participants unless they experience a chemotherapy-induced menopause. Adjuvant abemaciclib is permitted. The trial will be analyzed for (1) non-inferiority of recurrence according to randomization and (2) cost-effectiveness. The key secondary outcome is non-inferiority of recurrence for patients with low ROR_PT score tumors. The efficacy analyses will be performed Per Protocol using Invasive Breast Cancer Free Survival (IBCFS) as the primary outcome measure to limit the risk of a false non-inferiority conclusion. Recruitment of 4500 patients over 8 years will permit demonstration of up to 3% non-inferiority of test-directed treatment with at least 83% power, assuming 5-year IBCFS is 87% with standard management. An integrated qualitative recruitment study addresses challenges to consent and recruitment, building on experience from the feasibility study which found that a multidisciplinary approach is important for recruitment success. OPTIMA is strongly supported by a patient group which has helped design all patient documents and which is represented on the TMG. Results: The OPTIMA main trial opened in January 2017 and has continued to recruit throughout the COVID-19 pandemic. Overall recruitment as of 1 July 2022 was 2814 (2593 from UK, 221 from Norway). Patient characteristics are well balanced between the trial arms. Currently 95% of randomized participants are eligible for inclusion in the PP analysis. 66% of the MPA-directed arm participants have been allocated to endocrine therapy only. The test failure rate is &amp;lt; 1%. Conclusion: OPTIMA will provide robust unbiased evidence on test-directed chemotherapy safety for both postmenopausal and premenopausal women with 1-3 involved nodes as well as for patients with 4-9 involved nodes and for patients treated with abemaciclib. Funding: OPTIMA is funded by the UK NIHR HTA Programme (10/34/501) and in Norway by KLINBEFORSK and the Norwegian Cancer Society. Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the Department of Health. Trial Inquiries: OPTIMA@warwick.ac.uk Patient characteristics Citation Format: Robert Stein, Andreas Makris, Iain Macpherson, Luke Hughes-Davies, Andrea Marshall, Georgina Dotchin, David A. Cameron, Belinda E. Kiely, Caroline Wilson, Anne Armstrong, Helena M. Earl, Christopher J. Poole, Janice Tsang, Bjørn Naume, Daniel Rea, Hege Ohnstad, Peter S. Hall, Stuart A. McIntosh, Bethany Shinkins, Christopher McCabe, Adrienne Morgan, John MS Bartlett, Janet A. Dunn. OPTIMA, a prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early 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 OT3-32-01.

Abstract OT3-07-01: Real-World Data on First-line Treatment of HR-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE Study/LACOG 0221)

Abstract Background: It is estimated that 50 thousand patients live with metastatic breast cancer (MBC) in Brazil. A recent Brazilian registry (LACOG 0312) on MBC demonstrated a median overall survival (OS) by breast subtype of 15 months for triple negative, 23 months for HER2 positive, and 42 months for Luminal tumors, which are very similar to developed countries except the HER2 positive group which have limited access to targeted agents in the public health system. Recently, CDK 4/6 inhibitors were approved for the treatment of HR+ HER2-negative MBC with an improvement in progression-free survival (PFS) and ribociclib and abemaciclib demonstrating benefit in OS over endocrine therapy alone, establishing the standard of care in first-line setting for this BC subtype. In Brazil, disparities exist in the incorporation of novel anticancer agents between public and private health systems limiting treatment options for patients with HR+ HER2- negative MBC in the public system, which covers most of the population. The BRAVE study aims to describe the patient journey and current patterns of care for HR+ HER2-negative MBC to identify possible gaps and how health insurance type influences treatment patterns in Brazil. Trial Design: This is an observational, retrospective cohort study. All patients diagnosed with mBC (either de novo or recurrent) in the period of January 2018 to December 2020 at participating centers will be included. Data will be collected from medical records. No interventions are proposed. Enrollment of a total of 300 patients (150 patients from public health care system and 150 patients from private health care system) is planned. ClinicalTrials.gov identifier: NCT05034393. Eligibility: Inclusion criteria: women ≥18 years old; histologically confirmed HR-positive HER2-negative invasive breast cancer; HR-positive, defined as 1% to 100% of tumor nuclei positive for ER and/or PgR as per ASCO/CAP Guideline 2020 or Allred score of ≥3; HER2-negative, defined as IHC result is 0/1+ or 2+ with ISH negative as per ASCO/CAP Guideline 2018; diagnosed with de novo or recurrent metastatic breast cancer between January 2018 and December 2020. Exclusion criteria: male BC; first-line treatment for mBC received through clinical trial. Specific Aims: Primary objective is to describe the first-line (1L) treatment of HR-positive, HER2-negative mBC in Brazil. Secondary objectives are to describe progression-free survival (PFS) in the 1L setting until month 24; describe and compare the 1L treatment of HR-positive, HER2-negative mBC and PFS until month 24 according to the health care coverage (public vs. private); describe timelines from symptoms, histopathological diagnosis, molecular test, and treatment; describe the mBC pathological characterization; describe frequency of diagnostic tests to define breast cancer molecular subtypes; describe the subsequent line of treatment and corresponding PFS; describe overall survival (OS); evaluate PFS and OS according to visceral vs. non-visceral metastatic disease, primary endocrine resistance vs. acquired endocrine resistance, de novo versus recurrent disease, public vs. private health system and pre vs postmenopausal status. Statistical Methods: No a priori sample size calculation was performed. The expected sample size of 150 patients in each group allows description of the proportion of patients using CDK 4/6 inhibitors with two-sided 90% confidence interval ranging from 53.4% to 66.6% when the expected proportion is 60% in the private health system. Present Accrual and Target Accrual: A total of 12 sites of 14 planned were activated. The first patient was enrolled on February 8, 2022. As of June 24, 2022, a total of 122 patients were enrolled, 86 from public and 36 from private health system. The target accrual of 300 patients is expected to be completed by November 2022. Results are expected to be presented by April 2023. Funding: Novartis. Acknowledgements: SAS. Citation Format: Gustavo Werutsky, Tomás Reinert, Daniela D. Rosa, Romualdo Barroso-Sousa, Heloísa Resende, Poliana A. Signorini, Juliana G. Martins Fagundes, Jose Marcio B. Figueiredo, Eduardo Cronemberger, Aline C. Vieira, Jorge Henrique Santos Leal, Luiza Nardin Weis, Ludmila Thommen, Rafaela G. Jesus, Gustavo Gössling, José Bines. Real-World Data on First-line Treatment of HR-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE Study/LACOG 0221) [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 OT3-07-01.

Abstract OT2-19-02: Clinical evaluation of the efficacy and liquid molecular analysis of abemaciclib rechallenge upon progression to abemaciclib combination therapies for ER-positive HER2-negative metastatic breast cancer patients

Abstract Background: Abemaciclib is a drug approved for ER-positive and HER2-negative metastatic or recurrent breast cancer and those treatable in an early setting. Some patients with ER-positive and HER2-negative breast cancer pretreated with abemaciclib and endocrine therapy may still benefit from abemaciclib rechallenge, especially in case of acquired resistance to endocrine therapy. However, there is no evidence for abemaciclib rechallenge. To address this, a single-arm phase 2 trial is planned to determine whether abemaciclib rechallenge has clinical benefits. Translational research to evaluate the gene alteration and immunohistochemistry will be conducted as an accompanying research to determine the predictive biomarkers of resistance or sensitivity to abemaciclib. Patients and Methods: The eligible patients are histologically confirmed with ER-positive and HER2-negative invasive breast cancer, locally advanced or metastatic, and previously received no more than two lines of endocrine therapy. The patients who previously received abemaciclib in combination with endocrine therapy led to a clinical benefit, including complete response, partial response, or stable disease, during abemaciclib-based treatment (≥6 months). The patients who previously received chemotherapy, immune checkpoint inhibitors (excluding perioperative systemic treatment), everolimus, olaparib, and palbociclib for advanced or metastatic diseases are excluded. The patients will be treated with abemaciclib 150 mg orally q12h on days 1 to 28 of a 28-day cycle. The other endocrine drug prescribed was not used in previous treatment. We will evaluate the gene mutations and/or amplification of ESR1, PIK3CA, CCNE1, FGFR1, RB1, TP53, NF1, MYC, AR, and MET at the time of inclusion and three months after day 1 and ctDNA and immunostaining levels of HER3, PTEN, CCNE1, FGFR1/2, and AR at the time of inclusion. The primary endpoint is progression-free survival (PFS), while the secondary endpoints are overall response rate, clinical benefit rate, chemotherapy-free interval, overall survival (OS), safety, and evaluation of the mechanism of sensitivity and resistance to abemaciclib. The expected median PFS for the study treatment arm is 5.0 months compared to the previous data of 3.0 months. The number of necessary cases is 59, with a significance level of 5% (two-sided) and power of 80% during the two-year recruitment period and one-year follow-up period. In the planned total of 65 cases, 10% is considered inappropriate. The planned duration of enrollment and follow-up is two years and one year, respectively. The planned total study duration is four years. Subgroup analysis will be performed on ESR1 and PIK3CA mutations, disease site (visceral/bone only/other), previous lines of therapy for advanced or metastatic disease (first and second), endocrine therapy for pretreatment (aromatase inhibitors/fuluvestrant), performance status (0/1), organs involved (1/2/≥3), age (&amp;lt;65/≥65 years), and disease-free interval (&amp;lt;36 months/≥36 months) to examine the interaction of treatment effects on PFS and OS. This study was funded by Eli Lilly and Company. Citation Format: Meiko Nishimura, Takahiro Kogawa, Yuko Akaishi, Misato Ogata, Jun Masuda, Mitsuo Terada, Hitomi Sakai, Kazuki Nozawa, Sasagu Kurozumi, Takamichi Yokoe, Yukinori Ozaki Ozaki, Shu Yazaki, Mai Onishi, Tsutomu Iwasa, Takuma Onoe, Yuta Okumura, Sayaka Nakayama, Kanako Hagio, Yuko Takahashi, Hirokazu Tanino, Junji Tsurutani, Koji Matsumoto, Mototsugu Shimokawa, Toshimi Takano. Clinical evaluation of the efficacy and liquid molecular analysis of abemaciclib rechallenge upon progression to abemaciclib combination therapies for ER-positive HER2-negative metastatic breast cancer patients [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 OT2-19-02.

Clinical outcomes and Oncotype DX Breast Recurrence Score® in early-stage BRCA-associated hormone receptor-positive breast cancer.

BackgroundBRCA‐associated breast cancers tend to have distinctive features compared to sporadic breast cancers; further characterization can aid in optimizing treatment.MethodsThe study evaluated a patient cohort with early‐stage estrogen receptor positive, HER2 negative invasive breast cancer who had Oncotype DX Breast Recurrence Score® analysis and genetic testing for hereditary breast and ovarian cancer syndrome. Data on patients and their breast cancers with outcomes were collected and analyzed.Results745 patients were included, of whom 33 had pathogenic BRCA mutations (8 BRCA1, 25 BRCA2). Patients with BRCA mutations were younger and received more adjuvant chemotherapy, but less endocrine therapy and radiation therapy. BRCA‐associated breast cancers had less progesterone receptor expression, higher nuclear grade, and higher Oncotype DX Breast Recurrence Scores® with median Recurrence Score® 29, compared to 16 in cancers without mutations (p < 0.0001). Breast cancer recurrence developed in 18% of patients with BRCA mutations and 9% of patient without mutations, although multivariate analysis of relapse‐free survival was not significant, HR 1.519 (95% confidence interval [CI] 0.64–3.58; p = 0.3401). After adjusting for Recurrence Score®, overall survival by BRCA status was improved HR 0.448 (95% CI 0.06–3.34; p = 0.4333).ConclusionsBRCA‐associated early‐stage hormone receptor‐positive breast cancers have higher Oncotype DX Breast Recurrence Score® compared to those without mutations. BRCA status did not significantly impact relapse‐free survival and overall survival. Larger clinical trials are needed to further assess the findings, and if confirmed, could impact clinical management of BRCA‐associated breast cancers.

Impact of the EndoPredict genomic assay on treatment decisions for oestrogen receptor-positive early breast cancer patients: benefits of physician selective testing.

Genomic tests improve accuracy of risk prediction for early breast cancers but these are expensive. This study evaluated the clinical utility of EndoPredict®, in terms of impact on adjuvant therapy recommendations and identification of parameters to guide selective application. Patients with ER-positive, HER2-negative, and early-stage invasive breast cancer were tested with EndoPredict®. Two cohorts were recruited: one consecutively and another at clinical team discretion. Systemic treatment recommendations were recorded before and after EndoPredict® results were revealed to the multidisciplinary team. 233 patients were recruited across five sites: 123 consecutive and 110 at clinical team discretion. In the consecutive cohort 50.6% (62/123) cases were classified high risk of recurrence by EndoPredict®, compared with 62.7% (69/110) in the selective cohort. A change in treatment recommendation was significantly more likely (p < 0.0001) in the selective cohort (43/110, 39.1%) compared to the consecutive group (11/123, 8.9%). The strongest driver of selective recruitment was intermediate grade histology, whilst logistic regression modelling demonstrated that nodal status (p < 0.001), proliferative rate (p = 0.001), and progesterone receptor positivity (p < 0.001) were the strongest discriminators of risk. Whilst molecular risk can be predicted by traditional variables in a high proportion of cases, EndoPredict® had a greater impact on treatment decisions in those cases selected for testing at team discretion. This is indicative of the robust ability of the clinical team to identify cases most likely to benefit from testing, underscoring the value of genomic tests in the oncologists' tool kit.

Optimal Treatment Duration of Neoadjuvant Endocrine Therapy for Women Aged 60 Years or Older with Estrogen Receptor-Positive, HER2-Negative Invasive Breast Cancer.

Neoadjuvant endocrine therapy is not the standard of care for breast cancer, primarily because the optimal treatment duration remains unclear. This phase 2 prospective multicenter study analyzed time to progression, time to maximal response, and time to treatment failure for neoadjuvant exemestane. Inclusion criteria were women aged ≥60 years with Stage II or III breast cancer classified as estrogen receptor-positive/human epidermal growth factor receptor 2-negative. Response was defined as a ≥10% and minimum of 3 mm decrease in tumor size, as compared with the most recent or smallest value, and no new lesion. Progression was defined as a >10% and minimum of over 3 mm increase in tumor size, as compared with the most recent or smallest value, or a new lesion. Maximal response was defined as the final recorded response. This study included 24 women, most of whom had T2 N0 tumors with high estrogen receptor expression. We initially observed a response in 23 patients (96%); however, 6 patients (25%) later experienced progression. Time to progression, time to maximal response, and time to treatment failure ranged from 7 to 22 months (estimated median, 35), 1 to 22 months (estimated median, 10), and 2 to 22 months (estimated median, 22), respectively. Treatment duration varied widely, but the estimated optimal duration of neoadjuvant exemestane therapy was 22 to 35 months in patients seeking to avoid surgery and 10 months in patients wishing to receive breast-conserving surgery. Neoadjuvant exemestane therapy is long effective for older women with hormone-sensitive breast cancer.

Abstract PD4-08: Does genomic recurrence score predict for ipsilateral breast tumor recurrence after breast conservation therapy?

Abstract Purpose/ObjectivesGene profiling Recurrence Score (RS) assays are commonly used to identify patients with hormone receptor (HR) positive, HER-2 negative invasive breast cancer (IBC) who might benefit from systemic chemotherapy. More recently, the 21-gene recurrence score assay has been found to correlate with locoregional recurrence (LRR) after mastectomy (SWOG) or lumpectomy (NSABP). In the NSABP analysis, risk of ipsilateral breast tumor recurrence (IBTR) was not correlated with RS and was high in patients younger than 50 years of age irrespective of genomic score. However, tumor bed radiotherapy (RT) boost was not utilized in these protocols. The purpose of this study is to determine if RS predicts for IBTR or LRR in women treated with modern breast conserving therapy (BCT) using RT boost and optimal systemic treatment. Materials/MethodsWe performed a retrospective review of patients with HR positive, HER-2 negative IBC who underwent gene profile testing and were treated at our institution with BCT and sentinel lymph node biopsy (SLNB) from 2013 to 2017. Both node negative and node positive patients were included. The Oncotype® 21-gene recurrence score assay was used in 84%, Mammaprint® in 12%, and Prosigna® in 4%. 97% received hormonal therapy (HT), 18% chemotherapy (CHT), 58% hypofractionated RT, and 96% a surgical bed RT boost. IBTR and LRR were measured from the end of local treatment to IBTR or LRR, with death or last follow up date as censoring events. The Kaplan-Meier method was used to estimate event-time probabilities for the above endpoints. Predictors of IBTR/LRR were analyzed using log rank tests between groups and with Cox regression for continuous variables. P-values &amp;lt;0.05 were considered significant. Results 686 evaluable patients were identified with median follow-up of 50 months (Interquartile range [IQR] 36-64 months). Median age was 61 years (IQR 53-68 years). 76% had invasive ductal carcinoma, 64% grade 2 disease, and 18% positive SLNB. RS of any type was low in 60% of patients and intermediate or high in 40%. Four-year IBTR was 0.2% (95% Confidence Interval [CI] 0.0-0.6%) for any low risk RS and 1.6% (95% CI 0.0 - 3.2%) for intermediate or high-risk RS (p = 0.01). Tumor grade was also predictive for IBTR (p &amp;lt; 0.01), but age &amp;lt; 50 was not (p = 0.4). For patients younger than 50, four-year IBTR was 0.9% (95% CI 0.0 - 2.6%) and not affected by RS (p = 0.231). On multivariate analysis, grade remained a significant predictor for IBTR (p = 0.04), but RS did not (p = 0.08). Four-year LRR was 0.5% (95% CI 0.0-1.3%) in patients with a low risk RS and 3.8% (95% CI 1.3-6.3%) in those with intermediate or high risk (p &amp;lt; 0.01). Grade (p &amp;lt; 0.01) and pathologic tumor size (p &amp;lt; 0.01) were also correlated with LRR, although only RS (HR 5.14, 95% CI 1.02-25.9, p = 0.047) and pathologic tumor size on (HR 1.05, 95% CI 1.01- 1.09, p = 0.02) remained significant on multivariate analysis. Of the 125 patients with positive SLNB, 47% were treated with high tangents and 42% with comprehensive regional nodal irradiation. For node positive patients, LRR was not correlated with low versus intermediate or high RS (p = 0.07). However, if intermediate risk Oncotype scores were grouped with low risk Oncotype and Mammaprint scores, then LRR was 0.0% for low and intermediate risk and 9.1% for high risk (p &amp;lt; 0.01). ConclusionsIn this large single institution study, RS did not predict for IBTR in patients with HR positive, HER-2 negative invasive breast cancer in any age group treated with BCT utilizing a surgical bed RT boost and optimal systemic treatment. High RS did predict for high LRR because of higher regional recurrences and can be used as a guide to add comprehensive RT for node positive patients after BCT. Citation Format: Adam H Richman, Ankur K Patel, Atilla Soran, Emilia J Diego, Priscilla F McAuliffe, Ronald R Johnson, Adam Brufsky, Vikram Gorantla, Jennifer Steiman, Joanna S Lee, Sushil Beriwal. Does genomic recurrence score predict for ipsilateral breast tumor recurrence after breast conservation therapy? [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 PD4-08.

Association between Oncotype DX recurrence score and dynamic contrast-enhanced MRI features in patients with estrogen receptor-positive HER2-negative invasive breast cancer

BackgroundOncotype DX is a multigene assay used in breast cancer, and the result provided as a ‘recurrence score (RS)’ corresponds to the risk of a cancer recurrence and the chemotherapeutic benefit in estrogen receptor (ER)-positive human epidermal growth factor receptor (HER)2-negative invasive breast cancer. However, its accessibility is limited. PurposeTo evaluate whether magnetic resonance imaging (MRI) could be used to predict Oncotype DX RS in patients with ER-positive HER2-negative invasive breast cancer. Material and methodsWe enrolled 473 patients with ER-positive HER2-negative invasive breast cancer who underwent a preoperative MRI and Oncotype DX assay between January 2015 and December 2018. The MRI was reviewed and associations between Oncotype DX RS values were evaluated. Logistic regression analysis was used to identify independent predictors of high and low RS. ResultsOf the 485 cancers, 288 (59.4%) had low (<18), 155 (31.9%) had intermediate (18–30), and 42 (8.7%) had high (≥31) RS. Multiple logistic regression analysis revealed that a round shape (odds ratio [OR] = 2.554, P = 0.089) and low proportion of washout component (OR = 1.011, P = 0.014) were associated with low RS and that heterogeneously dense (OR = 3.205, P = 0.007) or scattered fibroglandular (OR = 3.776, P = 0.005) breast tissue, a non-spiculated margin (OR = 5.435, P = 0.007), and low proportion of persistent component (OR = 1.012, P = 0.036) were associated with high RS. ConclusionMRI features showed the potential for the discrimination of Oncotype DX RS in patients with ER-positive HER2-negative invasive breast cancer.

Prognostic Value of EndoPredict in Women with Hormone Receptor-Positive, HER2-Negative Invasive Lobular Breast Cancer.

Invasive lobular carcinoma (ILC) accounts for approximately 5%-15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients with invasive ductal carcinoma (IDC) or without distinction between the subtypes. Here, we investigate the prognostic value of EndoPredict (EPclin) in a large cohort of ILCs pooled from three phase III randomized trials (ABCSG-6, ABCSG-8, TransATAC). The primary objective of this analysis was to determine the prognostic value of EPclin for distant recurrence (DR) in years 0-10 in postmenopausal women with ILC. The primary outcome was DR. 470 women (17.9%) presented with ILC, 1,944 (73.9%) with IDC, and 216 (8.2%) with other histologic types. EPclin was highly prognostic in women with ILC [HR = 3.32 (2.54-4.34)] and provided more prognostic value than the Clinical Treatment Score [CTS; HR = 2.17 (1.73-2.72)]. 63.4% of women were categorized into the low EPclin risk group and they had a 10-year DR of 4.8% (2.7-8.4) compared with 36.6% of women in the high-risk group with a 10-year DR risk of 26.6% (20.0-35.0). EPclin also provided highly prognostic information in women with node-negative disease [HR = 2.56 (1.63-4.02)] and node-positive disease [HR = 3.70 (2.49-5.50)]. EPclin provided highly significant prognostic value and significant risk stratification for women with ILC. Ten-year DR risk in the EPclin low-risk groups were similar between ILC and IDC. Our results show that EPclin is informative in women with ILC and suggest that it is equally valid in both histologic subtypes.

Single Hormone Receptor-Positive Breast Cancers Have Distinct Characteristics and Survival

Estrogen receptor (ER) and progesterone receptor (PR) status is pivotal to determining the prognosis and treatment of human epidermal growth factor 2 (HER2) receptor-negative invasive breast cancer. Frequently ER-positive (ER+) and/or PR-positive (PR+) cancers are labeled nonspecifically as "hormone receptor-positive" although only one is positive. This study aimed to evaluate and characterize the ER+PR- and ER-PR+ breast cancer phenotypes in reference to ER+PR+ cancers. A retrospective cohort study of female patients with HER2-negative (HER2-) invasive breast cancer diagnosed in 2010-2015 was performed using the National Cancer Database. Cases were grouped into ER+PR+, ER-PR+, ER+PR-, and ER-PR- phenotypes to determine differences in patient demographics, tumor characteristics, and overall survival. Of 823,969 cases, 619,050 (75.1%) were ER+PR+, 79,777 (9.7%) were ER+PR-, 7006 (0.9%) were ER-PR+, and 118,136 (14.3%) were ER-PR-. Compared with the ER+PR+ group, the ER+PR- and ER-PR+ groups were more likely to be high-grade cancer (16.0% vs.34.2% and 80.0%, respectively; p < 0.001), to have lymphovascular invasion (17.9% vs.19.6% and 23.0%; p < 0.001), to be node-positive (13.5% vs.19.7% and 26.3%; p < 0.001), to be stage 4 cancer (3.6% vs.5.9% and 6.7%; p < 0.001), to have a higher multigene assay score (mean, 16.0 vs.27.8 and 38.1; p < 0.001), and to have a worse survival (90.6% vs.83.8% and 78.1%; p < 0.001). Single hormone receptor-positive breast cancer subtypes (ER+PR- and ER-PR+) are more likely to have unfavorable characteristics and worse survival than the ER+PR+ subtype, with the ER-PR+ subtype having outcomes similar to those for ER-PR- cancers. The single hormone receptor-positive subtypes, representing 10% of HER2- cancers, should be considered clinically distinct from ER+PR+ disease.