Risk Of Late Distant Recurrence Research Articles

Abstract PO1-02-03: Correlative analysis of Breast Cancer Index with CTS5 for prediction of extended endocrine benefit in the BCI Registry study

Abstract Background Hormone receptor-positive (HR+) breast cancer patients face a prolonged risk of late distant recurrence even after 5 years of primary adjuvant endocrine therapy and derive only a modest benefit from extended endocrine therapy (EET). The Breast Cancer Index (BCI) is a validated genomic assay that provides the risk of late (post 5 years) and overall (0-10 years) distant recurrence and predicts EET benefit in patients with HR+ disease. The predictive component of BCI, HOXB13/IL17BR ratio [BCI (H/I)], stratifies patients as Low- and High-Likelihood to benefit from EET and has been validated in the MA.17, Trans-aTTom, IDEAL, and B-42 trials. The Clinical Treatment Score post-5 years (CTS5) is a prognostic tool incorporating standard clinical risk factors such as age at diagnosis, tumor size, tumor grade, and nodal involvement to inform prognosis of late distant recurrence. A previous analysis in the IDEAL trial showed that CTS5 was not predictive of EET benefit. Here, we examine the relationship between BCI (H/I) and CTS5 in a large cohort from the BCI Registry study. Methods The BCI Registry study is an ongoing prospective study to evaluate the long-term clinical outcome, decision impact and medication adherence in HR+ early-stage breast cancer patients receiving BCI testing as part of routine clinical care. BCI (H/I)-Low and BCI (H/I)-High groups were determined using pre-specified cut-points. CTS5 scores were calculated using clinical information from the ClinCapture electronic data capture system and stratified into Low-, Intermediate-, and High-risk groups using published cut-points. Pearson’s correlation coefficient (r) was used to estimate the correlation between BCI (H/I) and CTS5 as continuous variables. Descriptive statistics were used to summarize the distribution of BCI (H/I) groups across all CTS5 risk categories. Results BCI and CTS5 results were reported for 1520 patients (75.1% T1; 53.4% grade II; 80.3% N0). BCI (H/I) classified 934 patients (61.4%) as BCI (H/I)-Low and 586 patients (38.6%) as BCI (H/I)-High. BCI Prognostic classified 705 patients (46.4%) as BCI-Low risk for late distant recurrence and 815 patients (53.6%) as BCI-High risk. CTS5 classified 945 patients (62.2%) as CST5-Low, 400 patients (26.3%) as CTS5-Intermediate, and 175 patients (11.5%) as CTS5-High. When analyzed as continuous variables, BCI (H/I) showed a weak correlation with CTS5 (r=0.18). When stratifying CTS5 risk categories by BCI (H/I) groups, 65.2% (N=616) of CTS5-Low patients were classified as BCI (H/I)-Low, while 34.8% (N=329) of CTS5-High Low patients were classified as BCI (H/I)-High. In addition, 57.8% (N=231) and 42.2% (N=169) of CTS5-Intermediate patients were classified as BCI (H/I)-Low and BCI (H/I)-High, respectively. Finally, 49.7% (N=87) and 50.3% (N=88) of CTS5-High patients were classified as BCI (H/I)-Low and BCI (H/I)-High, respectively. Conclusion BCI (H/I) consistently stratified CTS5 risk categories into separate BCI (H/I)-Low and BCI (H/I)-High groups, indicating that risk prognostication does not equate to prediction of benefit from EET. These results confirm previous findings in the IDEAL study demonstrating that CTS5 is not predictive of EET benefit and further substantiate the clinical utility of BCI as the only predictive biomarker for extended endocrine therapy benefit in patients with HR+ early-stage breast cancer. Citation Format: Naomi Dempsey, Jenna Wong, Natalia Siuliukina, Yi Zhang, Kai Treuner, Reshma Mahtani. Correlative analysis of Breast Cancer Index with CTS5 for prediction of extended endocrine benefit in the BCI Registry 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 PO1-02-03.

Abstract PO1-02-02: Update of RSClin with extended TAILORx follow-up and development and validation of a new tool for risk of late distant recurrence

Abstract Background: RSClin® (Sparano et al J Clin Oncol 2020, PMID 33306425) is an educational tool that estimates the 10-year risk of distant recurrence (DR) and the absolute benefit of chemotherapy in HR-positive, HER2-negative, node-negative early breast cancer. The RSClin tool integrates the Recurrence Score® (RS) result with the clinical-pathological features tumor grade, tumor size and patient age using patient-specific meta-analysis (PSMA) applied to the NSABP B-14, TAILORx and NSABP B-20 studies. Approximately 3 years of additional follow-up data have accumulated in the TAILORx study since the RSClin tool was developed, including 50% more DR events in the RS 11-25 group (375 vs. 250), and 46% more DR events in the overall population (561 vs. 384). Methods: The RSClin tool estimates were updated to include the extended follow-up data from TAILORx. As before, the PSMA included 10,004 women with hormone-receptor positive, HER2-negative, node-negative breast cancer from the NSABP B-14 (n=577) trial receiving endocrine therapy (ET) alone and the TAILORx trial receiving ET alone (n=4854) or chemotherapy (CT) plus ET (n=4573). The baseline risk estimate used TAILORx event rates with ET alone. Since there was evidence of differing hazard ratios in years 0-5 versus 5+, models using time-varying effects were used. A patient-specific estimator of absolute CT benefit was computed by combining a PSMA estimate of the individualized relative CT effect from the TAILORx and NSABP B-20 (n=550 HER2-negative) trials with risk estimates for ET alone. Similar methods were used to develop and validate a new tool for assessing the risk of late DR (from year 5 to 10) in patients who survive DR-free for 5 years on ET alone after surgery. External validation of DR risk estimation was performed in an independent cohort of 1098 women enrolled in the Clalit Health Service registry. Results: With the updated data, the model integrating RS result with clinical-pathological features was more informative for DR risk than either RS result alone or the clinical-pathological features alone, both for 10-year DR risk and for late DR risk (likelihood ratio tests, each p≤.001). The updated 10-year RSClin risk estimates are similar to the existing RSClin tool risk estimates with slightly lower risk estimates for very high RS results and more precise estimates for mid-range RS results. The updated chemotherapy effect estimates are slightly lower than for the existing RSClin. The updated RSClin tool 10-year risk estimates were strongly associated with DR risk in the independent Clalit registry (Cox regression p< .001) and closely approximated the observed DR risk (Lin concordance 0.87). The new tool’s late DR risk estimates beyond 5 years were strongly associated with late DR risk in the Clalit registry (Cox regression p=.002) and closely approximated the observed late DR risk (Lin concordance 0.92). Conclusions: The RSClin tool 10-year DR risk estimates have been updated to incorporate extended follow-up data from the TAILORx study. A new tool for assessing late DR risk has been developed and validated that provides more prognostic information than either clinical-pathological features or genomic risk used individually. Citation Format: Joseph Sparano, Michael Crager, Robert Gray, Gong Tang, Jess Hoag, Frederick Baehner, Charles Geyer, Steven Shak, Norman Wolmark, Salomon Stemmer. Update of RSClin with extended TAILORx follow-up and development and validation of a new tool for risk of late distant recurrence [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 PO1-02-02.

Abstract PO1-08-05: Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases

Abstract Purpose: The Clinical Treatment Score post-5 years (CTS5) score is a prognostic prediction tool to predict the risk of late distant recurrence in postmenopausal women with estrogen receptor-positive (ER+) breast cancer. Here we aimed to evaluate the prediction role of CTS5 in male breast cancer patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: ER+ early male and female breast cancer patients from the SEER database 2010-2013 were included. Clinicopathological features and the CTS5 score between the gender groups were compared using chi-square test. Overall survival (OS) and breast cancer-specific survival (BCSS) were estimated by Kaplan-Meier plots and compared between the groups with Log-rank test and multivariate cox proportional hazard regression models was used to determine the relationship between the CTS5 score and breast cancer survival outcomes in different gender cohorts. Results: A total of 65,729 ER+ breast cancer patients were included in the study and 611 were men. Male breast cancer was more likely to be diagnosed later in life (>50 years old, 87.1% vs 73.6%, p < 0.001), with more aggressive biological features (grade Ⅱ 51.6% vs 47.2%, p < 0.001; grade Ⅲ 37.8% vs 28.3%, p < 0.001) , and higher tumor burden (stage Ⅱ 45.8% vs 32.9%, p < 0.001, stage Ⅲ 17.5% vs 10.5%, p < 0.001) when compared to female counterparts. More male patients were CTS5 intermediate- or high-risk than female patients (high 7.9% vs 6.3%, intermediate 41.1% vs 24.6%, low 51.1% vs 69.1%, p < 0.001). Patients were divided into 0-5 year and >5 year cohorts based on whether they had a BCSS event within 5 years. In the >5 year cohort, patients with CTS5 high- or intermediate- risk had worse survival outcomes compared with low-risk cases in male and postmenopausal female patients but not in premenopausal female patients. In the 0-5 year cohort, the CTS5 score was not predictive for disease recurrence in male or postmenopausal patients. Conclusion: Male breast cancer patients were more likely to have aggressive tumors and worse survival outcomes. The CTS5 score could be applied to predict breast cancer-specific mortality risk beyond 5 years in male ER+ breast cancer patients. Citation Format: Fenhua Wang, Fang Ren, Jian Qian, Yunxia Xu, Jiayi Wu, Yu Zong, Xidong Gu. Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases [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 PO1-08-05.

Impact of the Breast Cancer Index for Extended Endocrine Decision-Making: First Results of the Prospective BCI Registry Study.

The Breast Cancer Index (BCI) test assay provides an individualized risk of late distant recurrence (5-10 years) and predicts the likelihood of benefitting from extended endocrine therapy (EET) in hormone receptor-positive early-stage breast cancer. This analysis aimed to assess the impact of BCI on EET decision-making in current clinical practice. The BCI Registry study evaluates long-term outcomes, decision impact, and medication adherence in patients receiving BCI testing as part of routine clinical care. Physicians and patients completed pre-BCI and post-BCI test questionnaires to assess a range of questions, including physician decision-making and confidence regarding EET; patient preferences and concerns about the cost, side effects, drug safety, and benefit of EET; and patient satisfaction regarding treatment recommendations. Pre-BCI and post-BCI test responses were compared using McNemar's test and Wilcoxon signed rank test. Pre-BCI and post-BCI questionnaires were completed for 843 physicians and 823 patients. The mean age at enrollment was 65 years, and 88.4% of patients were postmenopausal. Of the tumors, 74.7% were T1, 53.4% were grade 2, 76.0% were N0, and 13.8% were HER2-positive. Following BCI testing, physicians changed EET recommendations in 40.1% of patients (P<.0001), and 45.1% of patients changed their preferences for EET (P<.0001). In addition, 38.8% of physicians felt more confident in their recommendation (P<.0001), and 41.4% of patients felt more comfortable with their EET decision (P<.0001). Compared with baseline, significantly more patients were less concerned about the cost (20.9%; P<.0001), drug safety (25.4%; P=.0014), and benefit of EET (29.3%; P=.0002). This analysis in a large patient cohort of the BCI Registry confirms and extends previous findings on the significant decision-making impact of BCI on EET. Incorporating BCI into clinical practice resulted in changes in physician recommendations, increased physician confidence, improved patient satisfaction, and reduced patient concerns regarding the cost, drug safety, and benefit of EET.

Validation of CTS5 Model in Large-scale Breast Cancer Population and Combination of CTS5 and Ki-67 Status to Develop a Novel Nomogram for Prognosis Prediction.

More than half of patients with early-stage estrogen receptor-positive (ER+) breast cancer relapse after completing 5 years of adjuvant endocrine therapy, so it is important to determine which patients are candidates for extended endocrine therapy. The clinical treatment score after 5 years (CTS5) is a prognostic tool developed based on postmenopausal ER+ breast cancer to assess the risk of late distant recurrence (LDR) after 5 years of adjuvant endocrine therapy for breast cancer. We aimed to externally validate the prognostic value of CTS5 in premenopausal and postmenopausal patients and combined with Ki-67 to develop a new model to improve the ability of prognosis prediction. We included a total of 516 patients with early-stage ER+ breast cancer who had received 5 years of adjuvant endocrine therapy and were recurrence-free for 5 years after surgery. According to menopausal status, we divided the study population into 2 groups: premenopausal and postmenopausal women. The CTS5 of each patient was calculated using a previously published formula, and the patients were divided into low, intermediate, and high CTS5 risk groups according to their CTS5 values. Based on the results of the univariate analysis ( P <0.01), a multivariate COX proportional hazards regression analysis was conducted to establish a nomogram with significant variables ( P <0.05). The discriminative power and accuracy of the nomograms were assessed using the concordance index (C-index), calibration curve, and area under the time-dependent receiver operating characteristic curve. Discrimination and calibration were evaluated by bootstrapping 1000 times. Finally, we utilized decision curve analysis to assess the performance of our novel predictive model in comparison to the CTS5 scoring system with regard to their respective benefits and advantages. The median follow-up time was 7 years (6 to 9 years). The 516 women were categorized by CTS5 as follows: 246(47.7%) low risk, 179(34.7%) intermediate risk, and 91(17.6%) high risk. Using the CTS5 score as a continuous variable, patients' risk score was significantly positively associated with recurrence risk in both premenopausal and postmenopausal subgroups. For HER2- premenopausal patients and HER2+ postmenopausal patients, the CTS5 score was positively correlated with LDR risk. Patients with a Ki-67≥20% had a higher risk of LDR regardless of menopausal status. Using the CTS5 score as a categorical variable, the high-risk group of HER2- premenopausal patients had a higher risk of LDR. However, the CTS5 model could not distinguish the risk of LDR in different risk groups for HER2+ postmenopausal patients. In the high-risk group, patients with Ki-67≥20% had a higher risk of LDR, regardless of menopausal status. We developed a new nomogram model by combining the CTS5 model with Ki-67 levels. The C-indexes premenopausal and postmenopausal cohorts were 0.731 and 0.713, respectively. The nomogram model was well calibrated, and the time-dependent ROC curves indicated good specificity and sensitivity. Furthermore, decision curve analysis demonstrated that the new model had a wider and practical range of threshold probabilities, resulting in an increased net benefit compared with the CTS5 model. Our study demonstrated that the CTS5 model can effectively predict the risk of LDR in early-stage ER+ breast cancer patients in both premenopausal and postmenopausal patients. Extended endocrine therapy is recommended for patients with Ki-67≥20% in the CTS5 high-risk group, as well as premenopausal patients with HER2-. Compared with CTS5, the new nomogram model has better identification and calibration capabilities, and further research is required to validate its efficacy in large-scale, multicenter, and prospective studies.

114P Retrospective analysis to validate the CTS5 in patients from El Álamo IV registry and GEICAM adjuvant studies

Estimating the risk of late distant recurrence (DR) is an important goal for the management of hormone receptor-positive (HR+) early breast cancer (EBC) patients (pts) after 5 years of endocrine treatment (ET) without recurrence. The Clinical Treatment Score post–5 years (CTS5) tool was developed to estimate residual risk of Distant Recurrence (DR) after 5 years of ET (Dowsett 2018). CTS5 is a continuous score based on 4 clinical variables (number of positive nodes, tumor size, grade, and age) which distributes HR+/human epidermal growth factor receptor-negative (HER2-) EBC pts in 3 risk of DR groups depending on the score (low-risk: <3.13, intermediate-risk: 3.13-3.86 and high-risk: > 3.86). We performed a retrospective analysis of 5739 HR+/HER2- EBC pts to validate the CTS5 score as prognostic tool of late relapse, beyond 5 years. They were selected from El Álamo IV registry with pts diagnosed between 2002 and 2005 (N=3061) and 4 adjuvant GEICAM studies (9805, 9906, 2003-02 and 2003-10; N=2678) carried out from 1996 and 2006. Pts had to be distant recurrence free at 5 years from ET initiation. CTS5 classified 43.9% as low-risk, 32.2% as intermediate-risk and 23.9% as high-risk. A significant difference in DR was seen among the three groups, HR intermediate-risk vs low, 2.55 (95% CI, 1.85 to 3.52) and HR high-risk vs low, 5.77 (95% CI, 4.28 to 7.78). The continuous CTS5 (range: 1.2 - 6.06) was significantly prognostic (HR, 2.31; 95% CI, 2.05 to 2.61). DR percentage expected and observed by subgroups are described in the table. The CTS5 was able to classify Spanish patients according to different risk of late DR, independently of menopausal status, ET duration or CT treatment. However, the model seems to overestimate the number of events particularly in the high-risk group. This overestimation was more pronounced among patients treated with ET for less than 60 months or those not receiving CT.

Abstract P3-05-28: Impact of increased adiposity on extended aromatase inhibitor treatment in postmenopausal patients with estrogen receptor positive (ER+) breast cancer: a retrospective analysis of the SOLE trial

Abstract Background: The risk of late distant recurrence (≥ 5 years) in post-menopausal patients with ER+ BC remains significant even after standard adjuvant endocrine therapy (ET). Obesity, which has reached high proportions in Western Countries, is one of the modifiable factors that can contribute to BC recurrences. While body mass index (BMI) is an easily available surrogate measure of adiposity, it might not reflect accurately patient adiposity, especially in post-menopausal patients. We therefore hypothesize that mammary adipocyte measurements might better capture the adiposity of the patient. In this study, we retrospectively evaluated the prognostic role of both BMI and adipocyte measurements in the SOLE trial. Patients &amp; Methods: The SOLE trial (NCT00553410) consisted of 4,884 postmenopausal women with hormone receptor positive, lymph node-positive BC treated with 5 years of letrozole after having completed 4-6 years of adjuvant ET. BMI was available for 3,606 patients with ER+/HER2- BC and categorized according to the WHO classification (underweight: &amp;lt; 18.5, normal weight 18.5 – 24.9, overweight 25 – 29.9, obesity ≥ 30 kg/m2). Considering the small sample size, patients with underweight (n=35) were grouped together with patients with normal weight for the subsequent analyses. We evaluated the association between clinico-pathological characteristics and BMI using Fisher exact test and Kruskal-Wallis test. Given the previously reported association of BMI with distant recurrences (PMID: 21115856), we considered distant-relapse free interval (DRFI) as the main study endpoint. Cox regression analyses were adjusted for histology, chemotherapy (yes/no), type of local therapy, in addition to previously reported clinico-pathological variables (PMID: 29158011). Then, we conducted a stratified case-cohort study consisting of 311 patients (97 with distant relapse-cases) with successful digital assessment of adipocytes on normal mammary adipose tissue sample collected at surgery, as previously described (PMID: 33120083). Stratification factors were treatment arm and type of prior ET. Weighted Cox regression models (PMID: 17554753, 18712477) were used to evaluate prognostic association with adipocyte size (area in µm²) categorized in quartile of the 75th percentile (Q4 vs Q1-3), as done previously (PMID: 33753731). Results: 1392 (39%) patients were normal weight, 1315 (36%) were overweight and 899 (25%) were obese. Older age at diagnosis, lymph node involvement (≥4), large tumor size and menopausal status were associated with overweight and obesity. After a median follow-up of 84 months, no associations were found between DRFI and BMI in the univariable and multivariable analysis (adjusted HR overweight vs normal=0.99, 95%CI: 0.76 – 1.29, p=0.977 and HR obese vs normal=1.11, 95%CI: 0.84 - 1.47, p=0.425). In the case-cohort study, patients with larger adipocytes had an increased hazard of distant recurrence in the univariable and multivariable analysis (see table 1). Conclusion: In this study, we did not detect any association between BMI and survival outcomes. We however found that larger mammary adipocytes were independently associated with an increased hazard of distant recurrence. These results suggest that mammary adipocytes, which can be easily evaluated on H&amp;E slides using digital pathology, should be considered as a novel marker to evaluate the risk of late recurrence in patients with breast cancer. Citation Format: Edoardo Isnaldi, François Richard, Giuseppe Marano, Patrizia Boracchi, Marion Maetens, Giuseppe Floris, Guy Jerusalem, Andrea Gombos, Alastair M. Thompson, Erika Hitre, Stefan Aebi, Marco Colleoni, Patrizia Dell’Orto, Roswitha Kammler, Patrick Neven, Giuseppe Viale, Meredith Regan, Elia Biganzoli, Christine Desmedt. Impact of increased adiposity on extended aromatase inhibitor treatment in postmenopausal patients with estrogen receptor positive (ER+) breast cancer: a retrospective analysis of the SOLE trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-28.

Clinical Treatment Score Post-5 Years as a Tool for Risk Estimation of Late Recurrence in Thai Patients With Estrogen-Receptor-Positive, Early Breast Cancer: A Validation Study.

The risk of late distant recurrence (LDR) of estrogen receptor (ER)-positive breast cancer continues even after 5 years of endocrine treatment. Clinical Treatment Score after 5 years (CTS5) was developed and validated as a tool to assess the risk of LDR using data from Tamoxifen, Arimidex Alone or in Combinations (ATAC) and Breast International Group 1-98 (BIG1-98) trials. This study aimed to externally validate CTS5 in a real-world cohort of patients treated at an academic center in Thailand. The study was a retrospective analytical research study of early-stage, ER-positive breast cancer patients. The primary endpoint was LDR. The risk of LDR was determined using the CTS5 calculator. Cox regression model and Kaplan-Meier survival analysis were applied for prognostic validation of CTS5. Calibration was performed by comparing observed LDR to expected LDR using the Hosmer-Lemeshow (H-L) test. A total of 323 women were included with a median follow-up period of 11.6 years. The rate of LDR was 10.8%. The CTS5 was prognostic for LDR. C-index of the area under the ROC curve was 0.672. There was no significant difference between actual and expected numbers of LDR with an observed (O) LDR events to expected (E) number of LDR events ratio of 0.99 (0.86-1.12) (H-L P = .79) indicating a proper calibration in this cohort. Our study validated that CTS5 is accurate in predicting the risk of LDR in ER-positive breast cancer cases in Thai patients. Its performance seemed to be better in postmenopausal patients. CTS5 could be applied in routine clinical practice to improve decisions regarding prolonged endocrine therapy, particularly in resource-limited countries where molecular profiling are inaccessible.

The Breast Cancer Index Registry Study: Initial analysis of the first 1,000 patients.

e12513 Background: The Breast Cancer Index (BCI) is a gene expression-based biomarker that reports two results: BCI Predictive [BCI (H/I)], which predicts benefit from extended endocrine therapy (EET), and BCI Prognostic, which combines the Molecular Grade Index (MGI) with BCI (H/I) to provide individualized risk of both late (5-10 years) and overall (0-10 years) distant recurrence. The NCCN clinical practice guideline recommends use of BCI for prediction of benefit from EET in early stage, hormone receptor positive (HR+) breast cancer patients. Methods: The BCI Registry study was designed to prospectively evaluate the long-term clinical outcome, medication adherence and quality of life in HR+ early-stage breast cancer patients receiving BCI testing as part of routine clinical care. The BCI registry will enroll approximately 3,000 patients after completion of 4-7 years of primary adjuvant endocrine therapy. Patients will be followed for disease recurrence for at least 10 years from diagnosis. Patients extending endocrine therapy will be assessed annually for medication adherence. To evaluate the impact of BCI results on EET decision making, both the physician and patient will complete Decision Impact Questionnaires. Clinicopathological data are collected within the ClinCapture electronic data capture system. The BCI Registry Study is registered on ClinicalTrials.gov under NCT04875351. Results: The BCI Registry Study completed enrollment of the first 1,000 patients in January 2022. Clinical data were available for 942 patients (76.8% T1; 51.3% grade II; 75.4% N0). BCI test results were reported for 842 patients. 315 patients (37.4%) were classified as BCI (H/I)-High and 527 patients (62.6%) as BCI (H/I)-Low. Further, in node-negative (N0) patients, BCI classified 314 N0 patients (47.9%) with high risk for late distant recurrence and 342 patients (52.1%) with low risk. In node-positive (N1) patients, BCI classified 138 patients (74.2%) as high risk for late distant recurrence and 48 patients (25.8%) as low risk. The associated clinicopathological factors are shown in the table. Conclusions: The analysis of the first 1,000 BCI Registry patients confirms the expected distribution of clinicopathological factors. BCI by H/I status and prognostic risk groups are consistent with previous clinical validation studies. Clinical trial information: NCT04875351. [Table: see text]

Consensus on the utility of breast cancer multigene signatures in routine clinical practice: Results of the PROCURE Project.

e13639 Background: Several Breast Cancer Multigene Signatures (BCMS) are available to profile early breast cancer (eBC) that according to current evidence, can provide reliable information on the risk of recurrence but the knowledge regarding their real use in clinical practice is scarce. The PROCURE Project aims to establish recommendations on the use of BCMS in clinical practice. Methods: A Scientific Committee consisting of 8 European experts in BC, including oncologists, pathologists, and surgeons, developed a Delphi questionnaire that was administered twice to clinicians across different European centers. The questionnaire included 5 sections: 1) Panelists’ profile and experience with BCMS, 2) Current clinical practice in eBC and use of BCMS, 3) Panelists’ opinion on the utility of the BCMS in eBC according to patient profiles, 4) Agreement with a set of recommendations on the use of BCMS in clinical practice and 5) Identification of unmet needs and future applications of BCMS. 70% agreement was used to determine consensus on a topic. Results: 133 panelists from 11 European countries completed both rounds of the survey. Most of the panelists worked in a teaching hospital (86.5%) and 72.2% of them were medical oncologists. 93.6% of the panelists used BCMS routinely or in selected patients and 73.4% had more than 5 years of experience using BCMS. According to panelists, for being useful in clinical practice BCMS should consider clinical and pathological features of the disease (91%). Additionally, BCMS must provide both, prognostic and predictive information (82%), and information on the risk of late distant recurrence from 5 to 10 years (74%), all based on prospective randomized clinical trials (85%). BCMS must also provide accurate results to guide adjuvant chemotherapy decision (81%). Regarding recommendations for improving BCMS utility, 76% of the panelists agreed that hospitals policies on the use of BCMS must be based on clinical practice guidelines. Panelists also agreed that patients should have the right to access their BCMS results to take part in the treatment decision (86%) and more training is needed for patients (79%) as well as oncologists (84%) and pathologists (82%). Finally, panelists mostly disagree on the fact that BCMS must be performed in all patients when BC is suspected (76%). Conclusions: The high degree of importance that panelists attributed to the fact that a BCMS should provide both prognostic and predictive information, reflects a misconception on the utility of BCMS as they are primarily prognostic tools but not predictive about the effect of a therapeutic intervention. Also, consensus reached on the need of providing risk of late recurrence from 5 to 10 years shows that panelists evaluate the long-term treatment even in the early setting.

1577 Using CTS5 Calculator to Predict The 5-10-Year Risk of Late Distant Recurrence for Women With ER-Positive Breast Cancer Who Are Recurrence-Free 5 Years After Endocrine Therapy and To Reduce the Number of Patients Needing Discussion for The Extended Endocrine Therapy in The Breast MDTs: A Quality Improvement Project

Abstract Introduction The increasing number of patients has created a pressure on the services provided that aim to ensure the maximum level of care, particularly MDT meetings. Using the CTS5 calculator can readily reduce the number of patients needing discussion for EET. This is will prevent delays in decisions made for patients and more importantly, an evidence-based tool will be used for more accurate results. Method A retrospective data collection was undertaken from the Breast MDT records, initially dating from January to December 2018. Then when the optional use of CTS5 was established, data were retrieved from August to October 2019. As per guidance for the use of the CTS5 calculator; Women were deemed low risk if their 5–10-year risk is less than 5%, intermediate if between 5–10%, and high risk if their 5–10-year risk is more than 10%. Finally, a prospective data collected from January to March 2020 where an agreement was made for all involved Surgeons to use the CTS5 calculator. Results Before Introducing the CTS5 Calculator, in 2018, the number of patients was 1523 from which 66 were for EET 4.3%. When CTS5 Calculator was first introduced, 1st of August - 31st October 2019, the percentage reduced to 4.1% and from January to March 2020, a further reduction 3.9% was noticed. Conclusions The CTS5 calculator is an effective evidence-based tool used to predict the risk of 5-10 years recurrence in breast cancer patients. Implementing it will reduce the number of patients needing discussion in Breast MDTs, sparing meetings’ and patients’ time.

Prognostic Utility of Breast Cancer Index to Stratify Distant Recurrence Risk in Invasive Lobular Carcinoma.

The prognostic utility of Breast Cancer Index (BCI) for risk assessment of overall (0-10 years), early (0-5 years), and late (5-10 years) distant recurrence (DR) in hormone receptor-positive (HR+) invasive lobular carcinoma (ILC) was evaluated. BCI gene expression analysis was performed blinded to clinical outcome utilizing tumor specimens from patients with HR+ ILC from a multi-institutional cohort. The primary endpoint was time to DR. Kaplan-Meier analyses of overall, early, and late DR risk were performed, and statistical significance was evaluated by log-rank test and Cox proportional hazards regression. The prognostic contribution of BCI in addition to clinicopathologic factors was evaluated by likelihood ratio analysis. Analysis of 307 patients (99% ER+, 53% T1, 42% N+, 70% grade II) showed significant differences in DR over 10 years based on BCI risk categories. BCI low- and intermediate-risk patients demonstrated similar DR rates of 7.6% and 8.0%, respectively, compared with 27.0% for BCI high-risk patients. BCI was a significant independent prognostic factor for overall 10-year DR [HR = 4.09; 95% confidence interval (CI), 2.00-8.34; P = 0.0001] as well as for both early (HR = 8.19; 95% CI, 1.85-36.30; P = 0.0042) and late (HR = 3.04; 95% CI, 1.32-7.00; P = 0.0224) DR. In multivariate analysis, BCI remained the only statistically significant prognostic factor for DR (HR = 3.49; 95% CI, 1.28-9.54; P = 0.0150). BCI is an independent prognostic factor for ILC and significantly stratified patients for cumulative risk of 10-year, early, and late DR. BCI added prognostic value beyond clinicopathologic characteristics in this distinct subtype of breast cancer.

Abstract PD2-11: Breast cancer index is a molecular signature of endocrine responsiveness that determines extended endocrine benefit independent of prognostic risk

Abstract Background: For patients with early stage, hormone receptor positive (HR+) breast cancer, extension of endocrine therapy beyond 5 years reduces the ongoing risk of late distant recurrence and new primary breast cancer but is associated with potentially serious toxicities and side effects that can impair quality of life. While risk stratification by clinicopathological factors and prognostic biomarkers is recommended to guide patient selection, predictive biomarkers that are directly informative of therapeutic response are critical for clinical utility. Breast Cancer Index (BCI) is a gene expression-based signature that reports: 1) BCI Prognostic (BCI Score), which combines the Molecular Grade Index (MGI) with the HOXB13/IL17BR (H/I) ratio to provide individualized risk of late (post-5y) distant recurrence, and 2) BCI Predictive (BCI H/I), which predicts benefit from extended endocrine therapy. In this study, BCI and endocrine benefit from 5 vs 2.5y of extended letrozole were examined by comparing the deterministic effects of prognostic risk vs endocrine response in patients treated in the IDEAL trial.Methods: 908 patients with available tumor tissue were included in this pre-specified and blinded analysis, with recurrence-free interval (RFI) as the primary endpoint. Kaplan-Meier and Cox proportional hazards regression were performed using pre-defined assay cut-points. Clinically high prognostic risk was defined as pN+ and ≥pT2; low prognostic risk was defined as pN0 or pN1 and pT1 or G1. Genomic risk was defined by BCI prognostic categories (High vs Low risk). Results: Patients classified with endocrine responsive disease by BCI (H/I)-High status showed a statistically significant benefit from 5 vs 2.5y of letrozole irrespective of clinical risk, whereas those classified as BCI (H/I)-Low did not show benefit in either clinical risk category. Both clinically High and Low risk patients derived a similar magnitude of benefit when stratified as BCI (H/I)-High (12.5% and 15.1%, respectively). Evaluation of BCI (H/I) predictive performance in the context of BCI prognostic risk categories showed similar results. In particular, patients with High Risk/High Likelihood to benefit showed significantly improved outcomes with extended therapy (HR 0.42 [0.20-0.89]; absolute benefit 10.7%; P=0.020), whereas those with High Risk but Low Likelihood to benefit did not show response to extended endocrine therapy (HR 1.05 [0.58-1.88]; absolute benefit -0.7%; P=0.880), despite considerable risk of late distant recurrence (~20%). Conclusion: Results from this study highlight distinct tumor biology underlying recurrence risk vs endocrine responsiveness in HR+ early stage breast cancer. BCI (H/I) as a molecular signature to identify patients with endocrine responsive disease is a key determinant of benefit and improved outcome with extended endocrine therapy. Prediction of endocrine benefit with BCI (H/I) is a more actionable approach vs risk assessment to individualize discontinuation of or continued treatment with prolonged durations of endocrine therapy. Prognostic RiskBCI Predictive NHR (95% CI)P valueClinical RiskHigh Risk: N+/ T2+ (N=353)High BCI(H/I)1620.32 (0.10-0.98)0.035Low BCI(H/I)1911.13 (0.55-2.31)0.742Low Risk: N0 or N1 &amp; T1 or grade 1 (N=404)High BCI(H/I)1910.15 (0.03-0.66)0.004Low BCI(H/I)2130.75 (0.33-1.70)0.484Genomic RiskHigh BCI Score(N=621)High BCI(H/I)3410.42 (0.20-0.89)0.020Low BCI(H/I)2801.05 (0.58-1.88)0.880Low BCI Score(N=227)High BCI(H/I)600.35 (0.04-3.38)0.344Low BCI(H/I)1670.64 (0.22-1.92)0.425 Citation Format: Gerrit-Jan Liefers, Iris Noordhoek, Kai Treuner, Hein Putter, Yi Zhang, Jenna Wong, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Cornelis JH Van De Velde, Catherine A Schnabel. Breast cancer index is a molecular signature of endocrine responsiveness that determines extended endocrine benefit independent of prognostic risk [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 PD2-11.

Validation of Clinical Treatment Score post-5\xa0years (CTS5) risk stratification in premenopausal breast cancer patients and Ki-67 labelling index

This study aimed to validate the Clinical Treatment Score post-5 years (CTS5)-based risk stratification in a cohort comprising pre- and postmenopausal patients with estrogen receptor (ER)–positive breast cancer. We investigated the clinicopathologic parameters including Ki-67 labelling index (LI) to identify factors affecting late distant recurrence (DR). Women with ER-positive breast cancer who were free of DR for 5 years were identified between January 2004 and December 2009. We investigated the risk of late DR (5–10 years) according to the CTS5 risk group. Cox regression analysis was used to determine the prognostic performance of CTS5 and identify factors associated with late DR. In all, 680 women were included. Of these, 379 (55.7%) were premenopausal and 301 (44.3%) were postmenopausal. At a median follow-up of 118 months, 32 women had late DR. CTS5 was a significant prognostic factor for late DR in both pre- and postmenopausal women. In the low CTS5 group, high Ki-67 LI (> 20%) was a significant risk factor for late DR. CTS5 is a useful tool for assessing the risk of late DR in pre- and postmenopausal women with ER-positive breast cancer. Extended endocrine therapy can be considered in patients with high Ki-67 LI (> 20%) in the low CTS5 group.

Identifying oncogenic drivers associated with increased risk of late distant recurrence in postmenopausal, estrogen receptor-positive, HER2-negative early breast cancer: results from the BIG 1-98 study.

In postmenopausal, estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer, the risk for distant recurrence can extend beyond 5 years of adjuvant endocrine therapy. This study aims to identify genomic driver alterations associated with late distant recurrence. Next generation sequencing was used to characterize driver alterations in primary tumors from a subset of 764 postmenopausal estrogen receptor-positive/HER2-negative patients from the BIG 1-98 randomized trial. Late distant recurrence events were defined as ≥5 years from time of randomization). The association of driver alterations with distant recurrence-free interval in early and late time periods was assessed using Cox regression models. Multivariable analyses were carried out to adjust for clinicopathological factors. Weighted analysis methods were used in order to correct for over-sampling of distant recurrences. A total of 538 of 764 (70%) samples were successfully sequenced including 88 (63%) early and 52 (37%) late distant recurrence events after a median follow up of 8.1 years. In univariable analysis for late distant recurrence, PIK3CA mutations (58.8%) were significantly associated with reduced risk [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.20-0.82, P= 0.012], whereas amplifications on chromosome 8p11 (10.9%) (HR 4.79, 95% CI 2.30-9.97, P < 0.001) and BRCA2 mutations (2.3%) (HR 5.39, 95% CI 1.51-19.29, P= 0.010) were significantly associated with an increased risk. In multivariable analysis, only amplifications on 8p11 (P= 0.002) and BRCA2 mutations (P= 0.013) remained significant predictors. In estrogen receptor-positive/HER2-negative postmenopausal early breast cancer, PIK3CA mutations were associated with reduced risk of late distant recurrence, whereas amplifications on 8p11 and BRCA2 mutations were associated with increased risk of late distant recurrence. The characterization of oncogenic driver alterations may aid in refining treatment choices in the late disease setting, and help identify potential drug targets for testing in future trials.

Adherence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor (HR)-positive breast cancers.

527 Background: Evidence suggests continuing endocrine therapy (ET) beyond 5 years (yr) may reduce breast cancer recurrence in early stage HR+ breast cancers. Given the modest benefit and potentially serious adverse effects of extended ET (EET), improved approaches to identify patients who are at increased risk of late distant recurrence and who derive benefit from EET are critical. Guidelines recommend shared decision-making between oncologists and patients. The adherence rate to EET by 5 yr is only 50-60%. BCI is a gene-expression assay used to predict late distant recurrence and is predictive of benefit from EET. We assessed adherence to EET in women who had BCI testing. Methods: Women with stage I-III HR+ breast cancer s/p 3.5 yr of adjuvant ET and had BCI testing at our institution (8/2013-7/2015) were included. Pts who had &lt; 4 yr of follow-up since BCI testing were excluded. Information including demographics, tumor characteristics, treatment history, number DXA scans, history of osteopenia/osteoporosis were collected. Data on medication adherence was based on prescriptions in the electronic health record. Results: 102 pts were included in our analysis. The median age was 61yr (46-89 yr). The majority of pts had stage I (63%), N0 (77%) and HER2- (90%) disease. 50 pts (46%) received chemotherapy. 44 (43%) received tamoxifen and 79 (77%) had an aromatase inhibitor. BCI categorized 61 (60%) pts as low risk, 26 (25%) as intermediate, and 15 (15%) as high risk for late distant recurrence. 61 (60%) and 41 (40%) pts were predicted to have low and high likelihood of benefit from EET, respectively. All 15 (100%) pts categorized as high risk for late recurrence were predicted to have a high likelihood to benefit from EET; all were recommended to continue EET by their oncologist and all 15 elected EET. 11 (73%) completed 10 yr or were on EET at last follow-up. Of the 4 (27%) pts who stopped before 10 yr, 1 pt had metastatic recurrence and 3 had intolerable side effects. Pts on EET underwent an avg of 1.91 DXA scans, compared with 1.23 for those who stopped ET at 5 yr (p = 0.003). At a median follow-up of 10 yr from diagnosis, there were 2 metastatic (1/15 in the high risk and 1/26 in the intermediate risk group) and 1 local recurrence (1/61 in the low risk group). Conclusions: In pts who continued ET beyond 5 years based on BCI testing and discussion with their oncologist, the rates of adherence and persistence to EET were higher than those previously published. EET may increase the number of DXA scans performed.

Abstract P5-06-08: Predicting distant recurrence of ER+ HER2- breast cancer after 5 years of endocrine therapy: The CTS5-tool validation in real life

Abstract Purpose: Extended adjuvant hormone therapy improves estrogen receptor (ER)-positive breast cancer outcome. The total duration of endocrine therapy is still a subject for debate. The CTS5 score, developed by Dowsett et al1., predicts late distant recurrence (LDR) between years 5 and 10 after diagnosis in ER-positive invasive breast cancers in postmenopausal women. This LDR risk might be used to select patients for extended endocrine therapy. The CTS5 score is calculated using age at the start of endocrine therapy, tumor size, grade, and lymph node status. The aim of this study is the validation of this tool in a series of women from the UZ Leuven. Methods: This retrospective cohort study included 1125 postmenopausal women consecutively diagnosed with invasive estrogen receptor (ER) positive breast cancer who stopped endocrine therapy after 4.5 to 5.5 years. Tissue was tested for ER positivity and considered positive if &amp;gt;1% of tumor nuclei were stained. HER2 status was defined according to ASCO guidelines. Statistical analysis was performed by Cox proportional hazards models which determined the prognostic performance of the CTS5 score for LDR. Results: A total of 1125 patients were included in this analysis, of which 1097 had a known HER2 status and 1023 were negative. 62 of 1125 (5.5%) developed an LDR between years 5 and 10. The continuous CTS5 was a significant predictor for LDR (HR =2.69 (1.99-3.60), p&amp;lt;0.001). The tool was not significant in the HER2 positive population (n=74), but numbers were small with only 5 LDR recorded (HR=0.92 (0.32-2.66), p=0.88). Further analysis was performed in a strictly HER2-negative cohort. In this cohort, 8 of the 401 patients (2.0%) with a CTS5 predicted low risk (&amp;lt;5% LDR risk) developed LDR, in the intermediate risk group (5-10% LDR risk) 16 out of 336 (4.8%) and in the high risk group (≥10% LDR risk) 32 out of 286 (11.2%) developed LDR. Conclusion: In our series of postmenopausal women, CTS5 accurately predicts late distant recurrence in ER-positive, HER2-negative early invasive breast cancers. The CTS5-score, identifying a patient group with LDR risk of ≥5%, might be used to discuss the benefits of extended endocrine therapy for individual patients. However, the exact predictive value for the benefit of prolonged therapy can only be based on a randomized controlled trial (RCT) using the LDR risk as a stratification factor. It would be of great value to expand the study population, especially HER2-positive tumors, and define the prognostic performance of the CTS5 score in premenopausal women. Further research is needed. 1. Dowsett, M. et al. Integration of Clinical Variables for the Prediction of Late Distant Recurrence in Patients With Estrogen Receptor-Positive Breast Cancer Treated With 5 Years of Endocrine Therapy: CTS5. J. Clin. Oncol. 36, 1941-1948 (2018). Citation Format: Josephine Van Cauwenberge, Ivana Sestak, Kevin Punie, Hans Wildiers, Giuseppe Floris, Ignace Vergote, Patrick Berteloot, Toon Van Gorp, Ann Smeets, Els Van Nieuwenhuysen, Sileny Han, Ines Nevelsteen, Caroline Weltens, Hilde Janssen, Patrick Neven. Predicting distant recurrence of ER+ HER2- breast cancer after 5 years of endocrine therapy: The CTS5-tool validation in real life [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-08.

Abstract P5-06-22: Validation of CTS5 in premenopausal breast cancer patients and the role of Ki67 among risk-stratification groups

Abstract Background: The Clinical Treatment Score at 5 years (CTS5) could be applied to identify the patients who could recommend an extension of endocrine therapy more than 5 years. In the low-risk group by CTS5, there is a limited benefit in extending endocrine therapy when patients are free from distant recurrence (DR) for 5 years. However, it raises concerns that late recurrence could occur even in the low-risk group of CTS5, and thus an issue to find factors affecting late recurrence arises in those. Furthermore, it remains unclear whether CTS5 could be adopted for premenopausal women in same context. In this study, we investigated data from patients with ER-positive breast cancer who had been free of 5-years distant recurrence. We aimed whether CTS5 is helpful to predict late DR in premenopausal and which affects late DR in the low-CTS5 group. Methods: From January 2006 to December 2013, 666 patients who had ER-positive breast cancer and had been free from 5 years DR after operation were identified. Of these, we calculated CTS5 scores using clinical variables. About 60% of the patients were premenopausal (393 of 666; 59%). To identify factors associated with late DR in the low-CTS5 group, binary logistic regression analysis was used. Results: Among all patients, late DR occurred in 25 patients. Of all patients, 402 women (60.4%) were with CTS5 low-risk group, and 10 of them (2.5%) had late DR. There were also 73 women (11%) CTS5 high-risk group, of whom 9 (12.3%) had late DR. In Kaplan-Meier analysis, the incidence of late DR was significantly increased in the high-CTS5 group (P &amp;lt; 0.001). Similarly, premenopausal women had higher rates of late DR in the high-CTS5 group (P = 0.049). In the low-CTS5 group, patients with late DR had higher Ki-67 labelling index (L.I.) compared with those without late DR (patients with Ki-67 level above 20; late DR 2/10 (22.2%) vs. without late DR 20/390 (5.1%), p = 0.027). In the multivariable analysis, Ki-67 level was found as a significant predictor for late DR in low-CTS5 group [odds ratio (OR), 11.870; CI 95%, 1.821-77.383; P = 0.010]. In other intermediate- or high-CTS5 groups, Ki67 L.I. was not associated with late DR. Conclusion: We found that CTS5 was useful to identify premenopausal women who are at risk of late DR, although CTS5 algorithm was developed by cohorts consisted of postmenopausal women. Also, the Ki67 level is helpful estimate a substantial risk of late DR in the low-CTS5 patients who are expected to have low chance of DR after 5 years endocrine therapy. Univariable and multivariable analysis in CTS5-low risk groupUnivariableMultivariableNo late DR(n=392)Late DR(n=10)p valueOR(95% CI)p valueAge49.7(±9.56)48.0(±9.32)0.5841.002(0.932-1.078)0.956pT stagepT1352(89.8%)7(70.0%)0.0451pT240(10.2%)3(30.0%)4.600(1.030-20.551)0.046pN stagepN0355(90.6%)10(100%)0.3081pN137(9.4%)0(0%)00.998Histologic gradeLow195(49.7%)6(60.0%)0.7141Intermediate182(46.4%)4(40.0%)0.381(0.085-1.719)0.210High15(3.8%)0(0%)00.998Ki67≤ 20369(94.1%)7(70.0%)0.0271&amp;gt; 2020(5.1%)2(20.0%)11.870(1.821-77.383)0.010Unknown3(0.8%)1(10.0%) Citation Format: Janghee Lee, Sung Gwe Ahn, Chihwan Cha, Soong June Bae, Dooreh Kim, Soeun Park, Joon Jeong. Validation of CTS5 in premenopausal breast cancer patients and the role of Ki67 among risk-stratification groups [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-22.

Abstract P2-11-18: Clinical validity of CTS5 for late recurrence in Chinese patients with early HR-positive breast cancer

Abstract Objective: The large majority of hormone receptor-positive (HR+) breast cancer patients will be treated with hormone therapy at least five years to decrease the risk of cancer recurrence or distance metastases. EBCTCG meta-analysis identify extending endocrine therapy could further late recurrence for some patients, however, accompanying with more side effects. Estimating risk of late distant recurrence (DR) is an important goal for managing women with HR+ breast cancer after 5 years of endocrine treatment without recurrence. New research confirms that an algorithm, called CTS5, can accurately identify patients who are at a significantly low risk of their breast cancer returning at a later stage in ATAC and BIG1-98 cohort. The aim of this study was to investigate the predictive value of CTS5 in Chinese HR+ early breast cancer. Patients and Methods: The CTS5 was tested in a retrospective cohort of breast cancer from Liaoning Cancer Hospital between 2002 and 2009. Among 831 patients with distant recurrence-free and be alive at 5 years, the patients were tested and calculated for CTS5, a prognostic score for post-5-year risk of DR, in HR+ early breast cancer after adjuvant endocrine therapy. The cut-off values for separate the risk category were 3.13 and 3.86 from the final CTS5 in ATAC and BIG1-98. The primary end point was distant recurrence in years 5~10 in HER-2 positive and HER-2 negative cohorts. Results: Continuous and categorical CTS5 score was significantly prognostic for late DR for total sample (n=831) and HER-2 negative cohorts (n=634). CTS5 (based on ATAC/BIG1-98 data) risk stratification defined in the total cohort as low (&amp;lt; 5% DR risk, years 5 to 10), intermediate (5% to 10%), or high (&amp;gt; 10%) identified 35.0% of our cohort as low risk (291/831), 28.52% as intermediate risk (237/831) and 36.46% as high risk (303/831). In HER-2 negative data, CTS5 risk stratification defined in the 634 cohort from 2002 to 2009 as low risk with an observed DR rate of 6.15% during years 5 to 10, intermediate risk with an observed DR rate of 11.24% and high risk with an observed DR rate of 28.78%. CTS5 stratifies HER2-negative cohort into three distinct risk groups with higher observed DR than that in ATAC/BIG1-98 trial, however, the separation was less accurate in HER2-positive cohort than in HER2-negative cohort. The observed DR rate was 25.81% in low, 27.94% in intermediate and 37.76% in high groups in HER2-positive cohort. From years 5 to 10, 63% of node-negative patients were low risk, with a DR rate of 5.7% (14/245). Conclusion: The study confirmed that CTS5 was effective at predicting late recurrence of breast cancer after 5 years in Chinese cohort. However, higher observed rate was indicated due to the bias of the majority from Department of Medical Oncology rather than Department of Breast Surgery. Further large-sample study was designed to validate CTS5 in low-risk and intermediate groups with similar endocrine therapy. Citation Format: Junnnan Xu, Tao Sun. Clinical validity of CTS5 for late recurrence in Chinese patients with early HR-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-18.

Endocrine-responsive lobular carcinoma of the breast: features associated with risk of late distant recurrence

BackgroundInvasive lobular carcinomas (ILCs) account for 10–15% of all breast cancers. They are characterized by an elevated endocrine responsiveness and by a long lasting risk of relapse over time. Here we report for the first time an analysis of clinical and pathological features associated with the risk of late distant recurrence in ILCs.Patients and methodsWe retrospectively analyzed all consecutive patients with hormone receptor–positive ILC operated at the European Institute of Oncology (EIO) between June 1994 and December 2010 and scheduled to receive at least 5 years of endocrine treatment.The aim was to identify clinical and pathological variables that provide prognostic information in the period beginning 5 years after definitive surgery. The cumulative incidence of distant metastases (CI-DM) from 5 years after surgery was the prospectively defined primary endpoint.ResultsOne thousand eight hundred seventy-two patients fulfilled the inclusion criteria. The median follow-up was 8.7 years.Increased tumor size and positive nodal status were significantly associated with higher risk of late distant recurrence, but nodal status had a significant lower prognostic value in late follow-up period (DM-HR, 3.21; 95% CI, 2.06–5.01) as compared with the first 5 years of follow-up (DM-HR, 9.55; 95% CI, 5.64–16.2; heterogeneity p value 0.002).Elevated Ki-67 labeling index (LI) retained a significant and independent prognostic value even after the first 5 years from surgery (DM-HR, 1.81; 95% CI 1.19–2.75), and it also stratified the prognosis of ILC patients subgrouped according to lymph node status.A combined score, obtained integrating the previously validated Clinical Treatment Score post 5 years (CTS5) and Ki-67 LI, had a strong association with the risk of late distant recurrence of ILCs.ConclusionWe identified factors associated with the risk of late distant recurrence in ER-positive ILCs and developed a simple prognostic score, based on data that are readily available, which warrants further validation.