Metastatic Breast Cancer Database Research Articles

Real-world outcomes in patients with brain metastases secondary to HR+/HER2- MBC treated with abemaciclib and local intracranial therapy.

Real-world data are limited for patients with brain metastases secondary to metastatic breast cancer (MBC) and treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). This study describes real-world outcomes in patients with hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2-) MBC with brain metastases diagnosis before abemaciclib initiation. A nationwide electronic health record-derived de-identified MBC database (January 2011-December 2021) was assessed retrospectively. Patients with HR+/HER2- MBC who were treated with abemaciclib (monotherapy or in combination) following diagnosis of brain metastases were included. Real-world best response reflected clinician-documented response assessment of the brain imaging (intracranial) and change in disease burden following radiographic imaging (extracranial); these were reported descriptively. Time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (rwOS) were assessed using Kaplan-Meier methods from abemaciclib initiation (index date). Among 82 included patients (mean age 57.0 years; 98.8% female), 22.0% and 19.5% received CDK4/6i and chemotherapy before abemaciclib initiation, respectively, and the majority (80.5%) received radiation/local surgery to the brain before abemaciclib initiation. Patients mostly received abemaciclib as monotherapy (n = 6) or in combination with endocrine therapy (n = 68). Median TTD was 7.1 (95% CI 4.6-11.3) months, rwPFS was 9.2 (95% CI 6.0-11.6) months, and rwOS was 20.8 (95% CI 13.9-26.0) months. Intracranial and extracranial objective response rates, as determined by treating physicians, were 45.1% (n = 23/51) and 56.7% (n = 34/60), respectively. Intracranial and extracranial clinical benefit rates were 62.7% (n = 32/51) and 70.0% (n = 42/60), respectively. In this real-world study of patients diagnosed with brain metastases and initiating abemaciclib, most patients received radiation/local surgery to the brain before abemaciclib initiation. Although the outcomes in this real-world study are encouraging, it is unclear if the benefit was due to local therapy, abemaciclib, or the combination, and causality cannot be inferred. Further prospective clinical studies are needed to confirm the clinical benefit of this approach.

Abstract PO4-10-04: Treatment differences by race and age in metastatic hormone receptor-positive/HER2-negative breast cancer

Abstract Introduction: Black and younger patients are more likely to have aggressive forms of breast cancer. Endocrine therapy (ET) plus a CDK4/6 inhibitor is the standard of care first-line therapy for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (MBC). Recent data has shown better outcomes with this approach compared to chemotherapy, even for patients with aggressive disease. Our study looked at differences in first-line treatment among Black and younger women with HR+/HER2- MBC. Methods: Clinical characteristics, treatment, and outcomes of patients diagnosed with HR+/HER2- MBC between 2011-2022 were retrieved from the UNC Metastatic Breast Cancer Database. Log binomial regression modeling compared treatment choices by group, and Cox proportional hazards regression modeling evaluated progression-free survival (PFS) from the start of treatment. Results: 524 patients were included in this analysis. 30% were young patients (< 50 years of age), 20% were Black patients, 62% had only 1 site of metastasis and 51% had visceral involvement. When looking at first-line treatment for metastatic disease, 21% of overall patients had received chemotherapy. The likelihood of receiving chemotherapy was higher for younger verses (vs) older patients (29% vs 18%, RR=1.63, p=0.004), for Black vs White patients (31% vs 18%, RR=1.71, p=0.002), and for those with visceral vs non-visceral involvement (26% vs 16%, RR=1.67, p=0.004). A model including age, race, and visceral involvement showed similar findings. Among patients who received ET as the first line treatment for metastatic disease, the likelihood of receiving CDK 4/6 inhibitors in addition to ET was lower for young Black patients compared to young White patients (41% vs 74%, RR=0.55, p=0.02). However, among older patients >=50, no significant difference was seen by race (Blacks 60% vs Whites 56%, RR=1.1, p=0.61). Adjusting for visceral involvement showed similar findings. Patients who received ET (with or without CDK 4/6 inhibitors) had better PFS compared to patients receiving chemotherapy as first-line therapy (HR 0.65, 95% CI 0.49, 0.88, p=0.005), this held true after adjusting for age, race, treatment group and visceral involvement (HR 0.7, p=0.02). A stratified analysis showed similar findings within Black patients (HR 0.42, p=0.003), and young patients (HR 0.55, p=0.01). Conclusion: Overall, Black and younger patients were more likely to receive chemotherapy as the first-line treatment for metastatic disease. Among patients who received ET as the first-line treatment for MBC, young Black patients were less likely to receive CDK 4/6 inhibitors compared to young White patients. Further studies are needed to outline the multi-level factors contributing to the identified disparities in care among patients with HR+/HER2- MBC. Citation Format: Yara Abdou, Joannie Ivory, Allison Deal, Ally Wardell, Amy Wheless, Claire Dees, Lisa Carey. Treatment differences by race and age in metastatic hormone receptor-positive/HER2-negative breast cancer [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 PO4-10-04.

Real-world patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer.

Tucatinib is an oral human epidermal growth factor receptor 2 (HER2)-directed therapy approved in combination with trastuzumab and capecitabine for use in patients with previously treated HER2+ metastatic breast cancer (MBC) with/without brain metastases (BM). To inform clinical decision-making, it is important to understand tucatinib use in real-world clinical practice. We describe patient characteristics, treatment patterns, and clinical outcomes for tucatinib treatment in the real-world setting. This retrospective cohort study included patients diagnosed with HER2+ MBC (January 2017-December 2022) who received tucatinib treatment in a nationwide, de-identified electronic health record-derived metastatic breast cancer database. Patient demographics and clinical characteristics were described at baseline (prior to tucatinib initiation). Key outcomes included real-world time to treatment discontinuation (rwTTD), time to next treatment (rwTTNT), and overall survival (rwOS). Of 3,449 patients with HER2+ MBC, 216 received tucatinib treatment (n=153 with BM; n=63 without BM) and met inclusion criteria. Median (range) age of patients was 56 (28-84) years, 57.9% were White, and 68.5% had Eastern Cooperative Oncology Group performance status ≤1. Median (IQR) follow-up from start of tucatinib treatment was 12 (6-18) months. Among all patients who received tucatinib treatment, median (95% CI) rwTTD was 6.5 (5.4-8.8) months with 39.8% and 21.4% remaining on treatment at 12 and 24 months, respectively. Median (95% CI) rwTTNT was 8.7 (6.8-10.7) months. Patients who received the approved tucatinib triplet combination after ≥1 HER2-directed regimen in the metastatic setting had a similar median (95% CI) rwTTD (any line: 8.1 [5.7-9.5] months; second-line (2L) and third-line (3L): 9.4 [6.3-14.1] months) and rwTTNT (any line: 8.8 [7.1-11.8] months; 2L and 3L: 9.8 [6.8-14.1] months) to the overall population. Overall, median (95% CI) rwOS was 26.6 (20.2-not reached [NR]) months, with similar findings for patients who received the tucatinib triplet (26.1 [18.8-NR] months) and was NR in the subgroup limited to the 2L/3L population. Tucatinib treatment in the real-world setting was associated with a similar median rwTTD, rwTTNT, and rwOS as in the pivotal HER2CLIMB trial, with particular effectiveness in patients in the 2L/3L setting. These results highlight the importance of earlier use of tucatinib in HER2+ MBC.

Distribution and outcomes of HER2-low and HER2-zero metastatic breast cancer in Black and younger women.

1109 Background: Black and younger patients with breast cancer (BC) have higher mortality. This racial disparity has been attributed to different BC biology, access to care, and treatment. With the advent of new antibody-drug conjugates (ADC) for metastatic BC (MBC), “HER2-negative” has been subdivided into HER2-low (IHC 1+ or 2+/ISH-negative) and HER2-0 (IHC 0). Little is known about these subcategories among Black and younger women with MBC. Methods: Clinical characteristics, treatment, and outcomes of patients diagnosed with HER2-negative MBC between 2011-2022 and with follow-up through a progression-free survival event on first-line therapy (PFS1) were retrieved from the UNC Metastatic Breast Cancer Database; hormone receptor (HR) and HER2 categories were by clinical criteria from the pathology report. Analyses were limited to HER2-negative BC and stratified/controlled by HR status. Fisher’s exact tests were used to compare HER2 status across race and age. The Kaplan Meier method and log-rank tests, as well as Cox proportional hazards models estimated PFS1. Results: The cohort included 772 MBC patients (56% HER2-low and 44% HER2-0), 22% Black women and 30% < 50 years old at MBC diagnosis. There were no differences in proportion with HER2-low by race or age (p>0.5). Patients with HER2-low had better observed median PFS1 compared to HER2-0, however, most of these differences were non-significant: overall (HR+ 12.2 vs 9.8m, p=0.11, HR- 4.3 v 3.3m, p=0.29) and within race and age categories (see table). In Cox modeling, Black women had worse PFS1 (p=0.03), that was no longer apparent after adjusting for HR status (p=0.1), there was no difference by age. Patients with HER2-0 had worse PFS1 (p=0.0005), which remained after adjusting for HR status (p=0.05). In a multivariable model comparing HER2-0 to HER2-low, adjusting for race and HR status, PFS1 remained shorter in the HER2-0 group (hazard ratio: 0.84, CI 0.692 – 1.015, p=0.07). Among those treated with uniform first-line therapy, better PFS1 was observed in HER2-low disease. This included 137 HR+ MBC treated with ET + CDK4/6i (mPFS1 14.3 v 10.3m, p=0.33) and 170 HR- MBC treated with chemotherapy (mPFS1 4.0 v 3.1m, p=0.22) with no variation by race or age. Conclusions: Within HER2-negative MBC, distribution of HER2-low and HER2-0 cancers does not differ by race and age. The clinical benefit of first-line therapy is strongly driven by HR status regardless of race and age, and is greater in HER2-low cancers although this cohort did not include HER2-directed ADCs. [Table: see text]

Abstract P4-03-30: Patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer

Abstract Background: Tucatinib is an oral HER2-targeted therapy that was approved by the FDA in April 2020 for use in combination with trastuzumab and capecitabine for treatment of patients with previously treated HER2+ metastatic breast cancer (MBC). In the randomized HER2CLIMB trial median (95% CI) overall survival (mOS) and progression-free survival (PFS) for patients receiving tucatinib with trastuzumab and capecitabine were 21.9 (18.3, 31.0) and 7.8 (7.5, 9.6) months, respectively. HER2CLIMB utilized a placebo + trastuzumab + capecitabine comparator arm and included patients with active and stable brain metastasis (BM). Objectives: Describe patient characteristics, treatment patterns, and clinical outcomes for tucatinib-based treatment in the real-world setting. Methods: This retrospective cohort study included patients treated for HER2+ MBC between January 2017 and March 2022 in the nationwide de-identified electronic health record-derived Flatiron Health Metastatic Breast Cancer database who received tucatinib-based treatment outside of a clinical trial setting. Demographic and clinical characteristics of patients were described at baseline (MBC diagnosis) as well as at initiation of each oncologist-defined, rule-based line of therapy (LOT). Key outcomes included time to next treatment (TTNT), persistence, and mOS. Results: Of 2,057 patients treated for HER2+ MBC in the study period who met the inclusion criteria, 154 received tucatinib-based treatment. Of these patients, 18 (12%), 44 (29%), 33 (21%) and 59 (38%) received tucatinib-based treatment in the first-line (1L), second-line (2L), third-line (3L), and fourth-line or further (4L+) respectively. Median age at MBC diagnosis was 54 years. Median follow-up from tucatinib-based treatment initiation was 8.6 months. Overall, 106 (69%) had BM prior to initiating tucatinib therapy (14 [78%], 37 [84%], 20 [61%], and 35 [59%] in 1L, 2L, 3L, and 4L+ respectively). Those with BM initiated tucatinib-based treatment after a median of 2 prior therapies, compared with 2.5 in the non-BM group. The most common metastatic treatment regimens prior to 2L tucatinib-based treatment were trastuzumab + pertuzumab-based, and the most common regimens immediately following 2L tucatinib-based treatment were trastuzumab-based and trastuzumab deruxtecan. The most common regimens immediately prior to and following 3L tucatinib-based treatment were T-DM1 and trastuzumab deruxtecan, respectively. The median (95% CI) TTNT was 8.4 (6.3, 11.3) months overall, and 12.8 (5.5, not reached [NR]) months, 9.8 (4.8, NR) months, and 9.5 (6.1, 15.3) months in 1L, 2L, and 3L, respectively, the median OS was not reached overall (Table 1). Of patients with sufficient follow-up since treatment initiation, 65% (62/96) remained on tucatinib-based treatment after 6 months and 40% (20/50) after 12 months. Conclusion: The majority of patients receiving tucatinib-based treatment in clinical practice have BM at treatment initiation, constituting a larger proportion of the population than in HER2CLIMB (47.5% of patients). Tucatinib-based treatment use in the real-world setting is associated with a similar mOS and TTNT as in HER2CLIMB. Table 1: Median overall survival and time to next treatment in HER2CLIMB and this study *Time to next treatment was used as a proxy for progression-free survival in the HER2CLIMB clinical trial population. CI, confidence interval; mOS, median overall survival; NR, not reached; TTNT, time to next treatment. Citation Format: Peter A. Kaufman, Edward Neuberger, Ling-I Hsu, Naomi Schwartz, Karen Bartley, Shu Wang, Yutong Liu, Matthew T. Blahna, Brian T. Pittner, Gabriel Wong, Carey Anders. Patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic 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 P4-03-30.

RF28 | PSUN185 The effects of diabetes and glycemic control on cancer outcomes in individuals with metastatic breast cancer

Abstract Background While a well-established relationship between diabetes and breast cancer exists, it remains unclear how diabetes impacts breast cancer outcomes. This study aims to determine the impact/association of diabetes and hyperglycemia on cancer progression and mortality in individuals with metastatic breast cancer. Methods Patients with metastatic breast cancer between 2010-2021 were identified using the metastatic breast cancer database at a single academic center. The Research Patient Data Registry, a data warehouse of all patients receiving care in the hospital network was then used to determine the diabetes status of each participant. A participant was categorized as having diabetes if they fulfilled pre-specified criteria (international classification of diseases (ICD) 9 or 10 code for diabetes, or a hemaglobin A1c ≥6.5%, or a random blood glucose (RBG) ≥200 mg/dL and documented use of glucose-lowering agents), while controls were defined as individuals who did not fulfill the previous criteria. We evaluated the effects of diabetes on 1) overall survival (OS) and 2) the interval from initiation of first-line metastatic therapy to initiation of a second-line regimen due to documented progression of disease (a surrogate measure of progression-free survival). The impact of glycemic control on OS and duration of first-line therapy was also assessed. Results We compared 244 patients with diabetes (median age 57.6 years) to 244 patients without diabetes, who were matched for age, gender, ethnicity and hormone-receptor (HR) status. OS at 5 years (diabetes: 54%, CI; 47-62% vs. controls: 56%, CI; 49-63%, p=0.65) and freedom from initiating a second-line regimen at 2 years (diabetes: 43%, CI; 36-50% vs. controls: 44%, CI; 36-51%, p=0.33) were not statistically different between groups. However, in an 8-year landmark subgroup analysis, OS was better amongst controls than those with diabetes (diabetes [n=27]: 67%, CI; 48-86% vs. Controls [n=28]: 87%, CI; 73-100%, p=0.047at 10 years). Poor glycemic control (median RBG >180 mg/dL or median HbA1c >7%) was not associated with increased mortality at 5 years but was associated with a trend towards worse freedom from initiating a second-line regimen at 2 years when compared to good glycemic control. In a sub-group analysis based on HR status, there were no differences in OS at 5 years, or freedom from initiating a second-line regimen at 2 years between the two glycemic groups (≤180 mg/dL vs >180 mg/dL on two or more occasions in a month) for any of the HR subgroups. Conclusions These data provide some reassurance that hyperglycemia may not be a major contributor to overall mortality in the first 5 years, in most individuals with metastatic breast cancer. However, amongst longer-term survivors, diabetes was associated with worse survival, suggesting that individualized diabetes and glycemic goals should, therefore, be considered in patients with metastatic breast cancer. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:51 p.m. - 12:56 p.m.

The Effects of Diabetes and Glycemic Control on Cancer Outcomes in Individuals With Metastatic Breast Cancer.

It is unclear whether diabetes and glycemic control affects the outcomes of breast cancer, especially among those with metastatic disease. This study aims to determine the impact of diabetes and hyperglycemia on cancer progression and mortality in individuals with metastatic breast cancer (MBC). Patients with a diagnosis of MBC between 2010 and 2021 were identified using the MBC database at 2 academic institutions. We evaluated the effects of diabetes and glycemic control on overall survival (OS) and time to next treatment (TTNT). We compared 244 patients with diabetes (median age 57.6 years) to 244 patients without diabetes (matched for age, sex, ethnicity, and receptor subtype). OS at 5 years [diabetes: 54% (95% CI 47-62%) vs controls: 56% (95% CI 49-63%), P = 0.65] and TTNT at 1 year [diabetes: 43% (95% CI 36-50%) vs controls: 44% (95% CI 36-51%), P = 0.33] were similar between groups. A subgroup analysis comparing those with good glycemic control and those with poor glycemic control among patients with specific receptor subtype profiles showed no differences in OS at 5 years or TTNT at 1 year. In an 8-year landmark subgroup analysis, there was worse OS among individuals with diabetes compared to controls, and OS was found to be better among those with good glycemic control compared to those with poor control. Diabetes was not associated with increased mortality in individuals with MBC at 5 years. However, diabetes and hyperglycemia were associated with worse OS among a cohort of longer-term survivors. These findings suggest that individualized diabetes and glycemic goals should be considered in patients with MBC.

Treatment patterns and their impact on the outcome of patients with HR+/HER2+ metastatic breast cancer in a large real-world cohort.

1043 Background: The place of endocrine therapy (ET) in the treatment of hormone receptor-positive (HR+), HER2+ metastatic breast cancer (MBC) is still not clearly defined. Data suggest that blocking both HR and HER2 signaling pathways could be an efficacious strategy to overcome secondary resistance. Methods: We aimed to retrospectively evaluate the impact of first line (L1) therapy for HR+/HER2+ MBC patients (pts) included between 2008- 2017 in the French real-world ESME MBC database (NCT03275311). Our primary endpoints were median overall survival (mOS) and median first progression-free survival (mPFS1). We used descriptive statistics and the Kaplan-Meier method to report patient characteristics and outcomes. Cox proportional hazards models and a propensity score were constructed to report and adjust for prognostic factors. Results: From the 23,501 female pts in the ESME MBC cohort, 1,790 pts had HR+/HER2+ MBC treated with Trastuzumab (T, n=1,089) or Trastuzumab-Pertuzumab (TP, n=701) during L1. Among them, 1,584 pts received antiHER2 therapy+CT+/-ET and 206 pts, antiHER2+ET only. Pts with antiHER2+CT+/-ET had more often ECOG performance status 0 (29.5% vs 15.8%, p<0.001), grade III tumors (36.6% vs 25.6%, p=0.007), time to MBC < 6 mo (51.6% vs 29.1%, p<0.001), TP as antiHER2 therapy (43.2% vs 9.4%, p<0.001), ≥3 metastatic sites (23.2% vs 14.8%, p=0.007), visceral metastasis (56.5% vs 42.4%, p<0.001), and less often bone-only disease (18.4% vs 35%, p<0.001) than pts with antiHER2+ET. In multivariable analysis, antiHER2+CT+/-ET was not superior to antiHER2+ET (Table), while TP was superior to Trastuzumab, and this result was confirmed by matching pts using a propensity score ( p=0.76 for mOS and p=0.85 for mPFS1). Using the time-dependent ET variable among pts with antiHER2+CT, pts with maintenance ET had significantly better PFS1 and OS than those without (adjusted HR for PFS1=0.70 [95%CI 0.60-0.82], adjusted HR for OS=0.47 [95%CI 0.39-0.57], p<0.001). Conclusions: These data suggest that endocrine therapy could be an interesting less toxic alternative to chemotherapy in combination with antiHER2 therapy as first line treatment for HR+/HER2+ MBC pts.[Table: see text]

Abstract P4-05-02: Impact of hormone receptor status on clinicopathological characteristics and outcomes among HER2-positive metastatic breast cancer patients in the ESME database

Abstract Introduction. Evidence suggests that human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients have different clinical characteristics and outcomes according to the hormone receptor (HR) status. We aimed to evaluate the impact of HR status in this population extracted from a large real-world database. Methods. We performed a retrospective analysis of HER2+ MBC patients (pts) included in the real world ESME MBC database (NCT03275311) between 2008 and 2017. Descriptive statistics, the Kaplan-Meier method and Cox proportional hazards models were used to report characteristics, outcomes and prognostic factors. Results. Of 4,145 HER2+ MBC pts eligible for our analysis, 1,449 (35%) had HR-negative (HR-), while 2,696 (65%) had HR-positive (HR+) tumors. Pts with HR- tumors had metastases earlier (median 9.3 vs 28.0 mo from primary cancer), had more often de novo MBC (47.6% vs 38.1%), grade III tumors (50.9% vs 33.6%), visceral metastases (70.9% vs 60.8%) and less often bone only disease (8.4% vs 21.1%) compared to those with HR+ tumors, all p<0.001. Pts with HR+ MBC received less frequently an anti-HER2+ targeted therapy during first line of treatment than pts with HR- tumors (74.9% vs 90.8%, p<0.001). Pts with HR- MBC had significantly worse outcomes than those with HER2+/HR+ MBC, with median overall survival (OS) 42.0 mo [95% CI 38.8-45.2] vs 55.9 mo [95% CI 53.7-59.4], p<0.001, and median progression-free survival (PFS) 9.8 mo [95%CI 9.2-11] vs 12.2 mo [95%CI 11.5-12.9], p=0.012, respectively. The independent prognostic value of HR status was confirmed in a multivariable analysis for OS (HR- versus HR+, hazard ratio=1.25 [1.13-1.39], p<0.001) but not for PFS (hazard ratio=1.03 [95%CI 0.95-1.13], p=0.8) (Table 1 for OS). The multivariable analysis also included tumor grade, age at and time to MBC diagnosis, presence of visceral metastases, number of metastatic sites and performance status as prognostic factors. In the HR+ population, ER and PR statuses were not prognostic. Conclusions. These data confirm the remaining strong and independent adverse prognostic effect of negative hormone receptors among pts with HER2+ MBC treated in the past 12 years. Cox multivariable model for overall survival in patients with HER2-positive MBCCategoriesNHazard ratio95% CIp valueTumor gradeGrade I/II17711<0.001Grade III15741.13[1.03-1.25]NA5811.15[1.01-1.31]ER/PR statusER+/PR+14571<0.001ER+/PR-9711.03[0.92-1.16]ER-/PR+1021.03[0.77-1.36]ER-/PR-13961.25[1.13-1.39]Age at MBC diagnosis<55 years17561<0.001≥55 years21701.26[1.16-1.38]Time to MBC diagnosis<6 months16351<0.0016-24 months5082.53[2.22-2.89]24-60 months8721.75[1.56-1.96]≥60 months9111.19[1.06-1.35]Visceral metastasesNo14061<0.001Yes25201.54[1.38-1.71]No of metastatic sites<330911<0.001≥38351.65[1.48-1.84]ECOG PSPS 010101<0.001PS 18021.62[1.4-1.87]PS 2-43923.34[2.83-3.95]NA17222.34[2.07-2.64] Citation Format: Luc Cabel, Matthieu Carton, Veronique Dieras, Thierry Petit, Severine Guiu, Corinne Veyret, Anthony Goncalves, Lionel Uwer, Paule Augereau, Jean-Marc Ferrero, Christelle Levy, Florence Dalenc, Isabelle Desmoulins, Marie Ange Mouret-Reynier, Marc Debled, Thomas Bachelot, Jean-Christophe Eymard, Barbara Pistilli, Jean Sebastien Frenel, Michael Chevrot, Audrey Mailliez, Marcela Carausu. Impact of hormone receptor status on clinicopathological characteristics and outcomes among HER2-positive metastatic breast cancer patients in the ESME database [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 P4-05-02.

Clinicopathological characteristics and prognosis of breast cancer patients with isolated central nervous system metastases in the multicentre ESME database.

Background:As a result of progress in diagnosis and treatment, there is a growing prevalence of metastatic breast cancer (MBC) with isolated CNS metastases. This study describes the largest-to-date real-life cohort of this clinical setting and compares it to other clinical presentations.Methods:We retrospectively analysed the French Epidemiological Strategy and Medical Economics (ESME) MBC database including patients who initiated treatment for MBC between 2008 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Descriptive statistics and multivariate Cox model were used.Results:Of 22,266 patients, 647 (2.9%) and 929 (4.2%) patients had isolated first-site CNS metastases or combined with extra-CNS metastases, with longer OS for the group with isolated CNS metastases (16.9 versus 13.9 months, adjusted HR = 1.69 (95% CI: 1.50–1.91), p < 0.001). Among the 541 (2.4%) patients with isolated CNS metastases and no intrathecal therapy (excluding leptomeningeal metastases), HER2+ cases were preponderant over TN or HR+ /HER2− cases (41.6% versus 26.1% versus 28.5%, respectively, p < 0.01). The treatment strategy consisted of a combination of local treatment and systemic therapy (49.2%), local treatment only (35.5%) or systemic therapy only (11.4%), or symptomatic therapy only (3.9%). Median PFS was 6.1 months (95% CI: 5.7–6.8). Median OS was 20.7 months (95% CI: 17.3–24.3), reaching 37.9 months (95% CI: 25.9–47.6) in the HR+ /HER2+ subgroup. Older age, TN subtype, MBC-free interval of 6–12 months, lower performance status, and WBRT were associated with poorer survival. Patients who received systemic therapy within 3 months from MBC diagnosis had longer OS (24.1 versus 16.1 months, p = 0.031), but this was not significant on multivariate analysis [HR = 1.0 (95% CI: 0.7–1.3), p = 0.806].Conclusions:Patients with isolated CNS metastases at MBC diagnosis represent a distinct population for which the role of systemic therapy needs to be further investigated in prospective studies.

Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases in a large real-life database

BackgroundLeptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high morbidity/mortality rates. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models.MethodsThe Epidemiological Strategy and Medical Economics (ESME) MBC database (NCT03275311) includes all consecutive patients who have initiated treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan–Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots.ResultsOf the 22 266 patients included in the database between 2008 and 2016, 312 received IT therapy and were selected for our analysis. Compared with non-IT-treated patients, IT-treated patients were younger at MBC relapse (median age: 52 years versus 61 years) and more often had lobular histology (23.4% versus 12.7%) or triple-negative subtype (24.7% versus 13.3%) (all P < 0.001). Median OS was 4.5 months [95% confidence interval (CI) 3.8-5.6] and 1-year survival rate was 25.6%. Significant prognostic factors associated with poorer outcome on multivariable analysis were triple-negative subtype (hazard ratio 1.81, 95% CI 1.32-2.47), treatment line ≥3 (hazard ratio 1.88, 95% CI 1.30-2.73), ≥3 other metastatic sites (hazard ratio 1.33, 95% CI 1.01-1.74) and IT cytarabine or thiotepa versus methotrexate (hazard ratio 1.68, 95% CI 1.28-2.22), while concomitant systemic therapy was associated with better OS (hazard ratio 0.47, 95% CI 0.35-0.62) (all P < 0.001). We validated two previously published prognostic scores, the Curie score and the Breast-graded prognostic assessment, both with C-index of 0.57.ConclusionsMBC patients with LM treated with IT therapy have a poor prognosis. We could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used.

Abstract PD10-11: Efficacy of Platinum-based first-line chemotherapy among metastatic breast cancer (MBC) patients according to the germline BRCA1/2 mutational status: An analysis of the French ESME MBC database

Abstract Background: Platinum-based chemotherapy regimens (PtCT) have been shown to increase treatment efficacy when combined to neoadjuvant standard of care treatment of triple negative breast cancers (TNBC). In the metastatic breast cancer (MBC) setting, preclinical and clinical data suggest that PtCT could be more efficient than non-platinum based ones (non-PtCT) among patients (pts) with germline BRCA1/2 mutations (gBRCAm). However, published data remain controversial on this topic, particularly for MBC. We evaluated the progression-free (PFS) and overall survival (OS) under first-line PtCT and non-PtCT among gBRCAm carriers in ESME, a nationwide real-life MBC database. Methods: ESME MBC database (NCT03275311), is a unique national cohort of all consecutive pts who initiated a first-line treatment for MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. Women with HER2- MBC and known hormone receptors (HR) and gBRCA1/2 (before or in the 6 first months of metastatic disease, gBRCAm / wild type / not tested) status, who received a first-line MBC CT were selected. Patients with other germinal mutations were considered as wild type. Primary objectives were OS and PFS under first-line CT (PtCT vs. non-PtCT) in the TNBC gBRCA1/2m population.Secondary objectives were OS and PFS during first-line CT (PtCT vs. non-PtCT) in the TNBC wild-type and “not tested” population, as well as among the HR+/HER2- pts.To avoid guarantee time bias related to oncogenetic testing, analyses were performed at baseline (CT initiation) and different landmark time points (3-month or 6-month after CT initiation). Thus, BRCA status was defined according to oncogenetic testings performed before the landmark time, and patients who progressed or censored before the landmark time were excluded. Results: 10,164 pts (2,794 TNBC; 7,370 HR+/HER2-) were included in this analysis. Pts who received PtCT were significantly younger, affected by a gBRCA1/2m, had a high histological grade and/or TNBC tumor, with more frequent visceral and central nervous system spreading than non PtCT ones. Median follow-up was 51.1 months [95%CI 49.6; 52.6]. All reported results were based on the gBRCA status defined at CT initiation and on multivariable analysis adjusted on age at MBC diagnosis, de novo MBC status, type and number of metastases. In the gBRCA1/2m TNBC population (N=132), PtCT was independently associated with a better PFS compared to non-PtCT (HR=0.56, 95%CI 0.38-0.84, p=0.005), without significant difference in OS (HR=0.79, 95%CI 0.51-1.23, p=0.29).No difference was seen in wild-type BRCA1/2 TNBC pts (N=269) according to the CT regimen, while, in the larger population of untested TNBC (N=2,393), PtCT was associated with worse OS (HR=1.18, 95%CI 1.03-1.34, p=0.016) compared to non-PtCT regimens, without significant difference in PFS (HR=1.07, 95%CI 0.95-1.22, p=0.26). No significant difference was seen regarding PFS nor OS in gBRCA1/2m HR+/HER2- pts (N=124) and in the wild-type BRCA1/2 HR+/HER2- population.However, in the larger population of untested HR+/HER2- pts (N=6,836), PtCT was independently associated with worse OS (HR=2.15, 95%CI 1.79-2.59, p&amp;lt;0.001) and PFS (HR=1.57, 95%CI 1.33-1.86, p&amp;lt;0.001) compared to non-PtCT regimens. Results were similar in landmark analyses at 3-month or 6-month after CT initiation. Conclusions: This large-scale real-life analysis suggests higher efficacy of PtCT in term of PFS in gBRCA1/2m TNBC pts. The small sample size and post-1st line treatments may preclude observing a significant OS difference. PtCT appeared however associated with worse outcomes in untested TNBC and HR+/HER2- pts. These results emphasize the need for BRCA1/2 characterization before considering these regimens in the MBC setting. Citation Format: William Jacot, Amélie Lusque, Audrey Mailliez, Thibault De la Motte Rouge, Luc Cabel, Christelle Levy, Anne Patsouris, Isabelle Desmoulins, Lionel Uwer, Marianne Leheurteur, Mathieu Robain, Olivier Caron, Thomas Bachelot, Thomas Filleron, Jean-Sébastien Frenel, Suzette Delaloge. Efficacy of Platinum-based first-line chemotherapy among metastatic breast cancer (MBC) patients according to the germline BRCA1/2 mutational status: An analysis of the French ESME MBC database [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 PD10-11.

Abstract PD10-08: Outcomes of germline BRCA carriers versus non-carriers in the french national metastatic breast cancer ESME cohort 2008-2016

Abstract BACKGROUND: Approximately 5% of breast cancer (BC) patients (pts) carry a deleterious germline BRCA mutation (gBRCAm). Retrospective studies suggest that overall survival (OS) is equivalent between gBRCAm carriers and non-carriers with metastatic BC (MBC). We aimed to use the large ESME multicentre national MBC database to compare outcomes of gBRCAm carriers, gBRCA wild-type (WT) and not tested (NT) pts. METHODS: We used the large ESME MBC database (NCT03275311), a unique national cohort of all consecutive pts who initiated a first-line treatment for MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. All pts with data available regarding gBRCA testing were selected for the present analysis. 26 pts with non-BRCA germline mutations were classified in the WT group. The primary endpoint was OS from date of treatment initiation in the 3 groups of patients: gBRCAm, gBRCA WT and gBRCA NT.Secondary endpoints were progression-free survival under first line treatment (PFS1), clinical and biological characteristics of the 3 groups and prognostic factors for OS. Multivariable analyses included the main known prognostic factors (age at MBC, MBC subtype, disease-free interval, presence of visceral disease, number of metastatic sites). They were conducted using Cox proportional analyses. RESULTS: 20624 pts were included in this analysis (414 gBRCAm, 1710 WT, 18500 gBRCA NT). Pts and disease characteristics are summarized in table 1. As expected, patients with gBRCAm were younger and had a higher rate of TNBC and G3 tumors. Median follow-up was 50.5 months (95%CI 49.7-51.5). Non-adjusted median OS was 30.6 months [21.9-34.3] in the gBRCAm group, 35.8 [32.2-37.8] in the WT and 39.3 [38.3-40.3] in NT groups. Median PFS1 was 7.9 months [6.6-9.3] in the gBRCAm group, 7.8 [7.3-8.5] in the WT and 9.7 months [ 9.5-10.0] in the NT groups. In multivariable analyses, OS and PFS were not significantly different between MBC patients with gBRCA and others (respective HRs 1.01 [0.88;1.17], p=0.87 and 0.94 [0.84;1.06], p=0.31). CONCLUSION: In this large scale real-life ESME MBC database analysis, outcomes of gBRCAm carriers with MBC do not differ from non carriers or not tested subgroups, when adjusted for other prognostic factors. Table 1: characteristics of patients and diseasegBRCAm. gBRCA WT. gBRCA NT Pvalue (chi-2)N = 414 N = 1710 N = 18500 Age (years) median [range]45 [23-82]48 [20- 88]61 [22-103]p&amp;lt;0.0001Grade 3 N (%) Missing data202 (57.7) 64598 (41.1) 2545337 (34.5)3036p&amp;lt;0.0001Triple negative breast cancer N (%)158 (38.2)370 (21.6)2331 (12.6)p&amp;lt;0.0001De novo MBC N (%)74 (17.9)359 (21)5914 (32)p&amp;lt;0.0001Disease-free interval (months) median [range]39.0 [-1.5- 425.7]36.3 [-2.1- 549.6]31.8 [-2.9- 657.8]p&amp;lt;0.0001Metastatic sites ≥3 N (%)113 (27.3)349 (20.4)3943 (21.3)p=0.008Visceral metastases N (%)279 (67.4)964 (56.4)10659(57.6)p=0.0002Central Nervous System Metastases N (%)66 (15.9)132 (7.7)1145 (6.2)p&amp;lt;0.0001 Citation Format: Audrey Mailliez, Veronique D'Hondt, Amelie Lusque, Olivier Caron, Luc Cabel, Antony Goncalves, Marc Debled, Laurence Gladieff, Jean-Marc Ferrero, Thierry Petit, Marie-Ange Mouret-Reynier, Jean-Christophe Eymard, Jean-Sébastien Frenel, Thibault De La Motte Rouge, Gaëtane Simon, Suzette Delaloge. Outcomes of germline BRCA carriers versus non-carriers in the french national metastatic breast cancer ESME cohort 2008-2016 [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 PD10-08.

Abstract PS16-06: Identification of pathogenic FGFR1, FGFR2, and FGFR3 alterations in cell-free DNA (cfDNA) from patients with metastatic breast cancer

Abstract Background: FGFR alterations are a known mechanism of resistance against breast cancer systemic therapies with higher FGFR RNA expression in breast cancer brain metastases compared to their primary tumors. While the genomic characterization of FGFR alterations has occurred from bulk breast tumors, the frequency and type of FGFR alterations in metastatic breast cancer (MBC) have not been fully characterized from cfDNA. The purpose of this study was to identify the incidence of FGFR1, FGFR2, and FGFR3 genomic alterations in cfDNA from patients with MBC and elucidate which FGFR alterations may increase FGFR kinase activity or may function as mechanisms of resistance against the FDA approved FGFR inhibitor, erdafitinib. Methods: We queried 16,053 reports from Guardant Health between June 2015 - October 2019 to identify the incidence of FGFR1, FGFR2, and FGFR3 alterations detected in cfDNA from MBC. We classified each alteration type into the following categories: copy number variation (CNV), fusion, indel, or single nucleotide variant (SNV). Focus was placed on characterizing FGFR1, FGFR2, and FGFR3 SNVs. We compared known activating mutations in EGFR, ERBB2, and BRAF with homologous regions in FGFR1, FGFR2, and FGFR3. In silico modeling with PyRx was used to dock erdafitinib onto FGFR1 (PDB 4V05), FGFR2 (PDB 5B7V), and FGFR3 (PDB 6LVM) kinases. Three-dimensional in silico analyses with ChimeraX was utilized to further determine which alterations may increase FGFR1, FGFR2, and FGFR3 kinase activity or may induce resistance against erdafitinib. Results: The incidence of nonsynonymous alterations occurring in FGFR1, 2213 (13.8%); FGFR2, 1017 (6.3%); and FGFR3, 144 (0.9%) were identified in the Guardant Health MBC database. FGFR1, FGFR2, and FGFR3 alterations are detailed in Table 1. We identified 40 (9.15%) and 167 (38.2%), 55 (7.2%) and 310 (40.4%), and 31 (27.4%) and 32 (28.3%) mutations occurring in the transmembrane/juxtamembrane and kinase domains of FGFR1, FGFR2, and FGFR3, respectively. Hotspot mutations were observed at R54C/S/G/R and N546K/D/S in FGFR1, D304N and N549K/D/S in FGFR2, and at S408/F/C/L/Y in FGFR3. We aligned FGFR1, FGFR2, and FGFR3 with homologous kinases and found 12 unique samples with mutations in our FGFR1 dataset corresponded to known activating mutations in EGFR and ERBB2; 18 samples with mutations in our FGFR2 dataset corresponded to known activating mutations in EGFR, ERBB2, and BRAF; and 1 mutation in our FGFR3 dataset corresponded to a known activating mutation in ERBB2. FGFR1 mutations C488S, V492M, M535I, L569V and FGFR2 mutations L550V, E565A, Y566N, S568C, G570R, G685E are postulated to induce resistance against erdafitinib. Conclusions: We found that 21% of MBC in this dataset harbor FGFR genomic alterations detected from cfDNA. Novel somatic alterations in FGFR1, FGFR2, and FGFR3 were identified from Guardant Health that were not detected in the public domain. A portion of FGFR SNVs occurred at known homologous kinase activating mutations in EGFR, ERBB2, and BRAF suggesting these specific FGFR mutations may increase FGFR kinase activity and might be actionable therapeutic targets in breast cancers harboring these mutations. Three dimensional analyses of the FGFR protein tyrosine kinase further illustrate which specific alterations may increase FGFR kinase activity or induce resistance against erdafitinib. Table 1. Incidence and type of FGFR alterations in Guardant Health MBC databaseGeneCNV (%)Fusion (%)Indel (%)SNV (%)FGFR11770 (80%)-6 (0.3%)437 (19.7%)FGFR2224 (22%)15 (1.5%)11 (1.1%)767 (75.4%)FGFR3-24 (16.7%)7 (4.9%)113 (78.4%) Citation Format: Mary Love Taylor, Benjamin Mayro, Leylah Drusbosky, Robin Batchelder, P. Kelly Marcom, Carey Anders, Jeremy Force. Identification of pathogenic FGFR1, FGFR2, and FGFR3 alterations in cell-free DNA (cfDNA) from patients with metastatic breast cancer [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 PS16-06.

Real-world Evaluation of Oral Vinorelbine in the Treatment of Metastatic Breast Cancer: An ESME-MBC Study.

Vinorelbine is indicated for use in the treatment of MBC as a single agent or in combination but there is little real world data on this molecule and even less on its oral form. We exploited the Unicancer Epidemiology Strategy Medical-Economics (ESME) metastatic breast cancer (MBC) database to investigate current patterns of use of oral vinorelbine (OV), as well as outcomes of patients receiving this drug. Data were collected retrospectively from women and men treated for MBC between 2008 and 2014 at one of 18 French Comprehensive Cancer Centres. The efficacy of OV was evaluated in terms of progression-free (PFS) and overall survival (OS) and treatment duration. The population and patterns of OV usage were also described. A total of 1806 patients (11% of the ESME MBC database) were included in this analysis. OV was prescribed as monotherapy (46%) or in combination (29%), especially with capecitabine. mainly in later treatment lines. Median PFS was 3.3 months: 2.9 months for single agent, 3.6 months for combination therapy. Median OS was 40.9 months. Real-world data offer complementary results to the data from traditional clinical trials, but they concern a much larger population. In this ESME MBC cohort, OV was only prescribed to a small subset of MBC patients. OV was mainly given as single agent to patients with heavily pre-treated MBC; less commonly, it was co-administered with capecitabine or anti-HER2, in earlier lines of therapy. PFS was modest but in line with previous reports.

Impact of age at diagnosis of metastatic breast cancer on overall survival in the real-life ESME metastatic breast cancer cohort

BackgroundYoung age is a poor prognostic factor in early stage breast cancer (BC) but its value is less established in metastatic BC (MBC). We evaluated the impact of age at MBC diagnosis on overall survival (OS) across three age groups (<40, 40 to 60 and > 60 years(y)). MethodsESME MBC database is a national cohort, collecting retrospective data from 18 participating French cancer centers between January 01, 2008 and December 31, 2014. ResultsAmong 14 403 women included, 1077 (7.5%), 6436 (44.7%) and 6890 (47.8%) pts were <40, 40–60 and > 60 y respectively. Pts <40 had significantly more aggressive presentations than other age groups: more frequent HER2+ (25.7 vs 15.3% in >60y) and triple negative subtypes (27.4 vs 14.6% in >60y), and more frequent visceral involvement (36.3 vs 29.8% in >60y). At a median follow-up of 48 months, median OS differed across age groups: 38.8, 38.4 and 35.6 months for pts <40, 40–60 and > 60y, respectively (p < 0.0001). Compared to pts <40y, older pts had a statistically significant higher risk of death (all causes of death included), although of limited clinical value (HR = 1.1, IC 95%:1.01–1.20). There was a significant trend for better OS in pts <40y with HER2+ and luminal diseases. A possible explanation is a greater use of anti-Her2 therapies as first-line treatments: 86.6, 81.9 and 74.9% for pts <40, 40–60 and > 60y, respectively (p < 0.0001). ConclusionAlthough young age seems associated with more aggressive presentations at diagnosis of MBC, it has no deleterious effect on OS in this large series.

Abstract P5-06-18: Prediction of PFS and OS under third and fourth line chemotherapy among metastatic triple-negative breast cancer patients in the national multicenter ESME metastatic breast cancer cohort

Abstract Background: Amongst metastatic breast cancer (MBC) patients (pts), those with triple-negative breast cancer (mTNBC) have a poor prognosis. Although chemotherapy (CT) remains the cornerstone therapy, its benefit on outcome is not established beyond second line while side effects increase and impair quality of life. Factors predicting for efficacy might help guiding in the treatment decision process. The purpose of this study was to evaluate factors predicting for progression-free survival (PFS) and overall survival (OS) in the third or fourth line treatment in pts with mTNBC within the National multicenter ESME cohort, and to build a nomogram based on the selected variables. Methods: The ESME (Epidemiological Strategy and Medical Economics) MBC database (NCT03275311) is a unique national Metastatic Breast Cancer cohort built from existing information systems, pharmacy records and patients’ electronic medical records (EMR), with homogenous on-site collected information. This prospective cohort includes all consecutive pts who initiated a first-line treatment for a MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. We searched for independent prognostic factors under third and fourth line chemotherapy (PFS3 and PFS4, OS3 and OS4) for mTNBC patients, using COX proportional hazard regression models. Variables included in the model were pts and tumour (primary cancer and MBC) characteristics, as well as observed PFS under previous lines of therapy. We built prognostic nomograms based on main prognostic factors retrieved. Nomograms’ prediction ability were evaluated by concordance index (C-index), calibration and subgroup analysis. We used a 6-month cut-off for each PFSx. Results: Among 22266 women in the ESME cohort, 2922 had a mTNBC. 1792 (61%), 1074 (37%) and 598 (20%) mTNBC pts respectively received at least 2, 3 or 4 lines of CT in the metastatic setting, with a median follow-up of 53.3 months (range 4.6-103). The median PFS3, PFS4, OS3 and OS4 were 2.3 months 95%CI [2.3-2.5], 2.1 months 95%CI [1.9-2.3], 6.6 months 95%CI [6.3-7.2] and 5.9 months 95%CI[5.2-6.4], respectively. PFS1, PFS2 and number of metastatic sites ≤3 at baseline were identified as prognostic factors by multivariate analysis both for OS3 and OS4 (HR 0.76 95%CI[0.66-0.88], HR 0.55 95%CI[0.46-0.65], HR 1.36 95%CI[1.14-1.62], all p&amp;lt;0.001, and HR 0.76 95%CI[0.63-0.91], p&amp;lt;0.001, HR 0.56 95%CI[0.45-0.7], p&amp;lt;0.001, HR 1.37 95%CI[1.07-1.74], p=0.01, respectively). In addition, disease free-interval between primary cancer and metastatic relapse was identified as an independent factor for OS3 (p=0.01) and PFS3 for OS4 (HR 0.75 95%CI[0.57-0.98], p=0.03). Median PFS3, PFS4, OS3 and OS4 according to previous duration of PFS are shown in Table 1. Nomograms predicting for PFS3, PFS4, OS3 and OS4 respectively achieved a C-index of 0.59, 0.58, 0.62, 0.61. Conclusion: The previous duration of each PFS is a major prognostic factor of PFS and OS in TNBC in 3rd or 4rd of CT among mTNBC pts. However, nomograms predicting for PFS and OS this setting do not reach a clinical utilityTable 1: PFS and OS according to previous PFS duration Previous PFS 1/2 (months)N=OS3 months [95%CI]HR [95%CI]pPFS3 months[95%CI]HR [95%CI]p≤6/≤65245.2 [4.7-5.9]1&amp;lt;0.0012.1 [1.9-2.2]1&amp;lt;0.001&amp;gt;6/≤63127.3 [6.4-8.7]0.71 [0.61; 0.82]2.4 [2.2-2.6]0.86 [0.75; 1]≤6/&amp;gt;611211.3 [8.1-13.4]0.48 [0.38; 0.6]2.7 [2.3-3.5]0.69 [0.56; 0.85]&amp;gt;6/&amp;gt;612611.9 [9.9-15.2]0.43 [0.34; 0.54]3.5 [3.2-4.1]0.52 [0.42; 0.64]Previous PFS1/2/3N=OS4 months [95%CI]HR [95%CI]PFS4 months [95%CI]HRp≤6/≤6 /≤62284.5 [3.9-5.4]1&amp;lt;0.0011.8 [1.6-1.9]1&amp;lt;0.001≤6/≤6 /&amp;gt;6357.0 [4.1-10.9]0.7 [0.47; 1.04]2.1 [1.8-2.8]0.83 [0.57; 1.2]&amp;gt;6/≤6 /&amp;gt;6176.9 [4.3-NA]0.7 [0.4; 1.22]3.0 [1.6-NA]0.54 [0.31; 0.94]&amp;gt;6/≤6 /≤61665.6 [4.7-6.7]0.65 [0.52; 0.8]2.3 [1.9-2.7]0.66 [0.54; 0.81]&amp;gt;6/&amp;gt;6 /≤6567.8 [4.9-11.1]0.54 [0.38; 0.75]2.1 [1.8-2.4]0.87 [0.64; 1.18]≤6/&amp;gt;6 /≤6608.1 [6.7-12.7]0.45 [0.33; 0.63]2.4 [1.9-3.0]0.65 [0.49; 0.88]≤6/&amp;gt;6 /&amp;gt;61316.7 [5.9-NA]0.3 [0.16; 0.57]4.2 [2.3-NA]0.32 [0.17; 0.59]&amp;gt;6/&amp;gt;6 /&amp;gt;62310.7 [8.5-NA]0.25 [0.14; 0.45]4.8 [3.4-8.0]0.33 [0.21; 0.51] Citation Format: Luc Cabel, Matthieu Carton, Barbare Pistilli, Florence Dalenc, Laurence Vanlemnens, Christelle Levy, William Jacot, Marc Debled, Agnes Loeb, Bruno Coudert, Thubault De la Motte Rouge, Lilian Laborde, Carine Laurent, Emmanuel Chamorey, Damien Parent, Thierry Petit, Marie-Ange Mouret-Reynier, Geneviève Perrocheau, Claire Labreveux, Thomas Bachelot, Mathieu Robain, Florence Lerebours. Prediction of PFS and OS under third and fourth line chemotherapy among metastatic triple-negative breast cancer patients in the national multicenter ESME metastatic breast cancer cohort [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 P5-06-18.

Abstract P2-19-01: Impact of bone-only metastatic breast cancer on outcome in a real-life setting: A comprehensive analysis of 5,041 women from the ESME database

Abstract Background: Bone-only (BO) metastatic breast cancer (MBC), defined as bone as unique site of metastasis at MBC diagnosis, is thought to carry a better prognosis among MBC. However, only small retrospective series and data from selected randomized controlled trials have been reported so far. Based on a national database, we aimed at providing a large comprehensive analysis of BO MBC, and at evaluating its impact on clinical outcome. Methods: The ESME MBC platform (NCT03275311) is a French multicenter retrospective real-life database using a clinical trial-like methodology to collect data from 18 French Comprehensive Cancer Centers. It includes data from each newly diagnosed MBC patient having initiated at least one treatment between 2008 and 2016. BO cases occurring in women were retrieved and compared to the overall non-BO population, regarding treatment effects and survival. Results: Of the 22,463 women selected in the database, 5,041 (22.4%) patients with BO disease were identified. Most (N=4,102, 81.4%) had HR+/HER2- disease while 644 (12.8%) and 295 (5.9%) patients had HER2+ or HR-/HER2- disease, respectively. Compared to non-BO MBC, BO MBC patients were older in the global cohort and in HR-/HER2- patients (mean age 61.0y versus 59.5y, and 59.3y vs 56.4y, all p&amp;lt;0.0001, respectively), and tumor histology was more frequently a lobular carcinoma in the global cohort, in HR+/HER2- and in HR-/HER2- patients (18.6% vs 10.8%, 20.6% vs 15.2%, 13.8% vs 3.2%, all p&amp;lt;0.0001, respectively). In addition, metastatic disease occurred de novo more frequently in BO MBC patients (37.9% versus 29.2%) (p&amp;lt;0.0001), and a statistically significant difference was also observed within each tumor subtype group. The management of bone disease included bisphosphonates or denosumab, radiotherapy, and invasive bone metastasis procedures in 3,913 (77.6%), 2,929 (58.1%), and 1,154 (22.9%) patients, respectively. Median follow up was 52.4 months (95% CI [50.8-54.2]) in BO population and 50.9 months (95% CI [49.7-51.8]) in non-BO population. BO MBC patients had improved median progression-free survival (PFS) 1, regarding first-line treatment, and overall survival (OS) compared to non-BO MBC, globally and within each tumor subtype group (Table). Indeed, 5-year OS rates reached up to 43%, 54% and 16% in HR+/HER2-, HER2+ and HR-/HER2- BO MBC groups, respectively. This suggests that a substantial number of these patients could be considered as long survivors. In the BO MBC cohort, de novo BO MBC patients had a higher 5-year OS rate than relapsed BO MBC patients. BO disease was an independent prognostic factor of OS (hazard ratio 0.68 (95% CI [0.65-0.72]), p&amp;lt;0.0001) together with age, tumor subtype, grade, adjuvant treatment and metastatic-free interval. Conclusion: This large comprehensive study is the largest cohort of BO MBC to date. BO MBC has a distinct presentation from non-BO MBC and carry a better prognosis compared to non-BO MBC. A significant proportion of BO MBC patients have a very long survival and may benefit from aggressive local therapy, as stereotactic radiotherapy. Dedicated studies are warranted to tailor the management of these patients. Funding: This work was supported by UNICANCER. The ESME MBC database is supported by an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analyses and publications are totally managed by R&amp;D UNICANCER independently of the industrial consortium. TableBOBOBOBOnon-BOnon-BOnon-BOnon-BON (%)median OS monthsmedian PFS1 months5-year OS rate %N (%)median OS monthsmedian PFS1 months5-year OS rate %(95% CI)(95% CI)(95% CI)(95% CI)(95% CI)(95% CI)Overall population5,041 (100%)52.1 (50.3-54.1) 13.1 (12.6-13.8) 43.41 (41.66-45.15)15,054 (100%)34.7 (34.0-35.6) 8.5 (8.3-8.7) 30.55 (29.62-31.48)HR+/HER-4,102 (81.4%)52.6 (50.5-54.8)13.6 (13.0-14.3)43.52 (41.56-45.46)9,127 (60.6%) 39.0 (37.8-40.1)9.6 (9.3-9.9)32.69 (31.47-33.93)HER2+644 (12.8%)66.4 (59.8-71.9) 14.9 (12.9-17.3) 54.49 (49.54-59.16)3,265 (21.7%) 46.5 (44.2-48.9)10.6 (10.1-11.3)39.88 (37.77-41.98)HR-/HER2-295 (5.9%)20.8 (18.3-27.4) 5.6 (4.9-7.5)16.21 (11.21-22.02)2,662 (17.7%) 14.3 (13.6-15.1)4.8 (4.6-5.0)10.89 (9.4-12.5)De novo MBC patients1,909 (37.9%)58.6 (55.4-62.1)17.9 (17.0-18.9)48.24 (45.28-51.14)4,399 (29.2%) ---Relapsed MBC patients3,132 (62.1%)48.3 (46.5-50.5)10.7 (10.2-11.2)40.51 (38.34-42.67)10,655 (70.8%)--- Citation Format: Marion Bertho, Julien Fraisse, Anne Patsouris, Paul Cottu, Suzette Delaloge, David Pérol, Anne Jaffré, Anthony Goncalves, Marie-Paule Lebitasy, Véronique D'Hondt, Florence Dalenc, Jean-Marc Ferrero, Christelle Levy, Patrick Arveux, Roman Rouzier, Frédérique Penault-Llorca, Lionel Uwer, Jean-Christophe Eymard, Mathias Breton, Michaël Chevrot, Marianne Leheurteur, Michel Velten, Gaëtane Simon, Jean-Sébastien Frenel. Impact of bone-only metastatic breast cancer on outcome in a real-life setting: A comprehensive analysis of 5,041 women from the ESME database [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 P2-19-01.

Abstract P3-08-43: Comprehensive analysis of lymphopenia in large-scaled early and metastatic breast cancer database cohort

Abstract Background: Lymphopenia is frequently observed in advanced cancer patients even before initiation of systemic anti-cancer treatment. The aim of this study is to investigate the pre-treatment lymphopenia as a prognostic factor for breast cancer specific survival (BCSS), distant recurrence free survival (DRFS) in patients with early breast cancer (EBC) and overall survival (OS), OS2 (from diagnosis with stage IV to death) with metastatic breast cancer (MBC) in large-scaled early and metastatic breast cancer database cohort. Methods: We reviewed demographic, clinical, pathologic, and survival data from Yonsei Breast Cancer Center Registry. In large scaled database, 5252 patients who underwent surgery with stage I-III EBC at the Yonsei Cancer Center between 2006 and 2015 were included and 1481 patients who were newly diagnosed de novo or recurrent MBC were included. The pre-treatment lymphocyte count was obtained from complete blood count (CBC) assay before the initiation of any treatment. Lymphopenia was defined as an absolute lymphocyte count (ALC) &amp;lt; 1000/mm3. Clinicopathologic factors, such as human epidermal growth factor 2 (HER2) receptor, hormone receptor (HR) status and metastatic site, were reviewed. To evaluate the prognostic factors, Kaplan-Meier, log-rank, and Cox regression analysis were performed. Results: Of 5211 eligible EBC patients, 2690 (51.6%) stage I and 1857 (35.6%) stage II patients was included. De novo and recurrent MBC patients were 260 (31.0%) and 576 (69.0%). The incidences of pre-treatment lymphopenia were 3.0% (154/5211) in EBC and 14.5% (121/836) in MBC: 10 (3.9%) in de novo stage IV and 117 (19.3%) in recurrent stage IV. There was no difference in pre-treatment lymphopenia incidence among histologic subtypes in EBC cohort, but it was significantly higher in triple negative breast cancer (TNBC) in MBC. EBC patients with HBsAg positive showed higher incidence of pre-treatment lymphopenia than HBV negative patients (7.3% vs. 2.9%, p=0.003). In MBC cohort, patients with early distant recurrent (less than 2 year) disease (35.8%, p&amp;lt;0.001), HER2-negative (39.7%, p&amp;lt;0.001), liver &amp; brain metastasis (25.7%, p=0.028 &amp; 30.5%, p=0.024) and without adjuvant endocrine therapy (25.8%, p&amp;lt;0.001) were higher incidence of pre-treatment lymphopenia. In EBC cohort, pre-treatment lymphopenia would not prognostic factor in DFRS, OS and BCSS. However, in MBC cohort, pre-treatment lymphopenia group showed a significant difference in overall survival compared to normal lymphocyte count group (mOS2 19.7 vs 40.1 months, p&amp;lt;0.0001). In de novo stage IV MBC, there is no survival difference in baseline lymphopenia as in EBC cohort. In contrast, in recurrent stage IV MBC, pre-treatment lymphopenia group showed poor survival regardless to previous exposure to neo/adjuvant chemotherapy (mOS2 in naïve chemotherapy group: lymphopenia vs no lymphopenia 19.7 vs 73.2months (p&amp;lt;0.001); mOS2 in previous chemotherapy group: 18.2 vs 35.7months, (p&amp;lt;0.001)). In multivariate Cox regression analysis, pre-treatment lymphopenia (HR 1.59; 95% CI 1.25-2.03; p&amp;lt;0.001), early recurrent (&amp;lt;2 years) (HR 1.61; 1.27-2.04; p&amp;lt;0.001), visceral metastases (HR 1.48; 1.12-1.95; p=0.005), and TNBC subtype (HR 1.85; 1.37-2.49; p&amp;lt;0.001) were independent prognostic factors for OS2 in recurrent stage IV MBC. Conclusions: In this large-scaled and retrospectively analyzed a dataset, we showed highest incidence of pre-treatment lymphopenia in recurrent MBC, not affected by previous chemotherapy exposure. Pre-treatment lymphopenia was a significant poor prognostic factor in recurrent stage IV MBC, but not in EBC or de novo stage IV MBC. Citation Format: Jee Hung Kim, Min Hwan Kim, Gun Min Kim, Byeong-Woo Park, Young Up Cho, Seung Il Kim, Seho Park, Hyung Seok Park, Ji Ye Kim, Hyun Cheol Chung, Soonmyung Paik, Joohyuk Sohn. Comprehensive analysis of lymphopenia in large-scaled early and metastatic breast cancer database cohort [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 P3-08-43.

Treatment and outcomes in patients with central nervous system metastases from breast cancer in the real-life ESME MBC cohort

AimThe aims of the present study were to describe treatment patterns and survival outcomes in patients with central nervous system metastases (CNSM) selected among metastatic breast cancer (MBC) patients included in a retrospective study from the Epidemiological Strategy and Medical Economics (ESME) MBC cohort. MethodsNeurological progression-free survival (NPFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Significant contributors to NPFS were determined using a multivariate Cox proportional hazards model. ResultsAfter a median follow-up of 42.8 months, of 16 701 patients included in the ESME MBC database, CNSM were diagnosed in 24.6% of patients. The most frequent treatments after diagnosis of CNSM were whole-brain radiotherapy (WBRT) (45.2%) and systemic treatment (59.3%). Median OS and NPFS were 7.9 months (95% CI: 7.2–8.4) and 5.5 months (95% CI: 5.2–5.8), respectively. In multivariate analysis, age >70 years (vs <50 years; HR = 1.40; 95% CI: 1.24–1.57), triple-negative tumours (vs HER2-/HR+; HR = 1.87; 95% CI: 1.71–2.06), HER2+/HR-tumours (vs HER2-/HR+; HR = 1.14; 95% CI: 1.02–1.27), ≥3 metastatic sites (vs < 3; HR = 1.32; 95% CI: 1.21–1.43) and ≥3 previous treatment lines (vs < 3; HR = 1.75; 95% CI: 1.56–1.96) were detrimental for NPFS. A time interval between selection and CNSM diagnosis superior to 18 months (vs <9 months; HR = 0.88; 95% CI: 0.78–0.98) was associated with longer NPFS. ConclusionsThis study describes current treatment patterns of MBC patients in a “real life” setting. Despite advances in stereotactic radiation therapy, most of the patients still received WBRT. More research is warranted to identify patient subsets for tailored treatment strategies.