Survival In Metastatic Breast Cancer Research Articles

Racialized economic segregation and inequities in treatment initiation and survival among patients with metastatic breast cancer.

Racialized economic segregation, a form of structural racism, may drive persistent inequities among patients with breast cancer. We examined whether a composite area-level index of racialized economic segregation was associated with real-world treatment and survival in metastatic breast cancer (mBC). We conducted a retrospective cohort study among adult women with mBC using a US nationwide electronic health record-derived de-identified database (2011-2022). Population-weighted quintiles of the index of concentration at the extremes were estimated using census tract data. To identify inequities in time to treatment initiation (TTI) and overall survival (OS), we employed Kaplan-Meier methods and estimated hazard ratios (HR) adjusted for clinical factors. The cohort included 27,459 patients. Compared with patients from the most privileged areas, those from the least privileged areas were disproportionately Black (36.9% vs. 2.6%) or Latinx (13.2% vs. 2.6%) and increasingly diagnosed with de novo mBC (33.6% vs. 28.9%). Those from the least privileged areas had longer median TTI than those from the most privileged areas (38 vs 31days) and shorter median OS (29.7 vs 39.2months). Multivariable-adjusted HR indicated less timely treatment initiation (HR 0.87, 95% CI 0.83, 0.91, p < 0.01) and worse OS (HR 1.19, 95% CI 1.13, 1.25, p < 0.01) among those from the least privileged areas compared to the most privileged areas. Racialized economic segregation is a social determinant of health associated with treatment and survival inequities in mBC. Public investments directly addressing racialized economic segregation and other forms of structural racism are needed to reduce inequities in cancer care and outcomes.

Abstract PO5-06-03: Impact of curative-intent treatment on survival for metastatic breast cancer limited to distant lymph nodes

Abstract BACKGROUND: Metastatic breast cancer limited to distant lymph nodes is classified as stage IV but potentially represents an anatomically distinct entity amenable to curative treatment. Its optimal management is unclear, with existing studies limited by small sample sizes and short follow-up durations. We sought to investigate the impact of curative-intent treatment on breast cancer-specific survival (BCSS) and overall survival (OS) for patients with this diagnosis. METHODS: Three cohorts of patients diagnosed with breast cancer from 2010 to 2019 were identified from the Surveillance, Epidemiology, and End Results 17 registries database. The curative cohort consisted of patients with metastatic breast cancer involving only distant lymph nodes who received a combination of chemotherapy, surgery to the primary site, and radiotherapy (curative-intent treatment). The palliative cohort included patients who underwent chemotherapy but not curative-intent treatment. The N3c cohort was comprised of patients with ipsilateral supraclavicular lymph node metastases but no distant metastases who received curative-intent treatment. Weighting based on covariate balancing propensity scores was performed to balance age, sex, race, median household income, year of diagnosis, T stage, histology, pathological grade, and ER/PR/HER2 status between the cohorts. Weight-adjusted multivariable Cox regression models with the same covariates were then used to compare the BCSS and OS of the three cohorts. RESULTS: A total of 2,089 patients with a median follow-up of 37 months were eligible for analysis, of whom 577 (27.6%) were in the curative cohort, 905 (43.3%) were in the palliative cohort, and 607 (29.1%) were in the N3c cohort. After propensity score weighting, the maximal standardized mean difference for all covariates was less than 0.1. Five-year BCSS for patients in the weight-adjusted curative, palliative, and N3c cohorts were 63.0% (95% CI 58.1-68.3), 46.7% (42.4-51.4), and 66.4% (61.4-71.8), respectively; and five-year OS were 57.9% (53.0-63.2), 41.2% (37.2-45.7), and 62.2% (57.3-67.6), respectively. Compared to the palliative cohort, the curative cohort exhibited better BCSS (HR 0.47, 95% CI 0.38-0.57; P&amp;lt; 0.001) and OS (HR 0.48, 95% CI 0.40-0.58; P&amp;lt; 0.001). In contrast, the N3c cohort had similar BCSS (HR 0.93, 95% CI 0.73-1.17; P=0.53) and OS (HR 0.96, 95% CI 0.77-1.19; P=0.68) to the curative cohort. CONCLUSIONS: Patients treated curatively for metastatic breast cancer limited to distant lymph nodes had higher BCSS and OS than those receiving palliative chemotherapy and similar BCSS and OS to patients receiving curative-intent treatment for ipsilateral supraclavicular lymph node metastases. These results support the use of aggressive multimodal therapy for select stage IV breast cancer patients with only distant nodal metastases and, if confirmed, suggest that a substantial portion of such patients may be undertreated. Citation Format: Yang Xu. Impact of curative-intent treatment on survival for metastatic breast cancer limited to distant lymph nodes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-03.

Abstract 3707: Characterization of estrogen receptor expression on CTCs during CDK4/6i treatment in HR+/HER2- metastatic breast cancer: Results from the PACE phase II study

Abstract Background Circulating tumor cells (CTCs) are associated with worse survival in metastatic breast cancer (MBC). The PACE study (NCT03147287) enrolled patients (pts) with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) MBC after progression on CDK4/6 inhibitor (CDK4/6i) and endocrine therapy, and randomized pts to fulvestrant (ful) alone; ful with palbociclib; or ful, palbociclib, and avelumab [Mayer et al., SABCS 2022]. Pts with ≥5 CTCs appear to derive benefit from treatment combinations vs ful alone. In this feasibility analysis, we evaluated estrogen receptor (ER) expression on CTCs to further investigate their monitoring/predictive potential.Methods Blood samples were collected from pts enrolled in the PACE study at: baseline (T1), first tumor assessment (T2) and progression (T3). CTCs were enumerated using the CellSearch platform and samples were classified as CTChigh or CTClow (cutoff ≥5 CTCs). CTChigh samples underwent ER expression quantification with the ACCEPT software [Zeune et al. 2017]. ER expression intensity (ERint) was measured through the Marker Characterization function for each CTC; the average was calculated for each sample. Results From the 220 enrolled pts, a total of 409 samples (166, 153 and 90 collected at T1, T2, and T3, respectively) were analyzed for ER. Overall, 236 samples were CTClow (T1 = 91, T2 = 97, T3 = 48) and 173 were CTChigh (T1 =75, T2 =56, T3 =42). ER was quantified on 3928, 1853, and 2209 CTCs collected at T1, T2, and T3, respectively. Overall, 32.2% of CTCs were ER negative (ER-).The samples’ median ERint showed a numerical decrease from T1 to T3 (T1 = 7.27, T2 = 4.58, T3 = 1.31). Similarly, the % of ER positive (ER+) CTCs per sample decreased from baseline to progression: 26.3%, 14.0%, 5.5% at T1, T2, T3, respectively.CTChigh samples were then classified as ER+ or ER- (ER+ = mean ER_int &amp;gt;0). At T1, 91 (54.8%) samples were CTClow, 67 (40.4%) were CTChigh/ER+, and 8 (4.8%) were CTChigh/ER-. At progression, 48 (53.3%) samples were CTClow, 26 (28.9%) were CTChigh/ER+, and 16 (17.8%) samples were CTChigh/ER-. A numerical increase in the proportion of CTChigh/ER- samples was thus observed from baseline to progression (4.8 to 17.8%).Conclusions Herein we demonstrated the feasibility of evaluating and quantify ER expression on CTCs with a software-assisted approach to reduce inter-operator variability. In the PACE study, ER expression on CTCs was decreased at progression compared to baseline, possibly suggesting a mechanism associated with treatment resistance. Future analyses are needed to investigate the correlation between ER expression levels on CTCs with survival and treatment response. This, together with information about the mutational status of ESR1 by ctDNA sequencing, might provide a new perspective on the development of resistance to ful and CDK4/6i in HR+/HER2- MBC. Citation Format: Mara Serena Serafini, Carolina Reduzzi, Lorenzo Gerratana, Rinath Jeselsohn, Reshma L. Mahtani, Cynthia X. Ma, Angela DeMichele, Jane Lowe Meisel, Kathy D. Miller, Yara Abdou, Elizabeth C. Riley, Rubina Qamar, Priyanka Sharma, Sonya Reid, Harold J. Burstein, Sara M. Tolaney, Michelle K. DeMeo, Yuan Liu, Eric Gauthier, Yue Ren, Meredith M. Regan, Huiping Liu, Erica L. Mayer, Massimo Cristofanilli. Characterization of estrogen receptor expression on CTCs during CDK4/6i treatment in HR+/HER2- metastatic breast cancer: Results from the PACE phase II study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3707.

Effects of socioeconomic status and race on survival and treatment in metastatic breast cancer.

Race and socioeconomic factors affect outcomes in breast cancer. We aimed to assess the effect of race and neighborhood socioeconomic status (SES) on overall survival and treatment patterns in patients with metastatic breast cancer (MBC). This is a retrospective cohort study involving patients (N = 1246) with distant breast cancer metastases diagnosed at UPMC Magee Women's Breast Cancer Clinic from 2000-2017. Overall survival and treatment patterns were compared between races (Blacks and whites) and SES groups (defined using Area Deprivation Index). Low SES, but not tumor characteristics, was associated with Black race (P < 0.001) in the study population. Low SES (Median [Interquartile Range, IQR] survival 2.3[2.2-2.5] years vs high SES 2.7[2.5-3.1] years, P = 0.01) and Black race (Median [IQR] survival 1.8[1.3-2.3] years, vs white 2.5[2.3-2.7] years P = 0.008) separately were associated with worse overall survival in patients with MBC. In the Cox Proportional Hazard model with SES, race, age, subtype, number of metastases, visceral metastasis, and year of diagnosis as covariates, low SES (Hazard ratio 1.19[1.04-1.35], P = 0.01), but not Black race (Hazard ratio 1.19[0.96-1.49], P = 0.12), independently predicted overall survival in MBC. Moreover, patients from low SES neighborhoods and Black race received fewer lines of chemotherapy than high SES and whites. In conclusion, low neighborhood SES is associated with worse outcomes in patients with MBC. Poor outcomes in Black patients with MBC, at least in part is driven by socioeconomic factors. Future studies should delineate the interplay between neighborhood SES, race, and their effects on tumor biology in MBC.

Disparities with influenza vaccine use in long-term survivors of metastatic breast cancer.

Elderly women diagnosed with metastatic breast cancer (MBC) are living longer, however their primary care management may be sub-optimal. Influenza results in preventable hospitalizations and deaths. Guidelines recommend the influenza vaccine for those > 65 years and those with cancer but use is unknown. A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. Patients were included if they were diagnosed with MBC from 1/1/2008-12/31/2017 and were ≥ 65 years of age. The primary outcome was influenza vaccine use among patients surviving ≥ 3-years. We conducted multivariable analyses using demographic and clinical factors to identify associations with vaccine use. We compared utilization to cancer-free controls. We identified 1,970 patients with MBC that survived for ≥ 3 years. The median age at diagnosis was 73 years. Furthermore, 1,742 (88%) patients were White, and 153 (8%) patients were Black. Only 1,264 (64%) received an influenza vaccine at least one time and 51% received the vaccine at least two times. A multivariable model found lower odds of vaccine receipt for Black patients (OR = 0.48; 95%CI 0.34-0.68, p < 0.001) and higher odds for patients that saw primary care in the year prior to diagnosis (OR = 1.91, 95%CI 1.57-2.33, p < 0.001). Patients with MBC had lower odds of vaccine use compared to cancer free controls (OR = 0.85, 95%CI 0.74-0.97, p < 0.001). Over 1/3 of long-term MBC survivors in our cohort did not receive the influenza vaccine. Black patients are about half as likely to be vaccinated. Given the known benefit of the vaccine, improving uptake could be an important strategy to improve outcomes.

Patterns of treatment and outcomes of patients with brain-only metastatic breast cancer.

We characterized the risk factors and survival of metastatic breast cancer (MBC) patients with brain metastases (BrM) as the first and only site of disease in a large, retrospective cohort. MBC patients treated for BrM with radiation at a quaternary institution between 2005 and 2019 were identified. MBC patients with BrM but without concurrent extracranial metastases (ECM) or leptomeningeal disease (LMD) were classified as brain-only. Factors associated with brain-only MBC, brain-specific progression free survival (bsPFS) and overall survival (OS) were investigated. A total of 691 patients with MBC and BrM were analyzed. Among them, 67 patients (9.7%, n = 67/691) presented with brain-only MBC without concurrent ECM/LMD. Within this subgroup, 40 patients (5.8%, n = 40/691) remained free of any ECM or LMD, while 17 patients (2.5%) developed LMD, and 10 patients (1.4%%) developed ECM with a median follow-up of 8 months (IQR 2-35). Patients with brain-only MBCwere more likely to have a single BrM [OR 3.41 (1.62-7.19), p = 0.001] and either HER2+ [OR 3.3 (1.13-9.65), p = 0.03] or TNBC [OR 4.09 (1.42-11.74), p = 0.009] subtypes. Patients who presented with brain-only MBC also had significantly longer OS [HR 0.45, (0.22-0.86), p = 0.008] and a trend toward longer bsPFS [HR 0.67 (0.44-1.03), p = 0.05] compared to those with concurrent ECM/LMD. Patients with brain-only MBC had a longer bsPFS and OS than those with ECM. Patients with HER2+ and TNBC were more likely to have brain-only disease compared to those withHR+/HER2-MBC.

Three-Year Progression-Free Survival of Metastatic Breast Cancer Treated With the Palbociclib and Letrozole Combination.

Karam, Imad MD1; Nair, Hari MD2; Ghani, Sofia MD3; Khalid, Bilal MD3 Author Information

Real World Experience of Second-Line Treatment Strategies after Palbociclib and Letrozole: Overall Survival in Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

Background: We analyzed real-world practice of second-line treatment in hormone receptor (HR)+ human epidermal growth factor receptor-2 (HER2)− metastatic breast cancer (MBC) following the first-line CDK4/6 inhibitor with letrozole. In addition, we evaluated the relationship between second-line treatment strategies and survival outcome. Methods: Using the clinical data warehouse, clinical information including MBC diagnosis, treatment and survival outcomes were collected. Results: In total, 305 patients were treated with the first-line palbociclib plus letrozole, and we evaluated 166 patients who were treated with second-line treatment. Of the 166 patients, 28.5% were treated with capecitabine (C), followed by exemestane with everolimus (EE) (27.3%) or cytotoxic chemotherapy other than capecitabine (T) (18.8%) and fulvestrant-based treatment or endocrine monotherapy (F) (12.7%). Eighteen patients (10.9%) were enrolled in clinical trials (CT). With regard to treatment strategies, and the median progression-free survival of second-line treatment in a metastatic setting (PFS2) was 7.4 months with C, 5.2 months with EE, 4.8 months with T, 3.6 months with F, and 3.6 months with CT (p = 0.066). In patients with visceral organ disease progression, C (31.3%) or T(31.3%) was the most common second-line treatment followed by EE (21.9%). Most of the 47 patients with bone metastasis alone were treated with EE (38.2%), followed by C (23.4%) and F (21.3%) (p = 0.008). The median overall survival of second-line treatment in a metastatic setting (OS2) was 42.3 months with C, 35.7 months with F, 30.7 months with EE, and 23.1 months with T. The median OS2 for those in CT was not reached (p = 0.064). ER driven BC, disease progression site and PFS2 were associated with OS and OS2 in HR+HER2− MBC (ps &lt; 0.05). Conclusions: We suggested the second line treatment strategy was important to improve prognosis in patients with HR+/HER2− MBC, especially given the recent standardization of first-line treatment and the many available second-line options.

Incidence of interstitial lung disease and cardiotoxicity with trastuzumab-deruxtecan in patients with breast cancer: A systematic review and single-arm meta-analysis.

e13033 Background: The new antibody-drug conjugated directed to HER2, Trastuzumab-Deruxtecan (T-DXd), has shown the benefit of progression-free survival and overall survival in metastatic breast cancer (mBC) patients after progression to ≥1 HER2 targeted therapies. Interstitial lung disease (ILD) and cardiotoxicity are the most significant and concerning toxicities related to T-DXd. We performed a systematic review and meta-analysis to assess the incidence and severity of those adverse events (AE) in mBC patients treated with T-DXd. Methods: We comprehensively searched Pubmed, Cochrane, and Scopus databases for randomized clinical trials (RCT) and observational cohort studies, including mBC patients with HER2-low or -positive expression who have received at least one dose of T-DXd. The DESTINY-Breast02 study was also included after its presentation at the SABCS 2022. The statistical analysis was performed using R software, and the results are presented as pooled analysis in forest plots. Results: We included nine studies: three phase III RCTs, three phase II and two phase I non-RCTs, and one retrospective cohort comprising 1,443 patients with a mean follow-up of 14.9 months. The median age of our population ranged from 53 to 59 years. Most were non-Asian (40.5%) and presented with hormone-receptor positive mBC (66.8%). In a pooled analysis, the incidence of ILD was 13.0% (179 patients; 95%CI 11.0 to 13.0). Patients enrolled in phase III clinical trials had an ILD rate of 12.0%, while the observational cohort reported a numerically higher rate of 18.0%. Most ILD cases, 84.9% (152 patients), were mild (grade 1 or 2). Grade 3 or 4 AE were reported in 13 patients (7,3%), and grade 5 in 14 patients (7,8%). Decreased left ventricular ejection fraction (LVEF) was seen in 3.6% (95%CI 3.0 – 5.0%), and most patients were asymptomatic. Eleven patients developed prolonged QT interval, and four had left ventricular dysfunction and cardiac failure. Conclusions: Our meta-analysis reinforces the importance of close vigilance for pulmonary and cardiac toxicities in mBC patients on treatment with T-DXd. Early detection and management by a multidisciplinary team following the most recent guidelines may improve the patient outcomes. [Table: see text]

Association of tumor infiltrating lymphocyte quantity with survival in patients (pts) with metastatic breast cancer (MBC) receiving microtubule-targeting agents: Post hoc analysis CALGB 40502 (Alliance).

1010 Background: Stromal tumor infiltrating lymphocyte (sTIL) quantity is prognostic in primary breast cancer, yet MBC is characterized by lower sTILs. No study has definitively evaluated the association of sTIL quantity with survival outcome in the metastatic (met) setting without checkpoint blockade. CALGB (Alliance) 40502 was a randomized phase 3 trial of 799 MBC pts receiving first-line chemotherapy, comparing paclitaxel, nab-paclitaxel or ixabepilone with or without bevacizumab. We hypothesized that sTILs quantity is associated with outcome in MBC. Methods: 582 submitted hematoxylin and eosin slide images from 443 unique pts were evaluable for sTILs in accordance with International TILs Working Group methods. Analysis of sTILs was based on most recent available tissue, with 161/443 (36.3%) having recurrent/met tissue. Using prespecified thresholds of &lt;5% (low) vs ≥5% (high) for sTIL distribution in the met setting, associations between sTILs low/high or as a continuous variable were evaluated with baseline characteristics and outcome. The primary objective was to evaluate the association of sTILs with progression-free survival (PFS) and overall survival (OS), with chemotherapy arm as a covariate. Results: High sTILs were more frequent among pts with hormone receptor (HR)-negative disease (64% HRneg vs 34% HRpos, p&lt;0.001), with no significant association with treatment arm, age, menopausal status, race/ethnicity, or body mass index (BMI). Among all evaluable slides, mean sTILs were higher for primary tumors than met (mean 13.3% primary vs 8.4% met, p=3e-4). Among non-lymph node met sites, sTILs ranged from 1.3% (bone) to 9.5% (lung). Among 100 unique pts with paired primary and met slides, the primary had significantly greater mean sTILs (10.5% vs 7.7%, p=0.008). For the primary objective, Cox proportional hazard model of sTILs low vs high was significantly associated with worse PFS (HR 1.34; 95% CI 1.1-1.63, p=0.004) and OS (HR 1.32; 95% CI 1.07-1.63, p=0.009) when controlling for treatment arm. When controlling for both treatment arm and HR status, association of sTILs low vs high demonstrated similar trends but did not reach statistical significance for PFS (HR 1.2; 95% CI 0.97-1.47, p=0.09) or OS (HR 1.14; 95% CI 0.91-1.43, p=0.2). There was no significant interaction between sTILs and chemotherapy arm (all p-interaction &gt;0.05). Conclusions: Immune activation measured by sTILs is significantly lower in met tumors than primary breast cancer and varies by met site. In this trial, sTILs were associated with progression-free and overall survival in chemotherapy-treated MBC, with a trend toward independent value adjusted for other prognostic features. Clinical trial information: NCT00785291 .

Effect of eribulin on epithelial-mesenchymal transition plasticity in metastatic breast cancer: An exploratory, prospective study.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in cancer metastasis and treatment resistance, which worsens prognosis. In phase III trials, eribulin improved overall survival in metastatic breast cancer (MBC) patients. In preclinical studies, eribulin suppressed EMT. However, clinical data on the use of eribulin for MBC patients are limited. In this exploratory, prospective study, we examined the effect of eribulin on EMT in MBC patients. Twenty-two patients aged 44-82 years with recurrent breast cancer or MBC were treated with eribulin. Breast cancer tissue samples were obtained before treatment and on Day 15 ± 5 of the first cycle of eribulin treatment. EMT markers (E-cadherin, claudin-3, vimentin, and N-cadherin) were analyzed using western blotting. EMT changes were evaluated based on the ratio of epithelial to mesenchymal markers before and after treatment in individual tumors. E-cadherin/vimentin, claudin-3/vimentin, E-cadherin/N-cadherin, and claudin-3/N-cadherin ratios were significantly higher after treatment (p=.007, p=.005, p=.006, and p=.011, respectively). Based on E-cadherin/vimentin, 65.0% of tumors shifted to an epithelial phenotype, as compared to 66.7% based on claudin-3/vimentin, 84.6% based on E-cadherin/N-cadherin, and 71.4% based on claudin-3/N-cadherin ratios. Thus, our results showed that eribulin suppressed EMT in breast cancer tissues.

Abstract P4-01-34: Benefits Provided by Antibody Drug Conjugates in Overall Survival Outweighs those in Progression-free Survival for Metastatic Breast Cancer: A Class Effect

Abstract Background: In metastatic breast cancer (MBC), the benefits of progression-free survival (PFS) and overall survival (OS) is not always proportional. This dissociation is related to the multiple other treatment options such as chemotherapy after disease progression and these treatments would contribute to the long post-progression survival. A constant improvement of PFS that translates into OS has been reported in anti-HER2 antibody containing treatments. In the era of antibody drug conjugates (ADC), we aim to examine the relationship between the increments of PFS and OS in MBC. Methods: We have used “ metastatic breast cancer” and “antibody drug conjugate” to search for clinical trials that report both PFS and OS. Hazard ratios (HR) and median survival were analyzed. Increments in PFS (delta PFS) and increments in OS (delta OS) were compared between studies. Results: A total of 5 trials were identified and summarized in table 1. The target of ADC is HER2 (N=4) or Trop2 (N=1). In DESTINY-Breast 03 trial, the control arm is another ADC (T-DM1). The control arms in all the other 4 trials are chemotherapy. The HR of PFS ranged from 0.28 to 0.65 and the HR of OS ranged from 0.48 to 0.68. The HR of PFS is smaller than HR of OS in all of the 5 trials. The median OS was not reached in 1 of the trials (DB-03) and was thus removed from the analysis for delta PFS and delta OS. In the comparison of delta PFS, the increments of median PFS fell between 2.9 and 4.8 months. The increments of median OS were between 5.4 and 6.6 months. All the delta OS are larger than the delta PFS in the four trials.Conclusion: Regardless of the antibody drug targets, ADC provides consistent improvements in median OS that surpasses the improvements in median PFS in metastatic breast cancer. The mechanism warrants further investigation. Citation Format: I-Chun Chen, Ching-Hung Lin, Yen-Shen Lu. Benefits Provided by Antibody Drug Conjugates in Overall Survival Outweighs those in Progression-free Survival for Metastatic Breast Cancer: A Class Effect [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 P4-01-34.

Single progesterone receptor-positive phenotype has the similar clinicopathological features and outcome as triple-negative subtype in metastatic breast cancer.

The same clinicopathological features and prognosis have been reported between single progesterone receptor-positive (sPR-positive) and triple-negative phenotype in early-stage breast cancer, but such similarity has not been studied in metastatic breast cancer (MBC). Therefore, the purpose of this study was to estimate the difference between sPR-positive phenotype and other phenotypes in MBC. Patients with HER-2-negative MBC were selected from the Surveillance, Epidemiology and End Results database. Pearson's χ2 test was used to compare the difference of clinicopathologic factors between sPR-positive phenotype and other phenotypes. Univariate and multivariate analyses were performed to evaluate the effects of hormone receptor (HoR) phenotypes and other clinicopathologic factors on the cancer-specific survival (CSS) and overall survival (OS). Overall, 10877 patients including 7060 patients (64.9%) with double HoR-positive (dHoR-positive), 1533 patients (14.1%) with single estrogen receptor-positive (sER-positive), 126 patients (1.2%) with sPR-positive and 2158 patients (19.8%) with double HoR-negative (dHoR-negative) were analyzed. The patients with sPR-positive or dHoR-negative were more likely to be younger, higher grade and tumor stage, visceral and brain metastasis than ER-positive phenotypes (P<0.001). MBC with sPR-positive had the similar CSS (HR: 1.135, 95%CI: 0.909-1.417, P=2.623) and OS (HR: 1.141, 95%CI: 0.921-1.413, P=0.229) as dHoR-negative, but worse outcome than ER-positive phenotypes. Chemotherapy significantly improved the survival for MBC, especially for sPR-positive MBC (CSS, HR: 0.39, 95%CI: 0.213-0.714, P=0.002; OS, HR: 0.366, 95%CI: 0.203-0.662, P=0.001). Patients with sPR-positive and triple-negative have similar biological behavior and prognosis in MBC. Chemotherapy may be a preferred recommendation for MBC with sPR-positive.

Circulating Glypican-4 Is a Predictor of 24-Month Overall Survival in Metastatic Breast Cancer

Introduction: Endocrine treatment combined with CDK4/6 inhibitors is the preferred treatment strategy in patients presenting with ER-positive/HER2-negative breast cancer, but the clinical course remains highly variable among individual patients. There is an unmet need for prognostic or predictive biomarkers in this important group of patients. Recently, we have identified circulating glypican-4 (GPC4) as a new biomarker of inferior outcomes in patients with metastatic colorectal cancer. The impact of plasma GPC4 levels on the survival of breast cancer patients is unknown and has been addressed in the present study. Methods: Our study included 47 patients with ER-positive/HER2-negative metastatic breast cancer prior to treatment with CDK4/6 inhibitors combined with endocrine therapy. The endpoint was overall survival (OS) at 24 months. GPC4 levels were measured in plasma using an enzyme-linked immunosorbent assay. Results: Increased circulating GPC4 levels were significantly linked to advanced age, postmenopausal state, visceral metastases, and invasive lobular carcinoma. During the 2-year observational follow-up period, 25.5% of patients died. The area under the receiver operating characteristic curve (ROC-AUC) analysis revealed an AUC of 0.713 [0.555–0.871]; p = 0.029 for OS; and an optimal cutoff value of GPC4 for predicting OS of 4.77 ng/mL. No patient showing GPC4 values below this cutoff died during the observational period. Cox regression analysis showed a hazard ratio of 2.14 [95% confidence interval: 1.24–3.67]; p = 0.006 for one standard deviation change of plasma GPC4. Conclusions: Our study suggests circulating GPC4 as a significant predictor of poor survival in metastatic breast cancer patients.

The effect of concomitant use of proton pump inhibitors with CDK 4/6 inhibitors on survival in metastatic breast cancer

To evaluate the difference of progression free survival between the patients using concomitant proton pump inhibitors and non-users in the patients using CDK 4/6 inhibitors with HR + and HER2 negative mBC. We included 86 patients with HR + and HER 2 negative mBC treated with CDK 4/6 inhibitors in this study. Patients were divided into two categories according to their status of PPI use. The primary end points was progression free survival (PFS). We compared PPI users and non-users. Forty-five (52.3%) patients used a PPI concomitantly with a CDK 4/6 inhibitor, and 41 (47.7%) did not. The median duration of follow-up was 10.68 (1.94-27.56) months. Of the patients, 50 (58.1%) palbociclib and 36 (41.9%) received ribociclib. The median progression free survival (mPFS) was 10.9months (95% CI: 7.5-14.27) in the group with concomitant PPI use with a CDK 4/6 inhibitor, whereas the median progression free survival could not be reached in the group without concomitant PPI use (p = 0.04). In addition, concomitant PPI use with palbociclib was associated with a shorter PFS; there was no significant difference between the concomitant PPI users and non-users in terms of PFS in the patients using ribociclib. Palbociclib and ribociclib are weak base drugs so their bioavailability is pH-dependent. PPIs can affect their solubility and their concentration in the plasma. Therefore, we must avoid concomitant use of PPIs and CDK 4/6 inhibitors. If we need to use concomitant PPI and CDK 4/6 inhibitors, we should prefer ribociclib than palbociclib.

CD133 is an independent predictive and prognostic marker in metastatic breast cancer

CD133 is a transmembrane glycoprotein and is considered the most common cell surface marker to identify cancer stem cells in hematological and solid tumors, including breast cancer. To evaluate the impact of immunohistochemical expression of CD133 on response rate and survival in metastatic breast cancer, as well as to correlate it with various demographics and clinicopathological characteristics. One-hundred metastatic breast cancer patients were prospectively recruited at the Medical Oncology Department at South Egypt Cancer Institute during the period from January 2018 to January 2020. There was a statistically significant correlation between CD133 positive patients with various adverse clinicopathological parameters such as high grade (p= 0.013), higher tumor (p= 0.001), and nodal staging (p= 0.024) during a median follow-up time of 17 months. In addition, Cases with CD133 positive expression had a significantly lower survival time than those with negative expression (3-years OS 37.4% versus 85.5%, p= 0.024). Regarding the response rate, CD133 positive patients had a lower response rate than negative patients (50% versus 54%, p= 0.012). Positive CD133 is correlated with poor prognosis in metastatic breast cancer patients.

Long-term treatment patterns and survival in metastatic breast cancer by intrinsic subtypes – an observational cohort study in Sweden

BackgroundLongitudinal, real-world data on the management of metastatic breast cancer is increasingly relevant to understand breast cancer care in routine clinical practice. Yet such data are scarce, particularly beyond second- and third-line treatment strategies. This study, therefore, examined both the long-term treatment patterns and overall survival (OS) in a regional Swedish cohort of female patients with metastatic breast cancer stratified by subtype in routine clinical practice during a recent eight-year period and correlation to current treatment guidelines.MethodsConsecutive female patients with metastatic breast cancer clinically managed at Uppsala University Hospital, Uppsala, Sweden, during 2009–2016 and followed until the end of September, 2017 (n = 370) were included and, where possible, classified as having one of five, intrinsic subtypes: Luminal A; Luminal B; human epidermal growth factor receptor 2-positive (HER2+)/ estrogen receptor-positive (ER+); HER2+/estrogen receptor-negative (ER-); or triple negative breast cancer (TNBC). Treatment patterns and OS were estimated by subtype using time-to-event methods.ResultsA total of 352/370 patients with metastatic breast cancer (mean age 67.6 years) could be subtyped: 118 (34%) were Luminal A, 119 (34%) Luminal B, 31 (8%) HER2+/ER-, 38 (11%) HER2+/Luminal, and 46 (13%) TNBC. The median number of metastatic treatment lines was 3. Most patients were on active treatment during follow-up (80% of the observation period), except for patients with TNBC who were on treatment for 60% of the observation time. Overall, 67% of patients died whilst on treatment. Among all patients (n = 370), median OS was 32.5 months (95% CI = 28.2–35.7). The 5-year survival rate was highest for HER2+/Luminal (46%) patients, followed by Luminal B (29%), Luminal A (28%), HER2+/ER- (21%), and TNBC (7%). Increasing age and number of metastatic sites also predicted worse survival.ConclusionsMetastatic breast cancer patients in Sweden, irrespective of subtype, generally receive active treatment until time of death. Survival varies considerably across subtypes and is also associated with patient characteristics. Regardless of differences in treatment patterns for Luminal A and B patients, long-term OS was the same.

Unmet Employment Related Needs of Metastatic Breast Cancer Survivors: A Work System Analysis

Metastatic breast cancer (MBC) is incurable breast cancer (i.e., stage IV) affecting approximately 165,000 women in the US, some of whom will live for years with MBC. Survivors living with MBC frequently experience functional impairments and sickness relating to treatment and their disease progression. Unlike “curable” cancers, MBC survivors are likely to deal with ongoing and/or evolving impairments due to cancer and cancer treatment until end of life, which presents challenges to work and employment. Little is known about the work-related needs of MBC survivors and the factors that impact individual survivors’ decisions to stay-or-leave work. The objective of this study is to understand the work system barriers and facilitators facing MBC survivors who were working at the time of MBC diagnosis. We conducted a survey of MBC survivors as a part of a larger research project to explore the importance of work and work-related decisions in this population. We conducted a secondary, deductive content analysis of a free-text response survey question guided by the Work System model. We identified a total of 77 excerpts, grouped into 12 barriers and 5 facilitators from survey responses of 133 MBC survivors. The person work system element resulted in the most barriers and facilitators, with numerous barriers relating to a lack of information available for MBC survivors. We only identified one excerpt relating to the technology work system element. Given the rapidly growing capabilities of technologies, there is a missed opportunity to design technologies that can support MBC survivors. The increased use of dedicated personnel (e.g., social work, navigators or financial counselors) and the development of patient-facing health IT may better support the unique needs of MBC survivors.

252P Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) as intermediate endpoints for survival in metastatic breast cancer: A real-world experience

Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) are two endpoints of clinical interest in patients with metastatic breast cancer (MBC). Their validation as intermediate endpoints for overall survival (OS), in a real-world setting, remains not fully established. We conducted a retrospective cohort study using the nationwide US Electronic Health Record-derived de-identified Flatiron Health database. The study population included pts diagnosed with MBC from Jan 1, 2011 through Feb 30, 2021. Kendall tau correlation between each surrogate endpoint (rwPFS and TTNT) and OS was evaluated using the Hougaard copula model. Kendall’s tau (τ) was calculated in the full cohort, and within each subgroup of metastatic disease, based on their prognostic significance, as defined by the occurrence of bone metastases (mets) only (subgroup 1), non-hepatic visceral mets +/- bone mets (subgroup 2), liver mets +/- other visceral and/or bone mets (subgroup 3), and one or more brain mets +/- other types of metastasis (subgroup 4). This work was supported by the imCORE network. Overall, 9,733 patients with MBC were included. Median age was 63 years (IQR: 54-72). Regarding sites of metastatic disease, subgroup 2 was most highly represented (n=4,188; 43.0%), followed by subgroup 1 (n=2,601; 26.7%), subgroup 3 (n=2,306; 23.7%) and subgroup 4 (n=638; 6.6%). Median OS in the overall population was 32.4 mos (95%CI: 31.2-33.3). Median rwPFS was 11.5 mos (95%CI: 11.1-11.9), and median TTNT was 11.1 mos (95%CI: 10.7-11.5). In the full cohort, the correlation of rwPFS with OS was 0.54, while that of TTNT with OS was 0.47 (Table).Table: 252PMedian OS, rwPFS and TTNT and Kendall tau correlation of each pair of evaluated endpoints.Overall Population (n=9,733)Subgroup 1 (n=2,601)Subgroup 2 (n=4,188)Subgroup 3 (n=2,306)Subgroup 4 (n=638)Median OS, months (95%CI)32.4 (31.2-33.3)44.3 (42.2-46.9)32.7 (31.0-34.0)22.6 (21.3-24.4)16.6 (14.8-19.7)Median rwPFS, months (95%CI)11.5 (11.1-11.9)18.5 (16.9-19.4)11.9 (11.4-12.7)8.2 (7.7-8.9)5.9 (4.9-6.7)Median TTNT, months (95%CI)11.1 (10.7-11.5)16.2 (15.1-17.9)11.3 (10.6-12.0)8.7 (8.2-9.2)6.7 (5.7-7.6)rwPFS-OS Correlation: τ (95%CI)0.54 (0.53-0.56)0.47 (0.45-0.50)0.54 (0.52-0.56)0.57 (0.55-0.59)0.60 (0.56-0.64)TTNT-OS Correlation: τ (95%CI)0.47 (0.46-0.48)0.37 (0.34-0.40)0.45 (0.43-0.46)0.54 (0.52-0.56)0.58 (0.55-0.62) Open table in a new tab Real-world PFS (rwPFS) and TTNT may represent meaningful intermediate endpoints for OS in patients with MBC overall, and within different disease subgroups.

Beta 2-Adrenergic Receptor in Circulating Cancer-Associated Cells Predicts for Increases in Stromal Macrophages in Circulation and Patient Survival in Metastatic Breast Cancer.

The usage of beta blockers in breast cancer (BC) patients is implicated in the reduction in distant metastases, cancer recurrence, and cancer mortality. Studies suggest that the adrenergic pathway is directly involved in sympathetic-driven hematopoietic activation of pro-tumor microenvironmental proliferation and tumor cell trafficking into the circulation. Cancer-associated macrophage-like cells (CAMLs) are pro-tumor polynucleated monocytic cells of hematopoietic origin emanating from tumors which may aid in circulating tumor cell (CTC) dissemination into the circulation. We examined the linkage between Beta-2 adrenergic receptor (B2AR) signaling in CAMLs and CTCs by establishing expression profiles in a model BC cell line (MDA-MB-231). We compared the model to CAMLs and CTCs found in patents. Although internalization events were observed in patients, differences were found in the expression of B2AR between the tumor cell lines and the CAMLs found in patients. High B2AR expression on patients’ CAMLs was correlated with significantly more CAMLs in the circulation (p = 0.0093), but CTCs had no numerical relationship (p = 0.1565). High B2AR CAML expression was also significantly associated with a larger size of CAMLs (p = 0.0073), as well as being significantly associated with shorter progression-free survival (p = 0.0097) and overall survival (p = 0.0265). These data suggest that B2AR expression on CAMLs is closely related to the activation, intravasation, and growth of CAMLs in the circulation.