Survival In Metastatic Breast Cancer Research Articles

Abstract CT144: Development of GMI-1359, a novel agent targeting tumor-microenvironment cross-talk in bone metastatic cancer

Abstract Pre-clinical and clinical data suggest that the bone marrow (BM) environment provides breast cancer (BC) cells a protective haven against chemotherapeutic insult, endocrine therapies, and immune recognition. Novel agents that intercept cross-talk between BC cells and the host could therefore improve the depth of response to therapies and potentially increase overall survival in metastatic BC. We have previously shown that bone metastatic BC cells reside in perivascular niches expressing high levels of SDF-1α (CXCL12) and E-selectin, two molecules for which emerging data have demonstrated a significant role in metastatic BC progression. Our prior pre-clinical studies have shown that E-selectin inhibition specifically prevents circulating BC cells from homing to the BM, whereas CXCR4 blockade mobilizes micrometastases from the marrow into circulation, where they may be sensitized to chemotherapeutic cell kill. Given the normal role of these molecules in host immune responses, E-selectin/CXCR4 blockade has additional potential to impact the tumor immune microenvironment. GMI-1359 is a small molecule, glycomimetic compound with dual inhibitory activity against E-selectin and CXCR4. We hypothesize that GMI-1359 can block E-selectin and CXCR4 binding to E-selectin ligands and SDF-1, disrupting the protective effects of the bone microenvironment on tumor cells. A single-center, phase 1b, open-label, single and multiple ascending dose study (NCT04197999) is therefore evaluating GMI-1359 in patients with HR+ metastatic breast cancer with bony metastases who are stable or minimally progressive on endocrine therapy, with or without a CDK4/6 inhibitor. To date, 2 patients have been enrolled and received single monthly doses of 3.5, 5.0 and 7.0 mg/kg followed by 3 daily doses of 7 mg/kg. Both patients have completed treatment with no dose limiting toxicities observed. Coincident with GMI-1359 administration at all dose levels, we observed mobilization of CD34+ cells coupled with a reduction in elevated serum sE-selectin levels, demonstrating the dual functionality of the compound. Initial peripheral blood immunophenotype data on one patient revealed a redistribution of myeloid derived suppressor cells and a shift in macrophage polarization from M2 to M1. Notably, we observed similar immune alterations in ongoing preclinical studies in the E0771 syngeneic BC mouse model. We found that orthotopically-engrafted mice treated with single agent 1359 had a significant increase in the ratio of CD8/Tregulatory cells isolated from the primary tumor and BM. We also observed a decrease in primary tumor M-MDSCs and lung metastasis-associated macrophages. In summary, our preliminary clinical data suggest that GMI-1359 is well-tolerated and elicits on-target effects expected from disruption of the host microenvironment. Ongoing clinical and preclinical work will define the efficacy of this strategy to enhance responses to chemo and immune therapies. Citation Format: P. Kelly Marcom, Trevor T. Price, Andrew S. Murray, William E. Fogler, John L. Magnani, Helen Thackray, Eric Feldman, Dorothy Sipkins. Development of GMI-1359, a novel agent targeting tumor-microenvironment cross-talk in bone metastatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT144.

The impact of radiological assessment schedules on progression-free survival in metastatic breast cancer: A systemic review and meta-analysis.

1086 Background: The impact of the interval of radiological assessment on the magnitude of benefit observed in randomized trials (RCTs) in metastatic breast cancer is undefined. Methods: All RCTs investigating anti-neoplastic drugs for metastatic breast cancer published between 2006 and 2019 were identified. Intervals for restaging were categorized as short ( < 9 weeks) or long (≥9 weeks). Hazard ratios (HRs) and 95% confidence intervals for progression-free survival (PFS) and overall-survival (OS) were pooled in a meta-analysis and compared between trials employing short and long restaging intervals assessed as subgroup analyses. Analyses were repeated for pre-specified subgroups according to disease subtype, drug type, whether experimental therapy was added to or replaced standard treatment and whether HR for PFS was < 1 or ≥1. Results: Eighty-nine studies comprising 95 comparisons and 44,901 patients were included. The magnitude of PFS benefit was non-significantly larger in trials which employed short compared to long restaging intervals (HR 0.79 vs. 0.86, p = 0.15). Short restaging interval was associated with significantly higher magnitude of effect on PFS in pre-specified subgroups including non-first line studies (HR 0.78 vs. 0.92, p = 0.04), studies with drugs replacing standard treatment (HR 0.86 vs. 1.04, p = 0.02) and studies performed exclusively in human epidermal growth factor receptor 2 (HER2) positive disease (HR 0.72 vs. 0.90, p = 0.02). Restaging interval was not associated with OS for all included studies (HR 0.92 vs. 0.93, p = 0.66) or for any of the pre-specified subgroups. Conclusions: Shorter restaging intervals are associated with a higher magnitude of effect of PFS, but not OS. Awareness of the impact of the restaging interval on quantification of intermediate endpoints such as PFS is important for the design and interpretation of RCTs.

112P Women with short survival after diagnosis of metastatic breast cancer: A population-based registry study

Despite therapeutic advances overall survival of metastatic breast cancer (MBC) at the population level has seen little improvement during the past decades. Short survival following diagnosis due to the biology of the disease or delays in access to cancer care might be contributing factors, which we aimed to investigate with this retrospective cohort study. Women diagnosed with MBC between Jan 1st 2005 and Dec 31st 2016 were identified using the population-based Stockholm-Gotland breast cancer registry. Data regarding demographic and clinicopathologic characteristics, survival and treatment were extracted retrospectively from the registry and from patient charts. Patients succumbing within 90 days following diagnosis of MBC were identified and their characteristics were compared with patients with longer survival. Between 2005 and 2016, 3124 patients were diagnosed with MBC, of which 498 (16.1%) died within 90 days of diagnosis. Nearly half of them (n=233) did not receive any antitumoral treatment. Patients with short survival were older (73.4 years [26.5 – 97.6] vs. 65.9 years [21.8 – 99.5], p<0.001) and had more commonly estrogen receptor (ER)-negative breast cancer (32.7% vs. 18.2%, p<0.001). Although a temporal reduction in the percentage of patients dying within 90 days from diagnosis was noted, from 2005-2008 (19.5%) to 2009-2012 (14.2%) and 2013-2016 (15.6%), the difference was not significant (p for trend 0.067). In multivariable analysis higher age, negative ER status and short distant recurrence-free interval (DRFI) were independent predictors for short survival, whereas time period and de novo metastatic disease were not. Nearly one out of six patients with MBC survived less than three months after diagnosis. Short survival after MBC diagnosis was associated with older age and aggressive tumor biology (ER-negativity, short DRFI). These data demonstrate a different spectrum of MBC at the population level, and can potentially inform on individualized follow-up strategies and treatment algorithms.

The Quality of End-of-Life Care for Women Deceased From Metastatic Breast Cancer.

Metastatic breast cancer (MBC) carries unique disease burdens with potential for poor-quality end-of-life (EOL) care. It is the purpose of this article to explore the association of poor-quality EOL care indicators according to key tumor, demographic, social, and clinical factors. End-of-life quality indicators were based on Emanuel and Emanuel's good death model in conjunction with Earle et al (2003). A single-institution retrospective chart review of women deceased from MBC between November 2016 and November 2019 with double-verification chart review was completed. Data were analyzed with descriptive, correlative, and comparative statistics. Total sample was N = 167 women, with 14.4% (n = 24) Black and 85.6% (n = 143) White. Mean (SD) age was 55.3 (11.73) years. Overall, MBC survival was 3.12 years (SD, 3.31): White women, 41.2 months (3.4 years), and Black women, 19 months (1.6 years). A total of 64.1% (n = 107) experienced 1 or more indicators of poor-quality EOL care. Patients more likely to experience poor-quality EOL care were older (P = .03), estrogen negative (P = .08), human epidermal growth factor receptor 2 negative (P = .07), from more deprived neighborhoods (P = .02), married (P = .05), and with physical (P = .001) and mental (P = .002) comorbidities. Understanding sociodemographic and clinical factors associated with poor EOL MBC care may be useful for proactive patient navigation.

Prevalence, pattern, and probability for goals of care discussions among women diagnosed with metastatic breast cancer.

High quality advanced cancer care includes goals of care (GOC) discussions and should be tailored according to clinical diagnosis, patient characteristics, and in concordance with patient's goals. Metastatic breast cancer (MBC) and treatment has heterogeneity according to subtype which makes the timing of initiating and continuing GOC discussions challenging. With an ever-increasing array of therapy, women with advanced stage disease are unique survivors in that they receive relatively aggressive cancer care to not only palliative symptoms but extend survival time. It is the purpose of this paper to explore the prevalence, pattern, and likelihood of having a GOC discussion according to key tumor, demographic, social, and clinical factors. A single-institution retrospective chart review of women deceased from MBC between November 2016 and November 2019 with double verification chart review was completed. Data were analyzed with descriptive, correlative, and comparative statistics. Total sample was N=167 women, with 14.4% (n=24) Black and 85.6% (n=143) White. Mean age was 55.3 years (SD 11.73). Overall, MBC survival was 3.12 years (SD 3.31), White women 41.2 (3.4 years) months, and Black women 19 (1.6 years) months. A total of 87.4% (n=146) participated in one or more GOC discussions. GOC discussions were more likely among those who were referred to palliative care (p<0.001) and social work (p=0.035) services. Of the GOC discussions, only 29.3% were conducted by the primary oncologist. Black women were more likely to have GOC discussion near death. Advanced stage cancers are treated, at times relatively aggressively, to extend survival time instead of merely offering palliation. This new paradigm of survivorship requires thoughtful integration of GOC conversations. Describing the current status of GOC discussions among a cohort of women deceased from MBC highlights the patients most vulnerable to having a GOC discussion avoided or delayed. These identified vulnerabilities will indicate where targeted interventions can be implemented in the future.

Abstract PS13-17: Capecitabine maintaining treatment improves progression-free survival in metastatic breast cancer: A prospective observational study of 669 cases

Abstract Background: Metastatic breast cancer (MBC) has poor prognosis, and the 5 yr-OS is less than 20%. Maintaining treatment post the chemotherapy could improve the OS and the life quality. However, we lack clinical consensus for the maintaining treatment. In this study, we aim to investigate the treatment outcome of capecitabine maintaining treatment. Methods: The study recruited 669 consecutive MBC patients who received chemotherapy from January 2016 through August 2019. 256 patients received capecitabine maintaining treatment after chemotherapy, including 163 patients with maintaining treatment after the first-line chemotherapy and 67 patients with maintaining treatment after the second-line chemotherapy. 413 patients did not receive capecitabine maintaining treatment after capecitabine-based chemotherapy. Kaplan-Meier curves were plotted and COX proportional hazards models with candidate risk factor analyses stratified by chemotherapy lines and maintaining treatment were assessed the impact of each candidate on progression-free survival (PFS). Circulating tumor DNA (ctDNA) analysis was performed to screen genetic aberrations that might lead to maintaining treatment response. Results: Capecitabine maintaining treatment group showed a significant improvement in PFS compared with non-maintaining group [hazard ratio = 0.53 (95% confidence interval = 0.41-0.68); log-rank test p&amp;lt;0.0001]. The median PFS was 19.9 months (95% CI: 15.6, 22.6) and 10.4 months (95% CI: 8.5, 14.9) in capecitabine-maintaining group and non-maintaining group, respectively. The 1st line maintaining treatment could achieve an optimal PFS (median 21.3, 95% CI: 16.1, 36.3). The median PFS of 2nd and 3rd line were 17.2 months and 10.8 months, respectively. Compared to the 2nd and 3rd line therapy, the 1st line maintaining therapy could significantly improve PFS [hazard ratio = 0.66 (95% confidence interval = 0.45-0.96); log-rank test p=0.03]. In addition, compared to non-maintaining group, more maintaining group benefited from capecitabine-based chemotherapy (CR+PR+SD: 99% vs 56%, p&amp;lt;0.0001). Patients with hormone receptor (HR)-positive would be more benefited from capecitabine-based chemotherapy. ctDNA analysis showed that in maintaining group, PIK3CA helical domain mutation (33%) and TP53 mutation (42.9%) concentrated in patients with poor PFS. Conclusion: Capecitabine maintaining treatment significant improves PFS in MBC patients. Treatment at earlier lines would be more efficient. While HR-positive patients benefited more from capecitabine-based chemotherapy, PIK3CA helical domain mutation and TP53 mutation might be responsible for the poor response to capecitabine maintaining treatment. Citation Format: Quchang Ouyang, Zhe-Yu Hu, Xiaohong Yang, Liping Liu, Jing Li, Huawu Xiao, Jianxiang Gao, Jun Lu, Hui Wu, Ning Xie, Xuming Hu, Can Tian, Zhengrong Shui, Min Cao. Capecitabine maintaining treatment improves progression-free survival in metastatic breast cancer: A prospective observational study of 669 cases [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 PS13-17.

Abstract PS9-43: Impact of educational workshops on patient-provider communication among Spanish-speaking metastatic breast cancer survivors and their caregivers: Results from the frankly speaking about cancer: Cáncer de seno métastatico evidence-based educational workshops

Abstract Background: Latina metastatic breast cancer survivors, in particular those of low socioeconomic status, often receive unsatisfactory medical care and experience poor physician-patient communication and relationships.1 Patient education about metastatic breast cancer can improve communication between Latina survivors and caregivers and their health care team.2 This analysis explores participants’ experiences gained from Cancer Support Community’s national evidence-based educational program, Frankly Speaking about Cancer: Cáncer de seno metástatico (Metastatic Breast Cancer). Methods: Frankly Speaking about Cancer (FSAC): Metastatic Breast Cancer is a comprehensive psychosocial educational program that provides information about current treatments, side effect management, and social and emotional challenges of an advanced breast cancer diagnosis. FSAC: Metastatic Breast Cancer was originally created in English and was then translated into Spanish to make the program more accessible to Spanish-speaking metastatic breast cancer survivors and caregivers in the US. 75 participants from 22 workshops across the country between 2018 and 2020 completed program evaluation surveys in Spanish and provided self-reported data on factors including pre- and post-workshop knowledge and intentions for patient-provider communication. Descriptive analyses and pre-and post-workshop comparisons were conducted to assess workshop outcomes. Results: Most workshop participants were metastatic breast cancer patients/survivors (n=46); the remainder served in the caregiving capacity and included spouses/partners (n=19) and family members (n=10). The average age of participants was 61 years old (s.d.= 24.14 years). Among those with metastatic breast cancer, more than half (54%) received the diagnosis within the last two years; and only 29% reported being moderately to highly involved in their treatment decisions. 76% of respondents reported experiencing emotional distress due to their/their loved one’s cancer. Pre- and post-survey results show a significant gain in reported knowledge about metastatic breast cancer (χ²= 13.4, p &amp;lt;.05). Caregivers of Latina metastatic breast cancer survivors also demonstrated a significant gain from pre- to post-workshop in knowledge about metastatic breast cancer treatment options, confidence to participate in treatment decision-making with their health care team, and confidence in asking questions about side effects of metastatic breast cancer and its treatment. As a final point, 68% of cancer patients/survivors and 72% of caregivers reported that because of the workshops, they felt better prepared to emotionally cope with their metastatic breast cancer experience. Discussion: Our findings indicate that educational workshops in Spanish can play a role in enhancing Latina patients’ self-perceived knowledge about metastatic breast cancer and empowering patients and caregivers to become active participants in their treatment decisions. These results underscore the importance of providing culturally specific educational resources to support patients and caregivers in their interactions with their health care team and advance breast health equity among Latinas. Citation Format: Claire Saxton, Maria B. Gonzalo, Richa Ruwala, Kirstin Fearnley, Alyssa Jaisle. Impact of educational workshops on patient-provider communication among Spanish-speaking metastatic breast cancer survivors and their caregivers: Results from the frankly speaking about cancer: Cáncer de seno métastatico evidence-based educational workshops [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 PS9-43.

Abstract PS7-87: Incidence, treatment and survival of patients with brain metastases at initial metastatic breast cancer diagnosis: A real-world experience in national cancer center, China

Abstract Background: To characterize the incidence, treatment and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China. Methods: The China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 to 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively. Results: Brain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40 -4.04; p &amp;lt;0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02-3.51; p =0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52-6.87; p =0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p=0.09). Factors that independently decreased BM death risk were ECOG&amp;lt;2, brain metastases only and multidisciplinary treatment. Conclusion: HER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive or triple-negative diseases or with extensive extracranial metastases. First-line TKI and multidisciplinary treatment helped to extend survival. Citation Format: Yiqun Li, Qiao Li, Hongnan Mo, Xiuwen Guan, Shaoyan Lin, Zijing Wang, Yimeng Chen, Ye Zhang, Dainan Zhang, Shanshan Chen, Ruigang Cai, Jiayu Wang, Yang Luo, Ying Fan, Peng Yuan, Pin Zhang, Qing Li, Fei Ma, Binghe Xu. Incidence, treatment and survival of patients with brain metastases at initial metastatic breast cancer diagnosis: A real-world experience in national cancer center, China [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 PS7-87.

Using a Twitter Chat to Rapidly Identify Barriers and Policy Solutions for Metastatic Breast Cancer Care: Qualitative Study.

BackgroundReal-time, rapid assessment of barriers to care experienced by patients can be used to inform relevant health care legislation. In recent years, online communities have become a source of support for patients as well as a vehicle for discussion and collaboration among patients, clinicians, advocates, and researchers. The Breast Cancer Social Media (#BCSM) community has hosted weekly Twitter chats since 2011. Topics vary each week, and chats draw a diverse group of participants. Partnering with the #BCSM community, we used Twitter to gather data on barriers to care for patients with metastatic breast cancer and potential policy solutions. Metastatic breast cancer survival rates are low and in large part conditioned by time-sensitive access to care factors that might be improved through policy changes.ObjectiveThis study was part of an assessment of the barriers to care for metastatic breast cancer with the goal of offering policy solutions for the legislative session in California.MethodsWe provided 5 questions for a chat specific to metastatic breast cancer care barriers and potential policy solutions. These were discussed during the course of a #BCSM chat on November 18, 2019. We used Symplur (Symplur LLC) analytics to generate a transcript of tweets and a profile of participants. Responses to the questions are presented in this paper.ResultsThere were 288 tweets from 42 users, generating 2.1 million impressions during the 1-hour chat. Participants included 23 patient advocates (most of whom were patients themselves), 7 doctors, 6 researchers or academics, 3 health care providers (2 nurses, 1 clinical psychologist), and 2 advocacy organizations. Participants noted communication gaps between patient and provider especially as related to the need for individualized medication dosing to minimize side effects and maximize quality of life. Timeliness of insurance company response, for example, to authorize treatments, was also a concern. Chat participants noted that palliative care is not well integrated into metastatic breast cancer care and that insurance company denials of coverage for these services were common. Regarding financial challenges, chat participants mentioned unexpected copays, changes in insurance drug formularies that made it difficult to anticipate drug costs, and limits on the number of physical therapy visits covered by insurance. Last, on the topic of disability benefits, participants expressed frustration about how to access disability benefits. When prompted for input regarding what health system and policy changes are necessary, participants suggested a number of ideas, including expanding the availability of nurse navigation for metastatic breast cancer, developing and offering a guide for the range of treatment and support resources patients with metastatic breast cancer, and improving access to clinical trials.ConclusionsRapid assessments drawing from online community insights may be a critical source of data that can be used to ensure more responsive policy action to improve patient care.

Ventriculoperitoneal Shunt for CNS Metastasis in Breast Cancer: Clinical Outcomes Based on Intrinsic Subtype

BackgroundLeptomeningeal metastasis (LM) is associated with a grave prognosis in breast cancer (BC) and can be controlled with a ventriculoperitoneal shunt (VPS). Information regarding LM and VPS based on intrinsic subtype is limited; thus, we investigated the clinical outcomes of BC treated with VPS. Patients and MethodsThe present retrospective study comprised 70 patients diagnosed with LM who received a VPS. The patients were divided into 4 groups based on BC subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HR+/HER2+, HR−/HER2+, and triple negative BC (TNBC). ResultsThe most common indications for VPS were uncontrolled intracranial pressure (57.1%) and uncontrolled headache (55.7%), which improved in 54 (77.1%) of 70 patients after VPS. The median overall survival (OS) after brain or LM and overall survival after VPS were 7.6 and 2.3 months, respectively. Anti-HER2 treatment was a significant prognostic factor for better OS after brain or LM based on multivariate analysis (hazard ratio, 0.15; 95% confidence interval, 0.04-0.57; P = .005), whereas TNBC was correlated with shorter OS after central nervous system metastasis (hazard ratio, 2.82; 95% confidence interval, 1.46-5.48; P = .002). ConclusionsThere were significant differences in clinical outcome based on the intrinsic subtype of patients with BC with LM who received a VPS. Anti-HER2 treatment in patients with HER2+ BC was associated with better survival in patients with metastatic BC with VPS insertion compared with those without. Survival of metastatic BC with VPS remained poor, especially in the TNBC subgroup.

Incidence, risk factors and survival of patients with brain metastases at initial metastatic breast cancer diagnosis in China

PurposeTo characterize the incidence, risk factors and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China. MethodsThe China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 and 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively. ResultsBrain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR + HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40–4.04; p < 0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02–3.51; p = 0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52–6.87; p = 0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p = 0.09). Factors that independently decreased BM death risk were ECOG<2, brain metastases only and multidisciplinary treatment. ConclusionHER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive disease at MBC diagnosis, and further prospective randomized study is warranted.

Rising Circulating Tumor DNA As a Molecular Biomarker of Early Disease Progression in Metastatic Breast Cancer

Accurate monitoring of therapeutic response remains an important unmet need for patients with metastatic breast cancer (MBC). Analysis of tumor genomics obtained via circulating tumor DNA (ctDNA) can provide a comprehensive overview of tumor evolution. Here, we evaluated ctDNA change as an early prognostic biomarker of subsequent radiologic progression and survival in MBC. Paired blood samples from patients with MBC were analyzed for levels of ctDNA, carcinoembryonic antigen, and cancer antigen 15-3 at baseline and during treatment. A Clinical Laboratory Improvement Amendments-certified sequencing panel of 73 genes was used to quantify tumor-specific point mutations in ctDNA. Multivariable logistic regression analysis was conducted to evaluate the association between ctDNA rise from baseline to during-treatment (genomic progression) and subsequent radiologic progression and progression-free survival (PFS). Somatic mutations were detected in 76 baseline samples (90.5%) and 71 during-treatment samples (84.5%). Patients with genomic progression were more than twice as likely to have subsequent radiologic progression (odds ratio, 2.04; 95% CI, 1.74 to 2.41; P < .0001), with a mean lead time of 5.8 weeks. Genomic assessment provided a high positive predictive value of 81.8% and a negative predictive value of 89.7%. The subset of patients with genomic progression also had shorter PFS (median, 4.2 v 8.3 months; hazard ratio, 2.97; 95% CI, 1.75 to 5.04; log-rank P < .0001) compared with those without genomic progression. Genomic progression, as assessed by early rise in ctDNA, is an independent biomarker of disease progression before overt radiologic or clinical progression becomes evident in patients with MBC.

MYC Targets Scores Are Associated with Cancer Aggressiveness and Poor Survival in ER-Positive Primary and Metastatic Breast Cancer.

MYC is one of the most studied oncogenes that is known to promote cell proliferation. We utilized MYC targets v1 and MYC targets v2 scores of gene set variation analysis and hypothesized that these scores correlate with tumor aggressiveness and survival outcomes. We examined a total of 3109 breast cancer patients from TCGA, METABRIC, and GSE124647 cohorts. In each cohort, the patients were divided into high- and low-score groups using the upper third value as the cut off. As expected, higher scores were related to increased cell proliferation and worse clinical and pathologic features. High MYC targets scores were associated with worse survival, specifically in primary ER-positive breast cancer, consistently in both TCGA and METABRIC cohorts. In ER-positive breast cancer, high MYC targets v1, but not v2 score, was associated with high mutation load, and high MYC targets v1 and v2 scores were both associated with increased infiltration of pro- and anti-cancerous immune cells. We found that high MYC scores were associated with worse survival in metastatic breast cancer. Our findings show that the MYC targets v1 and v2 scores are associated with tumor aggressiveness and poor prognosis in ER-positive primary tumors, as well as in metastatic breast cancer.

Prognostic factors in metastatic breast cancer: a prospective single-centre cohort study in a Finnish University Hospital

ObjectivesAlthough novel early breast cancer prognostic factors are being continuously discovered, only rare factors predicting survival in metastatic breast cancer have been validated. The prognostic role of early breast cancer...

Clinical Correlations of Programmed Cell Death Ligand 1 Status in Liquid and Standard Biopsies in Breast Cancer.

Data regarding the prognostic value of programmed cell death ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) are lacking. However, CTCs could represent an alternative approach to serial biopsies, allowing real-time monitoring of cancer phenotype. We evaluated, in a dedicated prospective clinical trial, the clinicopathological correlations and prognostic value of PD-L1(+)-CTCs in 72 patients with metastatic breast cancer (MBC). Eighteen of 56 patients with available archival tissue presented at least one positive (≥1%) PD-L1 tumor sample. Baseline CTCs and PD-L1(+)-CTCs were detected in 57 (79.2%) and 26 (36.1%) patients. No significant correlation was found between PD-L1 tumors and CTC expression. In univariate analysis, triple negative (TN) phenotype, number of metastatic treatments, >2 metastatic sites, ≥5 CTCs and PD-L1(+)-CTCs were significantly associated with progression-free survival, while tissue PD-L1 expression was not. In multivariate analysis, TN phenotype, number of metastatic treatments and of metastatic sites were the only 3 variables independently associated with progression-free survival. Progesterone receptor negativity, TN phenotype, >2 metastatic sites and ≥5 CTCs were significantly associated with overall survival in univariate analysis. In multivariable analysis, TN phenotype and >2 metastatic sites were the only 2 independent variables. Unlike PD-L1(+)-tumor, PD-L1(+)-CTCs correlate to survival in MBC. Reappraisal of the role of PD-L1 expression by tumor tissue and by CTCs under anti-PD-1/PD-L1 treatment is necessary to evaluate its predictive value and potential role as a stratifying factor in strategies and trials for MBC patients with MBC. NCT02866149.

Carcinomatosis peritoneal secundaria a cáncer de mama ductal infiltrante sincrónico a adenocarcinoma de sigma. Revisión bibliográfica a propósito de un caso tratado en nuestro hospital

AimWe provide a literature review of the diagnosis, treatment and survival of metastatic breast cancer with peritoneal carcinomatosis. Patients and methodsWe present a case treated in our institution and discuss relevant clinical, diagnostic, and therapeutic features. ConclusionExtra-hepatic gastrointestinal metastasis from breast cancer is infrequent (8%-10%). The incidence of peritoneal carcinomatosis is low, with few cases reported in the literature, mostly from invasive lobular carcinoma. Our case of invasive ductal carcinoma is even less frequent.

Analysis of the StoRM cohort reveals physical activity to be associated with survival in metastatic breast cancer

Benefits of physical activity are widely demonstrated for early stage cancers but few studies have focused on metastatic disease. The purpose of this study was to determine the impact of physical activity on survival in patients with metastatic breast cancer. We conducted a secondary analysis of the national, multicentric, non-randomized, prospective cohort SNPs to Risk of Metastasis (StoRM) study. The level of physical activity was self-reported at inclusion and divided into three categories of physical activity: light level, moderate level, and vigorous level. Overall, 833 patients (56.2%) completed the physical activity questionnaire at baseline on average physical activity during the previous year: 11.6% had a light level of physical activity, 69.0% achieved moderate levels of physical activity and 19.3% reported vigorous levels of physical activity. After adjustment for confounding, physical activity was not statistically significantly associated with overall survival in the whole population. Subgroup analysis identified that both vigorous and moderate physical activity were associated with statistically significantly improved overall survival compared to light physical activity level only in the HER2 positive subgroup (HR 0.23; 95% CI 0.07–0.70, p = 0.01 and HR 0.38; 95% CI 0.15–0.96, p = 0.04). Physical activity done during the previous year was associated with survival in HER2 positive metastatic breast cancer patients. These results suggest that overall survival in metastatic breast cancer patients could be improved through physical activity which should be considered as a complementary intervention for these individuals. The study showed that moderate/vigorous levels of physical activity were associated with better overall survival, and that these associations remained statistically significant in multivariate analysis in the HER2 positive subgroup. These results have clinical relevance and justify the recommendations for physical activity interventions in metastatic breast cancer.

Systemic therapy for patients with breast cancer and one to three brain metastases (BM).

1090 Background: Despite advances in systemic therapies and improved overall survival of metastatic breast cancer (MBC) patients, the development of brain metastases (BMs) remains a challenging complication that affects quality of life and increases morbidity and mortality. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable systemic disease. Methods: We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) after diagnosis of the initial 1-3 BMs on the patient’s progression-free survival time (PFS), defined as time to death, to a second BMs or to extracranial metastases. All MBC patients with 1 to 3 BMs only (without extracranial disease) treated at our institution between 2002 and 2017 were identified. For each patient, full information on follow-up and administered therapies were mandatory for inclusion. Hazard ratios (HR) were calculated using the Cox proportional hazard model. We also computed the restricted mean survival time (RMST) up to 5 years of follow-up. Results: Among the 2645 patient with BM treated at our institution, 80 were included for analysis. In regards to primary BMs management in patients, 46 of 80 (57%) were treated by radiation therapy, 6 of 80 (7.5%) underwent surgical resection, and 28 of 80 (35%) were managed by a combination of surgery and radiation therapy. All patients had staging imaging documenting lack of extracranial metastases at the time of local therapy of BMs. Following the primary management of BM, we observed that providers changed systemic therapy in 32 of 80 (40%), defined as the CST group. CST included both initiation of therapy in 16 of 80 (20%) and switching of adjuvant therapy in 16 of 80 (20%). Median PFS among CST was 7.7 months vs. 7.2 months among no CST (HR = 0.855, 95% confidence interval (CI) 0.53-1.38, p = 0.52). 5-year RMST for the CST group was 16.6 months vs. 12.8 months in no CST group. The difference of 3.8 months (95% CI 4.3-11.8) was not statistically significant. Conclusions: Patients with 1-3 BMs without extracranial disease had a median PFS close to 7.5 months after local therapy. Consistent with current standard of care of maintaining the same systemic therapy approach upon developing isolated BMs, our findings did not demonstrate a significant difference in PFS between patients who experienced a change in systemic therapy compared to those who did not.

Improved survival in metastatic breast cancer: results from a 20-year study involving 1033 women treated at a single comprehensive cancer center

PurposeDiagnosis and treatment of breast cancer have changed profoundly over the past 25 years. The outcome improved dramatically and was well quantified for early stage breast cancer (EBC). However, progress in the treatment of metastatic disease has been less convincingly demonstrated. We have studied survival data of patients with metastatic breast cancer (MBC) from a large academic cancer center over a period of 20 years.MethodsData from 1033 consecutive MBC patients who were treated at the Department of Medical Oncology of the West German Cancer Center from January 1990 to December 2009 were retrospectively analyzed for overall survival (OS) and risk factors. Patients were grouped in 5-year cohorts, and survival parameters of each cohort were compared before and after adjustment for risk factors.ResultsOverall survival of patients with MBC treated at specialized center has significantly improved from 1990 to 2010 (hazard ratio 0.7, 95%CI 0.58–0.84). The increments in OS have become less profound over time (median OS 1990–1994: 24.2 months, 1995–1999: 29.6 months, 2000–2004: 36.5 months, 2005–2009: 37.8 months).ConclusionSurvival of patients with MBC has improved between 1990 and 2004, but less from 2005 to 2009. Either this suggests an unnoticed shift in the patient population, or a lesser impact of therapeutic innovations introduced in the most recent period.

Abstract P2-13-12: Predictors of social function and feelings of isolation among metastatic breast cancer survivors

Abstract Introduction: Living with cancer can present physical and emotional challenges. The symptoms and side effects of breast cancer and its treatment can be intensive and long lasting and may interfere with spending time with family, friends, and community. The aims of the present analysis were to 1) describe social functioning and isolation among metastatic breast cancer (MBC) survivors who received chemotherapy, and 2) identify factors related to poorer social functioning and greater concern about feeling isolated among survivors. Methods: 273 female MBC survivors from the Cancer Support Community’s Cancer Experience Registry® reported a history of chemotherapy, completed the PROMIS-29v2.0 health-related quality of life survey, and rated their level of concern (0=not at all; 4 = very serious) about key areas of life, including social isolation (CancerSupportSource®). We used multiple regression analysis to identify significant correlates of 1) social functioning (T-scores for PROMIS Ability to Participate in Social Roles and Activities scale), and 2) level of concern about “feeling lonely or isolated.” Independent variables included socio-demographic factors (age, employment, income, and race), clinical history (time since diagnosis, time between initial and metastatic diagnoses), treatment history (currently receiving chemotherapy or radiation; method of chemotherapy administration ever received), and physical symptom burden (daily interference from peripheral neuropathy (PN) and fatigue). Results: Participants were 86% White, 9% Black; mean age 53.4 (SD=11.2) years. Time between initial cancer diagnosis and metastatic diagnoses averaged 3.3 (SD=5.2; range 0-27) years. 56% were currently receiving chemotherapy; 24% radiation. 60% ever received both IV and oral chemotherapy, 30% IV only, 9% oral only. Scores for the 4-item PROMIS social functioning scale were significantly (p&amp;lt;.001) worse for MBC patients and survivors than the national average of T=50 for the U.S. population (95% CI=44.5-46.9, n = 246). When considering individual responses, 23.6% of MBC respondents reported substantially worse social functioning (&amp;gt;1SD) than the national average. 32.4% of MBC participants were moderately to very seriously concerned about feelings of social isolation. About two in three reported they have trouble doing want they want to do (% sometimes, often, or always) regarding their usual work (70%), activities with friends (67%), family activities (64%), and regular leisure activities with others (63%). In multivariate regression analysis, predictors of poorer social functioning (R2 = .564, p&amp;lt; .001, n = 134) included currently receiving chemotherapy (semipartial r = -.19, p &amp;lt; .01), greater PN interference (semipartial r = -.22, p &amp;lt; .001), and greater fatigue interference (semipartial r = -.49, p &amp;lt; .001). Predictors of concern about feeling lonely or isolated (R2 = .35, p&amp;lt; .001, n = 143) included greater PN interference (semipartial r = .16, p &amp;lt; .05) and fatigue interference (semipartial r = .37, p &amp;lt; .001). Significant associations with social functioning and concern about feeling isolated in bivariate analysis but not multivariate included lower income, unemployment, less time since diagnosis, and shorter interval between initial and metastatic diagnoses. Conclusion: Symptom burden, including peripheral neuropathy and fatigue, are associated with poorer social functioning and increased isolation among metastatic breast cancer survivors. Currently undergoing chemotherapy treatment is also associated with poorer social function, even after accounting for the contributions of symptom burden. Our results highlight the significant social impact of living with metastatic breast cancer and the value of tailored supportive care to address survivors’ unmet physical and socioemotional needs. Citation Format: Alexandra K Zaleta, Melissa F Miller, Shauna McManus, Kelly Clark, M. Claire Saxton. Predictors of social function and feelings of isolation among metastatic breast cancer survivors [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 P2-13-12.