A retrospective study of characteristics and survival in patients with breast cancer brain metastases classified by subtype using NCI SEER registry.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1031-1031
Author(s):  
Monika Devanaboyina ◽  
Morgan Marie Bailey ◽  
Danae M. Hamouda
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
De Novo ◽  
The United States ◽  
Breast Cancer Patients ◽  
Chi Square ◽  
Patients Âgés ◽  
Improve Patient Survival ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis

1031 Background: Breast cancer brain metastasis (BCBM) de novo is associated with the worst prognosis among all types of metastases in breast cancer (BC). Analysis of factors associated with BCBM stratified by subtype of BC could lead to earlier identification of metastasis. Methods: 1,268 patients with BCBM at the time of BC diagnosis and known clinical subtype (580 HR+/HER2-, 225 HR+/HER2+, 176 HR-/HER2+, and 287 HR-/HER2-) who were ≥ 20 years of age from 2010 to 2017 were identified using the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program 18 registry. Baseline characteristics and survival were analyzed using Chi-Square and Kaplan-Meier methods. Results: Patients with HR-/HER2+ BC were the most likely to present with BCBM, compared to all BC patients (prevalence of 13.9% vs. 4.7%; p<0.001). Further analysis demonstrated that HER2+ patients had an odds ratio of presenting with BCBM of 2.52 (95% CI: 2.24-2.84) compared to HER2- patients. Interestingly, in patients ages 20-39 with HR-/HER2+ BC, higher rates of brain metastases are noted within the BCBM group compared to all HR-/HER2+ breast cancer cases (28% vs. 7.6%; p<0.001). The same trend is seen within the HR-/HER2+ African American population, with those in the BCBM group experiencing higher rates of brain metastases compared to all BC cases with the same subtype (14.3% vs. 5.9%; p<0.001). Upon exploring insurance demographics, uninsured patients with HR-/HER2+ BCBM had much higher rates of brain metastases compared to all HR-/HER2+ BC cases (14.8% vs 6.4%; p=0.001). When examining TNM status, significant associations were noted between brain metastases and increased tumor and nodal status. Patients with T4 or N3 status with HR-/HER2+ BCBM exhibited much higher rates of metastasis compared to all BC cases with the same subtype (p<0.001). Analysis of survival outcomes showed a median overall survival of 12 months for patients with HR-/HER2+ BCBM. The results displayed in the table below show that HR-/HER2- BCBM patients had the lowest 5-year percent survival, while HR+/HER2+ BCBM patients had the highest 5-year survival. Conclusions: This SEER database study provides insight into the demographics, clinical variables, and outcomes for BC clinical subtypes, specifically HR-/HER2+, from 2010 to 2017 in the United States. HR-/HER2+ breast cancer patients within the noted high-risk populations should be made aware of the increased rates of brain metastases compared to the general BC population, as earlier identification of brain metastases within the HR-/HER2+ cohort could improve patient survival.[Table: see text]

EXTH-02. AAV MEDIATED BRAIN DELIVERY OF AN ADCC-ENHANCED ANTIBODY OBVIATES XENOGRAFT GROWTH IN MOUSE MODELS OF HER2+ BREAST CANCER BRAIN METASTASIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi163-vi163
Author(s):  
Dan Laks ◽  
Kenny Chen ◽  
Xiaoqin Ren ◽  
Ishan Shah ◽  
Usman Hameedi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Tumor Growth ◽  
Cancer Patients ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Aav Vector ◽  
Orthotopic Xenograft ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis

Abstract BACKGROUND HER2+ tumors constitute approximately 20% of breast cancer patients and are characterized by overexpression of the growth factor receptor HER2 (ERBB2), a cell proliferation driver. Effective anti-HER2 therapies confer prolonged patient survival necessitating the need for transformative treatments targeting brain metastases, a major cause of mortality in ~30-50% of HER2+ metastatic breast cancer patients. HER2-directed antibody immunotherapy, while efficacious for peripheral disease, has limited central nervous system exposure (CNS). To overcome these challenges, we transduced CNS cells with a novel AAV vector carrying an anti-HER2 antibody payload. METHODS We assessed the biochemical equivalence and functional effectiveness of AAV vector-encoded antibodies using in vitro assays. After selecting promising vector-encoded antibody candidates, a novel, blood-brain barrier penetrant AAV capsid was administered via i.v. dosing to an orthotopic xenograft mouse model of HER2+ brain metastases. Bioluminescent imaging provided a longitudinal measure of brain tumor burden. At study termination, we measured antibody biodistribution in cerebrospinal fluid (CSF), serum, and brain homogenates with AlphaLISA assays. RESULTS Using HER2+ breast cancer cell lines, we determined that an antibody-dependent cell cytotoxicity (ADCC) enhanced anti-HER2 antibody was most effective and demonstrated that AAV-vector encoded forms of the antibody performed comparably to recombinant reference antibodies. Following i.v. administration of a HER2 antibody encoding AAV vector, we measured &gt;1 ug/mL of the antibody in CSF. Importantly, AAV-mediated expression of the ADCC-enhanced HER2-directed antibody significantly abrogated tumor growth in orthotopic xenograft models. CONCLUSIONS Peripheral administration of an AAV vector was able to transduce brain tissue such that efficacious levels of HER2-directed antibodies were produced. This strategy was successful at preventing tumor growth in our physiologically relevant model of breast cancer brain metastases. Such a treatment modality should be further evaluated in patient derived PDX models to validate translational efficacy for human patients.

Survival by HER2 receptor status in stage IV breast cancer: SEER 2010-2012.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1032-1032 ◽  
Author(s):  
Alexandra Thomas ◽  
Seema Ahsan Khan ◽  
Charles Lynch ◽  
Mary Chen Schroeder
Keyword(s):  
Breast Cancer ◽  
De Novo ◽  
Reference Group ◽  
Cox Model ◽  
Stage Iv ◽  
The United States ◽  
Her2 Status ◽  
Her2 Receptor ◽  
Her2 Breast Cancer ◽  
Stage Iv Breast Cancer

1032 Background: Therapeutic advances have altered the course of once highly lethal HER2+ breast cancer (BC). We report survival in a recent population-based cohort by HER2 status, overall, and within hormone receptor(HR)+ BC. Methods: Surveillance, Epidemiology, and End Results Program data were queried to identify women diagnosed 2010-2012 with Stage IV BC as first cancer. Patients were grouped by HER2 and HR status. Kaplan Meier estimates of 3-yr observed survival (OS) were compared with log-rank tests. A multivariate cox model was fitted for the HER2+ cohort. Results: 3-yr OS for HER2+(any HR), HR+/HER- and triple-negative (TN) BC was 52.3%, 48.4% and 16.0% respectively (p<0.01 HER2+(any HR) vs TNBC; p=0.20 HER2+(any HR) vs HR+/HER2-). Across registries, OS for HER2+(any HR) BC ranged from 29.2% to 61.7% (p=0.05). On Cox model, survival in HER2+(any HR) BC was associated with age 50+ (Hazard ratio (HR) 1.84, 95% CI 1.45-2.34), HR+ status (HR 0.70, 0.58-0.84), high histologic grade (HR 1.30, 0.58-0.84), surgery (HR 0.40, 0.33-0.49), separated marital status (HR 1.72, 1.4-2.13), year 2012 (HR 0.81, 0.64-1.04), and registry (varies by reference group). For HR+ BC, OS also differed by HER2 status: 55.3% for HR+/HER+ and 48.4% for HR+/HER2- (p<0.01). 3-yr OS by HER2 status for women presenting with HR+ BC is shown (Table). Conclusions: Survival in de novo Stage IV HER2+ BC in the United States exceeds that in HER2- BC, with median survival >3 yrs. Survival was significantly better for HR+/HER+ BC than HR+/HER- BC. Disparate OS in HER2+ BC suggest opportunities may remain to fully realize advances in HER2-directed therapy. Given recent therapeutic advances, the trend of HER2+ survival gains from 2010 to 2012 will likely continue. [Table: see text]

Effect of type and timing of systemic therapy on risk of radiation necrosis in patients with HER2+ breast cancer brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14002-e14002
Author(s):  
Christine Park ◽  
Evan Buckley ◽  
Amanda E.D. Van Swearingen ◽  
Will Giles ◽  
James Emmett Herndon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Radiation Necrosis ◽  
Treatment Modalities ◽  
Conformity Index ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis ◽  
The Impact ◽  
Systemic Therapies

e14002 Background: It is estimated that 30% of patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer will develop brain metastases. Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) includes radiation therapy (stereotactic radiosurgery [SRS] or whole brain radiation), brain permeable systemic therapies, and in select cases, neurosurgical resection. A multimodal approach combining these different treatment modalities has improved the overall survival and functional outcomes of patients with BCBrM. Some HER2-directed systemic therapies, however, may increase the risk of radiation necrosis (RN), a longer-term consequence of SRS. This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM. Methods: This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 at Duke University with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters (total dose, fractions, clinical target volume [CTV], gross tumor volume [GTV], conformity index [CI], volume receiving 12 gray [V12Gy]), and timing (during [within 4 weeks of SRS] vs. not during SRS) and type of systemic therapy (HER2-directed therapy, mitosis inhibitors, DNA synthesis inhibitors, others) were evaluated. Results: Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age at time of SRS did not differ between those who developed RN and those who did not (mean 53.3 vs 50.4 years, respectively). There was a higher percentage of African Americans in the RN group (28.6% vs 11.1%, p = 0.3). There were no significant differences between the measured radiotherapy parameters—including dose, fraction, CTV, GTV, CI, V12Gy—between the two groups (all p > 0.05). Receipt of any type of systemic therapy during SRS did not differ between patients who did or did not develop RN (60.7% vs 55.6%, p = 0.97). However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during SRS compared to those did not develop RN (35.7% vs 5.6%, p<0.05). Conclusions: Patients with HER2 BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. This data supports a practice of holding HER2-directed therapy during SRS if medically acceptable. Further investigation of next generation HER2-directed therapies in a larger cohort of patients should be investigated to help guide best practice to minimize RN.

scholarly journals Systemic treatment of HER2-positive breast cancer patients with brain metastases: current status and exploratory case study in a Portuguese cohort

2021 ◽  
Vol 18 (1) ◽  
pp. 1-14
Author(s):  
Paulo Luz ◽  
Elsa Campoa ◽  
Rita Gameiro ◽  
Marta Vaz ◽  
Isabel Fernandes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Systemic Treatment ◽  
Local Treatment ◽  
Current Status ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
The Impact

Over the last years, the incidence of brain metastases in HER2 breast cancer patients has increased. Surgery and radiotherapy are the current standard local therapies. Nevertheless, it is unclear which and when systemic treatment should be applied in addition to local treatment. This work aims to present an updated review of current systemic treatment options for patients with HER2+ metastatic breast cancer with brain metastases and to present a case study of clinical cases that occurred in a Portuguese population. The methodology of this work included a literature search in PubMed for the impact of HER2-targeting agents, such as pertuzumab, trastuzumab emtansine (T-DM1), lapatinib, neratinib, trastuzumab deruxtecan, and tucatinib in the treatment of patients with HER2+ breast cancer with brain metastases. Then, a cohort of Portuguese patients with HER2+ breast cancer (n=44) was analyzed. In this exploratory study, considering a follow-up of 23.9 months, three patients (6.8%) developed brain metastases despite having shown a complete pathological response. The role of systemic treatment for patients with HER2 breast cancer with brain metastases has rapidly evolved following recent successes in phase II and III clinical trials. The biggest challenge is how to integrate systemic and local treatment in the management of these patients.

Neratinib: the emergence of a new player in the management of HER2+ breast cancer brain metastasis

2020 ◽  
Vol 16 (7) ◽  
pp. 247-254 ◽  
Author(s):  
Azadeh Nasrazadani ◽  
Adam Brufsky
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
Increased Risk ◽  
Breast Cancer Brain Metastasis

HER2-positive (HER2+) breast cancer has become an effectively treatable disease in the era of targeted therapies, and outcomes have improved such that prognosis of this subtype is demonstrated to be superior to HER2-negative disease. Despite these advances, durable responses in HER2+ metastatic disease are challenged by the increased risk for brain metastasis. Neratinib is an irreversible pan-HER kinase inhibitor that has emerged as an effective agent when combined with capecitabine for the management of HER2+ metastatic breast cancer patients with brain metastasis. The randomized, Phase III, NALA trial compares neratinib plus capecitabine to a currently prevailing regimen of lapatinib plus capecitabine and is provided herein. Analysis of NALA portends meaningful changes on the horizon for the management of HER2+ metastatic breast cancer.

scholarly journals PR93 CLINICOPATHOLOGICAL EVALUATION OF BRAIN METASTASES RECURRENCE IN METASTATIC HER2+ BREAST CANCER PATIENTS

The Breast ◽  
2013 ◽  
Vol 22 ◽  
pp. S51
Author(s):  
Ariadna Gasol Cudós ◽  
Serafin Morales Murillo ◽  
Ana Velasco Sánchez ◽  
Ana Serrate López ◽  
Elena Aguirre Ortega ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer
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