scholarly journals 320 Phase IIa study of alpha-DC1 vaccine against HER2/HER3, chemokine modulation regimen and pembrolizumab in patients with asymptomatic brain metastasis from triple negative or HER2+ breast cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A346-A346
Author(s):  
Shipra Gandhi ◽  
Peter Forsyth ◽  
Mateusz Opyrchal ◽  
Kamran Ahmed ◽  
Hung Khong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Disease Progression ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Th1 Cells ◽  
Her2 Breast Cancer

BackgroundBrain metastases develop in up to 50% patients with metastatic triple negative breast cancer (TNBC) and HER2+ BC and are an increasing source of morbidity and mortality. HER3, overexpressed in triple negative and HER2+ brain metastatic breast cancer (BMBC), is a resistance factor to HER2-targeted therapies and a driver of CNS metastasis. Disease progression is associated with loss of anti-HER2/3 immunity. We have demonstrated that alphaDC1 loaded with glioma-specific peptides induce intratumoral production of chemokines (CXCL9, CXCL10, CXCL11, CCL5) which attract CXCR3- and CCR5- expressing cytotoxic T-lymphocytes (CTLs) and T-helper 1 (Th1) cells to brain tumors, inducing clinical responses and long-term disease stabilization in patients with aggressive recurrent primary brain tumors. Our preclinical data show that Chemokine modulating (CKM) regimen [rintatolimod, interferon (IFN)-α2b and COX-2 inhibitor] also selectively attracts effector CTLs and Th1 cells (but not suppressive regulatory T-cells or myeloid-derived suppressor cells) into tumors. Importantly, CKM preferentially promotes CTL migration into tumor rather than healthy tissues, providing rationale for its systemic use. We hypothesize that anti-HER2/3 type 1 polarized DC1s in combination with CKM and anti-PD1 will result in improved Th1/CTL response against HER2/3 epitopes, reduce brain recurrence and systemic progression.MethodsThis is a phase II single-arm, non-randomized multicenter study (NCT04348747). Eligibility includes patients with triple negative and HER2+ BMBC ≥ 18 years, ECOG PS ≤ 1, normal marrow and organ function with asymptomatic untreated brain metastases who receive αDC1 q2 weeks x 3, with CKM [200 mg IV rintatolimod, IFN-α 20 million units/m2 IV, celecoxib 200 mg oral BID] on days 1-3 with second and third dose of αDC1, followed by pembrolizumab 200 mg IV. Thereafter, pembrolizumab is given every 3 weeks, along with αDC1 and CKM every 3 months as booster dose until disease progression, intolerable side effects or withdrawal from study, or up to 24 months. Baseline and 3-week post-CKM treatment peripheral (non-CNS) biopsies are required for six patients. Primary objective is CNS response rate (RR) using RANO-BM criteria. If no CNS response is observed after 12 patients, study will be terminated. If ≥ 1 response observed, then 9 more patients will be enrolled, for a total of 21 patients. If ≥ 3 CR observed, the proposed therapy will be considered promising for further study. Secondary objectives include non-CNS RR per RECIST v1.1, median CNS, non-CNS and overall progression-free survival, overall survival and safety. Analysis of change in intratumoral biomarkers is an exploratory objective.ResultsN/AConclusionsN/ATrial RegistrationNCT04348747Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-19-04120.

scholarly journals Breast Cancer: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Sheeba Cantanelli, MPAS, PA-C
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Vitamin D Levels ◽  
The Impact

Sheeba Cantanelli, MPAS, PA-C, of UT Southwestern Medical Center, Simmons Comprehensive Cancer Center, discusses results from studies evaluating adjuvant therapy with a PARP inhibitor in BRCA-mutated HER2-negative metastatic breast cancer; immunotherapy in the treatment of early-stage triple-negative breast cancer; adjuvant capecitabine after neoadjuvant chemotherapy in triple-negative breast cancer; the addition of palbociclib to fulvestrant in HR-positive, HER2-negative advanced breast cancer; and the impact of vitamin D levels on outcomes. Reporting is provided by The ASCO Post.

scholarly journals The Incidence of Brain Metastases Among Patients with Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Markus Kuksis ◽  
Yizhuo Gao ◽  
William Tran ◽  
Christianne Hoey ◽  
Alex Kiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Triple Negative ◽  
Screening Program ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Breast Cancer Brain Metastasis

Abstract Background Patients with metastatic breast cancer (MBC) are living longer, but development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. Methods Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to: breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with HER2+, triple negative, and hormone receptor (HR)+/HER2- MBC; pooled overall estimates for incidence were calculated using random effects models. Results 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0 – 34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5 – 40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9 – 36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10 – 0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09 – 0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03 – 0.08) for patients with HR+/HER2- MBC. Conclusion There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.

321 Phase I clinical trial assessing the combination of systemic chemokine modulatory regimen targeting TLR3 with neoadjuvant chemotherapy in triple negative breast cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A347-A347
Author(s):  
Shipra Gandhi ◽  
Mateusz Opyrchal ◽  
Cayla Ford ◽  
Victoria Fitzpatrick ◽  
Melissa Grimm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase I ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Standard Dose ◽  
Surrogate Marker ◽  
Comprehensive Cancer Center ◽  
Cancer Center

BackgroundNeoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS.MethodsIn this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner.ResultsN/AConclusionsN/ATrial RegistrationNCT04081389Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.

Survival outcomes in patients with IDC and ILC breast cancer: A well matched single institution study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13056-e13056
Author(s):  
Michael Grimm ◽  
Bhuvaneswari Ramaswamy ◽  
Maryam B. Lustberg ◽  
Robert Wesolowski ◽  
Sagar D. Sardesai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Her2 Status ◽  
Single Institution ◽  
First Line ◽  
Response To Chemotherapy ◽  
Significant Difference

e13056 Background: Invasive lobular carcinoma (ILC) accounts for only 10-15% of all invasive breast cancers but has distinct clinicopathologic characteristics and genomic profiles. In particular, metastatic lobular cancers (mILC) have unique sites of metastasis and it is unclear if the response to initial endocrine therapy differs from metastatic ductal cancers (mIDC). Therefore we have undertaken a single-institution, retrospective analysis to compare overall outcomes and response to initial endocrine therapy (ET) in patients (pts) with metastatic ILC and IDC. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts treated for metastatic IDC and ILC at The Ohio State University Comprehensive Cancer Center from January 1, 2004 to December 31, 2014. Pts diagnosed with mIDC were matched on age, year of diagnosis, estrogen receptor/progesterone receptor and HER2 status and site of metastasis 2:1 to patients diagnosed with mILC. Overall survival (OS) was defined as the time from metastasis to death or last known follow-up. Progression-free survival (PFS) was defined as time from metastasis to progression on first-line ET. Time to chemotherapy (TTC) was defined as time from starting ET for metastasis to initiation of chemotherapy. Kaplan Meier (KM) methods were used to calculate median OS, PFS and TTC. Results: A total of one hundred sixty one pts with metastatic breast cancer were included in this analysis. The demographic features between the two groups were well balanced and included in the table below. The median OS was 2.6 yrs (95% CI: 1.55, 3.22) for mILC and 2.2 yrs (95% CI: 1.95, 2.62) for mIDC. A subset of 111 patients who started on endocrine therapy were used in the PFS and TTC analyses. The median PFS following first-line ET was 2.2 yrs (95% CI: 0.1.0, 2.7) for mILC and 1.4 yrs (95% CI: 0.91, 1.90) for mIDC. Median TTC was 2.1 yrs (95% CI: 1.71, 4.92) for mILC and 2.4 yrs (95% CI: 1.90, 4.77) for mIDC. There was no statistically significant difference in outcomes between the two groups. Conclusions: Outcomes in patients with ILC and IDC have been varied, with several studies reporting that patients with ILC have worse outcomes and response to chemotherapy. Our retrospective study examining outcomes in mILC in comparison with mIDC showed no difference in OS. Given the concern of resistance to conventional therapies in patients with lobular cancers, it is reassuring to see that the median PFS on first line ET and TTC was similar to metastatic ductal cancers.[Table: see text]

A specific nomogram to predict subsequent brain metastasis in metastatic triple-negative breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1028-1028
Author(s):  
L. Pusztai ◽  
R. Rouzier ◽  
L. Pusztai ◽  
N. Ibrahim
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Patients ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Preventive Treatment ◽  
Correlation Factor ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Short Delay

1028 Background: The development of brain metastases is usually a fatal event in the history of breast cancer patients with metastatic disease other than brain (MDOB). We previously developed a global nomogram that includes immune-histochemical phenotype to predict the occurrence of brain metastasis (BM). We hypothesized that a nomogram specific to triple negative tumor (TN) could improve prediction BM occurrence in patients with MDOB, thus allowing allocation of preventive treatment more efficiently. Methods: Patients with metastatic BC presenting between 2000 and February 2007 treated at M. D. Anderson Cancer Center were included in this retrospective analysis. We tested 17 variables and developed a multivariate model to predict occurrence of subsequent BM in TN tumors and created a nomogram that could be used for individual prediction. The model was cross-validated by bootstrapping and compared to the global nomogram. Results: Among 2,136 patients with metastatic breast cancer including 641 patients with TN tumors, 362 developed BM during follow-up: young age, histological characteristics, short delay between initial diagnosis and MDOB, number of metastatic sites and initial number of metastatic nodes were significantly and independently associated with subsequent BM. The nomogram to predict BM developed on the TN population provided a better discrimination (area under the ROC curve [AUC] = 0.62) than the global nomogram (AUC = 0.58) for the TN tumors. Prediction with the specific nomogram and the global nomogram were highly correlated (correlation factor = 0.67, p < 0.0001). However, when a threshold at 15% was used, we observed 27% of discordant cases and the sensitivity of the specific nomogram was better. Conclusions: We developed a specific tool to predict subsequent BM in patients with metastatic TN breast cancer. This nomogram outperformed a global nomogram. No significant financial relationships to disclose.

Impact of brain metastases on health care costs in metastatic breast cancer: A multinational study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6555-6555
Author(s):  
M. D. Walker ◽  
K. Lykopoulos ◽  
E. McLeod ◽  
S. Cottrell ◽  
L. Christova
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Health Care Costs ◽  
Financial Burden ◽  
Metastatic Breast ◽  
Her2 Breast Cancer ◽  
The Uk ◽  
Care Costs

6555 Background: Incidence of brain metastases (BM) are thought to be particularly high among patients with ErbB2+ (HER2+) breast cancer and have been associated with a poor survival prognosis. A previous study identified such patients as a considerable financial burden for health systems in Germany and France when compared to metastatic breast cancer (MBC) without BM. The objective of this study was to extend that analysis to estimate health care costs in Italy, Spain and the UK. Methods: Patient treatment histories, including drugs, specialist visits, procedures, inpatient stays etc, were collected retrospectively from a panel of oncologists for women with MBC across Italy, Spain and the UK, last seen by the responding oncologist during Q3-Q4 2006 or Q3-Q4 2007. To identify ErbB2+ patients they all had to have received/were receiving trastuzumab (TZ) for MBC. Patients were sampled so as to ensure the collection contained a minimum of 50 cases with BM and 200 histories overall (remainder controls). All costs within the observation period (initiation of TZ to date last seen) were calculated from a payer's perspective for patients who had developed BM and those who had not. Linear stepwise regression took into account potential confounding of time related covariates. Results: The study included 268 Italian (146 cases), 215 Spanish (126 cases) and 243 UK patients (103 cases). BM diagnosis was associated with significantly more expensive treatment histories than those patients without. Service costs such as radiotherapy and hospital visits were found to be key drivers for these differences (p<.001). Conclusions: The significantly greater cost associated with treatment of BMs in ErbB2+ MBC patients from Italy, Spain and the UK is consistent with results from identical French and German analyses. Therapies that reduce the incidence of BMs may therefore decrease the overall financial burden of ErbB2+ MBC. [Table: see text] [Table: see text]

Coexpression of HER3 as a predictor of survival in HER2-positve breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 611-611
Author(s):  
Rupert Bartsch ◽  
Anna Sophie Berghoff ◽  
Zsuzsanna Bago-Horvath ◽  
Matthias Preusser ◽  
Guenther G. Steger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Triple Negative ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Fish Analysis ◽  
Breast Cancer Patients ◽  
Cancer Data ◽  
Her3 Expression

611 Background: Improved understanding of the pathobiology of the metastatic cascade as well as the identification of new prognostic markers may lead the path to the development of novel targeted agents in breast cancer patients (BC pts). Recently, HER3-expression was postulated as independent risk factor for metastatic spread. Methods: Pts of different BC subtypes (luminal, HER2-amplified, triple-negative) with metastatic disease were identified from a breast cancer data base. Tissue of the primary tumor was retrieved from the local pathology institute. Immunohistochemical staining of estrogen-receptor, progesterone-receptor, and HER2 and HER3 was performed. In HER2 equivocal cases, subsequent FISH analysis was performed. Results: Specimens of 110 pts (36/110 luminal, 35/110 HER2-amplified, 40/110 triple-negative) were available for this analysis. 23/110 (21%) specimens showed strong, complete, membranous staining for HER3 of at least 10% of all tumor cells. HER2/HER3 co-expression was observed in 12/110 (11%) specimens. HER3 showed a statistically significant association with HER2-expression (p=0.02; Chi square test). No correlation was observed for HER3-expression and overall survival (OS), incidence of brain metastases, or time to diagnosis of brain metastases in the entire patient cohort (p>0.05; log rank). In the HER2-amplified subgroup, however, HER3-expression was significantly associated with shorter OS (median 30 vs. 63 months; p=0.02; log rank test) and remained significant when entered into a multivariate model (p=0.02; Cox regression). Conclusions: HER2/HER3 co-expression is significantly associated with impaired OS in pts with HER2-positive metastatic breast cancer. Co-inhibition of HER2 and HER3 or inhibition of HER2/HER3 hetero-dimerization could improve prognosis of this patient population.

Referral patterns among patients with metastatic breast cancer in an integrated palliative care program.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 163-163 ◽  
Author(s):  
Rebecca Small ◽  
Jeffrey Belkora ◽  
Melanie Catherine Majure ◽  
Amy Jo Chien ◽  
Michelle E. Melisko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Palliative Care ◽  
Metastatic Breast Cancer ◽  
Metastatic Disease ◽  
Psychosocial Support ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Patient Acceptance ◽  
Referral Patterns

163 Background: ASCO recommends palliative care (PC) concurrently with oncologic treatment for patients with metastatic disease and there is emerging data about the benefits of early PC. However, little is known about referral patterns to specialty PC among patients who die of metastatic breast cancer. Methods: After years of offering a stand-alone outpatient PC consult service in our comprehensive cancer center, we established an integrated PC program in breast oncology (the “Advanced Breast Cancer (ABC) Program”) with a care coordinator, PC physician, and co-location with oncology. Among patients who died, we analyzed referral patterns, program participation, and end-of-life quality outcomes from October 2014 through May 2015. Results: 38 of 108 patients (35.2%) referred to and seen in ABC died, with an average of 2.9 PC visits (range 1-17) and 7 months (range 0-20) between referral and death. Reasons for referral among ABC patients who died included: symptom management (15 patients, 39.5%); goals of care discussions (12, 31.6%); psychosocial support (5, 13.2%); discharge referral from the inpatient PC team (4, 10.5%); and new diagnosis of metastatic disease (3, 7.9%). At the time of referral, average time since metastatic diagnosis was 23.6 months (range: 0-106); 10 patients (26.3%) had received > 3 lines of treatment. 15 referred patients (13.9%) died but were not seen by ABC: of those, 6 initiated hospice before they could be seen; 5 initially declined or deferred the referral but then were too sick to be seen in clinic by the time they agreed; and 4 were unwilling to accept extra appointments or did not follow-up to repeated outreach. 24 ABC patients who died (63.2%) were seen early (> 90 days before death), whereas in the year prior to the ABC clinic, among patients who died, only 11 of 44 (25%) who had received PC consultation received it early. 19 of 33 (57.6%) ABC patients for whom data was available utilized hospice, with only 2 (5.3%) using hospice < 3 days. Conclusions: Embedding and integrating a PC practice in breast oncology resulted in patients being seen earlier. Future efforts should be directed at further increases in earlier referrals by oncologists and in facilitating patient acceptance of early referrals.

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