Kimberly L Blackwell

Kimberly L Blackwell
Duke University | DU

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146
Publications
12,346
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9,523
Citations
Citations since 2017
18 Research Items
3665 Citations
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20172018201920202021202220230100200300400500600
20172018201920202021202220230100200300400500600
20172018201920202021202220230100200300400500600

Publications

Publications (146)
Article
Full-text available
The interplay between the immune system and tumor progression is well recognized. However, current human breast cancer immunophenotyping studies are mostly focused on primary tumors with metastatic breast cancer lesions remaining largely understudied. To address this gap, we examined exome-capture RNA sequencing data from 50 primary breast tumors (...
Article
Full-text available
Background: Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the effic...
Article
Purpose: This pilot study was performed to test our ability to administer neratinib monotherapy before clinically recommended craniotomy in patients with HER2-positive metastatic breast cancer to the central nervous system, to examine neratinib's central nervous system penetration at craniotomy, and to examine postoperative neratinib maintenance....
Article
Purpose: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts. Patients and methods: Patient...
Article
Background: Triple negative breast cancer (TNBC) remains a heterogeneous clinical phenotype with few, known therapeutic targets. PARP inhibitors (PARPi) are the first approved, targeted therapy in TNBC, limited to germline BRCA mutant (BRCAm) cancers that lack homologous recombination repair capacity. Even in this context, resistance quickly emerge...
Preprint
Full-text available
The interplay between the immune system and tumor progression is well recognized. However, current human breast cancer immunophenotyping studies are mostly focused on primary tumors with metastatic breast cancer lesions remaining largely understudied. To address this gap, we examined exome-capture RNA sequencing data from 50 primary breast tumors (...
Article
Backgroud: Immue-based therapy for metastatic breast cacer has had limited success, particularly i molecular subtypes with low somatic mutatios rates. Strategies to augmet T-cell ifiltratio of tumors iclude vaccies targetig established ocogeic drivers such as the geomic amplificatio of HER2. We costructed a vaccie based o a ovel alphaviral vector e...
Article
Full-text available
Fulvestrant is recommended for patients with hormone receptor-positive (HR+) advanced breast cancer (ABC) who progress after aromatase inhibitor therapy. As most patients in this setting have already developed mechanisms of resistance to endocrine therapy, targeting biological pathways associated with endocrine resistance in combination with fulves...
Article
Full-text available
Purpose: Seviteronel (INO-464) is an oral, selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) and androgen receptor inhibitor with in vitro and in vivo anti-tumor activity. This open-label phase 1 clinical study evaluated safety, tolerability, pharmacokinetics (PK), and activity of once-daily (QD) seviteronel in women with locally advanced...
Article
Background: Stromal tumor-infiltrating lymphocytes (TILs) might predict pathologic complete response (pCR) in patients with HER2-positive (HER2+) breast cancer treated with trastuzumab (H). Docetaxel (T), carboplatin (C), H, and pertuzumab (P) have immune-modulating effects. Pre- and post-treatment immune biomarkers in cancers treated with neoadju...
Article
e12527 Background: FUL is the recommended 2L treatment for patients whose HR+ ABC progressed after aromatase inhibitor (AI) therapy. In first line ABC adding targeted therapy, eg. cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) palbociclib or ribociclib, or mammalian target of rapamycin inhibitor (mTORi) everolimus (EVE), to endocrine therapy (ET)...
Article
1047 Background: In the randomized, phase III MONALEESA-2 study (NCT01958021), first-line therapy with ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor; 600 mg/day; 3-weeks-on/1-week-off) + letrozole (LET; 2.5 mg/day) in postmenopausal women with HR+, HER2– ABC significantly prolonged progression-free survival vs placebo (PBO) + LET (hazard r...
Article
1005 Background: Evidence-based treatments (tx) for metastatic, HER2+ BCBM are limited. We previously found a central nervous system (CNS) objective response rate (ORR) of 8% (95% CI 2-22%) for the irreversible, EGFR/HER2-targeted kinase inhibitor, neratinib. To enhance CNS activity, we evaluated the combination of neratinib + capecitabine in a sub...
Article
2049 Background: Breast cancer brain metastasis (BCBM) is frequent in advanced disease, has limited therapies, and is associated with poor prognosis. Increased stromal tumor infiltrating lymphocytes (sTILs) are prognostic in triple-negative breast cancer (TNBC) and predictive of therapeutic response in early breast cancer (BC). However, little is k...
Article
2072 Background: Brain metastases (BM) are an increasingly common consequence of breast cancer (BC). Knowledge of the microenvironment in primary BC and its impact on prognosis is evolving. A similar understanding of the microenvironment of BC metastases is lacking, particularly for the brain, where unique immune regulation governs stroma compositi...
Article
1038 Background: Endocrine therapy (ET) is the basis of first-line (1L) treatment for HR+ ABC. However, ET resistance are almost universal. At the first interim analysis (IA) of MONALEESA-2 (NCT01958021), ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + letrozole (LET) significantly prolonged progression-free survival (PFS) vs placebo (PBO...
Article
Background: Increased stromal tumor infiltrating lymphocytes (TILs) are predictive and prognostic for improved outcomes from neoadjuvant or adjuvant chemotherapy in triple negative breast cancer. Increased tumor mutational burden may promote neoantigens causing immune system upregulation. Microsatellite instability in gastrointestinal cancer predic...
Article
687 Background: Patients (pts) with chemotherapy refractory mCRC have a poor prognosis, with a median survival of approximately 6 months (mos). Ziv-aflibercept is FDA-approved in combination with FOLFIRI for the 2nd line treatment of mCRC, but its tolerability and activity in pts with chemotherapy refractory disease is unknown. We designed a phase...
Article
Aims Studies have suggested increased cancer incidence associated with long-term dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). We evaluated cancer incidence and treatment-related differences in an analysis of DAPT for ACS. Methods and results The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage...
Article
Full-text available
Purpose: The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in pl...
Article
Full-text available
This phase I/II dose-escalation study evaluated the efficacy, safety, and pharmacokinetics of pilaralisib (SAR245408), a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor, or voxtalisib (SAR245409), a PI3K and mammalian target of rapamycin inhibitor, in combination with letrozole in hormone-receptor-positive (HR+), human epidermal growth facto...
Article
To explore how symptoms and psychosocial factors are related to intentional and unintentional non-adherent medication taking behaviors. Included were postmenopausal women with hormone receptor positive, stage I-IIIA breast cancer, who had completed surgery, chemotherapy, and radiation, and were taking endocrine therapy. Self-administered, standardi...
Article
Background: The heterogeneity of TNBC includes a subtype that is androgen dependent and whose growth is inhibited by antiandrogen therapy. We conducted a multicenter phase II trial which established the activity of bicalutamide for the treatment of patients (pts) with metastatic ER/PR-negative breast cancer TBCRC011 (Gucalp CCR 2013). We now report...
Article
Background: In June 2013, our health system transitioned to an electronic medical record (EMR) which included collecting patient quality of life data at each clinic visit. We used the NCCN distress thermometer (DT), a short, simple to use, self-report measure which uses a 10-point scale from 0 (no distress) to 10 (extreme distress) as well as an as...
Article
We have previously reported that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns obtained from locally advanced breast cancer (LABC) patients prior to neoadjuvant therapy predicted pathologic clinical response. Genomic analyses were also independently conducted on the same patient population. This retrospective stu...
Article
Purpose: CALGB 40302 sought to determine whether lapatinib would improve progression-free survival (PFS) among women with hormone receptor-positive metastatic breast cancer treated with fulvestrant. Patients and methods: Eligible women had estrogen receptor-positive and/or progesterone receptor-positive tumors, regardless of human epidermal grow...
Article
Full-text available
Purpose Unresectable chest wall recurrences of breast cancer (CWR) in heavily pretreated patients are especially difficult to treat. We hypothesised that thermally enhanced drug delivery using low temperature liposomal doxorubicin (LTLD), given with mild local hyperthermia (MLHT), will be safe and effective in this population. Patients and methods...
Article
Full-text available
This study examined the relationships between physical symptoms, self-efficacy for coping with symptoms, and functional, emotional, and social well-being in women who were taking adjuvant endocrine therapy for breast cancer. One hundred and twelve women who were taking adjuvant endocrine therapy (tamoxifen or an aromatase inhibitor) for breast canc...
Article
Triple negative breast cancer (TNBC) represents a particularly aggressive and difficult to treat form of breast cancer. No specific genetic alterations have been described as characteristic of the disease, with the exception of association with BRCA1/2, EGFR, and KRAS mutations. In this study, we sought to define clinically actionable mutations in...
Article
Background: Unresectable breast cancer chest wall recurrence (CWR) following radiation is very difficult to treat and often responds poorly to standard chemotherapy. Symptoms include pain, reduced range of motion, disfigurement, and skin erosions with bleeding and infection. We hypothesized that thermally enhanced drug delivery using low temperatur...
Article
Full-text available
Basal-like breast tumors are typically (ER/PR/HER2) triple-negative and are associated with a high incidence of brain metastases and poor clinical outcomes. The molecular chaperone αB-crystallin is predominantly expressed in triple-negative breast cancer (TNBC) and contributes to an aggressive tumor phenotype in preclinical models. We investigated...
Article
Triple negative metastatic breast cancer can be difficult to treat with primarily cytotoxic options. Nab-paclitaxel has demonstrated improved PFS and tolerability compared with standard cremophor-solubilized paclitaxel; based on this, we examined the efficacy and safety of combining weekly nab-paclitaxel with carboplatin and bevacizumab in TNMBC. I...
Article
Full-text available
Patients with hormone receptor-negative breast cancer (BC) generally do not benefit from endocrine-targeted therapies. However, a subset with androgen receptor (AR) expression is predicted to respond to antiandrogen therapies. This phase II study explored bicalutamide in AR positive, estrogen receptor (ER) and progesterone receptor (PgR)-negative m...
Article
Full-text available
Aerobic exercise training (AET) is an effective adjunct therapy to attenuate the adverse side-effects of adjuvant chemotherapy in women with early breast cancer. Whether AET interacts with the antitumor efficacy of chemotherapy has received scant attention. We conducted a pilot study to explore the effects of AET in combination with neoadjuvant dox...
Article
TPS651 Background: Overcoming endocrine resistance (ER) is a critical goal in the treatment of hormone receptor−positive (HR+) breast cancer (BC). Emerging in vitro evidence suggests that amplification and overexpression of fibroblast growth factor receptor 1 (FGFR1) is associated with ER. Up to 8% pts with HR+/ human epidermal growth factor recept...
Article
1076 Background: The FN rate for the approved regimen of TC is 5% in pivotal studies. Other small retrospective reports have reported FN rates as high as 20-35%. We report the incidence of FN from a large retrospective series of breast cancer patients receiving TC with or without pegfilgrastim (PF) for adjuvant therapy. Methods: We reviewed records...
Article
Background: Our group and others have identified a subset of ER/PR(−) breast cancers characterized by expression of the androgen receptor (AR) and androgen-dependent growth (Doane 2006). We conducted a proof-of-concept multicenter phase II study to test the efficacy of the AR-antagonist, bicalutamide for the treatment of AR(+) ER/PR(−) MBC (NCT0046...
Article
Full-text available
This multi-center Phase II study evaluated lapatinib, pazopanib, and the combination in patients with relapsed HER2+ inflammatory breast cancer. In Cohort 1, 76 patients were randomized 1:1 to receive lapatinib 1,500 mg + placebo or lapatinib 1,500 mg + pazopanib 800 mg (double-blind) once daily until disease progression, unacceptable toxicity, or...
Article
Phase III EGF104900 data demonstrated that lapatinib plus trastuzumab significantly improved progression-free survival (PFS) and clinical benefit rate versus lapatinib monotherapy, offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). Final...
Article
Full-text available
Sustained HER2 signaling at the cell surface is an oncogenic mechanism in a significant proportion of breast cancers. While clinically effective therapies targeting HER2 such as mAbs and tyrosine kinase inhibitors exist, tumors overexpressing HER2 eventually progress despite treatment. Thus, abrogation of persistent HER2 expression at the plasma me...
Data
Figure S4 showing inhibition of HER2-VIA-induced HER2 ubiquitination by lapatinib. SK-BR-3 cells were pretreated with the proteasome inhibitor MG132 (10 µM) and lapatinib for 30 minutes before HER2-VIA application for 2 hours. After the indicated treatment, cells were lysed and HER2 was precipitated using anti-HER2 rabbit antibody 29D8. Precipitate...
Data
Figure S5 showing the effect of human HER2-specific antibodies on HER2 tyrosine 877 phosphorylation. SK-BR-3 cells were stimulated for 1 hour with the indicated sera from either patients or mice. Protein samples were immunoblotted with anti-HER2 PY877 antibodies (upper panel) or anti-HER2 antibodies (lower panel).
Data
Figure S3 showing sucrose inhibits HER2-VIA-induced internalization of HER2. SK-BR-3 cells were treated with 20 µl HER2-VIA and then incubated with FITC 488-conjugated goat anti-mouse antibody on ice. The cells were then exposed to the following conditions and were then imaged by confocal microscopy: (a) incubation on ice for 1 hour; (b) incubation...
Article
LBA1 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Article
1006 Background: Patients (pts) with ER-/PR- MBC do not benefit from endocrine treatment (tx). Doane et al (Oncogene 2006;25:3994) described a subset of ER-/PR- BC with a gene expression profile similar to ER+ BC but characterized by AR expression and AR-dependent growth in vitro. Hence, we conducted a multicenter phase II trial (NCT00468715) of th...
Article
Full-text available
In early-stage breast cancer, adjuvant chemotherapy is associated with significant systemic toxicity with only a modest survival benefit. Therefore, there is considerable interest in identifying predictive markers of response to therapy. Doxorubicin, one of the most common drugs used to treat breast cancer, is an anthracycline chemotherapeutic agen...
Article
Background Zoledronic acid (ZA) in combination with endocrine therapy (ET) and ovarian ablation (OA) reported a DFS advantage in premenopausal women with early stage breast cancer (EBC) in ABCSG-12. Emerging evidence from pre-clinical studies suggests that ZA increases gamma/delta T-cells (GDT), an immune cell population with anti-tumor activity. T...
Article
Full-text available
Patients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccines induce polyclonal antibody responses against HER2 that demonstrate enhanced anti-tumor activity when co...
Data
Figure S1 showing flow cytometric assessment of the relative HER2-VIA and trastuzumab binding intensity to HER2-positive SK-BR-3 human breast tumor cells. SK-BR-3 cells were incubated with the indicated dilution of (A) HER2-VIA (1:100 to 1:102,400) or (B) trastuzumab (20 to 0.02 μg/ml) and then stained with the appropriate phycoerythrin-conjugated...
Data
Figure S1. Reduced phosphorylation of AKT following dHER ASCI immunization.
Article
Full-text available
Activation status of the phosphatidylinositol 3-kinase (PI3K) pathway in breast cancer brain metastases (BCBMs) is largely unknown. We examined expression of phospho(p)-AKT, p-S6, and phosphatase and tensin homologue (PTEN) in BCBMs and their implications for overall survival (OS) and survival after BCBMs. Secondary analyses included PI3K pathway a...
Article
A small subset of T cells (gamma-delta T cells) is able to recognize phosphoantigens that are overexpressed in some cancer cells and may selectively target and kill cancer cells with high levels of phosphoantigen. Moreover, nitrogen-containing bisphosphonates, such as zoledronic acid, are able to induce accumulation of specific phosphoantigens in s...
Article
A phase II study of dasatinib, an inhibitor of multiple oncogenic tyrosine kinases including Src, was conducted to evaluate 16-week progression-free rate and tolerability in patients with previously treated metastatic breast cancer (MBC). Real-time assessment of potential tissue biomarkers of Src inhibition was used to optimize dosing. Eligibility...
Article
Five randomized phase III trials - AVF2119g, E2100, AVADO, RIBBON-1, and RIBBON-2 - have reported data on the efficacy and safety of bevacizumab, combined with a variety of chemotherapy agents and in various settings, in patients with metastatic breast cancer (MBC). The E2100 trial demonstrated a significant improvement in progression-free survival...
Article
Full-text available
Breast cancer heterogeneity occurs as a consequence of the dysregulation of numerous oncogenic pathways as well as many non-genetic factors, including tumor microenvironmental stresses such as hypoxia, lactic acidosis, and glucose deprivation. Although the importance of these non-genetic factors is well recognized, it is not clear how to integrate...
Article
Full-text available
ErbB2 tyrosine kinase inhibitors (TKI) block tyrosine autophosphorylation and activation of the full-length transmembrane ErbB2 receptor (p185(ErbB2)). In addition to p185(ErbB2), truncated forms of ErbB2 exist in breast cancer cell lines and clinical tumors. The contribution of these truncated forms, specifically those expressed in tumor cell nucl...
Data
Supplementary Figures S1 to S18. This document contains Supplementary Figures S1 to S18.
Data
Supplemental Table S2. Summary of tumor samples. This document provides a summary of the tumor samples used in the study.
Data
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Supplementary methods. This document provides additional information about the methods used in the manuscript.
Data
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Supplemental Table S1. Summary of microenvironment signatures. This document provides a summary of the microenvironment signatures and parameters.
Article
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The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken by immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); however, targeting tumor antigen directly to APC in vivo would be a less complicated strategy. We wished to...
Article
Full-text available
Progression-free survival (PFS) was significantly longer for the lapatinib plus trastuzumab (L+T) arm than for L alone in a phase III, randomized, open-label study of women with human epidermal growth factor receptor 2 positive metastatic breast cancer who had documented progression on at least one T-containing regimen in the metastatic setting. Th...
Article
Full-text available
The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-cell responses in humans. Mixtures of human leukocyte antigen A2 (HLA-A2)-binding ovarian cancer-associa...
Article
Background: Brain metastases (BM) are a devastating consequence of advanced breast cancer (BC) for which novel, targeted therapies are urgently needed. The PI3K pathway plays a critical role in the initiation and progression of BC. Alterations in this pathway are implicated in approximately 50% of BC. The role of PI3K activation in BCBM has yet to...
Article
Full-text available
Hyperthermia has long been used in combination with radiation for the treatment of superficial malignancies, in part due to its radiosensitising capabilities. Patients who suffer superficial recurrences of breast cancer, be it in their chest wall following mastectomy, or in their breast after breast conservation, typically have poor clinical outcom...
Article
Full-text available
Hyperthermia (HT) has a proven benefit for treating superficial malignancies, particularly chest wall recurrences of breast cancer. There has been less research utilising HT in patients with locally advanced breast cancer (LABC), but available data are promising. HT has been combined with chemotherapy and/or radiotherapy in the neoadjuvant, definit...
Article
An independent Adjuvant Cardiac Review and Evaluation Committee (ACREC) systematically reviewed cases of symptomatic heart failure events to uniformly define the cardiac event rate across two large trials (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-31 and North Central Cancer Treatment Group [NCCTG] N9831) that assessed the addit...
Article
Full-text available
The prognosis for locally advanced breast cancer (LABC) patients continues to be poor, with an estimated five-year survival of only 50-60%. Preclinical data demonstrates enhanced therapeutic efficacy with liposomal encapsulation of doxorubicin combined with hyperthermia (HT). Therefore this phase I/II study was designed to evaluate the safety and e...
Article
Preclinical studies in ErbB2-positive cell lines demonstrated a synergistic interaction between lapatinib and trastuzumab, suggesting that dual blockade is more effective than a single agent alone. EGF104900 compared the activity of lapatinib alone or in combination with trastuzumab in patients with ErbB2-positive, trastuzumab-refractory metastatic...