Jeremy Force

Positions:

Assistant Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

D.O. 2011

University of New England

Internal Medicine Residency

Indiana University, School of Medicine

Hematology/Oncology Fellowship, Medicine

Duke University School of Medicine

Grants:

A Randomized Phase II clinical trial assessing the Efficacy and Safety of MK-3475 (pembrolizumab) in combination with carboplatin and gemcitabine in patients with metastatic triple negative breast cancer

Administered By
Duke Cancer Institute
Awarded By
Fox Chase Cancer Center
Role
Principal Investigator
Start Date
End Date

Phase II Study of Combination Ruxolitinib (INCB018424) with Preoperative Chemotherapy for Triple Negative Inflammatory Breast Cancer protocol # TBCRC 039

Administered By
Duke Cancer Institute
Awarded By
Johns Hopkins University
Role
Principal Investigator
Start Date
End Date

A Phase II randomized study to evaluate the immunologic and antitumor activity of concurrent VRP-HER2 vaccination and Pembrolizumab for patients with advanced HER2-overexpressing breast cancer

Administered By
Duke Cancer Institute
Awarded By
Merck Sharp & Dohme
Role
Principal Investigator
Start Date
End Date

TBCRC 047

Administered By
Duke Cancer Institute
Awarded By
Johns Hopkins University
Role
Principal Investigator
Start Date
End Date

Publications:

Treatment Patterns and Outcomes of Women with Breast Cancer and Supraclavicular Nodal Metastases.

BACKGROUND: In 2002, breast cancer patients with supraclavicular nodal metastases (cN3c) were downstaged from AJCC stage IV to IIIc, prompting management with locoregional treatment. We sought to estimate the impact of multimodal therapy on overall survival (OS) in a contemporary cohort of cN3c patients. METHODS: Women ≥ 18 years with cT1-T4c/cN3c invasive breast cancer who underwent systemic therapy were identified from the 2004-2016 National Cancer Database. We compared three patient cohorts: (a) cN3c + multimodal therapy (systemic therapy, surgery, and radiation); (b) cN3c + non-standard therapy; and, (c) cM1. Logistic regression identified factors associated with receipt of multimodal therapy and Kaplan-Meier was used to estimate unadjusted OS. The Cox proportional hazards model estimated effects of diagnosis and treatment on OS after adjustment. RESULTS: Overall, 1827 (3.7%) patients with cN3c disease and 46,919 (96.3%) cM1 patients were identified. Of cN3c patients, 74.5% (n = 1362) received multimodal therapy and 25.5% (n = 465) received non-standard therapy; receipt of multimodal therapy was associated with improved 5-year OS (multimodal: 59% vs. M1: 28% vs. non-standard: 28%, log-rank p < 0.001). Adjusting for covariates, non-standard therapy was associated with an increased risk of death compared with receipt of multimodal therapy (HR 2.20, 95% CI 1.71-2.83, p < 0.001). Private insurance was the only patient characteristic associated with a greater likelihood of receiving multimodal therapy (OR 2.81; 95% CI, 1.64-4.82; p < 0.001). CONCLUSION: Women with cN3c breast cancer who received multimodal therapy demonstrated improved overall survival when compared with patients undergoing non-standard therapy and those with metastatic (M1) disease. Although selection bias may contribute to worse overall survival among cN3c patients undergoing non-standard therapy, national guidelines should encourage locoregional treatment in carefully selected patients.
Authors
Tamirisa, NP; Ren, Y; Campbell, BM; Thomas, SM; Fayanju, OM; Plichta, JK; Rosenberger, LH; Force, J; Hyslop, T; Hwang, ES; Greenup, RA
MLA Citation
Tamirisa, Nina P., et al. “Treatment Patterns and Outcomes of Women with Breast Cancer and Supraclavicular Nodal Metastases.Ann Surg Oncol, vol. 28, no. 4, Apr. 2021, pp. 2146–54. Pubmed, doi:10.1245/s10434-020-09024-1.
URI
https://scholars.duke.edu/individual/pub1460793
PMID
32946012
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
28
Published Date
Start Page
2146
End Page
2154
DOI
10.1245/s10434-020-09024-1

Biomarkers of Immune Checkpoint Blockade Response in Triple-Negative Breast Cancer.

OPINION STATEMENT: Immune checkpoint blockade (ICB) has revolutionized the treatment landscape across multiple solid tumor types. In triple-negative breast cancer (TNBC), clinical benefit for the addition of ICB to chemotherapy has been shown in both the metastatic and early stage disease settings. A minority of patients with TNBC will truly benefit from ICB, with many tumors unlikely to respond, and ICB can cause additional toxicities for patients to incur. In clinical practice, ICB-based regimens are emerging as standard-of-care treatment options in TNBC subpopulations. Atezolizumab in combination with nab-paclitaxel is recommended as first-line treatment for patients with PD-L1-positive metastatic TNBC. Clinical trials are needed to confirm this benefit and evaluate if additional biomarkers may allow for improved patient selection. Trials investigating ICB in early-stage breast cancer show promise for the benefit of combination ICB with neoadjuvant chemotherapy. However, longer follow-up is required before ICB can be considered as standard-of-care treatment in the early stage setting. In both metastatic and early stage TNBC, novel biomarkers to improve patient selection are now under investigation. These include multiplex IHC to profile immune cell subtypes (such as tumor infiltrating lymphocytes) or RNA gene expression profiling to detect signatures suggestive of a T-cell-inflamed microenvironment. Detecting somatic mutations through tumor next-generation DNA sequencing may predict resistance mechanisms or suggest sensitivity to ICB monotherapy or in combination with other forms of systemic therapy. These biomarker platforms may allow for a more granular analysis of immune activity and should be further investigated in prospective studies with the aim of personalizing ICB-focused therapies in TNBC.
Authors
Isaacs, J; Anders, C; McArthur, H; Force, J
MLA Citation
Isaacs, James, et al. “Biomarkers of Immune Checkpoint Blockade Response in Triple-Negative Breast Cancer.Curr Treat Options Oncol, vol. 22, no. 5, Mar. 2021, p. 38. Pubmed, doi:10.1007/s11864-021-00833-4.
URI
https://scholars.duke.edu/individual/pub1476464
PMID
33743085
Source
pubmed
Published In
Current Treatment Options in Oncology
Volume
22
Published Date
Start Page
38
DOI
10.1007/s11864-021-00833-4

Identification of pathogenic ROSI alterations in cell-free DNA (cfDNA) from patients with breast cancer.

Authors
Force, JM; Taylor, ML; Drusbosky, L; Yen, J; Marcom, PK; Anders, CK; Marks, JR
MLA Citation
Force, Jeremy Meyer, et al. “Identification of pathogenic ROSI alterations in cell-free DNA (cfDNA) from patients with breast cancer.Journal of Clinical Oncology, vol. 38, no. 15, 2020.
URI
https://scholars.duke.edu/individual/pub1467186
Source
wos-lite
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date

Surgery for Men with Breast Cancer: Do the Same Data Still Apply?

BACKGROUND: Men represent a small proportion of breast cancer diagnoses, and they are often excluded from clinical trials. Current treatments are largely extrapolated from evidence in women. We compare practice patterns between men and women with breast cancer following the publication of several landmark clinical trials in surgery. PATIENTS AND METHODS: Patients with invasive breast cancer (2004-2015) from the National Cancer Data Base were identified; subcohorts were created based on eligibility for NSABP-B06, CALGB 9343, and ACOSOG Z0011. Practice patterns were stratified by gender and compared. Cox proportional hazards regression analyses were utilized to estimate the association between OS and gender. RESULTS: Of the 1,664,746 patients identified, 99% were women and 1% were men. Among NSABP-B06 eligible men, mastectomy rates did not change (consistently ~ 80%), and their adjusted OS was minimally worse compared with women (HR 1.19, 95% CI 1.11-1.28). Following publication of CALGB 9343, omission of radiation after lumpectomy was less likely in men and lagged behind that of women, despite similar OS (male HR 0.92, 95% CI 0.59-1.44). Application of ACOSOG Z0011 findings resulted in deescalation of axillary surgery for men and women with comparable OS (male HR 0.69, 95% CI 0.33-1.45). CONCLUSIONS: Uptake of clinical trial results for men with breast cancer often mirrors that for women, despite exclusion from these studies. Furthermore, when study findings were applied to eligible patients, men and women demonstrated similar survival. Observational studies can help inform the potential application of study findings to this unique population and improve patient enrollment in clinical trials.
Authors
MLA Citation
Plichta, Jennifer K., et al. “Surgery for Men with Breast Cancer: Do the Same Data Still Apply?Ann Surg Oncol, vol. 27, no. 12, Nov. 2020, pp. 4720–29. Pubmed, doi:10.1245/s10434-020-08901-z.
URI
https://scholars.duke.edu/individual/pub1452159
PMID
32705510
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
27
Published Date
Start Page
4720
End Page
4729
DOI
10.1245/s10434-020-08901-z

Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.

PURPOSE: Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we hypothesized that targeted vaccination against an oncogenic driver in combination with ICB could direct and enable antitumor immunity in advanced cancers. EXPERIMENTAL DESIGN: Our models of HER2+ breast cancer exhibit molecular signatures that are reflective of advanced human HER2+ breast cancer, with a small numbers of neoepitopes and elevated immunosuppressive markers. Using these, we vaccinated against the oncogenic HER2Δ16 isoform, a nondriver tumor-associated gene (GFP), and specific neoepitopes. We further tested the effect of vaccination or anti-PD-1, alone and in combination. RESULTS: We found that only vaccination targeting HER2Δ16, a driver of oncogenicity and HER2-therapeutic resistance, could elicit significant antitumor responses, while vaccines targeting a nondriver tumor-specific antigen or tumor neoepitopes did not. Vaccine-induced HER2-specific CD8+ T cells were essential for responses, which were more effective early in tumor development. Long-term tumor control of advanced cancers occurred only when HER2Δ16 vaccination was combined with αPD-1. Single-cell RNA sequencing of tumor-infiltrating T cells revealed that while vaccination expanded CD8 T cells, only the combination of vaccine with αPD-1 induced functional gene expression signatures in those CD8 T cells. Furthermore, we show that expanded clones are HER2-reactive, conclusively demonstrating the efficacy of this vaccination strategy in targeting HER2. CONCLUSIONS: Combining oncogenic driver targeted vaccines with selective ICB offers a rational paradigm for precision immunotherapy, which we are clinically evaluating in a phase II trial (NCT03632941).
Authors
Crosby, EJ; Acharya, CR; Haddad, A-F; Rabiola, CA; Lei, G; Wei, J-P; Yang, X-Y; Wang, T; Liu, C-X; Wagner, KU; Muller, WJ; Chodosh, LA; Broadwater, G; Hyslop, T; Shepherd, JH; Hollern, DP; He, X; Perou, CM; Chai, S; Ashby, BK; Vincent, BG; Snyder, JC; Force, J; Morse, MA; Lyerly, HK; Hartman, ZC
MLA Citation
Crosby, Erika J., et al. “Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.Clin Cancer Res, vol. 26, no. 17, Sept. 2020, pp. 4670–81. Pubmed, doi:10.1158/1078-0432.CCR-20-0389.
URI
https://scholars.duke.edu/individual/pub1453955
PMID
32732224
Source
pubmed
Published In
Clinical Cancer Research
Volume
26
Published Date
Start Page
4670
End Page
4681
DOI
10.1158/1078-0432.CCR-20-0389

Research Areas:

APOBEC
BRCA genes
Breast--Cancer--Immunotherapy
Cancer/testis Antigens
Homologous Recombination
Inflammatory Breast Cancer
Nanostring
Tumor Immune Microenvironment
Tumor Infiltrating Lymphocytes
X Chromosome Inactivation
X chromosome--Abnormalities