Sarah Sammons

Positions:

Assistant Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2012

Thomas Jefferson University, Sidney Kimmel Medical College

Internal Medicine Residency

University of Maryland School of Medicine

Hematology-Oncology Fellowship

Duke University School of Medicine

Grants:

Phase II Multicenter Study of Durvalumab (MEDI4736) and Olaparib in PlatinumTreated Advanced Triple Negative Breast Cancer ¿ DORA

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

Determining the clinical efficacy and predictive biomarkers of mirvetuximab soravtansine (IMGN853) in folate receptor alpha (FRA) expressing, chemotherapy refractory triple negative breast cancer

Administered By
Medicine, Medical Oncology
Awarded By
National Comprehensive Cancer Network
Role
Principal Investigator
Start Date
End Date

TNBC Study

Administered By
Duke Clinical Research Institute
Awarded By
AstraZeneca AB
Role
Principal Investigator
Start Date
End Date

A Randomized, Multicenter, Double-blind, Placebo-controlled Phase 3 Study of Nivolumab VersusPlacebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Patients WithHigh-risk, Estrogen Receptor-Positive (ER+), Human Epider

Administered By
Duke Cancer Institute
Awarded By
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
End Date

A Phase 1a/1b Study of LY3484356 Administered as Monotherapy and in Combination with Abemaciclib to Patients with ER+, HER2-Locally Advanced or Metastatic Breast Cancer

Administered By
Duke Cancer Institute
Awarded By
Eli Lilly and Company
Role
Principal Investigator
Start Date
End Date

Publications:

HER2-positive breast cancer

The treatment of HER2-positive (HER2+) metastatic breast cancer (mBC) has drastically evolved with the clinical success and approval of several HER2-directed therapies, including trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1), and lapatinib. Standard of care first-line therapy for HER2+ mBC is the combination of pertuzumab, trastuzumab, and a taxane. After progression, T-DM1 is the most supported choice for second-line therapy. Once patients have received trastuzumab, pertuzumab, and T-DM1 in the metastatic setting, there is little evidence for the optimal sequence or duration of HER2-directed therapy, and clinical trials should be considered. Continuing HER2-targeted therapies following progression on trastuzumab has shown benefit. Lapatinib combination therapies are clinically efficacious in heavily pretreated populations. Sequential single-agent chemotherapy with trastuzumab is a reasonable approach in later lines of therapy.
Authors
Sammons, S; Blackwell, K
MLA Citation
Sammons, S., and K. Blackwell. “HER2-positive breast cancer.” HER2-Positive Breast Cancer, 2018, pp. 63–74. Scopus, doi:10.1016/B978-0-323-58122-6.00004-0.
URI
https://scholars.duke.edu/individual/pub1462962
Source
scopus
Published Date
Start Page
63
End Page
74
DOI
10.1016/B978-0-323-58122-6.00004-0

Real-world Evidence of Diagnostic Testing and Treatment Patterns in US Patients With Breast Cancer With Implications for Treatment Biomarkers From RNA Sequencing Data

Objective/Background: We performed a retrospective analysis of longitudinal real-world data (RWD) from patients with breast cancer to replicate results from clinical studies and demonstrate the feasibility of generating real-world evidence. We also assessed the value of transcriptome profiling as a complementary tool for determining molecular subtypes. Methods: De-identified, longitudinal data were analyzed after abstraction from records of patients with breast cancer in the United States (US) structured and stored in the Tempus database. Demographics, clinical characteristics, molecular subtype, treatment history, and survival outcomes were assessed according to strict qualitative criteria. RNA sequencing and clinical data were used to predict molecular subtypes and signaling pathway enrichment. Results: The clinical abstraction cohort (n = 4000) mirrored the demographics and clinical characteristics of patients with breast cancer in the US, indicating feasibility for RWE generation. Among patients who were human epidermal growth factor receptor 2-positive (HER2 ), 74.2% received anti-HER2 therapy, with ∼70% starting within 3 months of a positive test result. Most non-treated patients were early stage. In this RWD set, 31.7% of patients with HER2 immunohistochemistry (IHC) had discordant fluorescence in situ hybridization results recorded. Among patients with multiple HER2 IHC results at diagnosis, 18.6% exhibited intra-test discordance. Through development of a whole-transcriptome model to predict IHC receptor status in the molecular sequenced cohort (n = 400), molecular subtypes were resolved for all patients (n = 36) with equivocal HER2 statuses from abstracted test results. Receptor-related signaling pathways were differentially enriched between clinical molecular subtypes. Conclusions: RWD in the Tempus database mirrors the overall population of patients with breast cancer in the US. These results suggest that real-time, RWD analyses are feasible in a large, highly heterogeneous database. Furthermore, molecular data may aid deficiencies and discrepancies observed from breast cancer RWD. Longitudinal real-world data (RWD) from a large cohort of patients with breast cancer (n = 4000) were analyzed to test whether results were consistent with previous clinical studies and demonstrate real-world evidence validity. Then, whole-transcriptome sequencing was evaluated as a complementary diagnostic tool (n = 400). The cohort mirrored the general population with breast cancer in the United States, indicating real-world evidence feasibility, whereas transcriptome profiling supported and augmented standard diagnostic tests. + +
Authors
Fernandes, LE; Epstein, CG; Bobe, AM; Bell, JSK; Stumpe, MC; Salazar, ME; Salahudeen, AA; Pe Benito, RA; McCarter, C; Leibowitz, BD; Kase, M; Igartua, C; Huether, R; Hafez, A; Beaubier, N; Axelson, MD; Pegram, MD; Sammons, SL; O'Shaughnessy, JA; Palmer, GA
MLA Citation
URI
https://scholars.duke.edu/individual/pub1472859
Source
scopus
Published In
Clinical Breast Cancer
Published Date
DOI
10.1016/j.clbc.2020.11.012

Receptor discordance in breast cancer brain metastases: when knowledge is power.

MLA Citation
Sammons, Sarah, et al. “Receptor discordance in breast cancer brain metastases: when knowledge is power.Neuro Oncol, vol. 22, no. 8, Aug. 2020, pp. 1060–61. Pubmed, doi:10.1093/neuonc/noaa131.
URI
https://scholars.duke.edu/individual/pub1457339
PMID
32479604
Source
pubmed
Published In
Neuro Oncol
Volume
22
Published Date
Start Page
1060
End Page
1061
DOI
10.1093/neuonc/noaa131

The Dysregulated Pharmacology of Clinically Relevant <i>ESR1</i> Mutants is Normalized by Ligand-activated WT Receptor.

The estrogen receptor (ER/<i>ESR1</i>) is expressed in a majority of breast cancers and drugs that inhibit ER signaling are the cornerstone of breast cancer pharmacotherapy. Currently, aromatase inhibitors are the frontline endocrine interventions of choice although their durability in metastatic disease is limited by activating point mutations within the ligand-binding domain of <i>ESR1</i> that permit ligand-independent activation of the receptor. It has been suggested that the most commonly occurring <i>ESR1</i> mutations would likely compromise the clinical activity of selective estrogen receptor downregulators and selective estrogen receptor modulators (SERMs) when used as second-line therapies. It was unclear, however, how these mutations, which are likely coexpressed in cells with ER<sup>WT</sup>, may impact response to ER ligands in a clinically meaningful manner. To address this issue, we dissected the molecular mechanism(s) underlying <i>ESR1</i>-mutant pharmacology in models relevant to metastatic disease. These studies revealed that the response of <i>ESR1</i> mutations to ligands was dictated primarily by the relative coexpression of ER<sup>WT</sup> in cells. Specifically, dysregulated pharmacology was only evident in cells in which the mutants were overexpressed relative to ligand-activated ER<sup>WT</sup>; a finding that highlights the role of allelism in determining ER-mutant pharmacology. Importantly, we demonstrated that the antagonist activity of the SERM, lasofoxifene, was not impacted by mutant status; a finding that has led to its clinical evaluation as a treatment for patients with advanced ER-positive breast cancer whose tumors harbor <i>ESR1</i> mutations.
Authors
Andreano, KJ; Baker, JG; Park, S; Safi, R; Artham, S; Oesterreich, S; Jeselsohn, R; Brown, M; Sammons, S; Wardell, SE; Chang, C-Y; Norris, JD; McDonnell, DP
MLA Citation
Andreano, Kaitlyn J., et al. “The Dysregulated Pharmacology of Clinically Relevant ESR1 Mutants is Normalized by Ligand-activated WT Receptor.Molecular Cancer Therapeutics, vol. 19, no. 7, July 2020, pp. 1395–405. Epmc, doi:10.1158/1535-7163.mct-19-1148.
URI
https://scholars.duke.edu/individual/pub1440745
PMID
32381587
Source
epmc
Published In
Molecular Cancer Therapeutics
Volume
19
Published Date
Start Page
1395
End Page
1405
DOI
10.1158/1535-7163.mct-19-1148

The Evolving Complexity of Treating Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer: Special Considerations in Older Breast Cancer Patients-Part I: Early-Stage Disease.

The median age for breast cancer diagnosis is 62 years, but a disproportionate number of patients are over the age of 75 years and the majority of those have hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative cancers. This review provides a logical algorithm to guide providers through the many complicated issues involved in adjuvant systemic therapy decisions in older patients with hormone receptor-positive, HER2-negative breast cancer. For this subtype of breast cancer, the mainstay of treatment is surgery and adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor (AI). Adjuvant chemotherapy is added to the treatment regimen when the benefits of treatment are deemed to outweigh the risks, making the risk-benefit discussion particularly important in older women. Traditional tools for cancer risk assessment and genomic expression profiles (GEPs) are under-utilized in older patients, but yield equally useful information about cancer prognosis as they do in younger patients. Additionally, there are tools that estimate life-limiting toxicity risk from chemotherapy and life expectancy, which are both important issues in the risk-benefit discussion. For very low-risk cancers, such as non-invasive and small lymph node (LN)-negative cancers, the benefits of any adjuvant therapy is likely outweighed by the risks, but endocrine therapy might be considered to prevent future new breast cancers. For invasive tumors that are > 5 mm (T1b or larger) or involve LNs, adjuvant endocrine therapy is recommended. Generally, AIs should be included, though tamoxifen is effective and should be offered when AIs are not tolerated. Bone-preserving agents and high-dose vitamin D are options to preserve bone density or treat osteoporosis, especially in older women who are taking AIs. Where the risk-reducing benefit from adjuvant chemotherapy outweighs the toxicity risk, adjuvant chemotherapy should be considered. Adjuvant chemotherapy has similar benefits in older and younger patients and standard regimens are preferred. Several exciting clinic trials are underway and have included older patients, including those adding molecularly targeted agents, cyclin-dependent kinase (CDK) 4/6 inhibitors and everolimus, to endocrine therapy in the adjuvant setting. The high incidence of breast cancer in older women should drive us to design clinical trials for this population and emphasize their inclusion in ongoing trials as much as possible.
Authors
Sammons, S; Sedrak, MS; Kimmick, GG
URI
https://scholars.duke.edu/individual/pub1433298
PMID
32100240
Source
pubmed
Published In
Drugs Aging
Volume
37
Published Date
Start Page
331
End Page
348
DOI
10.1007/s40266-020-00748-z