Rachel Elizabeth Factor
· Associate Professor of PathologyVerifiedDuke University · Pathology
Active 1997–2026
About
Rachel Elizabeth Factor is an Associate Professor of Pathology at Duke University and a member of the Duke Cancer Institute. She is based at Duke Medicine Circle in Durham, North Carolina. Her professional role involves teaching, research, and clinical activities within the Department of Pathology. As a faculty member, she contributes to the academic and research missions of Duke University, with a focus on pathology and cancer research.
Research topics
- Computer Science
- Medicine
- Pathology
- Biology
- Pharmacology
- Oncology
- Internal medicine
- Computational biology
- World Wide Web
- Genetics
Selected publications
Spatial proteomics of breast ductal carcinoma in situ reveal distinct regional differences
Scientific Reports · 2026-03-13
articleOpen accessBreast ductal carcinoma in situ is a common non-invasive clinical finding that can progress to invasive breast cancer (IBC). Spatial proteomics can provide an additional dimension to our understanding of this disease and its capacity to progress. A subset (n = 103 patients) of a previously established cohort of primary DCIS specimens with known clinical outcomes was analyzed using a multiplexed proteomic platform (Nanostring GeoMx) for simultaneous quantitative measurement of 53 antigens. 1262 spatially distinct regions of interest (ROIs) (1226 ROIs after filtering) were collected, including inside DCIS epithelium, adjacent stroma, co-existing benign breast epithelium, and biopsy sites. We identified two predominant subgroups of DCIS, ER high/HER2 low and ER low/HER2 high. Levels of tumor associated proteins varied between benign and DCIS, between ER + and ER- patients, and between different regions within the DCIS epithelium. In addition, we identified several immune-related antigens (CD127, CD8, and PD-L2) within the DCIS epithelium that are associated with invasive progression. Comparison of antigen levels in matched ipsilateral breast events (both DCIS recurrences and IBC) demonstrates an effect of hormonal therapy on the phenotype of subsequent cancers. This study adds a spatially resolved proteomic dimension to our understanding of DCIS, its microenvironment, and its propensity to progress to IBC.
Cureus · 2025-03-01
articleOpen accessPhyllodes tumors (PTs) of the breast are rare fibroepithelial neoplasms with high rates of local recurrence (LR) for which surgical excision remains the mainstay of treatment. The recommended surgical margin width is debated and varies based on the histologic grade. We present a case of a middle-aged woman with a well-circumscribed borderline PT who underwent margin re-excision, with a distinct focus of the PT detected at a previously negative margin. Given the high rates of LR and potential for histologic upgrade at the time of recurrence, combined with the current limited understanding of peritumoral tissue and possible satellite foci, a wide negative margin remains the recommendation for borderline PTs.
Cancer Research · 2025-04-21 · 1 citations
articleEnd stage breast cancer often presents with oligometastatic tumors and lacks effective treatment options. Previous studies leveraged post-mortem tissue procurement (also called rapid autopsy) programs to collect tumors shortly after death for profiling by bulk whole exome sequencing (WES). This has revealed substantial heterogeneity in the genomes of metastatic estrogen receptor-positive (ER+) and triple-negative breast cancers. In order to understand the heterogeneity of both the genotypes, transcriptional phenotypes, and evolution of these tumors, we collected multi-site metastatic tumors from two end-stage ER+ breast cancer patients enrolled in the LEGACY rapid post-mortem tissue procurement trial. Metastatic tumors were profiled using WES and single-nuclei RNA sequencing (snRNA-seq). We reconstructed high resolution phylogenies for each patient using the mutation called from the snRNA-seq reads to determine the subclonal architecture of cancer cells. Based on the mutation patterns, the gene expression profiles, and the subclonal architecture, we found that the tumors in each patient were divided into two distinct subtypes. A majority of the tumors were grouped into a subtype characterized by a high intra-tumor heterogeneity, with many cell lineages shared widely across metastasis, indicating extensive and undirected dissemination. The cancer cells of this subtype exhibited an EMT gene expression signature. In contrast, the second tumor subtype observed was rare and demonstrated little intra-tumor heterogeneity, a proliferative gene expression signature, and an interferon response signature present widely across cells in the microenvironment. Across all tumors, macrophages comprised the majority of the immune cells. Low diversity tumor macrophages exhibited strong activation of multiple interferon signaling pathways compared to high diversity tumor macrophages. Interestingly, these macrophages expressed a mixture of M1 and M2 polarization markers as STAT1, SOCS1, ISG15, ISG20, MX1, MX2, OAS1, OAS3 that did not correspond to classical M1 or M2 polarization states. This contrast demonstrates that multi-site metastatic tumors and their microenvironment adopt dichotomous states, which may contribute to the difficulties in treating progressive disease. It also underscores the need for a comprehensive and personalized late-stage therapeutic strategy to target the diversity of existing tumor phenotypes. Citation Format: Isaac Bishara, Xuan Liu, Jason l. Griffiths, Patrick A. Cosgrove, Jasmine R. McQuerry, Jiayi Liu, Kena K. Ihle, Eliza R. Bacon, Feng Chi, Pierre Wallet, Vince Grolmusz, Diana Simons, Benjamin Copeland, Lance Pflieger, JinFeng Chen, Sumana Majumdar, Terron T. Crowder, Rena Emond, Rachel Factor, David D. Bowtell, Adam L. Cohen, Daniel D. Schmolze, Peter P. Lee, Lusine Tumyan, James R. Waisman, Andrea Bild, Aritro Nath, Jeffrey T. Chang. End-stage breast cancer metastases manifest as two subtypes with distinct dissemination patterns, proliferation/EMT signatures, and immune microenvironments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5133.
Journal of Clinical Pathology · 2025-08-19 · 1 citations
articleAIMS: For phyllodes tumours (PT), local and distant recurrence rates increase with higher grades and are difficult to predict. The Singapore nomogram has been used to predict recurrence events for PT. We aimed to test this nomogram for accuracy in a US cohort and to compare with a histological score. METHODS: Patients with PT were selected from a prospective institutional database. Histological parameters and margin status were used to estimate the nomogram score and the histological score, as previously defined. Multivariable analyses were used to estimate the association of recurrence-free survival (RFS) with individual factors, nomogram score and histological score. Harrel's C-index was estimated. RESULTS: Of 81 PT cases, 25.9% were benign, 40.7% borderline and 33.3% malignant. Recurrences occurred in 33.3% (n=27). The adjusted RFS analysis including the four factors used in the Singapore nomogram performed well (C-index of 0.78). However, despite a higher nomogram score being associated with increased risk of recurrence (HR 1.03, 1.01-1.05, p=0.007), the individual numeric scale defined in the nomogram only moderately fit our data (C-index of 0.66). Patients with higher histological scores also had an increased risk of recurrence (HR 1.25, 1.07-1.47, p=0.005; C-index of 0.70). CONCLUSION: Histological score more accurately predicted PT recurrence in our cohort, which includes a higher proportion of higher-grade PT. Refining the nomogram to include factors specific to malignant PT and factors with more variance, as well as refining the assigned weights, may result in improved performance. This study identifies an opportunity for international collaboration to refine the predictive model.
Research Square · 2025-10-29
preprintOpen accessJournal of Pathology Informatics · 2025-03-08
erratumOpen accessSenior authorCorresponding[This corrects the article DOI: 10.1016/j.jpi.2022.100092.].
Laboratory Investigation · 2025-03-01
articleOpen accessSenior authorCancer Research · 2025-04-21
articleAbstract Introduction: Ductal carcinoma in situ (DCIS) is a potential precursor to invasive breast cancer (IBC). The trajectory of an individual’s DCIS, if it will progress to IBC or remain as DCIS is difficult to predict. Currently >80% of DCIS is detected through mammographic screening of breast calcifications. Despite the close association of calcifications with DCIS, their role in the development of DCIS and/or its progression to IBC remains largely unexplored. In this study, we present a spectroscopy based analytical approach to probe chemical compositional changes of both DCIS associated breast calcifications and surrounding soft tissue aiming to identify a cohort at increased risk for invasive progression. Experimental Procedures: Tissue samples from 316 DCIS patients without invasive cancer were obtained from multiple centres as part of the PRECISION consortium (The Netherlands, UK and USA). Three consecutive tissue sections were obtained each of the tissue biopsies. Mid-infrared (mid-IR) and Raman hyperspectral imaging was performed independently on two sections that were left unstained. The third H&E-stained section was used to annotate calcifications and histopathological features. All DCIS samples had known outcome (i) ‘pure DCIS as controls’ (DCIS without progression to invasion) (n=193), (ii) ‘DCIS with progression to invasion as cases’ (DCIS from patients who subsequently developed invasive disease after initial treatment) (n=123). Spectral features of DCIS calcifications and surrounding soft tissue were used as inputs for analysis. Data was divided into a discovery and a validation set. Cluster analysis followed by Principal component analysis fed linear discriminant analysis was carried out on the discovery set to develop DCIS prediction models. Results: For the Raman data, a mean area under the receiver operating characteristic curve (AUROC) value of 0.85 was obtained using calcification spectral features, and 0.75 using soft tissue spectral features in distinguishing controls from cases (N=118 vs 52). Similar analysis on the IR data showed a mean AUROC value of 0.68 for calcification, 0.78 for epithelial and 0.80 for stromal components (N=97 vs 61). Preliminary analysis shows changes in phosphate to carbonate ratio and variations in magnesium whitlockite content in calcifications, and protein secondary structural changes in soft tissue, between the two groups. The models will be tested independently on the validation set and the outcomes will be presented at the AACR conference. Conclusion: Spectroscopic chemical analysis of breast calcifications and soft tissue show promise in predicting the likely progression of DCIS to IBC. Pending further independent validation, these techniques appear to be novel image-based risk assessment tools that can potentially be utilised to inform DCIS prognosis and treatment options. Citation Format: Jayakrupakar Nallala, Doriana Calabrese, Sarah Gosling, Esther Lips, Ihssane Bouybayoune, Rachel Factor, Sarah Pinder, Lorraine King, Jeffrey Marks, Thomas Lynch, Donna Pinto, Alastair Thompson, Elinor Sawyer, Jelle Wesseling, Shelley Hwang, Keith Rogers, Nick Stone, Grand Challenge PRECISION consortium. Predicting the prognosis of ductal carcinoma in situ through chemical analysis of breast microcalcifications and soft tissue using infrared and Raman spectroscopy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3353.
Clinical Cancer Research · 2025-06-13 · 1 citations
articleAbstract Background: Over 50,000 women in the United States will be diagnosed with ductal carcinoma in situ (DCIS) this year alone. Almost all of these diagnoses will be made in completely asymptomatic individuals with a highly variable risk of progression to invasive cancer. In some low-risk malignancies, “watchful waiting,” is offered as a treatment option. Such an approach is likely reasonable for some DCIS and could reduce the harms of treatment while helping to identify those most likely to benefit from more aggressive therapy. To date, this approach has not been tested in a clinical trial setting. Methods: The COMET study (Comparing an Operation to Monitoring, with or without Endocrine Therapy for low risk DCIS; AFT-25) is a large pragmatic randomized non-inferiority trial that compares oncologic outcomes between patients randomized to guideline concordant care (GCC; surgery +/- radiation therapy) or active monitoring (AM). The study population were women seeking treatment for DCIS at one of the Alliance Clinical Trial sites. Eligible participants were age>40 with low-intermediate grade estrogen and/or progesterone receptor positive, HER2 receptor negative (if HER2 tested) DCIS on core biopsy without microinvasive or invasive cancer. The choice for endocrine therapy was offered in both groups. Participants in the AM group had surgical intervention only upon diagnosis of invasive progression. All study endpoints were collected prospectively. Results: This is the first planned interim Intention-to-Treat (ITT) analysis of the COMET trial primary endpoints at a median follow up of XX months. We will present patient characteristics for the 997 participants who enrolled in the study and were randomized to either GCC or AM. The primary endpoint to be presented is whether the ipsilateral invasive cancer rate for AM is non-inferior to that for GCC. Characteristics of invasive cancer events in the two groups will be compared. Secondary endpoints (rates of mastectomy, radiation, chemotherapy) and survival endpoints between groups will also be presented. Conclusion: These data will provide the first randomized trial evidence of whether an active monitoring strategy is a safe alternative for women with low-risk DCIS. Longer-term data could support practice changing guidance as to how DCIS is managed and treated and will have future implications for treatment guidelines for these excellent prognosis patients. Citation Format: Eun-Sil Hwang, Terry Hyslop, Thomas Lynch, Marc D Ryser, Anna Weiss, Anna Wolf, Kelsey Norris, Meredith Witten, Lars Grimm, Stuart Schnitt, Sunil Badve, Rachel Factor, Elizabeth Frank, Deborah Collyar, Desiree Basila, Donna Pinto, Mark A Watson, Robert West, Louise Davies, Jenny Donovan, Ayako Shimada, Yutong Li, Yan Li, Antonia V Bennett, Shoshana Rosenberg, Jeff Marks, Eric Winer, Marc Boisvert, Armando Giuliano, Kelsey Larson, Kathleen Yost, Priscilla McAuliffe, Lisa Carey, Alastair Thompson, Ann H Partridge. Early Oncologic Outcomes Following Active Monitoring or Surgery (+/- Radiation) for Low Risk DCIS: the Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET) Study (AFT-25) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr GS2-05.
Cancer Research · 2024-03-22
articleAbstract Metastatic breast cancers show variable clinical responses due to inherent heterogeneity, both within tumors and among patients. Studies mainly examine molecular diversity across different patients' tumors and genetic variance within a single tumor. Yet, the variability among multiple tumors or metastases in a single patient remains underexplored. Our study investigates this intrapatient heterogeneity, examining cell and tumor evolution from a single genetic source in metastatic breast cancer. In a warm procurement trial involving 6 patients with multi-site tumors, samples were collected for detailed molecular analysis. Whole exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq) were used to analyze genetic similarities and disparities. WES data revealed mutational patterns and copy number alterations, showing homogeneity and heterogeneity in tumors within patients. Further, phylogenetic analysis with scRNA-seq variant calls paired with transcriptional phenotypes uncovered a MYC-enriched subclonal population in a metastatic site. Integrating WES and scRNA-seq data provided a clearer understanding of the genomic and phenotypic features in and between patients. Our WES study revealed significant interpatient variations in genetic drivers and CNA profiles. Among five patients, two showed APOBEC and HR mutations, linked to increased tumor mutations. Despite general genetic homogeneity, there were exceptions. Tumors in Patient 3's upper lymph nodes had distinct genetics compared to abdominal tumors. Unique genetic patterns were also noted in the pancreas and mesentery of Patients 3 and 7, respectively. Genetic findings were supported by transcriptional analysis, showing distinct expression patterns in specific sites. Phylogenetic analysis highlighted intratumor heterogeneity, as shown by variations in phylogenetic composition and gene expression across samples. Notably, in patients with the most samples (Patients 3 and 7), a conserved cell clade, evolved early and primarily located in a single site, displayed a high proliferation gene expression signature closely associated with Myc activity. This underscores the importance of early clonal expansions in tumor evolution and suggests potential therapeutic targets in these early, proliferative cells. Our study highlights the vital role of intrapatient heterogeneity in understanding cancer complexity and treatment resistance. By analyzing genetic and phenotypic variability in multi-site tumors within patients, and Myc's key role in tumor growth and evolution, our research offers new insights into tumor evolution. This underscores the need for personalized oncology treatments based on each patient's tumor genetics. Citation Format: Isaac Bishara, Xuan Liu, Jason Griffiths, Jiayi Liu, Patrick Cosgrove, Jasmine R. McQuerry, Feng Chi, Pierre Wallet, Vince K. Grolmusz, Benjamin Copeland, Lance Pflieger, Jinfeng Chen, Sumana Majumdar, Grace Ronquillo, Terron Crowder, Rena Emond, Rachel Factor, Eliza Barragan, David Bowtell, Adam Cohen, Daniel D. Schmolze, Peter Lee, Kena Ihle, Lusine Tumyan, Aritro Nath, James Waisman, Andrea Bild, Jeff Chang. Exploring intrapatient heterogeneity in metastatic breast cancer: Insights into tumor evolution from a warm procurement trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7353.
Frequent coauthors
- 99 shared
Philip S. Bernard
University of Utah
- 65 shared
Carol Sweeney
University of Utah
- 63 shared
Bette J. Caan
Kaiser Permanente
- 63 shared
Lawrence H. Kushi
Kaiser Permanente
- 59 shared
Marilyn L. Kwan
Kaiser Permanente
- 59 shared
Laurel A. Habel
Kaiser Permanente
- 58 shared
Erin Weltzien
- 57 shared
Adrienne Castillo
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