About

Angela M DeMichele, MD, MSCE, FASCO, is the Mariann T. and Robert J. MacDonald Professor in Breast Cancer Care Excellence at the University of Pennsylvania. She is a Senior Scholar at the Center for Clinical Epidemiology and Biostatistics and serves as Co-Leader of the Breast Cancer Program at the Abramson Cancer Center. Additionally, she is Co-Director of the 2-PREVENT Breast Cancer Translational Center of Excellence and Director of Clinical/Translational Research in Solid Oncology within the Division of Hematology/Oncology. Her research expertise encompasses breast cancer, biomarkers, clinical trials, pharmacogenetics, cytokines, host immunogenetics, cancer survivorship, and molecular epidemiology. Her clinical focus includes breast cancer, neoadjuvant therapy, menopausal symptoms related to cancer, and cancer survivorship. Dr. DeMichele has contributed to numerous studies and publications in these areas, advancing understanding and treatment of breast cancer.

Research topics

• Internal medicine
• Medicine
• Oncology
• Gynecology
• Immunology
• Cardiology
• Biology

Selected publications

• Peripheral blood transcriptional profiling predicts tumor subtype and neoadjuvant chemoimmunotherapy outcomes in human breast cancer

  Science Translational Medicine · 2026-04-22

  article

  Dynamic biomarkers of therapy response are critical for precision oncology but often rely on serial tissue biopsies, which are invasive and not always feasible. In contrast, peripheral blood offers a minimally invasive, dynamic window into the evolving systemic immune landscape. Leveraging this, we performed RNA sequencing on 546 peripheral blood samples from 160 patients with high-risk stage II/III human epidermal growth factor receptor 2 (HER2)-negative breast cancer treated with either chemotherapy alone or in combination with immunotherapy (chemoimmunotherapy). Our analysis uncovered immune correlates of tumor subtype and treatment response. For example, samples from patients with triple-negative breast cancer exhibited elevated T cell receptor clonality and robust immune activation profiles. Among patients receiving chemoimmunotherapy, early responders demonstrated high baseline T cell receptor diversity, followed by rapid clonal expansion and activation of T cells after just one treatment cycle. We developed a multiparametric peripheral immune biomarker that integrated baseline and early on-treatment features to predict response to pembrolizumab, which was successfully validated in an independent cohort of 59 patients with breast cancer treated with neoadjuvant dostarlimab. These findings reveal the potential of blood-based immune monitoring to predict immunotherapy benefit, offering an accessible tool for tailoring treatment strategies in breast cancer.

  PublisherDOI

• Impact of Race, Socioeconomic Status, and Clinicopathologic Features on Clinical Outcomes in Triple-Negative Breast Cancer in the ECOG-ACRIN EA1131 Trial

  JCO oncology advances. · 2026-04-01

  articleOpen access

  A higher incidence of triple negative breast cancer (TNBC) and worse social determinants of health (SDOH) both contribute to racial survival disparities among Black women diagnosed with breast cancer. A post hoc analysis of the ECOG-ACRIN EA1131 study (adjuvant platinum versus capecitabine in stage II-III TNBC with residual disease after neoadjuvant chemotherapy) evaluated racial disparities in disease free survival (DFS) and overall survival (OS) among Black and White patients. Of 415 patients enrolled in EA1131, 376 were included in this analysis (308 White [82%] and 68 Black [18%]). Common characteristics included basal-subtype TNBC (77%), grade 3 disease (71%), residual stage II disease (49%), private insurance (70%), and a BMI ≥30 (49%). There were no racial differences in grade, clinical or pathological stage. Black patients were more likely to have basal-subtype TNBC (89% vs 75%; p=0.009), a BMI ≥30 (62% vs 46%; p=0.026), to reside within the lowest neighborhood socioeconomic index (nSES) quartile (39% vs 22%; p=0.008), and have Medicaid (32% vs 13%; p<0.001) compared to White patients. Despite these differences, there were no significant differences in DFS or OS by race (HR 0.99, 95% CI: 0.62-1.57 and HR 0.60, 95% CI: 0.32-1.12, respectively) among Black and White patients.

  PublisherDOI

• Disparities in the Surgical Management of the Axilla by Self-Identified Race in the Multicenter Neoadjuvant I-SPY2 Trial

  Annals of Surgical Oncology · 2025-07-23 · 1 citations

  articleOpen access

  BACKGROUND: Neoadjuvant chemotherapy (NAC) may allow de-escalation of axillary surgery; yet treatment disparities persist. We aimed to assess race-based disparities in use of axillary lymph node surgery (ALND) among patients who achieve a nodal response in the context of a large, multicenter NAC trial. METHODS: We conducted a retrospective analysis of the I-SPY 2 trial. All patients received NAC, but type of surgery was not mandated. Multivariable logistic regression was used to predict odds ratio (OR) of undergoing ALND by race while adjusting for clinical and demographic confounders, including age, region, tumor receptor subtype, clinical and pathologic node status (cN and ypN +/-, respectively), and clinical and pathologic tumor size (cT and ypT, respectively). RESULTS: Among 1394 patients, 79.4% identified as White, 11.2% Black, and 9.4% Asian/other. More than half (52.5%) were cN+ at baseline, and 66.9% were ypN- after NAC, with no significant differences in nodal downstaging by race. Overall ALND rates were higher in Black patients (50.6%) compared to White (37.5%) and Asian/other (38.9%) patients (p = 0.007). Notably, among those who converted from cN+ to ypN-, Black patients underwent ALND more frequently (62%) than White (41.2%) and Asian/other (40%) patients (p = 0.021). In multivariable analysis, Black patients had 70% higher odds of undergoing ALND compared with White patients (OR 1.7, 95% confidence interval (CI) 1.09-2.66, p = 0.02). CONCLUSIONS: Despite no differences in nodal downstaging, Black patients in I-SPY 2 were significantly more likely to undergo ALND. These disparities may stem from unmeasured patient, provider, or systemic factors affecting surgical planning.

  PublisherOA PDFDOI

• Combined prognostic impact of initial clinical stage and residual cancer burden after neoadjuvant systemic therapy in triple-negative and HER2-positive breast cancer: an analysis of the I-SPY2 randomized clinical trial

  Breast Cancer Research · 2025-06-23 · 8 citations

  articleOpen access

  BACKGROUND: Operable triple-negative (TNBC) and HER2-positive breast cancer are often treated with neoadjuvant systemic therapy (NAST). NAST response is highly prognostic, with pathologic complete response (pCR) being associated with low risk of recurrence or death. In contrast, residual disease (RD) after NAST is associated with higher risks and is an indication for escalated postoperative therapy. Recent studies suggest that tumor (T) size and nodal (N) status at diagnosis influence clinical outcomes independent of NAST response. We evaluated the impact of initial clinical stage on clinical outcomes according to response to NAST in I-SPY2. PATIENTS AND METHODS: Patients with stage II or III TNBC or HER2-positive breast cancer treated on the I-SPY2 trial (NCT01042379) with required data on clinical T size and N status prior to NAST, residual cancer burden (RCB) index, recurrence and survival were included. Survival outcomes, including event-free (EFS), distant recurrence-free (DRFS), and overall survival (OS), were assessed using multivariable Cox proportional hazard models. RESULTS: Among 1,033 patients (TNBC: 638, HER2-positive: 395), the median follow-up was 4.4 years (range 0.3-10.2). 47% achieved pCR (TNBC: 44%, HER2-positive: 51%). Smaller baseline T size, but not N status, was associated with higher pCR rates. However, in those not achieving pCR, RCB class was correlated with both baseline T size and N status in TNBC, and with baseline N status (but not T size) in HER2-positive. Among patients with RD, larger baseline T size was independently associated with worse EFS and DRFS in TNBC and HER2-positive, and with OS in TNBC; while N status was associated with EFS and DRFS in TNBC on univariate analysis only. We did not identify an association between baseline T size or N status and outcomes in patients achieving pCR. CONCLUSIONS: Tumor size at diagnosis remained an independent prognostic factor in patients with TNBC and HER2-positive breast cancer with RD after NAST. In contrast, patients achieving pCR had excellent outcomes regardless of initial disease extent, supporting the relevance of pCR as a surrogate endpoint in breast cancer. TRIAL REGISTRATION: I-SPY 2 TRIAL beginning December 31, 2009: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY 2), NCT01042379.

  PublisherOA PDFDOI

• Abstract P3-01-02: Impact of race, socioeconomic status and clinicopathological features on clinical outcomes in triple negative breast cancer in the ECOG-ACRIN EA1131 trial

  Clinical Cancer Research · 2025-06-13

  article

  Abstract Background: Racial disparities in breast cancer outcomes persist despite a decline in overall breast cancer mortality. Black women have a higher incidence of triple negative breast cancer (TNBC), worse social determinants of health (SDOH), and quality of cancer care, which contributes to racial survival disparities. The EA1131 study evaluated patients with clinical stage II-III TNBC with residual disease after completion of neoadjuvant chemotherapy to determine whether invasive disease-free survival (IDFS) would be improved with adjuvant platinum compared with capecitabine. Herein we report a post hoc analysis of EA1131 to evaluate whether racial disparities were observed among patients with residual TNBC. Methods: Our study population included Black and White patients in EA1131. Race was self-reported; participants who identified as part of a racial group with &amp;lt;15 patients or unknown race were excluded from this analysis (n=39). Our primary objective was to evaluate clinicopathological features, basal-subtype, SDOH, and survival outcomes by race in EA1131. The Agency for Healthcare Research Quality (AHRQ) neighborhood socioeconomic index (nSES) was calculated using residential zip codes linked to county level data on occupation, income, poverty, wealth, education, and crowding. Binary and categorical data were analyzed with Fisher’s exact test to evaluate differences in baseline characteristics by race. Cox regression analysis was used to estimate hazard ratios for DFS and overall survival (OS), adjusting for treatment arm, intrinsic subtype (basal vs non-basal), tumor grade, clinical stage prior to neoadjuvant treatment, pathologic stage after neoadjuvant treatment at the time of surgery, BMI, nSES index, and insurance type. Results: Of 415 patients enrolled in EA1131, 376 were included in this analysis (308 White [82%] and 68 Black [18%]). Most patients had basal-subtype TNBC (77%), grade 3 disease (71%), pathologic stage II disease (49%), private insurance (70%), and a BMI ≥30 (49%). There were no racial differences in grade, clinical or pathological stage. Black patients were more likely to have basal-subtype TNBC (89% vs 75%; p=0.009) and a BMI ≥30 (62% vs 46%; p=0.026) compared to White patients. Black patients were more likely to be in the lowest nSES index quartile (39% vs 22%; p=0.008) and have Medicaid (32% vs 13%; p&amp;lt;0.001), while White patients were significantly more likely to have private insurance (73% vs 57%; p=0.013). The median DFS for White patients was 42.6 months compared to 25.1 months for Black patients, but this numerical difference was not statistically significant (p=0.24). There were also no significant differences in DFS or OS by race (HR 1.03, 95% CI: 0.65-1.61 and HR 0.67, 95% CI: 0.36-1.22, respectively), after adjusting for potential confounders. Conclusion: Black patients with residual TNBC enrolled on EA1131 were more likely to have more aggressive basal-subtype tumors, to be obese, and to have lower socioeconomic status. Despite these factors, no significant differences in survival by race were observed. While this analysis was limited due to sample size, one possibility is that enrollment in a clinical trial, by minimizing differences in treatment received, has the potential to mitigate racial inequities in care. Larger studies are necessary to confirm these findings. Citation Format: Moriah Forster, Fengmin Zhao, Sarah Bell, Ingrid A. Mayer, Carlos L. Arteaga, William F. Symmans, Ben H. Park, Brian L. Burnette, Amye J. Tevaarwerk, Sofia F. Garcia, Karen L. Smith, Della F. Makower, Margaret Block, Kimberly A. Morley, Chirag R. Jani, Craig Mescher, Shabana J. Dewani, Bernard Tawfik, Lisa E. Flaum, Erica L. Mayer, William M. Sikov, Eve T. Rodler, Lynne I. Wagner, Angela M. DeMichele, Joseph A. Sparano, Ruth C. Carlos, Antonio C. Wolff, Kathy D. Miller, Sonya Reid. Impact of race, socioeconomic status and clinicopathological features on clinical outcomes in triple negative breast cancer in the ECOG-ACRIN EA1131 trial [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 P3-01-02.

  PublisherDOI

• Supplementary Table S1 from Circulating Tumor Cell Dynamics after CDK4/6 Inhibitor for Hormone Receptor–Positive Metastatic Breast Cancer: A Biomarker Analysis from the PACE Phase II Study

  2025-11-03

  articleOpen access

  &lt;p&gt;Multivariable Cox regression in terms of PFS. CTCs enumeration was corrected for ESR1, PIK3CA, RB1 mutational status and clinically relevant features (i.e., visceral involvement, duration of prior CDK4/6 inhibitor, endocrine sensitivity, therapy between prior CDK4/6i and randomization).&lt;/p&gt;

  PublisherDOI

• Supplementary Figure S2 from Circulating Tumor Cell Dynamics after CDK4/6 Inhibitor for Hormone Receptor–Positive Metastatic Breast Cancer: A Biomarker Analysis from the PACE Phase II Study

  2025-11-03

  articleOpen access

  &lt;p&gt;Changes in CTC enumeration between BL and R8W across treatment arms. Fulv (A), Fulv/Palb (B) and Fulv/Palb/Avel (C)&lt;/p&gt;

  PublisherOA PDFDOI

• Circulating Tumor Cell Dynamics after CDK4/6 Inhibitor for Hormone Receptor–Positive Metastatic Breast Cancer: A Biomarker Analysis from the PACE Phase II Study

  Clinical Cancer Research · 2025-08-25 · 1 citations

  article

  PURPOSE: Circulating tumor cells (CTC) are biomarkers associated with poor prognosis and treatment resistance in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). This analysis evaluates the prognostic role of baseline CTC enumeration and its interaction with treatment regimens in patients progressing on CDK4/6 inhibitors. EXPERIMENTAL DESIGN: The PACE trial is a phase II, multicenter, randomized study of patients with HR+/HER2- MBC experiencing progression on aromatase inhibitors and CDK4/6 inhibitors. Patients were randomized 1:2:1 to receive fulvestrant (F), F + palbociclib (F + P), or F + P + avelumab (F + P + A). Baseline CTCs were enumerated using CellSearch with a threshold of ≥5 CTCs/7.5 mL to classify patients as stage IVindolent or stage IVaggressive. Concurrent ctDNA analysis was performed using Guardant360. Progression-free survival (PFS) was the primary endpoint. RESULTS: Among 220 randomly assigned patients, 203 were evaluable for baseline CTCs; 76% had detectable CTCs and 49% were stage IVaggressive. Patients with de novo MBC were more frequently stage IVaggressive (47.5% vs. 30.8%). Baseline CTCs were prognostic with median PFS of 5.7 months for stage IVindolent and 3.5 months for stage IVaggressive patients [HR = 1.69; 90% confidence interval (CI), 1.27-2.24; P < 0.001]. In stage IVaggressive patients, F + P and F + P + A improved PFS versus fulvestrant alone (HR = 0.43; 90% CI, 0.25-0.71 and HR = 0.26; 90% CI, 0.14-0.49, respectively). No benefit was observed in stage IVindolent patients (interaction P = 0.0148 and P = 0.0033, respectively). CONCLUSIONS: Baseline CTC enumeration provides significant prognostic information in HR+/HER2- MBC. Stage IVaggressive patients derive greater benefit from F + P or F + P + A over fulvestrant alone, independent of clinical or ctDNA features. This highlights the potential of CTCs to guide treatment decision-making.

  PublisherDOI

• Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial

  Nature Medicine · 2025-09-02 · 22 citations

  article1st authorCorresponding
  PublisherDOI

• HER2DX and survival outcomes in early-stage HER2-positive breast cancer: an individual patient-level meta-analysis

  The Lancet Oncology · 2025-07-15 · 14 citations

  article
  PublisherDOI

Recent grants

• Project 3: Characterization of the biology of non-responders using Imaging and molecular analysis to inform treatment

  NIH · $36.3M · 2017–2028

• Secondary Prevention through Surveillance and Intervention

  NIH · $3.2M · 2016–2022

• Radiobiology and Imaging Program

  NIH · $93.0M · 1997–2027

• NIH Grant K23CA081009

  NIH · $640k · 2005

• NIH Grant R01CA104581

  NIH · $1.4M · 2010

Frequent coauthors

• Christina Yau

  University of California, San Francisco

  1422 shared

• Douglas Yee

  Masonic Cancer Center

  1290 shared

• AJ Chien

  Gemini Computers (United States)

  956 shared

• LJ Esserman

  UCSF Helen Diller Family Comprehensive Cancer Center

  945 shared

• Rita Nanda

  University of Chicago

  938 shared

• Debu Tripathy

  The University of Texas MD Anderson Cancer Center

  915 shared

• MC Liu

  865 shared

• Claudine Isaacs

  850 shared

Labs

• Angela M DeMichele LabPI

Awards & honors

• Mariann T. and Robert J. MacDonald Professor in Breast Cance…
• Senior Scholar, Center for Clinical Epidemiology and Biostat…
• Co-Leader, Breast Cancer Program, Abramson Cancer Center, Un…
• Co-Director, 2-PREVENT Breast Cancer Translational Center of…
• Director of Clinical/Translational Research in Solid Oncolog…