About

Gini Fleming, MD, is a Professor of Medicine at the University of Chicago, specializing in medical oncology with a focus on new drug development for advanced breast and gynecologic malignancies, including cervical, ovarian, and endometrial cancers. She directs the GYN medical oncology program and co-directs the Developmental Therapeutics program. Dr. Fleming has a background that includes an MD from the University of Illinois Chicago and a BA in Chemistry from Oberlin College. Her research encompasses validation of cancer risk calculators, clinical trials on genetic testing accessibility, and studies on treatment responses among diverse populations. She serves as the GYN section editor for the Journal of Clinical Oncology and has authored over 200 peer-reviewed publications, contributing significantly to the understanding and treatment of gynecologic and breast cancers.

Research topics

• Oncology
• Medicine
• Internal medicine
• Pathology
• Surgery
• Intensive care medicine
• Nuclear medicine
• Biology
• Radiology
• Bioinformatics
• Urology

Selected publications

• Relacorilant plus nab-paclitaxel demonstrates a progression-free survival benefit in ovarian cancer independent of tumor glucocorticoid receptor (GR) expression levels

  Gynecologic Oncology · 2026-04-23

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• Targeting androgen and glucocorticoid receptors for endometrial cancer treatment

  Gynecologic Oncology · 2026-02-01

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• Neighborhood deprivation & oncologic outcomes in cervical cancer at a large, urban, tertiary care and NCI referral center

  Gynecologic Oncology · 2026-02-01

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• Ovarian cancer cell glucocorticoid receptor activation increases myeloid-derived suppressor cell tumor infiltration

  Endocrinology · 2026-02-21 · 1 citations

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  High ovarian cancer cell glucocorticoid receptor (GR) expression is associated with reduced progression-free survival (PFS) despite standard debulking surgery and adjuvant chemotherapy. Although not previously linked to tumor-cell GR expression, a "cold" (immune-suppressive) ovarian cancer tumor microenvironment (TME) is also associated with poor prognosis. In this study, analysis of The Cancer Genome Atlas (TCGA) ovarian cancer database revealed that NR3C1 (GR) mRNA was positively correlated with immunosuppressive cytokine gene expression. Higher tumor NR3C1 expression also associated with gene expression encoding cellular markers of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). In vitro, GR activation in human and mouse ovarian cancer cell lines led to increased secretion of pro-tumorigenic cytokines, including G-CSF, M-CSF, TGFβ2, and CXCL2. Co-treatment with a GR agonist (mimicking endogenous cortisol) and a selective GR modulator (SGRM) significantly reduced cytokine secretion. In human xenograft mouse models, systemic administration of a SGRM decreased serum immunosuppressive cytokine concentrations and mouse MDSC tumor infiltration, suggesting that tumor-cell GR activity and cytokine secretion contribute to MDSC generation and recruitment. Additionally, in a syngeneic model of GR-positive ovarian cancer, both pharmacologic GR antagonism and tumor cell-specific GR knockdown reduced intratumoral and circulating MDSCs, as well as intratumoral Tregs. Collectively, these findings suggest that ovarian cancer-cell GR activity contributes to maintaining a highly immunosuppressive TME through secretion of tumor-derived cytokines. We conclude that ovarian cancer cell GR activity has a previously unrecognized role in inhibiting anti-tumor immunity and that systemic GR modulation could improve immunotherapy outcomes in ovarian cancer.

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• Investigating the mechanisms of resistance to trastuzumab-deruxtecan in endometrial cancers

  Gynecologic Oncology · 2026-04-23

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• Identifying premenopausal patients with early-stage hormone receptor–positive breast cancer at minimal risk of distant recurrence by breast cancer index

  The Breast · 2026-01-29

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  BACKGROUND: An adjusted Breast Cancer Index (BCI) model with an additional cutpoint identified postmenopausal women with hormone-receptor-positive node-negative disease at minimal (<5%) risk of distant recurrence (DR) within 10 years. METHODS: 2025 premenopausal patients with hormone-receptor-positive node-negative breast cancer, randomized to adjuvant endocrine therapy in SOFT and TEXT (35.6% and 40.4% received adjuvant chemotherapy, respectively), previously had BCI assessed. The additional BCI cutpoint re-classified a subset of the low-risk group into minimal-risk; those in intermediate- or high-risk groups were unchanged. The 10-year DR was estimated by Kaplan-Meier method. RESULTS: The adjusted BCI model re-classified 17.8 % and 19.6 % of node-negative disease in SOFT and TEXT into BCI minimal-risk groups; 43.2 % and 38.3 % remained classified in low-risk groups, respectively. In SOFT, the estimated 10-year DR was 2.3 % (95 %CI 0.9-6.0 %) and 4.1 % (95 %CI 2.6-6.5 %) in the minimal-risk and revised low-risk groups, respectively. In TEXT, the estimated 10-year DR was 2.0 % (95 %CI 0.7-6.2 %) and 4.6 % (95 %CI 2.8-7.7 %) in the minimal- and low-risk groups, respectively. CONCLUSIONS: This study confirmed prognostic ability of the minimal-risk BCI cutpoint to classify patients estimated to have minimal-risk of distant recurrence within 10 years among premenopausal patients treated for hormone-receptor-positive node-negative breast cancer, providing relevant information for personalizing adjuvant endocrine therapy. SOFT: (clinicaltrials.gov NCT00066690) TEXT: (clinicaltrials.gov NCT00066703).

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• A Deeper Dive into POLE-Mutated Endometrial Carcinomas

  The American Journal of Surgical Pathology · 2025-12-24 · 1 citations

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  POLE -mutated endometrial carcinomas ( POLE mut EC) have the most favorable prognosis among all TCGA molecular subgroups. Though the consequent "ultramutated" phenotype is recognized as a trademark feature, hypermutated tumors (10-100 mutations/megabase), as well as those that are histologically low-grade, have been described. Herein, we investigate 19 POLE mut ECs from a single institution to determine whether morphologic and genomic differences exist between tumors with high tumor mutational burden (TMB-H: 10-100 mutations/megabase) and ultra-high TMB (TMB-UH: >100 mutations/megabase). All tumors were FIGO stage I, of endometrioid histotype, and no patients recurred (median follow-up of 90 mo). Six previously described POLE exonuclease domain mutations were detected, with the 2 most common being P286R (n=7) and V411L (n=6). Seven ECs were TMB-H (median 76 mutations/megabase), and 12 TMB-UH (median 187 mutations/megabase). TMB-UH tumors were more frequently high-grade, with intratumoral heterogeneity, serous-like nuclei, and bizarre nuclei. Using an integrated approach, multiple classifiers were observed in both cohorts (53% of all tumors); however, those associated with MMRd were exclusive to TMB-UH ECs. All TMB-H ECs had a dominant (>50%) POLE mutational signature, in contrast to only 5 TMB-UH tumors. The remaining TMB-UH ECs demonstrated mixed signatures associated with mismatch repair deficiency (MMRd, n=4) or nonspecific signatures (n=3). All POLE mut tumors were enriched in single-nucleotide variants, while insertions-deletions were rare (maximum of 1.7%). In both groups, all harbored PTEN mutations, with other commonly recurring mutations including PIK3CA, ATRX, BRCA2, FBXW7 , and NF1 . ARID1A mutations were not identified in any TMB-H ECs. Although our cohort is small, the morphology of POLE mut ECs appears to be influenced by TMB, a phenomenon not yet described in the evolving landscape of these tumors. Taken in combination with differences in underlying genomic signatures, these findings provide an interesting springboard for better understanding POLE mut EC pathobiology.

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• Advances in uterine serous carcinoma and uterine carcinosarcoma.

  PubMed · 2025-05-01

  other1st authorCorresponding
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• Assessment of ovarian function suppression (OFS)-containing adjuvant endocrine therapy in premenopausal women by Breast Cancer Index.

  Journal of Clinical Oncology · 2025-05-28

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  557 Background: Breast Cancer Index (BCI) previously identified that premenopausal patients with HOXB13/IL17BR ratio (H/I)-Low tumors derived greater benefit than BCI(H/I)-High tumors from OFS-containing adjuvant endocrine therapy vs tamoxifen alone in the Suppression of Ovarian Function Trial (SOFT). This translational study of the Tamoxifen and Exemestane Trial (TEXT) was conducted to assess the predictive benefit of BCI (H/I) from exemestane (E) plus OFS over tamoxifen (T) plus OFS and validate the prognostic performance of BCI. Methods: Blinded BCI testing was performed in all available tumor samples from patients enrolled in TEXT, of which 1782 of 2660 had BCI successfully assessed and BCI categories assigned per established clinical cutpoints. Primary endpoints were breast cancer–free interval (BCFI) for predictive and distant recurrence–free interval (DRFI) for prognostic analyses. Per pre-specified SAP, a secondary analysis of predictive benefit combined the two OFS arms common to TEXT and SOFT (2896 of 4690 patients); clinicopathologic subgroup analyses were conducted in the combined TEXT+SOFT cohort. Cox proportional hazards models, stratified by chemotherapy use and nodal status, that included treatment assignment, BCI(H/I) status, and interaction term were used to assess BCI predictive performance by testing for treatment-by-BCI(H/I) interaction. The median follow-up was 13 years. Results: Among TEXT patients, 58% had BCI(H/I)-Low tumors.Patients with BCI (H/I)-Low tumors exhibited a 6.6% absolute benefit in 12-year BCFI (HR=0.61 [95% CI, 0.44-0.85]) for E+OFS versus T+OFS while those with BCI(H/I)-High tumors had an 6.3% absolute benefit (HR=0.78 [95% CI, 0.57-1.07]) (P-interaction = 0.29). Results were consistent in the combined TEXT+SOFT cohort and adjusting for clinicopathological variables. Clinical subgroup analyses consistently showed benefit of E+OFS vs T+OFS for BCI(H/I)-Low tumors, and more variable relative treatment effects among BCI(H/I)-High tumors, including by age. Post-hoc exploratory time-varying estimates suggested the treatment-by-BCI relationships may differ in years 0-5 vs &gt;5 years. BCI and BCIN+ as continuous indices were prognostic for distant recurrence in N0 (P = 0.0004) and N1 (P &lt; 0.0001) cancers. The 12-year DRFI was 96.3%, 90.3% and 84.9% for BCI-low, intermediate and high-risk N0 cancers, respectively. Conclusions: BCI was confirmed as prognostic in premenopausal women with HR+ early breast cancer enrolled in TEXT. BCI(H/I) status did not clearly predict differential benefit from E+OFS vs T+OFS. The TEXT results complement the prior results from SOFT, indicating premenopausal patients with BCI(H/I)-Low tumors benefit from more intensive endocrine therapy .

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• 15-year outcomes for women with premenopausal hormone receptor-positive early breast cancer (BC) in the SOFT and TEXT trials assessing benefits from adjuvant exemestane (E) + ovarian function suppression (OFS) or tamoxifen (T)+OFS.

  Journal of Clinical Oncology · 2025-05-28 · 15 citations

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  505 Background: Long-term follow-up of the SOFT and TEXT randomized trials has shown persistent reduction of recurrence from inclusion of OFS in adjuvant endocrine therapy, and clinically meaningful improvement in overall survival (OS) among patients at higher baseline risk of recurrence. We report a final update after a median follow-up of 15y in SOFT and 16.6y in TEXT. Methods: SOFT and TEXT enrolled premenopausal women with HR+ early BC from November 2003 to April 2011 (2660 in TEXT, 3047 in SOFT intention-to-treat populations). TEXT randomized women within 12 weeks of surgery to 5y E+OFS vs T+OFS; chemotherapy (CT) was optional and concurrent with OFS. SOFT randomized women to 5y E+OFS vs T+OFS vs T alone, within 12 weeks of surgery if no CT planned, or within 8 months of completing (neo)adjuvant CT. Both trials were stratified by CT use. The primary endpoint was disease free survival (DFS) which included invasive local, regional, distant and contralateral breast events, second non-breast malignancies and deaths. Secondary endpoints included invasive breast cancer-free interval (BCFI), distant recurrence free interval (DRFI) and OS. 20y data collection was completed in Q4’2024: 80% of surviving patients had final follow-up during or subsequent to 2020, for 70% it was during 2023-2024. 15y Kaplan-Meier estimates and hazard ratios (HR) with 95% CIs are reported. Results: There were 815 DFS events and 388 deaths reported in SOFT; and 669 DFS events and 325 deaths in TEXT. In SOFT, a moderate DFS benefit of T+OFS vs T (HR 0.85; 0.72-1.00) persisted, however 1/6 DFS events were not BC related; BCFI benefit was HR 0.82 (0.69-0.98). E+OFS vs T further reduced DFS events (HR 0.73; 0.61-0.86). The 15y DFS in SOFT was 67.0% for T, 70.5% for T+OFS and 73.5% for E+OFS. There were consistent but non-significant decreased hazards of death for T+OFS vs T (HR 0.87; 0.68-1.10) and E+OFS vs T (HR 0.85; 0.67-1.08). 15y OS was 85.3%, 86.7%, 86.9% respectively. For the TEXT+SOFT combined analysis of E+OFS vs T+OFS (n=2346 vs 2344) DFS, BCFI and DRFI continued as significantly improved for E+OFS over T+OFS. 15y DFS was 74.9% vs 71.3% (HR 0.82; 0.73-0.92). 15y OS was 87.8% vs 87.0% (HR 0.94; 0.80-1.11) respectively. 15y estimates by CT use are tabulated. Conclusions: The high level 15y final results of the SOFT and TEXT confirm a role for OFS- and aromatase inhibitor-containing adjuvant endocrine therapy for premenopausal women. Analysis is ongoing. Clinical trial information: NCT00066690 (SOFT) and NCT00066703 (TEXT) . 15y (%) Events SOFT Prior CT (n=1628) SOFT no CT (n=1419) CT+noCT T / T+OFS / E+OFS T / T+OFS / E+OFS DFS 536+279 60.9 / 63.0 / 66.3 73.9 / 79.1 / 82.1 DRFI 367+56 73.5 / 73.8 / 77.6 94.7 / 94.7 / 96.8 OS 318+70 77.4 / 79.4 / 79.8 94.4 / 95.1 / 95.2 TEXT CT (n=1607) TEXT no CT (n=1053) T+OFS / E+OFS T+OFS / E+OFS DFS 456+213 68.5 / 72.1 76.8 / 81.8 DRFI 286+69 79.0 / 81.3 91.6 / 94.6 OS 266+59 82.7 / 84.3 94.1 / 94.8

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Recent grants

• Alliance for Clinical Trials in Oncology Operations Center - GY11 Funded Extension

  NIH · $256.0M · 2014–2026

• NIH Grant U10CA041287

  NIH · $6.7M · 2015

Frequent coauthors

• Prudence A. Francis

  University of Melbourne

  488 shared

• Meredith M. Regan

  Dana-Farber Cancer Institute

  429 shared

• Carol Aghajanian

  422 shared

• Michael J. Birrer

  Winthrop Rockefeller Foundation

  416 shared

• Michael A. Bookman

  Kaiser Permanente

  408 shared

• Karen N. Price

  392 shared

• István Láng

  375 shared

• Kathleen N. Moore

  University of Oklahoma Health Sciences Center

  351 shared

Education

• M.D., Medicine

  University of Illinois

  1985

• B.A., Chemistry

  Oberlin

  1981