About

Dr. Leena Hilakivi Clarke is a Professor at the Hormel Institute with a background in Experimental Psychology and Physiology obtained from the University of Helsinki in 1987. She has held faculty positions at Georgetown University from 1991 to 2020, progressing from research Associate Professor to tenured full Professor. Her research focuses on studying the role of dietary factors in affecting breast cancer risk and mortality. She investigates how maternal diet and obesity during pregnancy can pre-program offspring’s risk of developing breast cancer, emphasizing persistent changes in the offspring’s epigenome, gut microbiota, and inflammatory pathways. Dr. Hilakivi Clarke also explores interventions during pregnancy or in adult offspring, such as bioactive food compounds, beneficial dietary fats, or anti-inflammatory herbs, to prevent breast cancer risk and recurrence. Additionally, her work examines the biological impacts of social isolation and loneliness on breast cancer outcomes, aiming to understand why socially isolated individuals have a higher risk of breast cancer mortality. She collaborates with experts in computational modeling and epidemiology to translate her preclinical findings into clinical applications.

Research topics

• Genetics
• Biology
• Medicine
• Internal medicine
• Immunology
• Biochemistry
• Cancer research
• Endocrinology
• Bioinformatics
• Physiology

Selected publications

• Abstract PS1-02-24: Physical activity level differences among Non-Hispanic White and Chinese American breast cancer survivors

  Clinical Cancer Research · 2026-02-17

  article

  Abstract INTRODUCTION: Increased physical activity (PA) in breast cancer patients has been associated with multiple benefits including lower fatigue, depression and anxiety levels, better tolerance of treatment related side effects, and lower cancer recurrence rates (1). The American Cancer Society recommends that cancer survivors undergo at least 150-300 minutes of moderate intensity activity or 75-150 minutes of vigorous activity per week and encourages meeting or exceeding these upper limits (2). Given limited data on PA in Chinese American breast cancer survivors, this study aimed to evaluate and better quantify PA in this population. METHODS: As a part of a broader prospective cohort study investigating survivorship in Chinese American breast cancer patients compared to Non-Hispanic white (NHW) patients over a 12-month period, participants underwent a baseline phone survey administered by trained staff. All participants were women aged over 18, diagnosed with stage 0-III breast cancer within 10 years, and had completed primary surgical or medical treatment. The survey included the Global Physical Activity Questionnaire developed by World Health Organization (WHO), which was used to evaluate time spent on moderate and vigorous activity during work, travel and leisure and to calculate weekly metabolic equivalent (MET) minutes per week for each group. Group differences were evaluated using T-tests for significance. RESULTS: A total of 133 NHW and 110 Chinese American patients completed the baseline survey. The average age was 56 for Chinese Americans and 59 for NHWs, and the difference was not statistically significant. The average BMI of Chinese Americans (23.6) was statistically significantly lower than that of NHWs (25.7). Chinese Americans spent an average of 71 minutes per week on vigorous activity and 424 minutes per week on moderate activity compared to NHWs who spent an average of 179 minutes per week and 627 minutes per week, respectively. Combined, Chinese Americans averaged 2266 MET-minutes per week, while NHWs averaged 3952 MET-minutes per week, this difference was statistically significant (p = 0.0053). Additionally, for patients reporting use of a step counter, the average daily step count for Chinese Americans was 6592 compared to 8432 for NHWs. The reported average daily sedentary time for Chinese Americans (337 minutes) was not statistically different from that for NHWs (348 minutes). CONCLUSION: While both groups exceeded recommended PA minimums, Chinese American women with breast cancer self-reported significantly lower levels of PA than their NHW counterparts. Further studies should focus on the impact of this discrepancy on survivorship and possible interventions to bridge the gap between the two groups to mitigate health disparity after breast cancer treatment. KEYWORDS: breast cancer; survivorship; exercise; disparity SOURCES: (1) Le Y, Gao Z, Gomez SL, Pope Z, Dong R, Allen L, Chang MW, Wang JH. Acculturation and Adherence to Physical Activity Recommendations Among Chinese American and Non-Hispanic White Breast Cancer Survivors. J Immigr Minor Health. 2019 Feb;21(1):80-88. doi: 10.1007/s10903-018-0721-x. PMID: 29569102; PMCID: PMC6151158. (2) Rock CL, Thomson C, Gansler T, Gapstur SM, McCullough ML, Patel AV, Andrews KS, Bandera EV, Spees CK, Robien K, Hartman S, Sullivan K, Grant BL, Hamilton KK, Kushi LH, Caan BJ, Kibbe D, Black JD, Wiedt TL, McMahon C, Sloan K, Doyle C. American Cancer Society guideline for diet and physical activity for cancer prevention. CA Cancer J Clin. 2020 Jul;70(4):245-271. doi: 10.3322/caac.21591. Epub 2020 Jun 9. PMID: 32515498. Citation Format: C. Cao, T. Shao, A. Tsang, M. Kwa, R. Brown, L. Chen, M. Schwartz, D. Roblin, M. H. Antoni, L. Hilakivi-Clarke, G. Kowk, A. Lin, K. Joseph, J. X. Osorio, J. H. Wang, S. Cai. Physical activity level differences among Non-Hispanic White and Chinese American breast cancer survivors [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-02-24.

  PublisherDOI

• Aromatics from fossil fuels and breast cancer

  iScience · 2025-03-10 · 7 citations

  reviewOpen access1st authorCorresponding

  through pregnant mothers to environmental pollutants or maternal obesity or both. These early life exposures are shown to increase daughter's later susceptibility to breast cancer by causing in the daughter (1) an increase in the number of structures in the breast in which breast cancer initiation takes place, (2) a suppression, perhaps epigenetically, in the ability of cells to repair DNA damage caused by PAHs by inhibiting expression of tumor suppressor genes, or (3) a persistent gut dysbiosis, which then impacts immune cells in the tumor microenvironment. Among the early life environmental pollutants that increase breast cancer susceptibility may be volatile aromatic BTEX compounds. Thus, aromatics from fossil fuels are likely to be involved in causing breast cancer, and efforts should be directed toward reducing human exposure to these compounds to prevent breast cancer.

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• Pyruvate kinase M2 activation reprograms mitochondria in CD8 T cells, enhancing effector functions and efficacy of anti-PD1 therapy

  Cell Metabolism · 2025-04-08 · 29 citations

  article
  PublisherDOI

• Preliminary Comparison of Dietary Intake Among Breast Cancer Survivors Who Are Asian American or Non-Hispanic White

  Current Developments in Nutrition · 2025-05-01

  articleOpen access
  PublisherDOI

• Abstract PO3-18-08: Rational therapeutic combination of Bromodomain and Extra-Terminal domain (BET) inhibitor and Fibroblast Growth Factor Receptor (FGFR) inhibitor for treatment of invasive lobular carcinoma

  Cancer Research · 2024-05-02

  article

  Abstract Background: Invasive lobular carcinoma (ILC) is the second most pervasive subtype after invasive ductal carcinoma (IDC), accounting for approximately 10-15% of all breast cancers. It is characterized by loss of E-cadherin expression and non-adherent tumor cells that invade the stroma in a “single-file” pattern. Women with ILC are typically diagnosed at an older age and later stage with ER-positive disease. ILC is more likely to exhibit late recurrence and metastasize to the gastrointestinal tract and urogenital tract compared with IDC. It is routinely treated with anti-endocrine therapy and chemotherapy, however, while not entirely chemo-refractory, displays a poor response to chemotherapy compared with IDC. As such, options for recurrent disease are limited and there is an urgent need to develop tailored therapy for ILC, especially for those patients that recur. The family of bromodomain and extra-terminal domain (BET) proteins, comprising BRD2/3/4/T, are epigenetic readers that bind to acetylated lysine residues on histones and recruit transcription factors to drive the expression of oncogenes. Previously. we discovered that BRD3 is a marker of poor prognosis in ILC and there is emerging evidence that BET inhibitors (iBET) are effective in diverse types of breast cancer. Here, we investigated the therapeutic potential of iBET in ILC, alone and in combination with FGFR inhibitors. Methods: IC50s for a panel of iBET using two typical ILC cell lines MDA-MB-134VI (MM134) and SUM44PE (SUM44) were determined. RNA-sequencing and Genexplain analysis was applied to reveal transcriptional networks, master regulators and potential resistance mechanisms. BRD3 and FGFR3 were knocked down using siRNA to evaluate their function in ILC cell lines. Furthermore, we utilized ILC cell-derived xenograft (CDX) models in SCID-beige mice established by mammary intraductal (MIND) implantation to evaluate the therapeutic potency of iBET alone or in combination with fibroblast growth factor receptor (FGFR) inhibitor in vivo. Results: We demonstrated that iBET significantly inhibited ILC cell growth in both 2D and 3D culture, with the greatest potency demonstrated by JQ1 and Mivebresib (ABBV-075). RNA-sequencing revealed dysregulated pathways in cell cycle division, DNA damage, apoptosis and MAPK signaling following iBET treatment. Reverse engineering of transcriptional profiles using Genexplain revealed that FGFR3 is a significantly upregulated master regulator (MTR) among 142 MTRs across both cell lines and both iBETs. Upregulation of FGFR3 after iBET treatment was verified at the protein level by Western blotting. We also show that BRD3 and FGFR3 knockdown significantly inhibited cell growth, which supports the key role both play in ILC progression. Further, we analyzed the iBET therapeutic effect when combined with the FGFR inhibitor, erdafitinib, as a strategy to overcome potential resistance due to FGFR upregulation post iBET treatment. This revealed that the combination of iBET and erdafitinib could inhibit ILC cell growth more effectively compared to using either agent alone. Furthermore, our in vivo study showed that JQ1 could inhibit tumor growth in a SUM44-MIND model and alleviate metastasis to peritoneum, bone and ovary compared with the vehicle group. Moreover, we also assessed the combination of mivebresib and erdafitinib in vivo. This revealed that iBET and an FGFR inhibitor work synergistically to decrease tumour burden and metastatic potential in both MM134-MIND and SUM44-MIND models. Conclusion: Our results provide evidence that iBET, either alone or in combination with erdafitinib, is remarkably effective at inhibiting ILC growth, both in vitro and in vivo and represents a rational therapeutic strategy for recurrent ILC patients in the future. Citation Format: Binbin Gao, Elspeth Ward, Anna Blümel, Emer Conroy, Rachel Moore, Grainne Cremin, Rachel Bleach, Kathryn Haley, Tríona Ní Chonghaíle, Andreas Lindner, Jochen Prehn, Yi Zhang, Idalia Cruz, Leena Hilakivi-Clarke, Georgios Sflomos, Cathrin Brisken, William Gallagher, Darran O'Connor. Rational therapeutic combination of Bromodomain and Extra-Terminal domain (BET) inhibitor and Fibroblast Growth Factor Receptor (FGFR) inhibitor for treatment of invasive lobular carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-18-08.

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• Supplementary tables from Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats

  2023-03-31

  supplementary-materialsOpen accessSenior author

  <p>Table S1: Ingredients of rat diets. Table S2: Responses of DMBA-induced ER+ mammary tumors to tamoxifen (TAM). Table S3. Primers used for quantitative real-time PCR</p>

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• Supplementary Figure S1 from Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats

  2023-03-31

  preprintOpen accessSenior author

  <p>Mammary tumor burden during tamoxifen (TAM) treatment in animals exposed to genistein (GEN).</p>

  PublisherDOI

• Social Isolation and Breast Cancer

  Endocrinology · 2023-08-16 · 15 citations

  articleOpen access1st authorCorresponding

  Although the role of life stressors in breast cancer remains unclear, social isolation is consistently associated with increased breast cancer risk and mortality. Social isolation can be defined as loneliness or an absence of perceived social connections. In female mice and rats, social isolation is mimicked by housing animals 1 per cage. Social isolation causes many biological changes, of which an increase in inflammatory markers and disruptions in mitochondrial and cellular metabolism are commonly reported. It is not clear how the 2 traditional stress-induced pathways, namely, the hypothalamic-pituitary-adrenocortical axis (HPA), resulting in a release of glucocorticoids from the adrenal cortex, and autonomic nervous system (ANS), resulting in a release of catecholamines from the adrenal medulla and postganglionic neurons, could explain the increased breast cancer risk in socially isolated individuals. For instance, glucocorticoid receptor activation in estrogen receptor positive breast cancer cells inhibits their proliferation, and activation of β-adrenergic receptor in immature immune cells promotes their differentiation toward antitumorigenic T cells. However, activation of HPA and ANS pathways may cause a disruption in the brain-gut-microbiome axis, resulting in gut dysbiosis. Gut dysbiosis, in turn, leads to an alteration in the production of bacterial metabolites, such as short chain fatty acids, causing a systemic low-grade inflammation and inducing dysfunction in mitochondrial and cellular metabolism. A possible causal link between social isolation-induced increased breast cancer risk and mortality and gut dysbiosis should be investigated, as it offers new tools to prevent breast cancer.

  PublisherOA PDFDOI

• Supplementary Figure S5 from Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats

  2023-03-31

  preprintOpen accessSenior author

  <p>Proliferation and apoptosis indexes in the mammary glands and tumors of genistein (GEN) fed and tamoxifen (TAM) treated rats.</p>

  PublisherDOI

• Data from Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats

  2023-03-31

  preprintOpen accessSenior author

  <div>Abstract<p><b>Purpose:</b> Whether it is safe for estrogen receptor–positive (ER+) patients with breast cancer to consume soy isoflavone genistein remains controversial. We compared the effects of genistein intake mimicking either Asian (lifetime) or Caucasian (adulthood) intake patterns to that of starting its intake during tamoxifen therapy using a preclinical model.</p><p><b>Experimental Design:</b> Female Sprague-Dawley rats were fed an AIN93G diet supplemented with 0 (control diet) or 500 ppm genistein from postnatal day 15 onward (lifetime genistein). Mammary tumors were induced with 7,12-dimethylbenz(<i>a</i>)anthracene (DMBA), after which a group of control diet–fed rats were switched to genistein diet (adult genistein). When the first tumor in a rat reached 1.4 cm in diameter, tamoxifen was added to the diet and a subset of previously only control diet–fed rats also started genistein intake (post-diagnosis genistein).</p><p><b>Results:</b> Lifetime genistein intake reduced <i>de novo</i> resistance to tamoxifen, compared with post-diagnosis genistein groups. Risk of recurrence was lower both in the lifetime and in the adult genistein groups than in the post-diagnosis genistein group. We observed downregulation of unfolded protein response (UPR) and autophagy-related genes (GRP78, IRE1α, ATF4, and Beclin-1) and genes linked to immunosuppression (<i>TGFβ</i> and <i>Foxp3</i>) and upregulation of cytotoxic T-cell marker <i>CD8a</i> in the tumors of the lifetime genistein group, compared with controls, post-diagnosis, and/or adult genistein groups.</p><p><b>Conclusions:</b> Genistein intake mimicking Asian consumption patterns improved response of mammary tumors to tamoxifen therapy, and this effect was linked to reduced activity of UPR and prosurvival autophagy signaling and increased antitumor immunity. <i>Clin Cancer Res; 23(3); 814–24. ©2017 AACR</i>.</p></div>

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Frequent coauthors

• Robert Clarke

  Hormel (United States)

  272 shared

• Anni Wärri

  University of Turku

  76 shared

• Lü Jin

  Peking University Shenzhen Hospital

  61 shared

• Katherine L. Cook

  Atrium Health Wake Forest Baptist

  61 shared

• Ayesha N. Shajahan‐Haq

  Georgetown University Medical Center

  55 shared

• Jianhua Xuan

  53 shared

• Fábia de Oliveira Andrade

  Hormel (United States)

  51 shared

• Xiyuan Zhang

  49 shared

Awards & honors

• 2017 Society for Endocrinology’s Journal Award