Clonal Hematopoiesis in Women With Breast Cancer

Overview

Journal J Clin Oncol

Date 2025 Jan 17

PMID 39823557

Authors

Christina Mayerhofer

Rachel A Freedman

Heather A Parsons

Ann H Partridge

Peter G Miller

Affiliations

Soon will be listed here.

Abstract

Purpose: Clonal hematopoiesis (CH) has been associated with a variety of adverse outcomes, most notably hematologic malignancy and ischemic cardiovascular disease. A series of recent studies also suggest that CH may play a role in the outcomes of patients with solid tumors, including breast cancer. Here, we review the clinical and biological data that underlie potential connections between CH, inflammation, and breast cancer, with a focus on the prevalence and impact of clonal hematopoiesis of indeterminate potential in patients with breast cancer.

Methods: We summarize data from multiple studies, including a series of cohorts of patients with breast cancer, to assess the prevalence of CH, the relationship between CH and exposure to cytotoxic therapy, and the correlation between CH and breast cancer-specific outcomes.

Results: Our findings indicate that CH is prevalent among patients with breast cancer, particularly those treated with cytotoxic therapies. However, there are no definitive data to support an association between the presence of CH and breast cancer-specific outcomes.

Conclusion: Current data do not support routine CH testing in patients with breast cancer, nor should the presence of CH influence decisions regarding breast cancer therapy in most patients. However, larger, long-term studies are necessary to further define the implications of CH in patients with breast cancer and guide clinical decision making.

References

Shumliakivska M, Luxan G, Hemmerling I, Scheller M, Li X, Muller-Tidow C . DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts. Nat Commun. 2024; 15(1):606. PMC: 10799021. DOI: 10.1038/s41467-023-43003-w. View

Kar S, Quiros P, Gu M, Jiang T, Mitchell J, Langdon R . Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis. Nat Genet. 2022; 54(8):1155-1166. PMC: 9355874. DOI: 10.1038/s41588-022-01121-z. View

Yura Y, Miura-Yura E, Katanasaka Y, Min K, Chavkin N, Polizio A . The Cancer Therapy-Related Clonal Hematopoiesis Driver Gene Promotes Inflammation and Non-Ischemic Heart Failure in Mice. Circ Res. 2021; 129(6):684-698. PMC: 8409899. DOI: 10.1161/CIRCRESAHA.121.319314. View

Agrawal M, Niroula A, Cunin P, McConkey M, Shkolnik V, Kim P . TET2-mutant clonal hematopoiesis and risk of gout. Blood. 2022; 140(10):1094-1103. PMC: 9461470. DOI: 10.1182/blood.2022015384. View

Leuraud K, Richardson D, Cardis E, Daniels R, Gillies M, OHagan J . Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS): an international cohort study. Lancet Haematol. 2015; 2(7):e276-81. PMC: 4587986. DOI: 10.1016/S2352-3026(15)00094-0. View

Gu M, Kovilakam S, Dunn W, Marando L, Barcena C, Mohorianu I . Multiparameter prediction of myeloid neoplasia risk. Nat Genet. 2023; 55(9):1523-1530. PMC: 10484784. DOI: 10.1038/s41588-023-01472-1. View

Kessler M, Damask A, OKeeffe S, Banerjee N, Li D, Watanabe K . Common and rare variant associations with clonal haematopoiesis phenotypes. Nature. 2022; 612(7939):301-309. PMC: 9713173. DOI: 10.1038/s41586-022-05448-9. View

Bolton K, Koh Y, Foote M, Im H, Jee J, Sun C . Clonal hematopoiesis is associated with risk of severe Covid-19. Nat Commun. 2021; 12(1):5975. PMC: 8514469. DOI: 10.1038/s41467-021-26138-6. View

Miller P, Sperling A, Gibson C, Viswanathan K, Castellano C, McConkey M . Contribution of clonal hematopoiesis to adult-onset hemophagocytic lymphohistiocytosis. Blood. 2020; 136(26):3051-3055. PMC: 7770567. DOI: 10.1182/blood.2020008206. View

10.

Genovese G, Kahler A, Handsaker R, Lindberg J, Rose S, Bakhoum S . Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014; 371(26):2477-87. PMC: 4290021. DOI: 10.1056/NEJMoa1409405. View

11.

Coombs C, Zehir A, Devlin S, Kishtagari A, Syed A, Jonsson P . Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes. Cell Stem Cell. 2017; 21(3):374-382.e4. PMC: 5591073. DOI: 10.1016/j.stem.2017.07.010. View

12.

Sella T, Fell G, Miller P, Gibson C, Rosenberg S, Snow C . Patient perspectives on testing for clonal hematopoiesis of indeterminate potential. Blood Adv. 2022; 6(24):6151-6161. PMC: 9791300. DOI: 10.1182/bloodadvances.2022008376. View

13.

Zagar T, Cardinale D, Marks L . Breast cancer therapy-associated cardiovascular disease. Nat Rev Clin Oncol. 2015; 13(3):172-84. DOI: 10.1038/nrclinonc.2015.171. View

14.

Qureshi R, Picon-Ruiz M, Aurrekoetxea-Rodriguez I, Nunes de Paiva V, DAmico M, Yoon H . The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development. Cell Metab. 2020; 31(6):1154-1172.e9. DOI: 10.1016/j.cmet.2020.05.008. View

15.

Freedman R, Li T, Sedrak M, Hopkins J, Tayob N, Faggen M . 'ADVANCE' (a pilot trial) ADjuVANt chemotherapy in the elderly: Developing and evaluating lower-toxicity chemotherapy options for older patients with breast cancer. J Geriatr Oncol. 2022; 14(1):101377. PMC: 10080267. DOI: 10.1016/j.jgo.2022.09.006. View

16.

Williams N, Lee J, Mitchell E, Moore L, Baxter E, Hewinson J . Life histories of myeloproliferative neoplasms inferred from phylogenies. Nature. 2022; 602(7895):162-168. DOI: 10.1038/s41586-021-04312-6. View

17.

Niroula A, Sekar A, Murakami M, Trinder M, Agrawal M, Wong W . Distinction of lymphoid and myeloid clonal hematopoiesis. Nat Med. 2021; 27(11):1921-1927. PMC: 8621497. DOI: 10.1038/s41591-021-01521-4. View

18.

Zink F, Stacey S, Norddahl G, Frigge M, Magnusson O, Jonsdottir I . Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood. 2017; 130(6):742-752. PMC: 5553576. DOI: 10.1182/blood-2017-02-769869. View

19.

Mayerhofer C, Sedrak M, Hopkins J, Li T, Tayob N, Faggen M . Clonal hematopoiesis in older patients with breast cancer receiving chemotherapy. J Natl Cancer Inst. 2023; 115(8):981-988. PMC: 10407695. DOI: 10.1093/jnci/djad065. View

20.

Bolton K, Ptashkin R, Gao T, Braunstein L, Devlin S, Kelly D . Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nat Genet. 2020; 52(11):1219-1226. PMC: 7891089. DOI: 10.1038/s41588-020-00710-0. View