Analysis of Ductal Carcinoma in Situ by Self-reported Race Reveals Molecular Differences Related to Outcome

Overview

Journal Breast Cancer Res

Specialty Oncology

Date 2024 Sep 2

PMID 39223670

Authors

Siri H Strand

Kathleen E Houlahan

Vernal Branch

Thomas Lynch

Belen Rivero-Guitierrez

Bryan Harmon

Fergus Couch

Kristalyn Gallagher

Mark Kilgore

Shi Wei

Angela DeMichele

Tari King

Priscilla McAuliffe

Christina Curtis

Kouros Owzar

Jeffrey R Marks

Graham A Colditz

E Shelley Hwang

Robert B West

Affiliations

Soon will be listed here.

Abstract

Background: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated.

Methods: We examined the molecular profile of DCIS by self-reported race (SRR) and outcome groups in Black (n = 99) and White (n = 191) women in a large DCIS case-control cohort study with longitudinal follow up.

Results: Gene expression and pathway analyses suggested that different genes and pathways are involved in diagnosis and ipsilateral breast outcome (DCIS or IBC) after DCIS treatment in White versus Black women. We identified differences in ER and HER2 expression, tumor microenvironment composition, and copy number variations by SRR and outcome groups.

Conclusions: Our results suggest that different molecular mechanisms drive initiation and subsequent ipsilateral breast events in Black versus White women.

References

Flanagin A, Frey T, Christiansen S . Updated Guidance on the Reporting of Race and Ethnicity in Medical and Science Journals. JAMA. 2021; 326(7):621-627. DOI: 10.1001/jama.2021.13304. View

Liu Y, West R, Weber J, Colditz G . Race and risk of subsequent aggressive breast cancer following ductal carcinoma in situ. Cancer. 2019; 125(18):3225-3233. PMC: 6717007. DOI: 10.1002/cncr.32200. View

Daemen A, Manning G . HER2 is not a cancer subtype but rather a pan-cancer event and is highly enriched in AR-driven breast tumors. Breast Cancer Res. 2018; 20(1):8. PMC: 5791377. DOI: 10.1186/s13058-018-0933-y. View

Turner B, Steinberg J, Weeks B, Rodriguez F, Cullen M . Race/ethnicity reporting and representation in US clinical trials: a cohort study. Lancet Reg Health Am. 2022; 11. PMC: 9302767. DOI: 10.1016/j.lana.2022.100252. View

Hu D, Li Z, Zheng B, Lin X, Pan Y, Gong P . Cancer-associated fibroblasts in breast cancer: Challenges and opportunities. Cancer Commun (Lond). 2022; 42(5):401-434. PMC: 9118050. DOI: 10.1002/cac2.12291. View

Giaquinto A, Sung H, Miller K, Kramer J, Newman L, Minihan A . Breast Cancer Statistics, 2022. CA Cancer J Clin. 2022; 72(6):524-541. DOI: 10.3322/caac.21754. View

Yanai H, Yoshikawa K, Ishida M, Tsuta K, Sekimoto M, Sugie T . Presence of myxoid stromal change and fibrotic focus in pathological examination are prognostic factors of triple-negative breast cancer: Results from a retrospective single-center study. PLoS One. 2021; 16(2):e0245725. PMC: 7877644. DOI: 10.1371/journal.pone.0245725. View

Waters E, Colditz G, Davis K . Essentialism and Exclusion: Racism in Cancer Risk Prediction Models. J Natl Cancer Inst. 2021; 113(12):1620-1624. PMC: 8634398. DOI: 10.1093/jnci/djab074. View

Borrell L, Elhawary J, Fuentes-Afflick E, Witonsky J, Bhakta N, Wu A . Race and Genetic Ancestry in Medicine - A Time for Reckoning with Racism. N Engl J Med. 2021; 384(5):474-480. PMC: 8979367. DOI: 10.1056/NEJMms2029562. View

10.

Fang W, Medrano M, Cote P, Portsche M, Rao V, Hong Y . Transcriptome analysis reveals differences in cell cycle, growth and migration related genes that distinguish fibroblasts derived from pre-invasive and invasive breast cancer. Front Oncol. 2023; 13:1130911. PMC: 10118028. DOI: 10.3389/fonc.2023.1130911. View

11.

Risom T, Glass D, Averbukh I, Liu C, Baranski A, Kagel A . Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma. Cell. 2022; 185(2):299-310.e18. PMC: 8792442. DOI: 10.1016/j.cell.2021.12.023. View

12.

Carey L, Perou C, Livasy C, Dressler L, Cowan D, Conway K . Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006; 295(21):2492-502. DOI: 10.1001/jama.295.21.2492. View

13.

Stark A, Stapp R, Raghunathan A, Yan X, Kirchner H, Griggs J . Disease-free probability after the first primary ductal carcinoma in situ of the breast: a comparison between African-American and White-American women. Breast Cancer Res Treat. 2011; 131(2):561-70. PMC: 4369400. DOI: 10.1007/s10549-011-1742-5. View

14.

Martin D, Boersma B, Yi M, Reimers M, Howe T, Yfantis H . Differences in the tumor microenvironment between African-American and European-American breast cancer patients. PLoS One. 2009; 4(2):e4531. PMC: 2638012. DOI: 10.1371/journal.pone.0004531. View

15.

Martini R, Delpe P, Chu T, Arora K, Lord B, Verma A . African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent. Cancer Discov. 2022; 12(11):2530-2551. PMC: 9627137. DOI: 10.1158/2159-8290.CD-22-0138. View

16.

Chen C, Pollack S, Hunter D, Hirschhorn J, Kraft P, Price A . Improved ancestry inference using weights from external reference panels. Bioinformatics. 2013; 29(11):1399-406. PMC: 3661048. DOI: 10.1093/bioinformatics/btt144. View

17.

Francis A, Thomas J, Fallowfield L, Wallis M, Bartlett J, Brookes C . Addressing overtreatment of screen detected DCIS; the LORIS trial. Eur J Cancer. 2015; 51(16):2296-303. DOI: 10.1016/j.ejca.2015.07.017. View

18.

Byrska-Bishop M, Evani U, Zhao X, Basile A, Abel H, Regier A . High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios. Cell. 2022; 185(18):3426-3440.e19. PMC: 9439720. DOI: 10.1016/j.cell.2022.08.004. View

19.

Ioannidis J, Powe N, Yancy C . Recalibrating the Use of Race in Medical Research. JAMA. 2021; 325(7):623-624. DOI: 10.1001/jama.2021.0003. View

20.

Solin L, Gray R, Baehner F, Butler S, Hughes L, Yoshizawa C . A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2013; 105(10):701-10. PMC: 3653823. DOI: 10.1093/jnci/djt067. View