Abstract
Ductal carcinoma in situ (DCIS) is a non-invasive breast neoplasia that accounts for 25% of all screen-detected breast cancers diagnosed annually. Neoplastic cells in DCIS are confined to the ductal system of the breast, although they can escape and progress to invasive breast cancer in a subset of patients. A key concern of DCIS is overtreatment, as most patients screened for DCIS and in whom DCIS is diagnosed will not go on to exhibit symptoms or die of breast cancer, even if left untreated. However, differentiating low-risk, indolent DCIS from potentially progressive DCIS remains challenging. In this Review, we summarize our current knowledge of DCIS and explore open questions about the basic biology of DCIS, including those regarding how genomic events in neoplastic cells and the surrounding microenvironment contribute to the progression of DCIS to invasive breast cancer. Further, we discuss what information will be needed to prevent overtreatment of indolent DCIS lesions without compromising adequate treatment for high-risk patients.
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Change history
15 December 2022
A Correction to this paper has been published: https://doi.org/10.1038/s41568-022-00542-6
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Acknowledgements
This work was supported by Cancer Research UK and by KWF Kankerbestrijding (reference C38317/A24043). A.K.C. acknowledges support from the CPRIT Single Cell Genomics Center (RP180684) for funding. N.E.N. acknowledges support from the US National Cancer Institute (RO1CA240526) and the CPRIT Single Cell Genomics Center (RP180684). E.S.H. is funded by RFA-CA-17-035 (NIH), 1505-30497 (PCORI), BCRF 19-074 (BCRF), DOD BC132057 and R01 CA185138-01. S.N.-Z. is funded by a Cancer Research UK Advanced Clinician Scientist Fellowship (C60100/A23916) and an NIHR Research Professorship (NIHR 301607) and is supported by the NIHR Cambridge Biomedical Research Centre (BRC-125-20014). D.C. is funded by the Cancer Research UK PRECISION award. E.S.H, A.M.T and D.C. are supported by the PCORI-funded COMET study through the Alliance for Clinical Trials in Oncology Foundation. J.J and J.v.R. acknowledge funding by the Oncode Institute. C.M. is supported by the AVL Donation Investment Fund of the AVL Foundation. The authors thank the Grand Challenge PRECISION Consortium Steering Group. They also thank T. Kumar and M. Edgerton from MD Anderson Cancer Center and E. J. Sawyer from King’s College London for their feedback and support in the preparation of the manuscript.
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A.K.C., M.M.A. and C.M. contributed equally to this work. J.W., A.K.C., M.A., C.M., A.M.T., J.v.R. and N.E.N researched data for the article. J.W., A.K.C., M.M.A., C.M., P.B., A.T., J.J., E.L., J.v.R., E.S.H., S.N.-Z. and N.E.N. made substantial contributions to discussion of the content. J.W., A.K.C., M.M.A., C.M., P.B., J.v.R., S.N.-Z. and N.E.N. wrote the manuscript. All authors were involved in the review and editing of the manuscript before submission.
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S.N.Z. has filed the following patents on the use of mutational signatures for clinical applications: PCT/EP2017/06029, PCT/EP2017/060289, PCT/EP2017/060279, PCT/EP2017/060298 and PCT/EP2017/084409. The other authors declare no competing interests.
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COMET: https://clinicaltrials.gov/ct2/show/NCT02926911?term=comet&cond=DCIS&draw=2&rank=1
LORD: https://clinicaltrials.gov/ct2/show/NCT02492607
LORETTA: https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000028298
LORIS: https://www.birmingham.ac.uk/research/crctu/trials/loris/index.aspx
Glossary
- Synchronous DCIS–IBC
-
Cases of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) that were diagnosed at the same time.
- Breast-conserving surgery
-
(BCS). Surgery to remove only part of the breast tissue.
- Active surveillance
-
Also called ‘active monitoring’, closely watching a patient’s condition but not giving any treatment unless the results of regularly scheduled tests show that the condition is getting worse.
- Lobular carcinoma in situ
-
A non-invasive neoplastic proliferation of discohesive cells, originating in the terminal duct lobular units.
- Sequential DCIS and/or IBC
-
General term for when ductal carcinoma in situ (DCIS) has recurred as DCIS or invasive breast cancer (IBC).
- Contralateral DCIS and/or IBC
-
General term for when ductal carcinoma in situ (DCIS) and/or invasive breast cancer (IBC) events occur on the opposite sides of the body.
- Ipsilateral DCIS and/or IBC
-
General term for when ductal carcinoma in situ (DCIS) and/or invasive breast cancer (IBC) events occur on the same side, often the same region, of the body as the initial DCIS.
- Pure DCIS
-
Ductal carcinoma in situ (DCIS) without invasive growth.
- Rudimental ductal tree
-
The small ductal network formed during embryonic stages, from which the adult network is formed during puberty.
- Sick lobes
-
A ductal tree with a normal phenotype that carries a large number of mutant cells, thereby priming it for tumour initiation.
- Mitochondrial D-loop
-
The non-coding displacement (D) loop of mitochondrial DNA, which lacks histone protection.
- Sequential DCIS–IBC
-
Ductal carcinoma in situ (DCIS) that has recurred as invasive breast cancer (IBC).
- Immunoediting
-
The process in which the immune system can constrain or promote tumour development through the stages of elimination, equilibrium and escape.
- Neoantigen load
-
The amount of mutations in neoplastic cells that translate into new (non-self) peptides that are presented by human leukocyte antigen at the cell surface.
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Casasent, A.K., Almekinders, M.M., Mulder, C. et al. Learning to distinguish progressive and non-progressive ductal carcinoma in situ. Nat Rev Cancer 22, 663–678 (2022). https://doi.org/10.1038/s41568-022-00512-y
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DOI: https://doi.org/10.1038/s41568-022-00512-y
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