Single-Cell Genetic Analysis of Ductal Carcinoma in Situ and Invasive Breast Cancer Reveals Enormous Tumor Heterogeneity yet Conserved Genomic Imbalances and Gain of MYC during Progression

Pure ductal carcinoma in situ (DCIS) is being diagnosed more frequently through breast screening programmes and is associated with an increased risk of developing invasive breast cancer. We assessed the clonal relatedness of 143 cases of pure DCIS and their subsequent events using a combination of whole exome, targeted and copy number sequencing, supplemented by single cell analysis. Unexpectedly, 18% of all invasive events after DCIS were clonally unrelated to the primary DCIS. Single cell sequencing of selected pairs confirmed our findings. In contrast, synchronous DCIS and invasive disease (n=44) were almost always (93%) clonally related. This challenges the dogma that most invasive events after DCIS represent invasive transformation of the initial DCIS and suggests that DCIS could be an independent risk factor for developing invasive disease as well as a precursor lesion.

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22. Invasive breast cancer after a diagnosis of ductal carcinoma in situ: does mode of presentation influence recurrence risk?

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2014.02.212 ◽

2014 ◽

Vol 40 (5) ◽

pp. 607

Author(s):

Shan Cheung ◽

Mary Booth ◽

David Dodwell

Keyword(s):

Breast Cancer ◽

Ductal Carcinoma In Situ ◽

Invasive Breast Cancer ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Recurrence Risk ◽

Mode Of Presentation

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Subsequent risk of ipsilateral and contralateral invasive breast cancer after treatment for ductal carcinoma in situ: incidence and the effect of radiotherapy in a population-based cohort of 10,090 women

Breast Cancer Research and Treatment ◽

10.1007/s10549-016-3973-y ◽

2016 ◽

Vol 159 (3) ◽

pp. 553-563 ◽

Cited By ~ 20

Author(s):

Lotte E. Elshof ◽

Michael Schaapveld ◽

Marjanka K. Schmidt ◽

Emiel J. Rutgers ◽

Flora E. van Leeuwen ◽

...

Keyword(s):

Breast Cancer ◽

Ductal Carcinoma In Situ ◽

Invasive Breast Cancer ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Population Based ◽

Subsequent Risk

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2–12 Incidence of Invasive Breast Cancer and Ductal Carcinoma In Situ in a Screening Program by Age: Should Older Women Continue Screening?

Breast Diseases A Year Book Quarterly ◽

10.1016/s1043-321x(05)80104-3 ◽

2005 ◽

Vol 16 (2) ◽

pp. 145-146

Author(s):

R.J. Brenner

Keyword(s):

Breast Cancer ◽

Older Women ◽

Ductal Carcinoma In Situ ◽

Invasive Breast Cancer ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Screening Program

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Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer

ISRN Oncology ◽

10.5402/2011/673790 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Andrei Dobrescu ◽

Monique Chang ◽

Vatsala Kirtani ◽

George K. Turi ◽

Randa Hennawy ◽

...

Keyword(s):

Breast Cancer ◽

Ductal Carcinoma In Situ ◽

Invasive Breast Cancer ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Receptor Expression ◽

Invasive Cancer ◽

Positive Staining ◽

Receptor Status

Background. To our knowledge, the hormone receptor status of noncontiguous ductal carcinoma in situ (DCIS) occurring concurrently in ER/PgR-negative invasive cancer has not been studied. The current study was undertaken to investigate the ER/PgR receptor status of DCIS of the breast in patients with ER/PgR-negative invasive breast cancer. Methods. We reviewed the immunohistochemical (IHC) staining for ER and PgR of 187 consecutive cases of ER/PgR-negative invasive breast cancers, collected from 1995 to 2002. To meet the criteria for the study, we evaluated ER/PgR expression of DCIS cancer outside of the invasive breast cancer. Results. A total of 37 cases of DCIS meeting the above criteria were identified. Of these, 16 cases (43.2%) showed positive staining for ER, PgR, or both. Conclusions. In our study of ER/PgR-negative invasive breast cancer we found that in 8% of cases noncontiguous ER/PR-positive DCIS was present. In light of this finding, it may be important for pathologists to evaluate the ER/PgR status of DCIS occurring in the presence of ER/PgR-negative invasive cancer, as this subgroup could be considered for chemoprevention.

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