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Long-term survival of women with basal-like ductal carcinoma in situ of the breast: a population-based cohort study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2010 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 10, 653- p.Article in journal (Refereed) Published
Abstract [en]

Background: Microarray gene-profiling of invasive breast cancer has identified different subtypes including luminal A, luminal B, HER2-overexpressing and basal-like groups. Basal-like invasive breast cancer is associated with a worse prognosis. However, the prognosis of basal-like ductal carcinoma in situ (DCIS) is still unknown. Our aim was to study the prognosis of basal-like DCIS in a large population-based cohort. Methods: All 458 women with a primary DCIS diagnosed between 1986 and 2004, in Uppland and Vastmanland, Sweden were included. TMA blocks were constructed. To classify the DCIS tumors, we used immunohistochemical (IHC) markers (estrogen-, progesterone-, HER2, cytokeratin 5/6 and epidermal growth factor receptor) as a surrogate for the gene expression profiling. The association with prognosis was examined for basal-like DCIS and other subtypes using Kaplan-Meier survival analyses and Cox proportional hazards regression models. Results: IHC data were complete for 392 women. Thirty-two were basal-like (8.2%), 351 were luminal or HER2-positive (89.5%) and 9 unclassified (2.3%). Seventy-six women had a local recurrence of which 34 were invasive. Another 3 women had general metastases as first event. Basal-like DCIS showed a higher risk of local recurrence and invasive recurrence 1.8 (Confidence interval (CI) 95%, 0.8-4.2) and 1.9 (0.7-5.1), respectively. However, the difference was not statistically significant. Also, no statistically significant increased risk was seen for triple-negative or high grade DCIS. Conclusions: Basal-like DCIS showed about a doubled, however not statistically significant risk for local recurrence and developing invasive cancer compared with the other molecular subtypes. Molecular subtyping was a better prognostic parameter than histopathological grade.

Place, publisher, year, edition, pages
2010. Vol. 10, 653- p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-142827DOI: 10.1186/1471-2407-10-653ISI: 000285299300001PubMedID: 21118480OAI: oai:DiVA.org:uu-142827DiVA: diva2:388331
Available from: 2011-01-17 Created: 2011-01-17 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Aspects of Progression in Breast Carcinoma: from ductal carcinoma in situ to invasive cancer
Open this publication in new window or tab >>Aspects of Progression in Breast Carcinoma: from ductal carcinoma in situ to invasive cancer
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the past decades our knowledge concerning breast cancer progression from ductal carcinoma in situ (DCIS) to invasive cancer has grown rapidly. However, molecular factors driving the progression are still largely unknown.

In the first study, we investigated tumor evolution in breast cancer by analyzing TP53 mutation status in tumors from various stages of the disease. Presence of the same TP53 mutations in both DCIS and invasive components from the same tumor indicates same cellular origin. The role of mutant TP53 in the progression of breast cancer is less clear and may vary between subtypes.

In the second study, we studied the prognosis of basal-like DCIS in a large population-based cohort. Basal-like DCIS was associated with about doubled but not statistically significant risk for local recurrence compared with the other molecular subtypes. Molecular subtype was a better prognostic parameter than histopathological grade.

In the third study, we studied markers in primary DCIS in relation to type of recurrence. Interestingly, recurrences after an ER-/HER2+, ER negative or EGFR positive primary DCIS were more often of the in situ type. The molecular subtype ER+/HER2+, FOXA1 positivity and FOXC1 positivity were risk factors for any recurrence.

In the fourth study, we proposed a histological classification system for a new entity: neoductgenesis. We also evaluated histologic criteria for neoductgenesis. According to our criteria, good agreements among pathologists were achieved. Neoductgenesis was related to more aggressive tumor biology and to mammographic features. The result indicates potential benefits for women earlier considered having pure DCIS but later diagnosed as breast carcinoma with neoductgenesis, suggesting a need to develop appropriate treatment regiments. Our findings have to be repeated and the relation to prognosis warrants further studies.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 38 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 735
Keyword
progression, ductal carcinoma in situ, breast cancer
National Category
Cancer and Oncology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-166745 (URN)978-91-554-8256-5 (ISBN)
Public defence
2012-02-25, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 13:00 (English)
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Available from: 2012-02-06 Created: 2012-01-13 Last updated: 2012-02-15Bibliographically approved

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