Evidence that molecular changes in cells occur before morphological alterations during the progression of breast ductal carcinoma

Castro, Nadia P.; Osório, Cynthia A. B. T.; Torres, Carolina Paes; Bastos, Elen Pereira; Mourão-Neto, Mário; Soares, Fernando Augusto; Brentani, Helena; Carraro, Dirce Maria

doi:10.1186/bcr2157

Cited by 132 publications

(136 citation statements)

References 41 publications

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“…Another hypothetical explanation for our null finding is that any beneficial effect of physical activity may operate at a relatively late stage in the development of the disease. The factors that lead to in situ tumors to progress into invasive breast cancer remains unclear and poorly defined (28,30). Furthermore, the exact biologic mechanisms for the association of physical activity with breast cancer are in general still speculative.…”

Section: Discussionmentioning

confidence: 99%

Prospective Study on Physical Activity and Risk of In Situ Breast Cancer

Steindorf

Ritte

Tjønneland

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Physical activity has been identified as protective factor for invasive breast cancer risk, whereas comparable studies on in situ carcinoma are rare.Methods: The study included data from 283,827 women of the multinational European Prospective Investigation into C7ancer and Nutrition (EPIC)-cohort study. Detailed information on different types of physical activity conducted during the prior year, such as occupational, recreational, and household activity, as well as on important cofactors, was assessed at baseline. Adjusted HRs for in situ breast cancer were estimated by Cox proportional hazards models.Results: During a median follow-up period of 11.7 years, 1,059 incidents of breast carcinoma in situ were identified. In crude and adjusted multivariable models, no associations were found for occupational, household, and recreational physical activity. Furthermore, total physical activity was not associated with risk of in situ breast cancer. Comparing moderately inactive, moderately active, and active participants with inactive study participants resulted in adjusted HRs of 0.99 [95% confidence interval (CI), 0.83-1.19], 0.99 (95% CI, 0.82-1.20), and 1.07 (95% CI, 0.81-1.40), respectively (P value of trend test: 0.788). No inverse associations were found in any substrata defined by age at diagnosis or body mass index (BMI) status.Conclusions: In this large prospective study, we did not find any evidence of an association between physical activity and in situ breast cancer risk. If not by chance, the contrast between our results for carcinoma in situ and the recognized inverse association for invasive breast cancer suggests that physical activity may have stronger effects on proliferation and late stage carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Prospective Study on Physical Activity and Risk of In Situ Breast Cancer

Steindorf

Ritte

Tjønneland

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…In tumours containing both IDC and DCIS (IDC-DCIS), it is unclear whether the IDC component arises directly from DCIS; in tumours lacking DCIS, however, it is assumed that IDC arises de novo. One recent study implicated DCIS as the precursor of IDC-DCIS based on concordant expression of immunohistochemical markers (Steinman et al, 2007), a conclusion that has since been supported by genomic data (Aubele et al, 2000;Alexe et al, 2007;Iakovlev et al, 2008), in turn creating a quest for biomarkers that predict invasive transformation of DCIS (Schuetz et al, 2006;Castro et al, 2008). Other studies have reported differences between DCIS and IDC-DCIS, suggesting that DCIS may not have been a precursor of the invasive component (Farabegoli et al, 2002); however, some of these studies have been limited either by failure to use pure IDC as a comparator (Patla et al, 2002) or else by small cohort sizes (Mylonas et al, 2005).…”

mentioning

confidence: 99%

Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer

et al. 2010

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BACKGROUND: The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC). METHODS: We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2. RESULTS: Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P ¼ 0.03), to occur in pre-menopausal women (P ¼ 0.002), and to be either ER-positive (P ¼ 0.002) or HER2-positive (Po0.0005), but less likely to be treated with breast-conserving surgery (P ¼ 0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P ¼ 0.02), and declined as the DCIS enlarged (Po0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (Po0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%). CONCLUSION: IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.

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“…Using a supervised classification, Hannemann et al identified a gene expression classifier of 35 genes, which differed between DCIS and IDC and a panel of 43 genes which could further separate between well-and poorly differentiated DCIS samples [19]. These findings were confirmed by Castro et al who showed that the tumor cells with the most divergent molecular features were from the pure DCIS cases, providing further evidence that molecular changes in cells occur before morphological alterations during the progression of IDC [20]. More recently, Lee and colleagues described a 74-gene profile which was able to correctly categorize 97% of all DCIS and 95% of all IBCs [21].…”

Section: Dcis Carcinogenesismentioning

confidence: 93%