Preliminary biological studies are able to demonstrate a biological difference between cancers with No-DCIS and those with IDC-DCIS. The current hypothesis for the presence of concomitant in situ disease in such cancers is that tumours do undergo cellular differentiation to transform into an invasive phenotype. This in turn led to the conclusion that this slow progression to the invasive component may then translate into a more favourable clinical prognosis7,8. Yet, only a handful of Western studies were able to recognize and associate this to possibly better prognostic features and clinical outcomes. Most yielded insignificant and inconsistent results9,10. The clinical significance and role of DCIS among the Asian population remains understudied.
In Singapore, screening mammography is highly subsidized, making it extremely affordable for asymptomatic women. With the increasing awareness for screening mammography, detection of early cancers has also been on the rise. However, currently, the presence of DCIS in invasive cancers has no impact on systemic treatment, which depends solely on the pathological characteristics of the invasive component11.
There has yet to be a common consensus between the clinical features and prognostic implications for tumours with concomitant DCIS. With progressive published data among the Westerns, it is widely accepted that patients with IDC-DCIS may present at a younger age with smaller sized tumours with few or no lymph nodal involvement9,10. Our results indicated that IDC-DCIS is associated with smaller sized tumours and a lower overall clinical stage, thereby concurring with the hypothesis that tumours with concomitant DCIS were less biologically aggressive.
Likewise, some studies have showed that tumours with concomitant DCIS are likely to express ER, PR and cerB2 positivity as compared to tumours with No-DCIS13–15. Others disagree12,15. Our results showed that IDC-DCIS subjects were likely to express positivity in ER, PR and cerB2 receptors and this was statistically significant. While our data suggest that IDC-DCIS cancers may imply a less aggressive phenotype for patients with hormonal receptor or Her2 receptor positive cancers, we do acknowledge that triple negative malignancies may exhibit different biological behavior.
Researchers have since supported the preliminary theory of this slow evolution in deriving the invasive component and thereby resulting in a possibly better clinical prognosis. This study did demonstrate that the group with No-DCIS had higher percentage of distant recurrences compared to the group with IDC-DCIS (20.6% vs 13.5%, p = 0.020). However, we were unable to draw a similar conclusion for local recurrence. This might be attributed to the small total number of patients in our cohort who had developed local recurrences over the surveillance period as a result of better compliance to local radiation therapy prescribed. Our study results also suggest that patients with No-DCIS were 1.6 times more likely to develop disease progression as compared to those with IDC-DCIS, in spite of the adjuvant treatment given. These results add weight to the current speculation that the absence of coexisting DCIS is associated with poorer prognostic features and outcomes among Asian patients, especially in terms of distant recurrences and disease progression. Unfortunately, due to our small sample size of breast cancer related deaths, we were unable to detect a significant difference in the breast cancer specific 5 year overall survival among the 2 groups.
The breast cancer specific 5 year overall survival rate was analysed with PSM. No significant results were found between the group with No-DCIS and IDC-DCIS (92.02%, 95%CI = 90.9% − 94.7%, p = 0.608). PSM is regarded as an advanced statistical technique to minimize any possible confounders in an observational study. It serves to reduce possible treatment assignment bias and mimic randomization16. We utilised PSM to assess if concomitant DCIS affects the 5 year breast cancer overall survival rate after adjusting for certain covariates as mentioned above but we were unable demonstrate a more favourable breast cancer specific 5 year overall survival rate. It might be attributed to the fact that both genomic profiles are highly similar17,18.
Lastly, we do recognize the limitations of this study. Being a retrospective analysis, any incomplete data namely, less detailed histology reports in the early years of the 21st century, had to be excluded. Other information such as patients’ details may have been missing during the early days of data entry. Other inherent biases associated with retrospective study have to be considered. Secondly, analysis of tumour specimens had been performed in the absence of central pathologic review, hence establishment of details such as presence of isolated tumour cells (ITC) infiltration and micrometastases (mic) in lymph nodes were absent. Thirdly, our sample size was too small to demonstrate a significant difference in the 5 year breast cancer specific survival. Unlike the Western studies, the clinical outcomes among Asians such as recurrences and disease free outcomes as a result from tumours with coexisting DCIS has been understudied19,20. This study, with a long median follow up of 94 months, is to add weight to current findings and further strengthen the belief that coexisting DCIS does lead to better tumour profile. We are the first to document the clinical significance of concomitant DCIS in the presence of invasive cancers in terms of disease progression and distant recurrences.