Dr Tanjina Kader

Australian research has found that more than 10% of cases of recurrent ductal carcinoma in situ (DCIS) of the breast are de novo tumours that occur independently of the primary lesion and have distinct genetic alterations.

A study presented at the 2022 AACR Annual Meeting used DNA sequencing to evaluate the clonal relatedness of 65 matched primary DCIS and recurrence tumour pairs. About half of the recurrences were invasive breast cancer (IBC). 

The study also included a set of 29 nonrecurrent DCIS cases.

It found that while the majority of recurrent cases were clonal, 12 percent of recurrent tumours were new primary lesions that developed de novo and were unrelated to the original DCIS. 

There was no significant difference in clonal relatedness whether the recurrence was IBC or DCIS.

Dr Tanjina Kader, a postdoctoral researcher at the Peter MacCallum Cancer Centre, said understanding whether a recurrence was a genetically distinct tumour from the primary could affect patient care. 

Yet it had been widely assumed that all recurrences were related to the primary DCIS. 

“These findings can influence how patients are managed in the clinic,” Dr Kader said in a press release from AACR.

“For example, the occurrence of a new primary lesion in the same patient suggests a high-risk breast environment in which new tumours may develop over the years. Therefore, such patients would be candidates for preventative breast removal surgery even if the tumour is small, and they might be referred to genetic testing to ascertain whether they have any genetic predisposition.” 

The researchers also found that specific variations in the TP53 gene were detected frequently in the recurrences related to the primary lesion, but were not common in the primary DCIS cases that didn’t recur and those that had non-clonal recurrence. 

She said the findings would have implications for the development and utility of future genetic biomarkers to predict recurrence.

“Further research is needed to understand the biology of DCIS recurrence, the progression from DCIS to invasive disease, and the role played by the tumour microenvironment and the immune system,” Dr Kader said.