Recurrent non-invasive breast tumors may not always be related to the primary lesion and determining this could improve treatment options.
Are all recurring non-invasive breast tumors related to a primary tumor? Not according to research presented by Tanjina Kader (Peter MacCallum Cancer Center; Melbourne, Australia) at the AACR Annual Meeting 2022 (8–13 April; New Orleans, LA, USA), a discovery that may improve treatment outcomes.
Ductal carcinoma in situ (DCIS) is the earliest form of breast cancer and is when some cells in the lining of the ducts in breast tissue start to turn cancerous. As the cancerous cells are contained inside the ducts, the lesion can be removed with surgery; however, DCIS recurs in approximately 25% of patients, and around half of these recurrences become invasive, with potentially life-threatening consequences.
It is assumed that all recurrences occurring in the same breast (ipsilateral) are related to the primary DCIS; however, this has never been proven. Kader commented: “Knowing how common new primary tumors are will help us determine whether or not a tumor biomarker can be used to predict the chance of an ipsilateral breast tumor because such a biomarker might not be effective in predicting new, unrelated tumors.”
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In order to understand how often a recurrence is a new tumor, the team assembled 65 pairs of primary DCIS and recurrence cases and performed DNA sequencing on each pair. They used multiple statistical approaches to analyze the resulting sequencing data and perform phylogenetic analyses of the tumor samples, which allowed them to establish if the tumors were derived from a common cancer cell.
“This is similar to building a family tree of the tumors based on the genetic events,” explained Kader. “We can estimate how distantly related the primary DCIS and recurrence pairs are to each other and to a potential original ancestor cell and we can track how the tumor pairs have evolved over time.”
The researchers discovered that 12% of recurrent tumors were, in fact, new primary tumors that had developed independently of the primary DCIS. They also found that variations in the TP53 gene were common in recurrences related to the primary tumor but not in those that developed independently. This raises questions about the use of genetic biomarkers for predicting reoccurrence, as it may lead to undertreatment.
The results suggest that when an individual has a DCIS recurrence, the treatment plan should include establishing whether the recurrence is related to the original tumor, as this will influence treatment options and outcomes. “For example, the occurrence of a new primary lesion in the same patient suggests a high-risk breast environment in which new tumors may develop over the years. Therefore, such patients would be candidates for preventative breast removal surgery even if the tumor is small, and they might be referred to genetic testing to ascertain whether they have any genetic predisposition,” concluded Kader.
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