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according to a study presented at the annual meeting of the American Association for Cancer Research.
If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.
Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.
But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.
For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.
They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.
The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.
The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.
“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.
“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.
The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.
This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.
Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”
The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.
A version of this article first appeared on Medscape.com.
according to a study presented at the annual meeting of the American Association for Cancer Research.
If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.
Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.
But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.
For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.
They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.
The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.
The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.
“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.
“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.
The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.
This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.
Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”
The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.
A version of this article first appeared on Medscape.com.
according to a study presented at the annual meeting of the American Association for Cancer Research.
If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.
Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.
But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.
For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.
They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.
The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.
The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.
“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.
“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.
The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.
This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.
Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”
The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.
A version of this article first appeared on Medscape.com.
FROM AACR 2022