comscoreBreast Cancer Recurrences May Have Different Genetics Than Primary Tumor

Breast Cancer Recurrences May Have Different Genetics Than Primary Tumor

A study suggests that when breast cancer recurs, its genetic makeup is much different from the primary tumor's genetic makeup.
Nov 10, 2015.This article is archived
We archive older articles so you can still read about past studies that led to today's standard of care.
Cells are the building blocks of every living thing. The instructions that tell a cell what to do are in genes within the center of the cell. Those genes are made of DNA (deoxyribonucleic acid). DNA can change or be damaged over time. Some DNA changes are harmless, but others can cause disease. Cancer cells are “born” when abnormal changes in DNA tell cells to grow faster and behave differently than they should. As these cancer cells multiply to form a tumor, they continue to change — becoming more and more different from each other.
As a cancer grows, new and different types of breast cancer cells are created within that same cancer. The mixture of cells that builds up over time becomes more and more complex. So even though every cell of a cancer is related to the same original "parent" cell, all the cells that make up a cancer are not the same. The idea that different kinds of cells make up one cancer is called "tumor heterogeneity."
Research on the genetic makeup of breast cancer tumors is ongoing in order to develop new treatments and management strategies.
Now a study suggests that when breast cancer comes back (recurs), its genetic makeup is much different from the primary tumor’s genetic makeup.
The study was presented on Sept. 27, 2015 at the European Cancer Congress 2015. Read the abstract of “The driver landscape of breast cancer metastasis and relapse.”
To look for differences in the genetics of primary and recurrent breast cancers, the researchers compared the genetics of 839 primary breast cancers and 161 recurrent breast cancers. The recurrent breast cancers were either local recurrences (coming back in the breast area) or metastatic recurrences (coming back in an area of the body away from the breast, such as the bones or liver).
The researchers found that a number of genes were enriched in the recurrent breast cancers that weren’t enriched in the primary cancers:
  • STAT3
  • ES41
  • FANCD2
  • FOX1
  • ARID1A
  • NF1
  • ARID1B
  • BRCA1
  • PIK3R1
  • AKT1
  • TP53
The ARID1A and the TP53 gene were the two most enriched genes in the recurrent tumors compared to the primary tumors.
The researchers found that certain genes were associated with specific subtypes of breast cancer, but it depended on whether the cancer was primary or recurrent:
  • TP53 genes dominated primary triple-negative breast cancers (cancers that have no receptors for estrogen, progesterone, or HER2).
  • PIK3CA was the most common gene associated with primary estrogen-receptor-positive cancers.
  • In recurrent cancers, PIK3CA was enriched in triple-negative cancer, but not estrogen-receptor-positive cancer.
  • TP53 dominated recurrent estrogen-receptor-positive cancer.
"Further work is required to determine if a high-risk subset can be identified at primary diagnosis and can subclones in the primary be informative," said Lucy Yates, of the Wellcome Trust Sanger Institute and lead author of the study. "A wide range of rare or unexpected cancer genes are implicated at relapse. We saw even greater inter- and intratumoral heterogeneity than anticipated, and they raise the question of whether the catalog of likely cancer genes in breast cancer may be even greater than anticipated.
"Most of all, these data highlight differences between primary and relapse samples,” she continued, “and, therefore, re-sampling throughout the disease is advisable."
This study offers more information about the genetics of breast cancer. While much more research needs to be done, each bit helps expand our understanding of the genes that seem to be associated with breast cancer.
If you’ve been diagnosed with recurrent breast cancer, you may want to talk to your doctor about this study. You can ask if the genetics of the recurrent cancer have been analyzed and, if so, how different they are from the primary cancer and how this might affect your treatment planning.
Stay tuned to Research News for the latest information on breast cancer genetics as well as new treatments that may target specific genes.

— Last updated on February 22, 2022, 9:55 PM

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