Breast cancer cells that spread to other parts of the body break off and leave the primary tumor at late stages of disease development, scientists from the Wellcome Trust Sanger Institute and their collaborators have found.

The results show that catching and treating breast cancer before it spreads is a realistic goal.1 It also opens the door to predicting which drugs will work against breast cancer that has already spread.

“As the cells that cause the spread of breast cancer leave relatively late, it means they are still quite similar to the cells in the primary tumor,” says Lucy Yates, PhD, MBBS, FRCR, MRCP, first author from the Wellcome Trust Sanger Institute and Guys and St Thomas’ NHS Trust. “Therefore by studying the genome of the primary breast cancer tumor, in the future we may be able to predict what cells that might have spread ‘look’ like, and potentially which treatments they will respond to.”

In this study, scientists investigated how breast cancer evolves from the original tumor in the breast to tumors that have spread, or metastasized. It has been controversial whether the breast cancer cells that spread to other parts of the body break off and leave the primary tumor in the breast at early or at late stages of cancer development. The team found that most of the genetic changes in the original breast tumor were also present in the metastatic tumors, showing that the cancer cells spread late in disease development.

The team sequenced the DNA of 299 tumors from 170 patients with breast cancer that either returned in the remaining breast—local relapse— or had spread—metastatic breast cancer.

Researchers found that in the time between breast cancer patients being diagnosed with primary cancer and the diagnosis of metastasis, the breast cancer cells had gained genetic changes, or mutations, that increased the aggressiveness of the tumour. This may explain why metastatic breast cancer is currently difficult to treat.

“Most women who have metastatic breast cancer do not have another biopsy of the cancer, and rarely have it analyzed using genetic sequencing,” says Per Eystein Lønning, MD, joint lead author from the University of Bergen and Haukeland University Hospital in Bergen. “In this study we found that in some cases, the metastatic tumors had particular genetic changes that could be targeted with treatments. We would not have seen these mutations by sequencing the primary tumor alone. Our results suggest that it should be more routine to biopsy the metastasis and have it genetically analyzed in order to open up clinical trials of treatment options for metastatic breast cancer.”


1. Yates LR, Knappskog S, Wedge D, et al. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell. 2017;32(2):169-184.e7; doi: 10.1016/j.ccell.2017.07.005.