Breast Cancer Recurrence: New Breakthrough Could Decrease the Risk of Breast Cancer Returning
Scientists at The Institute of Cancer Research (ICR) in London have discovered why breast cancer cells that have spread to the lungs may ‘wake up’ many years after spreading, and forming secondary tumors, known as breast cancer recurrence.
The study, published in the journal Nature Cancer and funded by Breast Cancer Now, reveals the mechanism that sets off this breast cancer “time bomb” that leads to breast cancer recurrence, and proposes a potential method to defuse it.
The most common type (about 80%) of breast cancer is fueled by the hormone estrogen, known estrogen receptor positive (ER+) disease. Patients with ER+ disease have a significant risk of their cancer returning in another part of their body up to 30 years after their original diagnosis and treatment. Secondary, or metastatic breast cancer, refers to the spread of breast cancer cells from the breast to other parts of the body including the lungs, bones and liver. This is known as stage 4 disease. Although this can be treated and slowed down, it cannot be cured. This is because metastatic cancer cells eventually become resistant to the currently available hormone therapies and chemotherapies.
This new study performed in mice demonstrates how molecular changes in the lung that occur during normal aging may support the growth of these secondary tumors.
Cancer Cells “Reawaken” in Response to a Normal Protein
The Platelet Derived Growth Factor (PDGF) family of normal protein molecules helps damaged tissues heal and grow. The study found that a form of PDGF-C, a form of PDGF which is normally present in the lung, plays a key role in influencing whether rogue, inactive breast cancer cells stay asleep or ‘wake up.’
The study found that in young mice, dormant ER+ breast cancer cells in the lungs only produce a small amount of PDGF-C. This is enough for these cells to stay alive, but not enough to grow and spread. Older mice have more PDGF-C in their lung tissue which awakens the cancer cells and helps them grow. Furthermore, these awakened, stimulated cells produce more PDGF-C themselves which further increases growth.
Blocking PDGF-C Slows the Growth of ER+ Breast Cancer Cells
Dr. Frances Turrell, postdoctoral training fellow in the Division of Breast Cancer Research at ICR said: “Cancer cells can survive in distant organs for decades by hiding in a dormant state. We’ve discovered how aging lung tissue can trigger these cancer cells to ‘reawaken’ and develop into tumors and uncovered a potential strategy to ‘defuse’ these ‘time bombs’.
Drugs that block PDGF-C could potentially prevent these dormant ER+ cells from waking up and growing. These drugs could potentially even prevent metastasis from happening in the first place. One such drug that prevents cells from recognizing PDGF-C is Imatinib. Imatinib is a drug currently used to treat certain types of blood cancer like chronic myeloid leukemia. In this study, mice were treated with Imatinib before and after the lung mets had grown. In both groups, there was less cancer growth in the lungs.
These results suggest that Imatinib could one day be used to prevent breast cancer recurrence by slowing down or even stopping the growth of lung mets in women and men with ER+ disease. It could also potentially be used as a preventative treatment in patients with early-stage breast cancer and a high risk of recurrence.
While the results of this study are very exciting, unfortunately, we are still several years away from this treatment becoming clinically available. This study has so far only been performed in mice and more studies are needed to ensure the same results can be safely duplicated in humans.
