Scientists have discovered why breast cancer cells that have spread to the lungs can ‘wake up’ after years of slumber – forming incurable secondary tumours.
Their research, funded by Breast Cancer Now, reveals the mechanism that sets off this breast cancer ‘ticking time bomb’ — and suggests a strategy to reverse it.
Patients with estrogen receptor-positive (ER+) breast cancer — the most common type — are at constant risk of their cancer recurring elsewhere in their body for many years or even decades after their initial diagnosis and treatment.
When breast cancer cells spread from the first breast cancer to other parts of the body, it is called secondary or metastatic breast cancer, and although it is treatable, it cannot be cured.
The new research, published today (Monday 13u March) in the magazine Nature Cancershowed how molecular changes within the lung that occur during aging can support the development of these secondary tumors.
The team from the Institute of Cancer Research London found that the protein PDGF-C, which is present in the lung, plays a key role in determining whether dormant breast cancer cells remain dormant or ‘wake up’.
They discovered that if the level of PDGF-C increases, which is more likely in an aging lung or when its tissue is damaged or scarred, it can cause dormant cancer cells to grow and develop into secondary breast cancer.
The researchers then investigated whether blocking PDGF-C activity could help prevent these cells from “reawakening” and developing secondary tumors.
Working with mice with ER+ tumors, researchers at the Now Toby Robins Breast Cancer Research Center at the Institute for Cancer Research targeted PDGF-C signaling with an existing cancer growth inhibitor called imatinib, which is currently used to treat patients with chronic myeloid leukemia.
The mice were treated with the drug both before and after the tumors developed. For both groups, the growth of lung cancer was significantly reduced.
Up to 80% of primary breast cancers are ER+ and there are around 44,000 cases in the UK each year*.
Dr Frances Turrell, postdoctoral fellow in the Breast Cancer Research Unit at the Institute of Cancer Research London, said:
“Cancer cells can survive in distant organs for decades hidden in a dormant state. We have discovered how aging lung tissue can cause these cancer cells to ‘reawaken’ and develop into tumors, and we have revealed a possible strategy to ‘kill’ them . ticking time bombs”. We now aim to better sort out how patients might benefit from the existing drug imatinib, and in the longer term aim to create more specific therapies that target the ‘reawakening’ mechanism.
Professor Clare Isacke, Professor of Molecular Cell Biology at the Institute of Cancer Research London, said:
“This is an exciting step forward in our understanding of advanced breast cancer — and how and why breast cancer cells form secondary tumors in the lungs.
“Next, we need to pinpoint when these age-related changes occur and how they differ between people, so we can create treatment strategies that prevent cancer cells from ‘reawakening’.”
Dr Simon Vincent, director of research, support and advocacy at Breast Cancer Now, which funded the study, said: “We know that for years after breast cancer treatment is completed, many women fear the disease will return. With approx. With 61,000 people living with secondary breast cancer in the UK, more research into understanding and treating it is vital.
“This exciting discovery brings us one step closer to understanding how we can slow or stop the growth of secondary ER+ breast cancer in the lung. It has the potential to benefit thousands of women living with this ‘ticking time bomb’ ” in the future, ensuring fewer patients receive the devastating news that the disease has spread.”
Rachel Davies, 38, lives in Swansea with her husband David, 38, and son Charlie, 16. She was diagnosed with ER+ breast cancer in 2021 and underwent a mastectomy, lymph node dissection, chemotherapy and radiotherapy.
After a scan in May 2022, three months after completing treatment, Rachel was told the cancer had spread to her sternum and later to her spine. She is now on a targeted cancer drug called ribociclib and hormone therapy and is scanned every three months.
Rachel said: “I’ve seen some women finish treatment and ring that bell and celebrate it’s over, and that always worries me as you can never be complacent that it won’t come back. Finding out the cancer had spread when the I thought Everything in the past was heartbreaking.That’s why it’s so important to research secondary breast cancer so we can find new ways to prevent women from going through what I’m going through.
“My life is very different now as I’ve had to leave my job in adult social services and give up the degree I was studying for. But I’m staying positive and trying not to let it get to me. It’s made me appreciate things more and I think it’s made me a better person. Research like this gives me hope for women going through breast cancer treatment in the future. I don’t want to waste my precious time being bitter or angry.”