A clinical trial led by researchers at Addenbrooke's Hospital in Cambridge has demonstrated remarkable results for patients with aggressive, inherited breast cancer. The study, published in Nature Communications, shows that administering the targeted drug olaparib alongside chemotherapy before surgery significantly improves survival rates for patients with BRCA1 or BRCA2 gene mutations.
The trial, named "Partner," involved 84 women with early-stage breast cancer across 23 sites in England, Scotland, and Wales. Among the 39 patients who received olaparib tablets following chemotherapy before surgery, 100% survived the critical three-year post-surgery period. In contrast, the control group of 45 patients who received only chemotherapy experienced nine relapses and six deaths, resulting in an 88% survival rate.
Innovative Treatment Approach
The groundbreaking aspect of this study lies in both the drug combination and the precise timing of administration. Patients in the treatment group began taking olaparib tablets 48 hours after each chemotherapy infusion. This strategic gap appears crucial to the treatment's success.
"It is rare that you see 100% survival at 36 months for this subtype of breast cancer," said Professor Jean Abraham, consultant at Addenbrooke's and professor of precision breast cancer medicine at the University of Cambridge, who led the trial. "We're incredibly excited about the potential of this new approach."
The researchers believe the 48-hour interval allows a patient's bone marrow to recover from chemotherapy while leaving tumor cells vulnerable to olaparib's targeted effects. This timing was reportedly inspired by a "chance conversation" between Professor Abraham and Mark O'Connor, chief scientist in Early Oncology R&D at AstraZeneca.
How Olaparib Works
Olaparib, also marketed as Lynparza, is the first targeted drug treatment specifically for cancers with mutations in the BRCA genes. It works by blocking a protein called PARP, which prevents cancer cells from repairing their DNA, ultimately causing these cells to die.
The drug is already available on the NHS but is typically administered after surgery for 12 months. The Partner trial's approach used olaparib for just 12 weeks before surgery, potentially offering both improved outcomes and cost savings.
Patient Impact
Jackie Van Bochoven, 59, from Cambridgeshire, was among the trial participants. Diagnosed with an aggressive breast tumor in 2019, she carries a faulty copy of the BRCA1 gene, which significantly increases lifetime cancer risk.
"When I had the diagnosis I was completely shocked," she told BBC News. "Six years on, I'm well and cancer free. It's amazing."
Van Bochoven's family history includes breast cancer in both her mother and sister. Her eldest daughter also carries the inherited BRCA gene mutation. "For my future generations, if they have got the BRCA gene, it is a new hope," she said.
BRCA Mutations and Cancer Risk
Around one in 400 people carry mutations in either the BRCA1 or BRCA2 genes. According to Cancer Research UK, approximately seven in ten women with these genetic changes will develop breast cancer, compared to about one in seven women without the mutations. For men with BRCA mutations, the breast cancer risks are much lower.
These genetic mutations gained public attention in 2013 when actress Angelina Jolie, a BRCA1 carrier, underwent a preventative double mastectomy.
Broader Applications
The findings from this study could potentially extend beyond breast cancer to other BRCA-related malignancies, including ovarian, prostate, and pancreatic cancers.
Michelle Mitchell, Chief Executive of Cancer Research UK, which funded the trial alongside AstraZeneca, commented: "While this research is still in its infancy, it is an exciting discovery that adding olaparib at a carefully-timed stage of treatment can potentially give patients with this specific type of breast cancer more time with their loved ones."
Next Steps
Professor Abraham and her team are now planning a larger follow-up study to confirm these promising results. The researchers aim to verify that the Partner approach offers not only improved survival but also less toxic treatment for patients while being more cost-effective compared to current standards of care.
If confirmed in a larger clinical trial, this treatment approach could benefit more than 1,200 patients annually in the UK alone.
The collaboration between NHS, academia, and industry reflects the vision of the planned Cambridge Cancer Research Hospital, which will bring together clinical expertise from Addenbrooke's Hospital with scientists from the University of Cambridge, Cancer Research UK Cambridge Centre, and industry partners to develop new cancer diagnostics and treatments.
