New approach to treating aggressive breast cancers shows significant improvement in survival

(Press-News.org) A new treatment approach significantly improves survival rates for patients with aggressive, inherited breast cancers, according to Cambridge researchers.

In a trial where cancers were treated with chemotherapy followed by a targeted cancer drug before surgery, 100% of patients survived the critical three-year period post-surgery.

The discovery, published today in Nature Communications, could become the most effective treatment to date for patients with early-stage breast cancer with inherited BRCA1 and BRCA2 gene mutations.

Breast cancers with faulty copies of the BRCA1 and BRCA2 genes are challenging to treat, and came to public attention when actress Angelina Jolie, a BRCA1 carrier, underwent a preventative double mastectomy in 2013.

Current standard treatment aims to shrink the tumour using chemotherapy and immunotherapy, before removing it through surgery. The first three years after surgery is a critical period, when there is the greatest risk of relapse or death.

The Partner trial took a different approach and demonstrates two innovations: the addition of olaparib and chemotherapy pre-surgery, and the benefits of careful timing of when the treatments are given to patients. Taken as tablets, olaparib is a targeted cancer drug already available on the NHS.

Led by Addenbrooke’s Hospital, part of Cambridge University Hospitals (CUH) NHS Foundation Trust and the University of Cambridge, the trial saw patients recruited from 23 NHS sites across the UK.

Results show that leaving a 48-hour “gap” between chemotherapy and olaparib, leads to better outcomes, possibly because a patient’s bone marrow has time to recover from chemotherapy, while leaving the tumour cells susceptible to the targeted drug.

Of the 39 patients who received chemotherapy followed by olaparib, only one patient relapsed three years after surgery and 100% of patients survived.

In comparison, the survival rate for the control arm was 88% three years after surgery. Of the 45 patients on the control arm who received chemotherapy only, nine patients relapsed, of whom six died.

Jackie Van Bochoven, 59, from South Cambridgeshire, was diagnosed in February 2019 with a small but aggressive tumour. She said: “When I had the diagnosis, I was completely shocked and numb, I thought about my children, and my mum and sister who were diagnosed with breast cancer. I was pretty worried.

“Six years on, I’m well and cancer free. I’m back at work, enjoying life and spending time with my family. When you’ve had cancer, I think you look at life differently and every day is a bonus.”

The findings have the potential to be applied to other cancers caused by faulty copies of BRCA genes, such as some ovarian, prostate and pancreatic cancers.

It may also have cost-saving benefits for the NHS, as patients currently offered olaparib take the drug post-surgery for 12 months, whereas patients on the trial took the tablets pre-surgery for 12 weeks.

Addenbrooke’s consultant and trial lead, Professor Jean Abraham said: “It is rare to have a 100% survival rate in a study like this and for these aggressive types of cancer. We’re incredibly excited about the potential of this new approach, as it’s crucial that we find a way to treat and hopefully cure patients who are diagnosed with BRCA1 and BRCA2 related cancers.”

Professor Abraham, who is also Professor of Precision Breast Cancer Medicine at the University of Cambridge, said trialling the 48-hour gap approach followed a “chance conversation” with Mark O’Connor, chief scientist in Early Oncology R&D at nearby AstraZeneca.

Mark O’Connor added: “The Partner trial highlights the importance of detecting and treating cancer early, and the value of innovative science in informing clinical trial design, in this case using bone marrow stem cells to identify the combination gap schedule. While the findings need to be validated in a larger study, they’re incredibly exciting, and have the potential to transform outcomes for patient populations who have unmet clinical need.”

This type of collaboration between NHS, academia and industry reflects the vision of Cambridge Cancer Research Hospital, a specialist cancer research hospital due to be built on Europe’s leading life sciences campus, the Cambridge Biomedical Campus. It will bring clinical expertise from Addenbrooke’s Hospital with world-class scientists from the University of Cambridge, Cancer Research UK Cambridge Centre, and industry partners together in one location to create new diagnostics and treatments to detect the earliest signs of cancer and deliver personalised, precision medicine.

Chief Executive of Cancer Research UK, Michelle Mitchell, said: “One of the best ways that we can beat cancer sooner is by making more effective use of treatments that are already available to us.

"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.

“Research like this can help find safer and kinder ways to treat certain types of cancer. Further studies in more patients are needed to confirm whether this new technique is safe and effective enough to be used by the NHS."

Professor Abraham and team are now planning the next phase of the research, which will look to replicate the results in a larger study and confirm that the Partner approach offers a less toxic treatment for patients as well as being more cost effective, compared to the current standard of care.

The Partner trial was sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by Cancer Research UK and AstraZeneca, and supported by the NIHR Cambridge Biomedical Research Centre, the Cancer Research UK Cambridge Centre and Addenbrooke’s Charitable Trust (ACT).

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