When Jackie Van Bochoven was diagnosed with an aggressive breast tumour in 2019, her family history of cancer—and a mutation in the BRCA gene, which raises the risk of various cancers—qualified her for a clinical trial that administered both chemotherapy and a drug, Olaparib, before surgery.
Olaparib is the first targeted treatment for cancers with mutations in the BRCA genes. Taken as tablets, it stops cancer cells from being able to repair their DNA by blocking a molecule called PARP, causing the cancerous cells to die.
“Six years on, I’m well and cancer-free,” says Bochoven. “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.”
Bochoven is one of 39 patients in the Cambridge-led trial who received chemotherapy followed by Olaparib before surgery. Remarkably, all 39 patients survived the critical three-year period post-surgery, and only one experienced relapse. In contrast, the control group, which received chemotherapy alone, had an 88% survival rate, with nine relapses and six deaths.
The results, published in Nature Communications, point to what could be the most effective treatment to date for early-stage breast cancers with inherited BRCA1 or BRCA2 gene mutations — genes that, when faulty, greatly raise the risk of breast and other cancers.
The Addenbrooke’s Hospital and the University of Cambridge trial tested a new approach to BRCA mutation treatment by implementing a carefully timed 48-hour gap between chemotherapy and the administration of Olaparib.
Results show that leaving a 48-hour “gap” between the two treatments 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.
“It is rare to have a 100% survival rate in a study like this and for these aggressive types of cancer,” says trial lead Professor Jean Abraham. “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.”
Abraham, who is also Professor of Precision Breast Cancer Medicine at the University of Cambridge, noted the 48-hour treatment gap idea came from a “chance conversation” with Mark O’Connor, a chief scientist in the oncology division at AstraZeneca.
“While the findings need to be validated in a larger study, they’re incredibly exciting,” says O’Connor. “They have the potential to transform outcomes for patient populations who have unmet clinical needs”.
The findings can also be applied to other cancers caused by faulty copies of BRCA genes, such as some ovarian, prostate and pancreatic cancers.
“Research like this can help find safer and kinder ways to treat certain types of cancer,” says the Chief Executive of Cancer Research UK, Michelle Mitchell. “Further studies in more patients are needed to confirm whether this new technique is safe and effective.”
Associate Professor Theresa Hickey, an internationally recognised breast cancer expert from the University of Adelaide, and a National Breast Cancer Foundation Research Fellow, offers an Australian perspective on the findings.
“Australia has been a world leader in advancing treatment options for one of the most aggressive forms of breast cancer, called triple negative breast cancer (TNBC), particularly for those that carry mutations in breast cancer risk genes BRCA1 and BRCA2,” she says.
“Last year, Olaparib was added to the Australian Pharmaceutical Benefits Scheme, meaning treatment with this drug will cost much less for a patient who may benefit from it.
“Although this trial was small and results need to be confirmed by other, larger trials, the results were exciting.”
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