By Billy Candra 
A novel treatment approach developed by Cambridge researchers has delivered a significant breakthrough, demonstrating a 100% three-year survival rate for patients with aggressive, inherited forms of breast cancer. This remarkable outcome stems from a clinical trial, known as the Partner trial, where cancers were treated with a carefully timed sequence of chemotherapy followed by the targeted cancer drug olaparib prior to surgery. The findings, published today in the esteemed journal Nature Communications, herald a potential paradigm shift, positioning this strategy as potentially the most effective treatment to date for patients diagnosed with early-stage breast cancer carrying inherited BRCA1 and BRCA2 gene mutations.
Understanding the Challenge: BRCA Genes and Aggressive Cancers
Breast cancers associated with faulty copies of the BRCA1 and BRCA2 genes represent a particularly challenging subset of the disease. These genes normally play a crucial role in repairing damaged DNA and are classified as tumour suppressor genes. When mutated, their ability to perform these vital functions is compromised, leading to an increased risk of developing various cancers, most notably breast and ovarian cancers, but also prostate and pancreatic cancers. Globally, it is estimated that approximately 1 in 400 people carry a BRCA mutation, accounting for 5-10% of all breast cancers and up to 15% of ovarian cancers.
These inherited cancers often present at a younger age and are typically more aggressive, frequently exhibiting characteristics such as triple-negative breast cancer (TNBC), which lacks receptors for oestrogen, progesterone, and HER2, making them harder to treat with conventional hormone therapies or targeted HER2 drugs. The formidable nature of these cancers gained widespread public attention in 2013 when actress Angelina Jolie, a known BRCA1 carrier, underwent a preventative double mastectomy, raising global awareness about genetic testing and prophylactic measures. Despite advances in oncology, the standard approach—which involves using chemotherapy and sometimes immunotherapy to shrink the tumour before surgical removal—still leaves a significant risk of relapse or death, particularly within the critical first three years post-surgery.
The Partner Trial: A Paradigm Shift in Treatment Strategy
The Partner trial, led by researchers from Addenbrooke’s Hospital, part of Cambridge University Hospitals (CUH) NHS Foundation Trust, and the University of Cambridge, introduced two critical innovations. The first was the integration of olaparib, a targeted cancer drug, into the neoadjuvant (pre-surgical) treatment regimen alongside chemotherapy. Olaparib, already available on the NHS and taken as tablets, is a PARP (poly-ADP ribose polymerase) inhibitor. PARP enzymes are involved in DNA repair, and by inhibiting them, olaparib exploits a vulnerability in cancer cells that already have faulty BRCA genes, leading to a phenomenon known as "synthetic lethality." This means that while neither a BRCA mutation nor PARP inhibition alone might be fatal to a cell, the combination is devastating for cancer cells, which rely on PARP to repair the DNA damage that BRCA-deficient cells are unable to fix.
The second, equally crucial innovation was the precise timing of these treatments. The trial demonstrated that leaving a strategic 48-hour "gap" between the administration of chemotherapy and olaparib yielded significantly better outcomes. This meticulously planned interval is hypothesised to allow a patient’s healthy bone marrow cells, which are also affected by chemotherapy, sufficient time to recover. Simultaneously, the tumour cells, already compromised by their BRCA mutations and initial chemotherapy, remain susceptible to the targeted action of olaparib. This strategic pause aims to minimise systemic toxicity to the patient while maximising the drug’s impact on the cancer. The genesis of this specific timing approach was itself a testament to scientific serendipity, stemming from a "chance conversation" between Professor Jean Abraham, the trial lead, and Mark O’Connor, chief scientist in Early Oncology R&D at nearby AstraZeneca, highlighting the collaborative spirit driving medical innovation.
The trial successfully recruited patients from 23 NHS sites across the UK, reflecting a broad national effort in cancer research. This multi-centre approach ensured diverse patient representation and robust data collection, underpinning the reliability of the findings.
Unprecedented Results and Patient Impact
The results of the Partner trial are nothing short of remarkable. Of the 39 patients who received the innovative regimen of chemotherapy followed by olaparib with the 48-hour gap, an astonishing 100% survived the critical three-year period following surgery. Only one patient in this cohort experienced a relapse within this timeframe. This outcome stands in stark contrast to the control arm of the study, where 45 patients received chemotherapy only, adhering to the then-standard treatment protocol. In the control group, the three-year survival rate was 88%, with nine patients relapsing and, tragically, six of them succumbing to the disease. The sheer difference in survival rates underscores the profound impact of the new approach.
For patients like Jackie Van Bochoven, 59, from South Cambridgeshire, these findings translate into renewed life and hope. Diagnosed in February 2019 with a small but aggressive tumour, Jackie recalled her initial shock and fear: "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." Her personal history, coupled with the aggressive nature of her own diagnosis, amplified her anxieties. However, after participating in the Partner trial, Jackie’s journey offers a powerful testament to its success. "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." Her experience vividly illustrates the life-altering potential of this research, moving from profound worry to vibrant recovery.
Redefining Care: Broader Implications and Cost-Effectiveness
The implications of the Partner trial extend far beyond the immediate success in breast cancer. The findings have the potential to be applied to other cancers caused by faulty copies of BRCA genes, including certain ovarian, prostate, and pancreatic cancers, where similar genetic vulnerabilities could be exploited. This opens doors for developing more effective treatments across a spectrum of difficult-to-treat malignancies, leveraging the same synthetic lethality principle.
Beyond clinical efficacy, the new approach also carries significant potential for cost-saving benefits for the NHS. Currently, patients offered olaparib typically take the drug post-surgery for a prolonged period, often 12 months. In contrast, patients on the Partner trial received the tablets pre-surgery for a much shorter duration of 12 weeks. This substantial reduction in treatment duration not only lessens the financial burden on healthcare systems but also potentially reduces patient exposure to medication, mitigating side effects and improving overall quality of life during treatment. The economic advantage could accelerate its adoption into standard clinical practice. This shift from prolonged post-surgical adjuvant therapy to a more concise, potent neoadjuvant regimen represents a strategic advantage for both patients and healthcare providers.
This innovative approach is a prime example of precision medicine in action, where treatment is tailored to the specific genetic profile of a patient’s cancer. By understanding the underlying molecular biology of BRCA-mutated tumours, researchers have been able to design a highly effective, targeted therapy, moving beyond a one-size-fits-all approach to cancer care.
Voices from the Forefront: Expert Commentary and Collaboration
Professor Jean Abraham, a consultant at Addenbrooke’s and Professor of Precision Breast Cancer Medicine at the University of Cambridge, articulated the profound significance of the trial’s results: "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." Her enthusiasm underscores the transformative potential this discovery holds for a patient population with historically limited options.
Mark O’Connor of AstraZeneca also highlighted the collaborative spirit and scientific rigour behind the trial. "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," O’Connor stated. He further acknowledged the need for future validation: "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 industry perspective reinforces the scientific merit and the potential for real-world impact.
Michelle Mitchell, Chief Executive of Cancer Research UK, emphasised the broader strategic implications of the research: "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." She added, "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." Mitchell’s statement, while optimistic, also prudently calls for further studies to confirm safety and effectiveness for widespread NHS use.
This type of profound collaboration between the NHS, academia, and industry is a hallmark of the vision driving the Cambridge Cancer Research Hospital. This specialist cancer research hospital, slated for construction on Europe’s leading life sciences campus, the Cambridge Biomedical Campus, aims to integrate clinical expertise from Addenbrooke’s Hospital with world-class scientists from the University of Cambridge, the Cancer Research UK Cambridge Centre, and industry partners. The goal is to accelerate the creation of new diagnostics and treatments, detect the earliest signs of cancer, and deliver truly personalised, precision medicine. The Partner trial serves as a powerful testament to the efficacy of this integrated approach.
The Road Ahead: Validation and Widespread Implementation
Encouraged by these highly positive outcomes, Professor Abraham and her team are now meticulously planning the next phase of research. This crucial step will involve a larger, confirmatory study designed to replicate the results in a broader patient population. The forthcoming study will also aim to definitively confirm that the Partner approach offers a less toxic treatment regimen for patients, in addition to its cost-effectiveness, compared to the current standard of care. This rigorous validation process is essential to ensure that the treatment can be safely and effectively rolled out across the NHS and potentially worldwide, transforming the lives of countless patients.
The Partner trial was a collaborative endeavour, sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. Crucially, it received vital funding from Cancer Research UK and AstraZeneca, with additional support from the NIHR Cambridge Biomedical Research Centre, the Cancer Research UK Cambridge Centre, and Addenbrooke’s Charitable Trust (ACT). This multi-institutional backing underscores the significance and collaborative nature of this groundbreaking research, poised to redefine the landscape of inherited breast cancer treatment.
