By Billy Candra 
A groundbreaking treatment strategy has dramatically improved survival rates for patients battling aggressive forms of inherited breast cancer, with Cambridge researchers reporting an unprecedented 100% survival rate over a critical three-year post-surgery period. This innovative approach, detailed in the prestigious journal Nature Communications, involved a meticulously timed regimen of chemotherapy followed by a targeted cancer drug prior to surgery, offering a new beacon of hope for individuals diagnosed with early-stage breast cancer linked to inherited BRCA1 and BRCA2 gene mutations.
Understanding Inherited Breast Cancer and the BRCA Genes
Breast cancers associated with faulty copies of the BRCA1 and BRCA2 genes are notoriously challenging to treat due to their aggressive nature and propensity for rapid progression. These genetic mutations gained significant public attention in 2013 when actress Angelina Jolie, a BRCA1 carrier, underwent a preventative double mastectomy, raising global awareness about the hereditary risks and the proactive measures available. While her decision highlighted preventative care, the focus of the Cambridge research is on improving outcomes for those already diagnosed with these specific, high-risk cancers.
The standard treatment protocol for such cancers typically involves a multi-modal approach: chemotherapy and often immunotherapy are administered first to shrink the tumour, followed by surgical removal. The initial three years following surgery are considered a critical window, during which the risk of cancer relapse or patient mortality is highest. Overcoming this hurdle represents a significant advancement in patient care and long-term prognosis.
The Partner Trial: A Novel Approach to Treatment
The "Partner" trial, a pioneering study led by Addenbrooke’s Hospital, part of Cambridge University Hospitals (CUH) NHS Foundation Trust, and the University of Cambridge, introduced two key innovations. The first was the integration of olaparib, an oral targeted cancer drug already available on the NHS, into the pre-surgical treatment regimen alongside chemotherapy. The second, and arguably more ingenious, innovation was the precise timing of these treatments.
Olaparib belongs to a class of drugs known as PARP inhibitors, which work by exploiting a weakness in cancer cells with BRCA mutations. These mutations impair the cells’ ability to repair damaged DNA, making them highly susceptible to PARP inhibition. By further disrupting DNA repair pathways, olaparib can selectively kill cancer cells while sparing healthy ones. Its inclusion before surgery aimed to enhance tumour shrinkage and improve the pathological complete response rate.
Patients for the Partner trial were recruited from 23 NHS sites across the UK, reflecting a broad national effort to gather robust data. The trial’s design sought to evaluate whether this enhanced pre-surgical regimen could outperform the existing standard of care.
Striking Results: A New Benchmark for Survival
The findings from the Partner trial have sent ripples of excitement through the oncology community. Of the 39 patients who received the innovative sequential treatment of chemotherapy followed by olaparib, only one experienced a relapse three years after surgery, resulting in an extraordinary 100% survival rate for the cohort. This outcome stands in stark contrast to the control arm of the study, which comprised 45 patients who received chemotherapy alone. In the control group, nine patients relapsed, and tragically, six of those patients died, leading to a three-year post-surgery survival rate of 88%. The significant disparity in outcomes underscores the profound impact of the new treatment strategy.
Professor Jean Abraham, a consultant at Addenbrooke’s and the lead for the Partner trial, as well as Professor of Precision Breast Cancer Medicine at the University of Cambridge, expressed profound optimism regarding the results. "It is rare to have a 100% survival rate in a study like this and for these aggressive types of cancer," she stated. "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."
A Patient’s Perspective: Jackie Van Bochoven’s Journey
Behind the statistics are real people whose lives have been transformed. Jackie Van Bochoven, 59, from South Cambridgeshire, was diagnosed in February 2019 with an aggressive, albeit small, tumour. Her family history of breast cancer – her mother and sister also having been diagnosed – compounded 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," she recounted.
Jackie participated in the Partner trial and, six years later, remains cancer-free and well. Her story is a testament to the potential of this new treatment. "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," she shared, her experience embodying the trial’s success. Her journey highlights the profound human impact of such medical breakthroughs, offering not just extended life, but a return to normalcy and a renewed appreciation for it.
The Science Behind the Success: The 48-Hour Gap
One of the most intriguing aspects of the Partner trial’s success lies in the meticulous timing of the drug administration. The research team discovered that introducing a 48-hour "gap" between the chemotherapy and the subsequent administration of olaparib led to significantly better outcomes. This specific timing is believed to allow a patient’s bone marrow to recover from the cytotoxic effects of chemotherapy, thereby mitigating some of the severe side effects. Simultaneously, this brief pause ensures that the tumour cells remain susceptible to the targeted action of olaparib.
This hypothesis emerged from what Professor Abraham described as a "chance conversation" with Mark O’Connor, chief scientist in Early Oncology R&D at AstraZeneca, a pharmaceutical company heavily involved in oncology research. O’Connor elaborated on the scientific rationale: "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." This insight into cellular recovery and drug susceptibility proved to be a critical factor in the trial’s design and subsequent success.
Expert Commentary and Collaborative Vision
The success of the Partner trial is not merely a scientific triumph but also a powerful example of effective collaboration between various stakeholders in the medical and scientific community. The trial was sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by Cancer Research UK and AstraZeneca, and further supported by the NIHR Cambridge Biomedical Research Centre, the Cancer Research UK Cambridge Centre, and Addenbrooke’s Charitable Trust (ACT).
Michelle Mitchell, Chief Executive of Cancer Research UK, underscored the broader implications of such 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 noted. "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." She also prudently added that "Further studies in more patients are needed to confirm whether this new technique is safe and effective enough to be used by the NHS."
Mark O’Connor of AstraZeneca further emphasized the significance of the findings, stating, "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 sentiment highlights the cautious optimism that accompanies such groundbreaking discoveries, acknowledging the need for further validation while celebrating the initial success.
This collaborative model perfectly aligns with the vision for the Cambridge Cancer Research Hospital, a specialist facility planned for Europe’s leading life sciences campus, the Cambridge Biomedical Campus. This hospital 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 foster an environment where new diagnostics and treatments can be rapidly developed to detect early signs of cancer and deliver personalized, precision medicine, making the Partner trial a prime example of the kind of innovation such a facility will champion.
Broader Implications and Future Directions
The potential impact of the Partner trial extends beyond inherited breast cancers. 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. This suggests a broader paradigm shift in the treatment of these genetically linked malignancies.
Furthermore, the new approach could offer significant cost-saving benefits for the NHS. Under current protocols, patients prescribed olaparib typically take the drug for 12 months post-surgery. In contrast, patients on the Partner trial received the tablets pre-surgery for a much shorter duration of 12 weeks. This reduction in treatment time could translate into substantial cost efficiencies for the healthcare system, in addition to potentially reducing the long-term burden on patients.
Professor Abraham and her team are now actively planning the next phase of research. This larger study will aim to replicate the impressive results in a broader patient population, confirming the efficacy and safety of the Partner approach. A key objective will also be to formally assess whether this innovative regimen offers a less toxic treatment for patients compared to the current standard of care, alongside its potential for cost-effectiveness. The ultimate goal is to validate these preliminary findings sufficiently to pave the way for widespread adoption within the NHS, transforming the lives of countless patients facing aggressive, inherited breast cancers.
Funding and Support
The successful execution of the Partner trial would not have been possible without the substantial support and funding from several key organizations. Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge served as the trial sponsors, ensuring the ethical and scientific rigor of the study. Financial backing was provided by Cancer Research UK and AstraZeneca, demonstrating a shared commitment to advancing cancer treatment. Additional vital support was rendered by the NIHR Cambridge Biomedical Research Centre, the Cancer Research UK Cambridge Centre, and Addenbrooke’s Charitable Trust (ACT), highlighting a robust ecosystem dedicated to medical innovation in the UK.
