By Billy Candra 
A pioneering treatment approach has demonstrated a remarkable 100% three-year survival rate for patients suffering from aggressive, inherited forms of breast cancer, marking a significant advancement in oncology. Researchers at Cambridge University have unveiled findings from the Partner trial, indicating that a carefully timed combination of chemotherapy and a targeted cancer drug, olaparib, administered before surgery, could become the most effective treatment to date for individuals diagnosed with early-stage breast cancer linked to inherited BRCA1 and BRCA2 gene mutations. This innovative strategy not only offers unprecedented survival outcomes but also presents potential cost-saving benefits for the National Health Service (NHS) and opens avenues for treating other BRCA-related cancers.
A Paradigm Shift in Treating BRCA-Mutated Breast Cancer
The study, published today in the prestigious journal Nature Communications, details a novel neoadjuvant (pre-surgical) regimen where patients received chemotherapy followed by olaparib. In a critical finding, all 39 patients who underwent this specific treatment sequence survived the crucial three-year period following surgery, a timeframe when the risk of relapse or death is highest for breast cancer patients. This outcome stands in stark contrast to the control arm of the trial, where 45 patients received chemotherapy alone, resulting in an 88% survival rate over the same three-year period. Of the nine patients in the control group who experienced a relapse, six tragically succumbed to the disease, underscoring the profound impact of the new combined approach.
Inherited mutations in the BRCA1 and BRCA2 genes are well-established risk factors for several cancers, most notably breast and ovarian cancers. These genes play a vital role in DNA repair, and when faulty, they compromise the cell’s ability to mend damaged DNA, leading to an increased likelihood of cancerous mutations. Cancers arising from these genetic defects are often aggressive and challenging to treat, making the search for effective therapies a global priority. Public awareness of BRCA mutations surged in 2013 when actress Angelina Jolie, a BRCA1 carrier, openly discussed her preventative double mastectomy, highlighting the genetic predisposition and the difficult decisions many individuals face.
The current standard of care for early-stage breast cancer, particularly aggressive subtypes, typically involves neoadjuvant chemotherapy, sometimes combined with immunotherapy, aimed at shrinking the tumour before surgical removal. While effective for many, the risk of recurrence remains a significant concern, especially within the first three years post-surgery. The Partner trial, led by Addenbrooke’s Hospital, part of Cambridge University Hospitals (CUH) NHS Foundation Trust, and the University of Cambridge, sought to improve upon these outcomes by introducing two key innovations: the inclusion of olaparib pre-surgery and, crucially, optimizing the timing of its administration relative to chemotherapy.
The Ingenuity of the "48-Hour Gap"
Olaparib, an orally administered targeted cancer drug, is a poly ADP-ribose polymerase (PARP) inhibitor. PARP enzymes are involved in DNA repair, and by inhibiting them, olaparib exploits the existing DNA repair deficiencies in BRCA-mutated cancer cells, leading to their death. It is already available on the NHS for certain indications. However, the Partner trial’s brilliance lies not just in the drug’s inclusion, but in the precise sequencing of treatments.
The trial revealed that introducing a 48-hour "gap" between the chemotherapy cycles and the administration of olaparib yielded superior results. Researchers hypothesize that this specific timing allows a patient’s bone marrow, which is highly susceptible to the toxic effects of chemotherapy, sufficient time to recover. Simultaneously, the tumour cells, still compromised by the initial chemotherapy damage, remain vulnerable to the targeted assault of olaparib. This strategic pause appears to maximize the therapeutic effect while potentially minimizing adverse side effects.
Professor Jean Abraham, a consultant at Addenbrooke’s Hospital and the trial lead, expressed immense excitement about the findings. "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," she stated. Professor Abraham, who also holds the position of Professor of Precision Breast Cancer Medicine at the University of Cambridge, revealed that the inspiration for trialling the 48-hour gap stemmed from a "chance conversation" with Mark O’Connor, chief scientist in Early Oncology R&D at AstraZeneca, highlighting the serendipitous nature of scientific breakthroughs often born from collaborative dialogue.
A Patient’s Journey: Six Years Cancer-Free
The human impact of these scientific breakthroughs is best illustrated through patient stories. Jackie Van Bochoven, 59, from South Cambridgeshire, was diagnosed in February 2019 with a small but aggressive tumour. Her diagnosis was particularly distressing given her family history of breast cancer, with both her mother and sister having battled the disease. "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 was one of the patients who benefited from the innovative Partner trial protocol. Six years on, her life has been transformed. "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 words reflecting the profound gratitude and renewed perspective that comes with overcoming such a formidable challenge. Her experience provides powerful anecdotal evidence supporting the trial’s promising statistical outcomes.
Broader Implications and Future Outlook
The implications of the Partner trial extend far beyond breast cancer. The findings have the potential to be applied to other cancers caused by faulty copies of BRCA genes, including certain types of ovarian, prostate, and pancreatic cancers, which also present significant treatment challenges. This broad applicability could revolutionize the treatment landscape for a wider spectrum of patients with inherited genetic predispositions to cancer.
Economically, the new approach also holds promise for the NHS. Currently, patients offered olaparib typically take the drug post-surgery for a period of 12 months. In contrast, patients on the Partner trial took the tablets pre-surgery for only 12 weeks. This significantly shorter duration of treatment could lead to substantial cost-saving benefits for the healthcare system, making a highly effective treatment more financially sustainable and accessible. Furthermore, the protocol’s potential to be less toxic than existing prolonged treatments could improve patient quality of life during therapy.
Mark O’Connor of AstraZeneca emphasized the broader significance of 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. 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 call for further validation underscores the rigorous scientific process required before widespread clinical adoption, yet the optimism surrounding the initial results is palpable.
A Vision for Collaborative Cancer Research
The success of the Partner trial is a testament to the power of collaborative research, bringing together diverse expertise from clinical practice, academia, and industry. This synergistic model reflects the vision behind the Cambridge Cancer Research Hospital, a specialist facility slated for construction on the Cambridge Biomedical Campus, Europe’s leading life sciences hub. This new 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 accelerate the discovery and development of new diagnostics and treatments, enabling the earliest possible detection of cancer and the delivery of truly personalized, precision medicine.
Michelle Mitchell, Chief Executive of Cancer Research UK, echoed the importance of leveraging existing treatments more effectively. "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 stated. "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 her team are now actively planning the next phase of research. This crucial follow-up study will aim to replicate the impressive results in a larger patient cohort. It will also seek to definitively confirm that the Partner approach offers a less toxic and more cost-effective treatment option for patients compared to the current standard of care. Such rigorous validation is essential for translating these groundbreaking findings into routine clinical practice, ensuring that the benefits can reach a wider patient population.
The Partner trial was a collaborative effort, sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. Its funding was provided by 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-faceted support highlights the collective commitment within the UK’s scientific and healthcare communities to push the boundaries of cancer treatment and improve patient outcomes globally. The promise of a 100% three-year survival rate offers a beacon of hope for thousands of individuals and families affected by aggressive inherited breast cancers, signaling a potential new era in precision oncology.
