A discovery made at the University of Sheffield and funded by Yorkshire Cancer Research has become the first treatment to be approved for secondary breast cancer patients with the BRCA gene mutation.
The US Food and Drug Administration (FDA) last week expanded the use of Lynparza (olaparib) to include the treatment of patients with certain types of breast cancer that have spread, and whose tumours have a specific inherited genetic fault.
About 4,300 women are diagnosed with breast cancer every year in Yorkshire. Breast cancer is the most common form of cancer in women in the UK, with more than 50,000 cases diagnosed each year and about 1.7 million worldwide. Approximately 20-25% of patients with hereditary breast cancers and 5-10% of patients with any type of breast cancer have a BRCA mutation.
BRCA genes repair damaged DNA and normally prevent tumour development. However, mutations of these genes may lead to certain cancers, including breast cancers.
It is hoped that the use of the drug in breast cancer patients will now also be approved by the European Medicines Agency so that patients throughout Europe can benefit from its life-extending properties.
Lynparza, which works by inhibiting the protein PARP, is already approved for the treatment of some women with ovarian, fallopian tube and peritoneal cancers and is currently being prescribed through the NHS.
Tumours with BRCA mutations rely on PARP to repair DNA, so when PARP is suppressed the BRCA mutated cell is unable to grow and eventually dies. Normal cells of the patient where BRCA still functions are not affected.
The novel element of the treatment is the fact that it is the mutation causing cancer that is exploited to specifically kill the cancer; this reduces the side effects often experienced with traditional anti-cancer treatments.
In 2005, Professor Thomas Helleday and his team of researchers at the University of Sheffield demonstrated how PARP inhibitors could be used as a tailored treatment for patients with BRCA2 mutations, which are seen in both hereditary ovarian and breast cancer. The discovery was patent protected and licensed to pharmaceutical company Astra-Zeneca who continued the development process and undertook successful clinical trials.
Jo Beagley, from Harrogate, has been living with ovarian cancer for the past three years. Having recently faced a recurrence, she is now taking Lynparza (olaparib), a pioneering new therapy discovered at the University of Sheffield with funding from Yorkshire Cancer Research.
Jo was diagnosed with stage 3 ovarian cancer in July 2014, aged 39. Following diagnosis she underwent a hysterectomy followed by chemotherapy and an angiogenesis inhibitor drug to keep the cancer managed.
Following this initial phase of active treatment Jo’s cancer remained managed for 18 months. During her treatment, Jo underwent genetic testing and discovered she carries the BRCA1 gene mutation which carries with it a higher than normal risk of both breast and ovarian cancer.
In June 2017, blood tests followed by a CT scan confirmed a recurrence of the ovarian cancer. Subsequently Jo underwent another round of chemotherapy which succeeded in getting the cancer managed once again. She has been taking Lynparza, a PARP inhibitor, for the past seven weeks. Lynparza has been shown to be particularly effective in keeping ovarian cancer under control amongst women with a BRCA gene mutation.
Jo said:
Facing up to a recurrence of my ovarian cancer was tough, but knowing that my treatment plan was to involve a drug that has been proven to be effective in women with a BRCA gene mutation gave me cause to be optimistic. Lynparza wasn’t in use at the time of my diagnosis so it is reassuring to know that revolutionary new drugs are being discovered; presenting new treatment options for ovarian cancer and now breast cancer.
Dr Helen Bryant, from the University of Sheffield’s Department of Oncology and Metabolism and lead author of the research paper that was published in Nature in 2005, said:
It is incredibly satisfying and exciting that ideas we developed in Sheffield have led to the development of a drug that will now be used to treat breast cancer patients. This is a massive step forward for patients who otherwise have limited treatment options.
This type of innovation in basic research has increased the visibility of cancer research in Yorkshire and attracted other world leading researchers to the area. It shows how important funding novel laboratory ideas at the grass roots level is to delivering life changing treatment options to patients.
Professor Helleday added:
This is fantastic news for breast cancer patients. I am delighted that after all the hard work carried out since 2005 when we made the original discovery, patients are now benefitting from this new therapy.
This could not have been achieved without the support of Yorkshire Cancer Research and the University of Sheffield. It is a fantastic example of academic institutions and charities collaborating to fund pioneering research.
The safety and effectiveness of Lynparza for the treatment of breast cancer was based on a clinical trial involving 302 patients with secondary breast cancer and a BRCA mutation. The trial measured the length of time the tumours did not have significant growth after treatment (progression-free survival). The median progression-free survival for patients taking Lynparza was seven months compared to 4.2 months for patients taking chemotherapy only.
The approval of Lynparza for breast cancer means that both the University of Sheffield and Yorkshire Cancer Research will continue to benefit financially from the work in which they invested in the early 2000s. These valuable funds will be re-invested to help improve the prevention, diagnosis and treatment of cancer in Yorkshire.
Dr Kathryn Scott, Chief Executive at Yorkshire Cancer Research, said:
We are incredibly proud that a treatment discovered in Yorkshire with funding from our charity, is now one step closer to the patient. It’s extremely rewarding to know that we have made a difference to the lives of people not only in Yorkshire, but across the world.
We have been supporting innovative research at our region’s universities and teaching hospitals for more than 90 years. The journey from lab to patient can be long, complicated and uncertain, so a successful outcome is a very exciting achievement. This new indication for Lynparza means that more cancer patients than ever before could benefit. Not only this, but the financial benefits which flow from our original research funding will undoubtedly have a huge benefit to our future mission to help more people avoid, survive and cope with cancer.
