Multi-gene testing at point of diagnosis can save all women with breast cancer

Reviewed by Kate Anderton, B.Sc. (Editor)Oct 3 2019

A lifetime model evaluating the financial, health and social impact of multi-gene testing (BRCA1/2/PALB2) at diagnosis for all breast cancer patients was found to be extremely cost effective for both UK and US health systems.

The analysis, published today in JAMA Oncology, suggests that just one year's testing could save 2102 cases of breast and ovarian cancer and 633 lives in the UK alone. In the US this would save 9733 cases of breast and ovarian cancer and 2406 lives.

The team now urge for policy to be changed so that all women diagnosed with a breast cancer are offered genetic testing. The research led by The Eve Appeal researcher Dr Ranjit Manchanda at Queen Mary University of London in collaboration with Dr Rosa Legood at the London School of Hygiene & Tropical Medicine found multi-gene testing to be cost effective in between 98-99% of the simulations for the UK health system, and 64-68% for the US health system.

The model simulated the effect of carrying out multigene testing, looking for alterations on the BRCA1, BRCA2 and PALB2 genes on each woman diagnosed with breast cancer compared to the current policy of restricted testing based on family history or clinical criteria. The study incorporated information from around 11,800 women who had been diagnosed with breast cancer in the UK, USA and Australia.

The modelling found multi-gene testing to be extremely cost-effective, with an incremental cost-effectiveness ratio (ICER) of £10,464 per quality adjusted life year (QALY) from the payer perspective in the UK. In the USA the ICER/QALY is $65,661/QALY (from the payer-perspective) or $61,618/QALY (from the societal-perspective). This is well below the threshold for NICE and policy makers to consider implementing this new strategy which is £20-£30,000 per QALY in the UK and $100,000/QALY in the USA.

The model analysed a number of scenarios from multi-gene testing on the women diagnosed with breast cancer and compared the costs and health impact to the current family history based policy. The model took into account costs of genetic testing, preventative surgery for women found to have a genetic alteration and for testing and preventative measures (screening or surgery) to other members of the family as well as the costs of cancer treatment and associated health outcomes.
This research was part of a collaboration with and supported by researchers from Kaiser Permanente Washington Health Research Institute, Manchester University, Southampton University, Melbourne University, University of Monash and Peking University.

Mutations on the BRCA genes put women at a higher risk of both ovarian (17-44%) and breast (69-72%) cancers, and also increases the risk of male breast cancer, prostate and pancreatic cancer. PALB2 is a breast cancer gene and is associated with a breast cancer risk of around 44%. Testing for the BRCA and PALB2 gene mutations offers women the opportunity to reduce their risk of cancer, either by increased monitoring (screening) or preventative surgery such as a double mastectomy and surgery to remove the ovaries and tubes (oophorectomy). Medication (chemo-prevention) can also reduce the risk of certain types of breast cancer.

Currently in the UK, USA and other health systems anyone diagnosed with an ovarian cancer is offered genetic testing at the point of diagnosis, which opens up the possibility of targeted treatments, as well as the potential to allow the prevention of other BRCA mutation related cancers, and for other direct family members to be offered testing. However, currently women diagnosed with breast cancer still need to meet the family history criteria for example of having two first degree relatives (parents/children or siblings) diagnosed with a BRCA related cancer to be eligible.

The research supports a policy change to bring breast cancer patient genetic testing in line with that currently used for women with ovarian cancer.

Genetic testing technology and its potential to prevent cancer is under-utilised. Limited awareness by healthcare professionals and the general public means that currently only 20-30% of eligible people are referred for genetic counselling and testing. 97% of people with the BRCA1/2 gene alterations are thought to not have been identified. Advances in technology, falling costs of testing and the cancer prevention potential of wider genetic testing provides us with a fantastic opportunity to make prevention a priority.

Dr Manchanda, his team and The Eve Appeal are now calling for the policy to be changed for all women diagnosed with a breast cancer to be automatically tested for alterations in the BRCA genes and PALB2. Which will enable many women to be empowered over their health and seek preventative measures, reducing the levels of cancer and saving lives.

Dr Ranjit Manchand from Queen Mary University of London, says:

Our findings support the concept of broadening genetic testing for breast and ovarian cancer genes to all women with breast cancer, beyond just the current criteria-based approach. This could prevent many more breast and ovarian cancers than the current testing strategy, saving many lives.

With the costs of testing falling this can provide huge new opportunities for cancer prevention and changes in the way we deliver cancer genetic testing. This approach can ensure that more women can take preventative action to reduce their cancer risk or undertake regular screening.

Athena Lamnisos, CEO, The Eve Appeal, says:

With cancer, prevention is better than cure. At The Eve Appeal, we are supporting research programmes that are seeking new ways to prevent cancer development and predict risk - trying to stop cancer before it starts. Breast cancer can be a devastating diagnosis. This research study provides exciting evidence that offering it to women at the point of diagnosis could save lives.

Dr Rosa Legood, Associate Professor at London School of Hygiene & Tropical Medicine, says:
 

Our analysis shows that testing all women with breast cancer for breast and ovarian cancer gene mutations is a more cost-effective strategy which can prevent these cancers in high risk women and save lives. This approach has important implications given the effective options that are available for breast and ovarian cancer risk management and prevention for women at increased risk.

Alison Dagul, who carries the BRCA alteration and has been diagnosed with both breast and ovarian cancer, says:

I found out I had ovarian cancer shortly after my breast cancer diagnosis, it was only after I had been diagnosed with both that I had BRCA testing. Thanks to BRCA testing my daughter, Gaby, now has the information she needs to make informed decisions about her health. She has already had a preventative double mastectomy, when she was 26, and she is now in the process of planning for surgery to prevent ovarian cancer. It is a horrible cloud to live under but I am so grateful she has had the chance I didn't, to prevent herself from getting these cancers.

BRCA testing can be done much quicker and cheaper than ever before and would save so many women's lives and prevent the heartbreak that a cancer diagnosis causes to their families.