Dr Ranjit Manchanda MD, MRCOG, PhD Professor & Consultant Gynaecological Oncologist NHS Innovation Accelerator (NIA) Fellow Integrated Academic Training Programme Director London Specialty School of Obstetrics & Gynaecology, Health Education England Cancer Research UK, Barts Centre | Queen Mary University of London Department of Gynaecological Oncology | Barts Health NHS Trust, Royal London Hospital London

Study Finds Multigene Testing For All Women With Breast Cancer Can Save Lives and Money

MedicalResearch.com Interview with:

Dr Ranjit Manchanda MD, MRCOG, PhD Professor & Consultant Gynaecological Oncologist NHS Innovation Accelerator (NIA) Fellow Integrated Academic Training Programme Director London Specialty School of Obstetrics & Gynaecology, Health Education England Cancer Research UK, Barts Centre | Queen Mary University of London Department of Gynaecological Oncology | Barts Health NHS Trust, Royal London Hospital London

Dr. Manchanda

Dr Ranjit Manchanda MD, MRCOG, PhD
Professor & Consultant Gynaecological Oncologist
NHS Innovation Accelerator (NIA) Fellow
Integrated Academic Training Programme Director
London Specialty School of Obstetrics & Gynaecology, Health Education England
Cancer Research UK, Barts Centre | Queen Mary University of London
Department of Gynaecological Oncology | Barts Health NHS Trust, Royal London Hospital
London 

MedicalResearch.com: What is the background for this study?

Response: Current national and international guidelines recommend genetic-testing (for BRCA genes) in women with breast cancer (BC) who fulfil recognised/established clinical criteria which are based on a history of cancer in the patient and family. However 50% of BRCA carriers do not fulfil these criteria. Thus the current  family-history or clinical-criteria based approach misses half the people at risk. Additionally only 20%-30% of patients eligible tend to get referred for and access BRCA testing. Newer genes like PALB2 which cause breast cancer have been identified and can also be tested for.

Knowing a patient’s mutation status (carrier identification) can have a number of benefits. After unilateral breast cancer, mutations carriers can choose contralateral prophylactic-mastectomy (CPM) or preventative mastectomy of the second breast to reduce their risk of developing contralateral breast cancer. Additionally they can opt for surgical prevention for ovarian-cancer (OC). Cancer affected carriers may become eligible for novel drugs (like poly-adenosine-diphosphate-ribose-polymerase (PARP) inhibitors) and other precision-medicine based novel drug therapies through clinical trials. A major advantage of genetic-testing is enabling testing relatives of breast cancer mutation carriers, to identify unaffected relatives carrying mutations who can benefit from early diagnosis and cancer prevention.

Testing everyone instead of being restricted by family history will identify many more mutation carriers and their family members who can benefit from precision prevention. A large proportion of these cancers are preventable in known unaffected mutations carriers.

MedicalResearch.com: What are the main findings? 

Response: In our study we compare two strategies of genetic testing in women with breast cancer.

Strategy-1: All women with breast cancer undergo BRCA1/BRCA2/PALB2 testing (multi gene testing).

Strategy-2: This is current practice where only those women who fulfil current family-history based clinical-criteria undergo BRCA-testing.

For the first time we show that moving to a strategy for multigene testing for all women with breast cancer diagnosed annually (irrespective of family history or any criteria) can prevent  an additional 1142 breast cancer and 959 ovarian cancer cases and 633 (breast/ovarian cancer) deaths in the UK; and prevent 5,478 breast cancer and 4,275 ovarian cancer cases and 2,406 (breast/ovarian cancer) deaths in the USA.

We have performed a comprehensive cost-effectiveness analysis and show that this new strategy would remain well below UK/NICE (National Institute of Health & Care Excellence) and US cost-effectiveness thresholds which are £20,000-£30,000/QALY (quality adjusted life year) and $100,000/QALY respectively. The incremental cost-effectiveness ratios are £10,464/QALY (from a payer-perspective) or £7,216/QALY (from a societal-perspective) in the UK or $65,661/QALY (form a payer-perspective) or $61,618/QALY (from a societal-perspective) in USA women.

MedicalResearch.com: What should readers take away from your report? 

Response: Our findings support changing current policy to expand genetic-testing to multigene testing (BRCA1, BRCA2 and PALB2 mutations) for all women with breast cancer. This approach will save many more lives and is cost-effective.

A similar approach has recently been implemented for ovarian cancer over the last few years and now we need to do it in breast cancer too.

Oncologists, surgeons and clinical nurse-specialists may need to provide pre-test counselling and genetic-testing, with genetic-services focusing on post-test counselling and support for women found to carry gene mutations. Such a model has been implemented in ovarian cancer pathways. There are other models too which have been successfully used to deliver genetic testing and counselling in ovarian cancer and can be extrapolated or explored for breast cancer. Implementation will need to be accompanied by a process of training and education for relevant clinicians/health professionals involved in the breast cancer care pathway so that they can understand the implications for management.

Costs of testing are falling and technological advances can now deliver large volume high throughput genetic testing. All this provides huge new opportunities for cancer prevention and changes in the way we deliver cancer genetic testing in health care. This approach can ensure that more women can take preventative action to minimise their future cancer risk through prevention or early diagnosis options.

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: What is needed is development and evaluation of implementation models and pathways to deliver this. Newer ‘context specific’ delivery models will be needed for implementing this approach.

We are interested in evaluating and undertaking analysis in other countries too and also in the development and evaluation of context specific implementation pathways for unselected testing at breast cancer diagnosis including in low and middle income countries.

Disclosures – these are listed in the paper. Please see paper.

I have received research funding from The Eve Appeal and Cancer Research UK into population testing and from Barts & the London Charity and Rosetree Charity outside this work, as well as an honorarium for grant review from Israel National Institute for Health Policy Research and honorarium for advisory board meeting for MSD and Astrazeneca. My work is supported through a NHS Innovation Accelerator Fellowship.

Disclosures from other co-authors-

Dr Buist and Dr Bowels- Grants from NCI. Dr Evans- Honorarium from Astrazeneca and grants from Manchester National Institute of Health Research Biomedical Research Centre. Dr Eccles- Grants from Cancer Research UK.  Dr Cuzick and Dr Brentnall- Grants from Cancer Research UK.

Citation:

Sun L, Brentnall A, Patel S, et al. A Cost-effectiveness Analysis of Multigene Testing for All Patients With Breast Cancer. JAMA Oncol. Published online October 03, 2019. doi:10.1001/jamaoncol.2019.3323

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Oct 4, 2019 @ 1:48 pm 

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