When is prophylactic mastectomy appropriate for women at high risk of breast cancer?

More women at high risk of breast cancer should be referred for mastectomies, say researchers from Queen Mary University and the London School of Hygiene & Tropical Medicine.

A new analysis has found that surgery is a cost-effective way to reduce the risk of developing breast cancer compared with mammography screening and drug treatment. Current guidelines on who is offered a mastectomy may need to be revised in light of this new evidence.

The analysis was published in the journal JAMA Oncology.

Doctors now use personalized risk prediction models that combine genetic and other data to identify women at increased risk of developing breast cancer. Each woman is then offered options — mammograms, MRIs, surgery, and medications — based on her risk level.

Prophylactic mastectomy (PRM) is recommended for women at high risk, but in practice it is only offered to those who have mutations (so-called pathogenic variants) in genes that increase the likelihood of developing the disease - BRCA1, BRCA2, PALB2.

Professor Ranjit Manchanda, from Queen Mary University of London, Dr Rosa Legood, from the London School of Hygiene & Tropical Medicine, and colleagues from the University of Manchester and Peking University, have developed a new economic evaluation model to pinpoint the level of risk at which mastectomy becomes more cost-effective.

In their model, the researchers used the National Institute for Health and Care Excellence (NICE) criteria for determining the cost-effectiveness of treatments.

The model showed that mastectomy was a cost-effective procedure for women aged 30 and over with a lifetime risk of breast cancer of 35% or more. Offering prophylactic mastectomy to this group of women could potentially prevent around 6,500 of the 58,500 annual cases of breast cancer in the UK.

Professor Manchanda, Professor of Gynaecological Oncology and Consultant Gynaecological Oncologist, said:

"For the first time, we have identified the risk level at which prophylactic mastectomy should be offered.
Our findings may have important clinical implications: to expand access to mastectomy beyond those with a known genetic predisposition to mutations in highly penetrant genes such as BRCA1, BRCA2, PALB2. This could prevent up to 6,500 cases of breast cancer in UK women each year. We recommend further research assessing the uptake, willingness and long-term impact of prophylactic mastectomy in this group."

Dr Legood, associate professor of health economics at the London School of Hygiene & Tropical Medicine, added:

"Prophylactic mastectomy is cost-effective for women aged 30 to 55 years with a lifetime risk of breast cancer of 35% or greater. These findings may expand access to individualized risk management strategies and help more women access preventive measures."

Dr Vineet Rajkumar, Head of Research at Rosetrees, said:

"Rosetrees is delighted to be funding this truly groundbreaking research that has the potential to positively impact the lives of women around the world."

The study used data from women aged 30 to 60 years with a lifetime risk of breast cancer of 17% to 50% who either underwent prophylactic mastectomy or received standard screening and drug prophylaxis, according to existing risk prediction models.

NICE standards define a treatment as cost-effective if it provides one extra year of healthy life for no more than £20,000–£30,000 per patient (the so-called willingness-to-pay, or WTP, threshold). The researchers’ model used an upper threshold of £30,000 per QALY (quality-adjusted life year).