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Surgery to remove breasts or ovaries effectively reduces the risk of breast or ovarian cancers. A new study looked at women at high risk of developing these cancers. They did not have cancer, but had a positive genetic test which demonstrated that their genes put them at high risk of developing it. Most of the women went ahead with the risk-reducing surgery, but they often delayed the procedure, sometimes for many years.  

Breast and ovarian cancer are two of the most common cancers in women. These cancers can run in families. Women who have close relatives who developed breast or ovarian cancer may be at increased risk themselves. Where there is a strong family history of breast or ovarian cancer, women can request a test to check for genes (called BRCA1 and BRCA2) that put them at risk.

Those with a positive genetic test, or a strong family history of one or both diseases, can opt to have risk-reducing surgery. This is a difficult decision for a healthy woman to make. 

This study is one of the largest studies to follow women with faulty versions of BRCA1 or BRCA2. It found that, 20 years after their test result, most had opted for surgery: 79% had their ovaries removed and 58% had breasts removed. But surgery was delayed by an average of two years after the test and sometimes much longer.

For women in the study, breast surgery reduced the risk of breast cancer by 94%. Ovarian surgery eliminated the risk of ovarian cancer. The researchers suggest that women at high risk need more encouragement to accept the procedures sooner.

What’s the issue?

One in eight women will be diagnosed with breast cancer in their lifetime. Ovarian cancer is one of the most common cancers in women.

Women with a strong family history of breast or ovarian cancer are at higher risk themselves. This might mean they carry faulty versions of one of two genes (BRCA1 and BRCA2). 

Following a positive genetic test, women who are healthy, with no signs of cancer, are offered surgery to reduce their risk of developing cancer in future. They are advised to have fallopian tubes (which carry eggs to the womb) and ovaries removed once their family is complete. They can also have breasts removed. To reduce the risk of cancer, women with BRCA1 mutations are advised to have this surgery by the age of 35; women with BRCA2 mutations by the age of 40.  

These procedures have important physical and psychological consequences. After removal of the ovaries, women can no longer become pregnant. And removal of the breasts can affect body image. Many  women have reconstructive surgery, in which implants or tissue from elsewhere in the body are used to make new breasts. Healthcare professionals carefully prepare women for these surgeries. 

Previous work showed that women who are younger, have more years of education and more cancer-related distress are more likely than others to undergo risk-reducing breast surgery. Women who were older, with a higher perceived risk of ovarian cancer were more likely to undergo risk-reducing ovarian cancer surgery.

In this study, researchers looked at the effectiveness of the surgeries in preventing breast and ovarian cancer. They wanted to know how many women at high risk had surgery, and how long they waited after a positive test before deciding to. 

What’s new?

This study included 887 women born between 1930 and 2002. They did not have cancer but they had all received a positive test for faulty versions of the BRCA1 or BRCA2 gene. 

The research team explored whether, and when, these women had breast or ovarian surgery. Women's records were studied for a maximum of 24 years from the time of their genetic test (the average follow-up was just over 6 years). The researchers noted deaths, and diagnoses of breast or ovarian cancer.  

The study found that, 20 years after the genetic test, many women had undergone risk-reduction surgery:

    • more than half (58%) had breast surgery 
    • four in five (79%) had ovarian surgery
    • with increasing age, women became more likely to have ovarian surgery but less likely to have  breast surgery. 

Risk-reduction surgery effectively reduced the risk of cancer:

    • only one in 100 of the women who had breast surgery were diagnosed with breast cancer afterwards; the procedure reduced their risk of breast cancer but not their overall risk of death
    • no woman who had ovarian surgery was diagnosed with ovarian cancer; the procedure again reduced risk of ovarian cancer but not their overall risk of death 
    • ovarian surgery did not reduce the risk of breast cancer; this was unexpected as this surgery reduces levels of the hormone oestrogen (which can increase the risk of breast cancer).

Women waited more than two years on average after the genetic test before having surgery:

    • for breast surgery, few women (7%) had the procedure within 6 months; the wait ranged from one week to almost 15 years
    • for ovarian surgery, almost one in three (29%) had the procedure within 6 months; the wait ranged from two weeks to almost 20 years.

Why is this important?

The research found that, compared with previous work, increasing numbers of women are now opting to have risk-reduction surgery. However, the average delay between receiving a positive genetic test and having surgery is more than two years. 

It is a difficult decision for a healthy woman to make. Appropriate counselling and discussion takes time and could account for some of the delay. Women may delay ovarian surgery until they have had children, or because of concerns about having an early menopause. But the researchers say that women at high risk need more encouragement to accept these procedures.

This study gives a full picture of the decisions made by women at high risk of these cancers.  The information could help other women with a positive genetic test. 

Surgery effectively reduced women’s risk of breast and ovarian cancer but it did not reduce their overall risk of dying compared to others in the study (who also had genes that put them at risk but chose not to have surgery). The researchers suggest this might be because women who did not have surgery would be particularly aware of the need for frequent screening. This would mean that any cancers are picked up and treated early.

Long-term follow-up is needed of women at high risk who have had preventive surgery. 

What’s next?

Further research is needed into the reasons why women delay having surgery. This knowledge would help clinicians and researchers address them and perhaps encourage women to have the surgery sooner. 

The researchers say that the delay between a positive genetic test and surgery needs to be shortened. Risk-reducing ovarian cancer surgery should be done shortly after a positive genetic test for women over 40 years (if they have BRCA2) or around 35 years of age (if they have BRCA1).

This study looked at specific genes (BRCA1 and BRCA2). But other genes also increase the risk of these cancers. Further work could explore whether a test for multiple high-risk genes (a polygenic risk score) might influence decisions about surgery. 

Some risk of cancer persists after risk-reducing surgery. Preventive and screening strategies are still needed, the researchers say.

You may be interested to read

This NIHR Alert is based on: Marcinkute R, and others. Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers. Journal of Medical Genetics 2021;0:1-8  

A beginner’s guide to BRCA1 and BRCA2: More information around the genes tested for in this study, BRCA1 and BRCA2 from The Royal Marsden NHS Foundation Trust.

Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer - guidance from NICE on risk-reducing surgery for breast and ovarian cancer.

Recent research from the same author on mastectomy for breast cancer prevention: Evans DG, and others. Uptake of bilateral-risk-reducing-mastectomy: Prospective analysis of 7195 women at high-risk of breast cancer. The Breast 2021;60:45-52

 

Funding: This work was supported by the NIHR Manchester Biomedical Research Centre.

Conflicts of Interest: The study authors declare no conflicts of interest.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.


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