Q&A with Prof Manchanda on the PROTECTOR Trial

This Ovarian Cancer Awareness Month we spoke to Prof Ranjit Manchanda, and asked him some questions about his new PROTECTOR trial, which has funding from The Eve Appeal. We spoke to him about his inspiration behind the trial and why he is working to help women at a higher risk of ovarian cancer, due to a BRCA alteration, reduce their risk whilst retaining their ovaries until their natural menopause.

What are the key things you would like everyone to know about the BRCA gene alterations and their risk:

There are two different types of BRCA genes, BRCA1 and BRCA2. Alterations (spelling mistakes) in these genes can cause them not to function properly, which causes men and women to be at increased risk of breast cancer and pancreatic cancer, women to be at increased risk of ovarian cancer, and men are at a higher risk of prostate cancer.

In the table below you can see the lifetime cancer risk of BRCA1 and BRCA2 compared to the general population:

  General Population Lifetime Risk BRCA1 Lifetime Risk BRCA2 Lifetime Risk
Breast Caner 12% 72% 69%
Ovarian Cancer 2% 44% 17%

If a woman is worried she might have the BRCA gene what can she do

If you have a family history of breast or ovarian cancer it is worth discussing this with your GP. If your GP feels that your family history may be due to a gene alteration, they will refer you to a Clinical Genetics centre.

If you have a personal history of breast cancer and are concerned, please discuss this with your Oncologist. 1 in 8 women in the UK sadly develop breast cancer and only a small proportion are due to a gene fault in BRCA1 or BRCA2. However, certain cases are more like to be BRCA related, such as if your breast cancer developed before you were 45, if other people in your family have also developed cancer or your cancer is oestrogen receptor negative.

If you have a personal history of ovarian cancer you may be eligible for genetic testing for BRCA1 & BRCA2, it will depend on the specific type of ovarian cancer. All women with a history of ‘High Grade Epithelial Ovarian Cancer’ are eligible for a genetic test.

The Eve Appeal supported research has urged for increasing access to BRCA testing to identify more people at risk who can then access early detection and preventive options and save more lives. Some important examples are recent research supporting (a) BRCA testing for all women with breast cancer and (b) offering BRCA testing to all individuals in the Jewish population whether or not they have cancer (GCaPPS study).

What options are currently open to women who have the BRCA gene to prevent ovarian cancer

For ovarian cancer there is no screening programme currently available on the NHS. Therefore, women with a BRCA mutation can only access ovarian cancer screening as part of a research trial such as one called ALDO (Avoiding Late Diagnosis of Ovarian Cancer). The most effective way to reduce ovarian cancer risk is to have risk-reducing surgery to remove the fallopian tubes and ovaries, called a salpingo-oophorectomy. It is often undertaken after having children from the age 35-40 years onwards.

However, having surgery is a very personal decision, and women with a BRCA alteration need to think about whether it is the right decision for them and when may be the right time for them to have this. Removal of ovaries in premenopausal women can lead to early menopause which has other health detrimental consequences. Talking to healthcare professionals, family members and families can help women decide.

Scientists now believe that most ovarian cancers arise from the tube not the ovary. Hence, removing the tubes alone as an initial step while preserving the ovaries can also provide reduction in ovarian cancer risk.

What inspired you and your team to look at running the PROTECTOR study

We feel passionately about improving women’s lives and preventing them from getting ovarian cancer. In an unaffected BRCA woman, ovarian cancer is a preventable disease.

During a woman’s life the ovaries produce important hormones. Naturally as we get older the ovaries eventually stop producing these hormones and women enter menopause. The average age for menopause in the UK is 51 years. Surgically removing the ovaries causes women who to immediately enter menopause. Research has shown that early menopause can have harmful side-effects, including an increased the risk of heart disease, brittle bones and memory problems. It also causes the classic symptoms associated with menopause such as hot flushes, mood changes and sexual issues. Women can take HRT (Hormone Replacement Therapy) to reduce some of these symptoms. However, HRT might not be suitable for women with a history of certain types of breast cancers. A number of women thus choose to delay preventive surgery until near or after menopause. The detrimental impact on long term health is a real concern for many.

What is the principle of the research

The PROTECTOR study is assessing whether a two-stage operation to reduce ovarian cancer risk may be an alternative for women who have not reached the menopause naturally.

The two stages involve:

  • Operation 1: removing the fallopian tubes, called ‘early salpingectomy’ (salping = fallopian tubes; ectomy = removal)
  • Operation 2: removing the ovaries, called ‘delayed oophorectomy’(oophor/o = ovaries; ectomy =removal) to be done at a time near to or after a woman has naturally reached menopause

The study assesses women’s views and the impact of this approach to prevent ovarian cancer on sexual function, hormone levels, quality of life and overall satisfaction. Outcomes from this new approach are compared to the traditional approach of removal of both tubes and ovaries at the same operation. We also compared this to the well-being of women who do not have an operation.

What are the benefits from the new surgical method and keeping a woman’s ovaries for longer:

By keeping the ovaries for longer women will retain the important female hormones produced by the ovaries. This means they should not suffer the harmful effects of early menopause, but will have some protection from ovarian cancer.

Do you think this method will be just as effective as current options:

As this is a new surgical option, we do not have an exact idea of how effective it will be. The exact level of benefit of reduction in ovarian cancer risk is unknown. The long term health impact is also unknown. For these reasons this operation should only be offered in a research trial. The PROTECTOR trial will compare the current option (Risk reducing salpingo-oophorectomy or removal of both tubes and ovaries) to this new surgical two-stage option. The PROTECTOR trial will also compare the outcomes with women who choose not to have surgery at all. This will give us a clearer understanding of the risks and benefits.

In what circumstances would a woman be eligible for the surgery to remove their Fallopian Tubes:

Women must have a confirmed gene alteration which increases the risk of ovarian cancer. These include alterations or faults in BRCA1, BRCA2, RAD51C, RAD51D and BRIP1 genes. If women do not have a confirmed gene alteration, they must have at least two first degree relatives (parent, sibling, child) who have been diagnosed with ovarian cancer. Additionally, women in the trial must be pre-menopausal.

How long until you think this method could be adopted into clinical practice, if all goes well in the study:

Research studies take many years to gather enough data and evidence to be able to conclude reliable results. It can take several years for the study to be completed and the changes to be adopted into clinical practice.

If you would like to take part, please ask your GP to refer you to your nearest recruitment centre which can be found using the interactive map found on the website. Please note that due to COVID19 (coronavirus) there may be some delay in recruitment. 

Alternatively, you can email a member of the PROTECTOR team on bci-protector@qmul.ac.uk for further details on how to take part.