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Angelina Jolie has had a double mastectomy, so what is BRCA1?

Actress Angelina Jolie’s op-ed in the New York Times explained that she opted to have a double mastectomy because she carries the hereditary BRCA1 gene, which she says increases her risk of breast cancer…

American actress Angelina Jolie has had a double mastectomy because she carries the faulty gene BRCA1. EPA/FACUNDO ARRIZABALAGA

Actress Angelina Jolie’s op-ed in the New York Times explained that she opted to have a double mastectomy because she carries the hereditary BRCA1 gene, which she says increases her risk of breast cancer by 87%. Her mother died from cancer after a ten-year struggle at the age of 56.

We asked an expert in breast cancer and genetics to explain more about the breast cancer genetic mutation and what it means for women.


What are the BRCA1 (and BRCA2) gene mutations?

BRCA1 and BRCA2 are genes that have been linked to hereditary breast and ovarian cancer. Women who inherit one of these faulty genes are at an increased risk of breast or ovarian cancer. Men who inherit a faulty gene may be at increased risk of prostate cancer. Breast cancer in men carrying BRCA2 has also been described in the medical literature.

These genes are important in helping repair breaks in the DNA in our cells, so a faulty gene can mean that DNA repair is less than optimal. In some people this can lead to the development of cancer.

Should I be getting tested for them?

Not routinely. In general terms, genetic testing should be carried out following counselling in a familial cancer centre after a proper assessment of risk.

Testing is offered to people who have developed breast or ovarian cancer where there are features that might suggest a mutation is present.

These can include an early age of onset of cancer, or cancer in both breasts, multiple cancers in the family, male breast cancer, ovarian cancer, certain ancestry (such eastern European Jewish ancestry), or where there is a known mutation in the family.

Sometimes the appearance of a tumour, reported by the pathologist can help make a decision regarding whether testing is necessary.

How are they tested for?

This is generally done through a blood sample.

What is the cost of the test/s and why?

At present testing for these genes in is expensive – but costs are coming down.

Once a mutation has been identified in a family member, other members can be tested and this is much cheaper.

How many people are affected?

About 5% of all breast cancers are hereditary, and can involve the BRCA1 or BRCA2 gene. That is why it is important to look for special features that suggest risk.

In our community the risk of carrying a gene is relatively rare at about 1:800 for each of the mutations.

Say I have the gene/s, what is the likelihood that I will develop (a) breast cancer and (b) ovarian cancer?

Having the gene does not mean that a woman will definitely develop either of the cancers.

The risk is believed to be on average somewhere between 40% and 65% for breast and 15% to 40% for ovary, depending on the gene.

In her op-ed, Angelina Jolie said her risk of developing breast cancer was 87% and that she had a 50% risk of developing ovarian cancer. This is because the risk for BRCA1 carriers can be higher than for BRCA2 carriers.

Jolie has reported the upper end of risk for breast cancer that was first described when the gene was discovered. Looking at the general population, the risk is probably less, but for some families with very striking family histories, it could be this high.

What are the treatment options?

If a cancer develops, it is often treated in a very similar fashion to other breast or ovarian cancers.

For breast cancer, sometimes women might consider more extensive surgery (such as mastectomies). There are new drugs called PARP inhibitors that are being developed tested for BRCA-associated cancers.

What are the prevention options?

There are a number of options. For breast cancer, this includes close monitoring which includes MRI scans and mammograms starting at a suitable age.

Breast cancer prevention drugs such as Tamoxifen are likely to be helpful and may even halve the risk of getting breast cancer.

Some women may consider mastectomy with breast reconstruction. The uptake of this option differs fro.

Importantly, due to the potential risk of ovarian cancer some women will be advised to have their fallopian tubes and ovaries removed at a suitable age (and after they have had children).

If this is carried out at age 40, it can halve breast cancer risk. It is known to be safe to give women hormone replacement therapy in most cases, so that they don’t experience menopausal symptoms.

What are the side-effects of mastectomies, if any?

These are generally minimal. In the short term, there can be surgical risks of infection and bleeding and, of course, cosmetic results (breast reconstruction) may differ.

What are the chances of survival for preventative measures vs treatment options?

The chances of survival for preventative measures are excellent and the risk of breast cancer is very substantially reduced. Since screening can detect cancer early, this helps improve outcomes.

Treatment for breast cancer has substantially improved over the last two decades, including for BRCA1 and BRCA2-associated cancers, so with proper treatment of early cancers, the outlook can be very good.

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25 Comments sorted by

  1. Richard Haren

    Consultant

    My concern for Ms Jolie and many other like minded women is that even with the mastectomy / hysterectomy if just a few cells remain they can become cancerous. It seems to me a better path to be aware and monitor the situation, not take the radical step without a lot of thought. So even with removal and reconstruction there are still real risks.

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    1. Chris O'Neill

      Retired Way Before 70

      In reply to Richard Haren

      "My concern for Ms Jolie and many other like minded women is that even with the mastectomy / hysterectomy if just a few cells remain they can become cancerous."

      Uncontrollable cancer cells rarely exist right from when you are born. They are generated throughout your life and are destroyed by your immune system throughout your life but with increasing risk of not being destuctible as you age.

      In Ms Jolie's case, considering her age (37) if a cancer were to kill her in the future without treatment, then that cancer would most likely have been generated by the mutation of a presently healthy cell, some time in the future.

      So the pre-emptive strategy relies on the young immune system's ability to destroy cancer cells while they are being generated and to stop them from being generated at all before the immune system ages.

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    2. Sue Ieraci

      Public hospital clinician

      In reply to Richard Haren

      ''not take the radical step without a lot of thought''

      Richard Haren, I highly doubt any woman would take this step without a huge amount of thought, and information.

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    1. Paul Miller

      logged in via LinkedIn

      In reply to Darren Parker

      Wow, such an authoritative citation! This must be totes for reals!

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  2. Tom Hennessy

    Retired

    One might wonder whether this gene defect responds the same as other gene defects.
    Scientists have shown when a faulty gene runs into iron , then , it manifests.
    "Scientists discover how iron levels and a faulty gene cause bowel cancer".
    "Mice with a faulty APC gene fed a diet low in iron did not develop bowel cancer".

    Or even just oxidation / free radicals.
    "Current knowledge supports the likelihood that interactions between the primary genetic defect and disruptions in the normal production of free radicals contribute to the pathophysiology of muscular dystrophies"

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    1. Sue Ieraci

      Public hospital clinician

      In reply to Tom Hennessy

      Tom Hennessy - all healthy tissues ''run into iron'' - it's a core part of Haemoglobin - the molecule that keeps the tissues oxygenated.

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    2. Tom Hennessy

      Retired

      In reply to Tom Hennessy

      Iron causes oxidation , DNA is damaged by oxidation.
      "Base excision repair of oxidative DNA damage and association with cancer and aging"
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639036/

      Another example of low iron levels good. The reason the plague researcher died when he had hemochromatosis , too much iron.

      "In normal mice, an injection of one million bacterial cells of V. vulnificus was needed to cause a lethal infection. In mice injected with iron , only one injected bacterial cell resulted in death!"

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  3. Jenny Graves

    Distinguished Professor of Genetics at La Trobe University

    The one thing that is left a bit confused by Geoff Lindeman’s useful article is the difference between “having a gene for …” and “having a mutation in the gene for…” Everyone has two copies of the BRCA1 and BRCA2 genes; they are critical for patching up damaged DNA. The problem arises in people who have a variant form of BRCA1 or BRCA2 that doesn’t do its normal job properly. These mutant “alleles” may differ just in one of the base pairs that make up the gene. It is these base differences that are detected by genetic testing.

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    1. Tom Hennessy

      Retired

      In reply to Jenny Graves

      How would this fit in her genetic makeup.

      “The innate capacity to repair damaged DNA seems to affect a woman’s chance of developing breast cancer.”
      “Deficient DNA repair appears to triple the risk of breast cancer, researchers have found.”

      They’ve tested a common substance found in plants.
      “Binding of inositol phosphate to DNA-PK and stimulation of double-strand break repair.”

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    2. Tom Hennessy

      Retired

      In reply to Tom Hennessy

      The fit might be , in the case of the lack of DNA repair because of the BRCA1 mutation , repair might be facilitated by inositol phosphate found in plant food instead ? Is one able to forstall the developement of the cancer by not allowing the mutation to cause the problems , by , simply supplying the body with DNA repair foods , specifically the tested inositol phosphate ? That way bypassing the defect , the lack of DNA repair caused by the BCRA1 mutatiion ?

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    3. Tom Hennessy

      Retired

      In reply to Tom Hennessy

      Repair mechanisms or food might reverse genetic defects , blueberries , for example , by raising HSP70 ?
      "New Method Fixes Broken Proteins to Treat Genetic Diseases"
      " Possible to restore the function of the mutant proteins by tricking the cell into increasing levels of Hsp70"
      http://www.sciencedaily.com/releases/2010/01/100115094105.htm

      "Blueberry supplemented diet reverses age-related decline in
      hippocampal HSP70 neuroprotection"
      http://www.ncbi.nlm.nih.gov/pubmed/15869824

      And this might be why.
      "Autophagy of HSP70 and chelation of lysosomal iron in a non-redox-active form"
      http://www.ncbi.nlm.nih.gov/pubmed/18989099

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  4. jose correa loureiro junior

    jailguard

    I can't beieve what she did. It's a pity some people can imagine the worse and feel justified by this conduct, and somehow inflict it to others through the media, this kind of living looking always through the rear mirror...If she had donne it, whithout giving much notice about it, it could be more convincing... To me, famous people sometimes seems to rely in public recognition e everything they do. And that is not a true, reliable relation. The public feedback is just a falacy carried out by the media, that doesn't loose the chance to show one more time it's proximity to it!

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  5. Chris Saunders

    retired

    Geoff, thank you for this article. I’ve been able to refer women to this after their shock horror reaction that "a young beautiful women would want to mutilate herself" or "where does it leave mothers who don't want to do this? Does it make them bad mothers?". There’s nothing like some reliable information to sooth the anxiety.

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    1. Sue Ieraci

      Public hospital clinician

      In reply to Chris Saunders

      Well-said, Chris.

      The language of ''mutilation'' is also very misleading - breast are not ''lopped off'' like some sort of macabre massacre - as if a woman is left with two gaping holes. What a misogynistic image!

      On the contrary - mastectomy involves dissecting out the breast tissue, leaving the chest wall underlying and the skin and subcutaneous tissue overlying, with scope for reconstruction. It's no picnic, but nor is it barbaric.

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    2. Chris Saunders

      retired

      In reply to Sue Ieraci

      Thanks for the graphics Sue. It all really does work for people to understand. To me the 87% definite chance of getting the cancer, that there were few alternatives and problematic time frames involved and so on required a serious risk assessment. This led me to see Angelina decision as very courageous. Another expression was “being butchered” in this case by assumed male doctors on a misled and ill-informed ‘rich’ (read more money than sense) young celebrity (read air-head). The reportage instigated release of our most unpleasant stereotyping. Something, I am sure Angelina would have anticipated before hand, but was concerned enough for the number of women in her situation to release it all out there.

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  6. John Bennett

    logged in via Facebook

    Greetings from Miami USA!

    What a wonderful blog, I stumbled into!

    And what a lively debate, that is important, topical, and highly entertaining, and it beats work!

    It does so remind me of the Rudyard Kipling blurb about ..."rages and slings of outrageous fortune" seeing the

    rock throwing from the sidelines, but I have my sneakers on, and can dodge them quite nicely.

    The BRCA debate is just starting. The field of genomics is exploding with the increased power of
    microscopy, and the…

    Read more
  7. Jana Stojanova

    logged in via Facebook

    I'm suprised there is very little talk about why the sequencing test is so expensive: Myriad, the company who discovered the causative mutations/polymorphisms patented the GENE. Not the test, the gene... and have had the patent since the late 90s. This is currently a case in the US supreme courts

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  8. Pip Cornall

    logged in via email @gracegawler.com

    What's behind the Jolie Media promo? Who profits? Who loses?

    I'm a director of a cancer charity and at times I'm pretty gullible. BUT when a celebrity or person with a large media status speaks out on a major issue we have to ask what's behind the promo. It may be nothing or it may be significant. In this world of image creation and media management we are wise if we are suspicious. Critical thinking it was called when I went to school.

    This morning I was alerted to two excellent articles about…

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    1. Chris O'Neill

      Retired Way Before 70

      In reply to Pip Cornall

      "These tests just happen to be patented by a for-profit corporation"

      It's not just the test that's patented, the gene itself is patented! So ANY test for that gene violates the patent for the gene.

      "a way that reduces and not increases the trauma and fear that comes with a diagnosis of cancer"

      That fear works extremely well in getting cooperation for treatment. Helps to cut down on patients questioning.

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    2. Chris Saunders

      retired

      In reply to Pip Cornall

      So Pip, what are you saying? Is Angelina doing it for the promo money? Seems a bit excessive. Is Angelina stupid? Yeah, again hard to believe. Angelina just happened to watch her mother die of cancer suspecting she shared the same gene. She has waited until she is very close to forty, the safe cut out point for developing the cervical cancer which her mother died from. She has reduced her risk of breast cancer from 87%, or a conservative estimate 60%, to 5%; a figure far below the average for…

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