Angelina Jolie’s Double Mastectomy: What We Know About BRCA Mutations and Breast Cancer

She wasn't yet diagnosed with cancer, but after finding a common gene mutation that often leads to breast cancer, she had the radical surgery to lower her risk.

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Oli Scarff / Getty Images

Angelina Jolie leaves Lancaster House after attending the G8 Foreign Minsters' conference in London, on April 11, 2013.

She doesn’t have cancer yet, but like many women with breast cancer mutations, she had the radical surgery to lower her risk.

Describing her decision as “My Medical Choice,” the 37-year-old actress revealed in an op-ed in the New York Times that she carries the BRCA1 gene mutation, which gives her an 87% risk of developing breast cancer at some point in her life. The abnormal gene also increases her risk of getting ovarian cancer, a typically aggressive disease, by 50%. To counteract those odds, Jolie wrote that she decided to have both her breasts removed.

(MORE: Cover Story: How to Cure Cancer)

While radical, her decision to pre-empt any future cancer is a common one, and backed by studies. In 2010, Australian scientists found that women with the BRCA1 or BRCA2 mutations who chose to have preventive mastectomies did not develop breast cancer over the three-year follow-up. What’s more, since the genetic abnormalities increase the risk of ovarian cancer, women who had their ovaries and fallopian tubes removed also dramatically lowered their risk of developing ovarian or breast cancers. TIME’s story about the study explained:

They were 89% less likely to develop ovarian cancer and 61% less likely to develop breast cancer over three years than their counterparts who did not have prophylactic surgery. Among the 250 study participants who underwent preventive mastectomies, none developed breast cancer during the study follow-up. Additionally, a patient’s surgical choice affected overall mortality rates, both cancer related and not: only 3 percent of surgery participants died at the time of the study follow-up versus 10 percent of those who avoided the surgery.

(MORE: The Changing Face of Breast Cancer)

And while the mutations are inherited – a mother with either aberration has a 50-50 chance of passing it on to her children – women who don’t get the mutation are not at increased risk of developing breast cancer, even if they belong to families with a history of the disease. Previous studies had suggested that women who did not have the mutations but had a mother or sister who did, could have up to a five times greater risk of developing different types of breast cancer, which led them to schedule frequent biopsies and even preventive mastectomies. The latest research, however, suggests that’s not necessarily the case. As I wrote in 2011:

But the new study counters those findings, concluding that the risk of breast cancer in women from BRCA families, who do not carry the mutations themselves, are no higher than that of women in families with other types of breast cancer. The study involved more than 3,000 families with breast cancer, including nearly 300 who had the BRCA1 or BRCA2 mutations.

The genetic test for the BRCA mutations isn’t done for every woman, or even for every woman who is at risk of developing breast cancer. Doctors recommend it for those who develop cancer at a young age, or have multiple family members with the disease. It’s expensive – up to $3000 – and insurers require that patients meet a threshold for needing the test before they cover its cost. Jolie is fortunate to be able to afford not just the test but the reconstructive surgery following the procedure as well. But she’s aware that not all women are even aware of the genetic screening and may not be able to afford the testing. She wrote that her goal in announcing her choice to remove her breasts prophylactically is to raise awareness of the test and the treatment options that women have if they are positive for the mutations.

Click here to read the full story on The Angelina Effect: Why Her Mastectomy Raises Key Issues About Genes, Health and Risk, available exclusively for TIME subscribers.
 
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24 comments
mugen10
mugen10

Your green diet may not be healthy as we have been educated wrongly.
- fat & butter is much much better than refined oil & margarine
- lack of macronutrient and micronutrient due to extensive farming.
- grain fed, antibiotic, hormone, cage egg etc. (cow eat grass, not grain)
- consume sea salt rather than table salt
- homogenised milk produce toxin
- additives, preservatives, coloring in food
- avoid sugar free product as it usually contains aspartame or saccharin
- avoid western medicine. it only cure the symptoms, not the cause, and contains toxic materials.
  Have you done your research on I3C supplement? its reaction product ICZ? not compatible for safe, long term use?

We lack off good nutrient and eat too much. Our gene is degenerating. Eat, fast, and live longer. Ever wonder why Asian got less cancer? less allergies? Don't trust my words, do your own research.  also, pardon my english...

idealmusic
idealmusic

I am an ovarian cancer survivor with the BRCA gene. I ate a healthy green diet before I got cancer including supplements like I3C and still got cancer. The gene does not respond as well to diet as cancer caused by environmental toxins.  EVERYONE in my family has gotten either ovarian, breast cancer or both due to the gene. Statistics really don't mean that much when you await a ticking time bomb. My family is very health conscious but the BRCA gene is not combatted by eating green and mean.   I have a very health conscious family. Also the BRCA gene is 1000's of years old when less toxins were used and people died back from the gene as well. I really resent when people who have little knowledge about this cancer and have not have had family members affected go off on an IGNORANT rampage against something they know nothing about and have not bothered to research properly. 


Read more: http://healthland.time.com/2013/05/14/angelina-jolies-double-mastectomy-what-we-know-about-brca-mutations-and-breast-cancer/#ixzz2TabOfDZr

rmqfpmoq
rmqfpmoq

Let me try to save everyone who cares about fact-checking some time by actually citing sources (scholarly articles will be cited by DOI when available).

Myriad Genetics, the firm that's patented the BRCA1 mutation test, doesn't actually put the risk at 87%. They've cleverly stated the risk is "up to 87%" [1]. It is the media that has misinterpreted this, but fault goes to both sides: the media for not checking wording, and Myriad Genetics for not providing better statistics.

So the first question that arises is, "what is the average risk of developing breast cancer for people with BRCA1 mutations?" (for those who remember high school genetics, this percentage for a given allele is called the "penetrance" of breast cancer for that allele).

And the answer is, it depends. Not just on the sources and the alleles considered, but more importantly the age.  The odds of developing it by a lower age are going to be lower than developing it by a higher age. The misleading Myriad Genetics statistic is by age 70 [1]. 

If we try to ask the question for this age, then we still get different answers depending on the study. There's a study in 1993 that says 82% [2], a study in 1994 that says 87% [3], a study in 1995 that says 85% [4], and a study in 1997 that says 56% (for the Jewish) [5]. A more recent study in 2003 puts the mean at 69% [6].

What's really valuable in cases like these are meta-analyses that screen through many studies to arrive at a more accurate statistic. One such meta-analyses in 2007 of ten studies puts it at around 57% [7]. This last article, however, provides much more useful data than just that. It also presents a nice table that summarizes the risk for developing breast and ovarian cancers by some future age for women at their current age [8]. If we take into account that Ms. Jolie is about 40, then this puts her risk for breast cancer by age 50 at 20%, by age 60 at 38%, and by age 70 at 49%. She's actually 37, so to be fair we'd need to raise the three percentages by about 1-2% to compensate.

The bottom line is, given what studies we have, we could realistically put her risks for developing breast cancer by age 70 around 70%. We could make that estimate more accurate if we had known what allele she had, but that's something only she and Myriad Genetics know.

So does this mean her prophylactic surgery was warranted? There are a lot of studies that say it helped. Two studies in 2001 and 2010 followed up women who had mastectomies, and found no incidences of breast cancer [9][10]. A study in 2004 found 2 incidences amongst 105 [11]. This last article gives a nice graph [12] to see how effective this was relative to follow-up time (BPM stands for bilateral prophylactic mastectomy).

Were there other options? Certainly. Tamoxifen has been shown to halve breast cancer risks in BRCA1 mutant carriers [13]. This isn't the same as eliminating the risk, but it's a staunch improvement. Though there are some nasty side effects to this medicine, including increased risk of cataracts, blood clots, and endometrial cancer.

Many people like to posit that Vitamin D intake has a substantial effect on breast cancer risks. And it does, at least for healthy women. A meta-analysis in 2007 of two studies indicates that women who were dosed with large amounts of Vitamin D had about half the risk as women who weren't [14]. However, I can find no studies that suggest whether Vitamin D has a substantial impact on breast cancer incidence in BRCA1 mutant carriers.

References

[1] http://www.myriad.com/products/bracanalysis/

[2] Easton D. F., Bishop, D. T., Ford, D., & Crockford, G. P. (1993). Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. American journal of human genetics, 52(4), 678.

[3] DOI: 10.1016/S0140-6736(94)91578-4

[4] Easton, D. F., Ford, D., & Bishop, D. T. (1995). Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. American journal of human genetics, 56(1), 265.

[5] DOI: 10.1056/NEJM199705153362001

[6] DOI: 10.1126/science.1088759 

[7] DOI: 10.1200/JCO.2006.09.1066

[8] http://jco.ascopubs.org/content/25/11/1329/T2.expansion.html

[9] DOI: 10.1056/NEJM200107193450301

[10] DOI: 10.1001/jama.2010.1237

[11] DOI: 10.1200/JCO.2004.04.188 

[12] http://jco.ascopubs.org/content/22/6/1055/F1.large.jpg

[13] DOI: 10.1002/ijc.21536

[14]  DOI: 10.1016/j.jsbmb.2006.12.007

MyrtoAshe
MyrtoAshe

The author of this article does everyone a disservice by not correcting that 87% estimate, which came from looking at very high risk families (they likely shared more than just the BRCA gene).

I am questioning how "informative" this is, vs. just leading us all to get chopped up out of fear, including Jolie--who would go in for a double mastectomy with the wrong statistic in mind? Doesn't she use the internet? Or have a consultant who can look up a few scientific studies?

SaadaMAli
SaadaMAli

You got to do what's best for you and your family. Good job Angie, what a thoughtful woman.

fnyc
fnyc

This video explains a lot about what's currently going on with gene patenting and specifically the BRCA genes, why the tests are so expensive, why you're limited as to where you can get the tests and is really interesting as I didn't know private companies could patent genes from the human body... 

http://youtu.be/ywj_a0Mulvk

thewholetruth
thewholetruth

She made a big mistake. Most of these genetic test and Mammograms show  consistent false positives. The human body and disease cannot be predicted this way! 

SEE HERE THESE TEST ARE OFTEN WRONG

http://youtu.be/6YsVyIxoOUU

JackKennedy1
JackKennedy1

Next we need "the psychological trigonometry of Her decision".

zemouse
zemouse

Glad to see so many men upholding the popular opinion that men are absolute idiots!!! 

StevenCremonni
StevenCremonni

if we weren't so freaking scared of the sun these days we wouldn't be so damn vitamin D deficient and breast cancer incidence would decrease...

my god...chopping off your breasts so you don't get breast cancer....horribly insane thinking

RozEliteMgmt
RozEliteMgmt

Good for her! She probably just wants to live longer just in case to see all her kids Grow. Her mom died pretty young so her reasons are understandble . http://loljam.com/post/6572

firmsoil
firmsoil

These radical procedure salesmen types have a century long history of chopping it off.... how unscientifically horrific!!!

HazeAndDrizzle
HazeAndDrizzle

I have survived medical near death so I am not  stranger to living with medical statistics. Apparently I have a 700% greater chance of being killed by a repeat of the same thing as somebody who never had it. Here I am 10 years later and still not struck down, yet. Why because that is a seven fold increase over a fairly small number. Still too high, it likely get me in the end but probably not today and something has to do it eventually. I see not reason to crawl "prophylactically" into a casket. Now if I had cancer chasing me I might be less sanguine amount a non-sudden demise but the moral of the story is these medical statistics keep changing. They are very treacherous to make drastic decisions, especially early in the game. I am would be quite cautious about advocating chopping off body parts when five to ten years from now it be obvious that was all a big mistake, or at least much more nuanced that initially assumed.

In this case the science is further hobbled by our near criminal patent system that puts people's lives at risk and keeps from getting clear answers. The article fails to note that cost of testing is entirely from that evil patent system. There are few things cheaper than sequencing DNA these days. It like worrying if you have enough electricity for your PC to compute your tax return. The times have changed.

SteveM789r
SteveM789r

NOOOOOOOOOOOOOO!!!!

Well, maybe it won't be so bad... I sure hope she supersized her new implants!

idealmusic
idealmusic

@mugen10 Thank you for responding. I'm on a vegan, low fat diet with a little omega 3 fish added a few times a week. The only fat I consume is a little olive oil and mono saturated fats like avocados and walnuts. I've taken i3C supplements for years (DIM is the best form IMO). I eat a lot of cruciferous veggies as well. I do not eat dairy, meat or eggs. I consume sugar in moderation - mainly from fruit. I guess what I'm really trying to say is that no matter how good your diet is, that if you have the BRCA gene that can overpower diet. I still think it's important to eat healthy but I also believe that with the BRCA gene it's also a good idea to take pre-emptive action. I've been there. . done that. . know people who haven't survived because they only relied on diet and life style. You need to do both when genetics work against you. I believe in integrative medicine.

idealmusic
idealmusic

@rmqfpmoq  Tamoxifen increases the risk of Ovarian Cancer while reducing the risk for Breast Cancer. I have the BRCA gene, am an ovarian cancer survivor and was advised to take Tamoxifen to reduce breast cancer risk. Well, that would be dangerous so I choose s double mastectomy. EVERYONE in my family has gotten either ovarian, breast cancer or both. Statistics really don't mean that much when you await a ticking time bomb. My family is very health conscious but the BRCA gene is not combatted by eating green and mean as well as environmental breast cancer. I have a very health conscious family. Also the BRCA gene is 1000's of years old when less toxins were used and people died back from the gene as well. I really resent when people who have little knowledge about this cancer and have not have had family members affected go off on an IGNORANT rampage against something they've done little research on. 

idealmusic
idealmusic

@StevenCremonniI am an ovarian cancer survivor with the BRCA gene. I ate a healthy green diet before I got cancer including supplements like I3C and still got cancer. The gene does not respond as well to diet as cancer caused by environmental toxins.  EVERYONE in my family has gotten either ovarian, breast cancer or both due to the gene. Statistics really don't mean that much when you await a ticking time bomb. My family is very health conscious but the BRCA gene is not combatted by eating green and mean.   I have a very health conscious family. Also the BRCA gene is 1000's of years old when less toxins were used and people died back from the gene as well. I really resent when people who have little knowledge about this cancer and have not have had family members affected go off on an IGNORANT rampage against something they know nothing about and have not bothered to research properly. 


Read more: http://healthland.time.com/2013/05/14/angelina-jolies-double-mastectomy-what-we-know-about-brca-mutations-and-breast-cancer/#ixzz2TabOfDZr


Read more: http://healthland.time.com/2013/05/14/angelina-jolies-double-mastectomy-what-we-know-about-brca-mutations-and-breast-cancer/#ixzz2Tad8YIpu

JohnnyVI1
JohnnyVI1

@robertclee13 @SteveM789r 

I'm sure he had ample respect for Angelina and her mighty bosom.  He just expressed the collective sentiments of all of us.  She didn't have cancer, she did this in advance, and good for her for doing it!  

She had implants put in.  We're all just hoping they look as incredible as her all natural pair.  She shows them off all the time, they're fair game for comment.