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Was a double mastectomy the right choice for Angelina Jolie?

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Hollywood movie star Angelina Jolie jumped the gun when she chose to have a double mastectomy after she discovered she had inherited a faulty BRCA 1 gene, a new study has discovered.

Although she had a greater risk of developing breast or ovarian cancer, she was as likely to survive her cancer as any other patient.

In fact, the survival rate is the same even between women who have a mastectomy and those who decide against surgery, say researchers at the University of Southampton in the UK. The take-home message to all women with a faulty BRCA gene is simple: Don’t panic, you have time.

Jolie caused a media storm around the world in 2013 when she announced she had had a double mastectomy because she carried a faulty BRCA 1 gene, which her doctors told her increased her risk of developing breast and ovarian cancer by 87 percent and 50 percent, respectively (although most say the increased breast cancer risk is around 60 percent).

By having the surgery, she said she had reduced her chances of ever getting cancer to just 5 percent.

Jolie’s mother, Marcheline Bertrand, who also had the faulty genes, died from ovarian cancer in 2007 when she was 56. Bertrand’s mother and sister had also died from cancer.

Fault in our genes

Everyone has BRCA (BReast CAncer) genes, which produce proteins that help suppress tumors and repair damaged DNA. But when they are mutated, or ‘faulty,’ they can lose their cancer-fighting abilities, making breast and ovarian cancer more likely, and it also raises the risk of prostate cancer in men.

In her New York Times editorial, in which she announced her decision, Jolie urged women to get checked in case they too carried the mutated genes. The ‘Angelina effect’ resulted in a 64 percent increase in the number of women in the US who had a BRCA test in the first 15 days after the article was published, at a cost of $13.8 million, researchers from Harvard Medical School have estimated. A test that checks the genes from a blood sample costs an average of $3,000, which is well beyond the budget of most Americans.1

But despite the increased screening, the rate of mastectomies remained the same, suggesting that women who had no family history were nonetheless panicked into having the expensive procedure, the researchers say.

Not so common

That isn’t so surprising, the Southampton researchers point out. One in 800 women carries mutated BRCA 1 or 2 genes, which cause just 5 percent of all breast cancers – and they’re not quite the death sentence that everyone thinks.

In their study, the researchers tracked the progress of 2,733 women who were no older than 40 when diagnosed with breast cancer. Of these, 12 percent – 338 women – had BRCA mutations. Rates of survival were checked at two, five and 10 years, and by the eighth year, 651 women had died from their cancer, and yet there was no difference in survival rates between women who had the faulty BRCA genes and those who didn’t. This was true even for women who elected to have a double mastectomy; in other words, radical surgery didn’t improve survival rates.2

BRCA mutations even seemed to have a protective effect among women with the rare, but aggressive, ‘triple-negative’ form of breast cancer. On average, just 77 percent of women with triple-negative cancer are alive five years after diagnosis, compared to 93 percent with standard breast cancer – and yet women who also had the BRCA mutation had a better prognosis at two years, although this reduced in later years.

Lead researcher Professor Diana Eccles said: “Women diagnosed with early breast cancer who carry a BRCA mutation are often offered double mastectomies soon after their diagnosis. However, our findings suggest that this surgery does not have to be immediately undertaken along with the other treatment, such as chemotherapy.”

An earlier study, carried out by the independent Cochrane Collaboration, discovered something similar. They reviewed all the research on just-in-case (prophylactic) breast removal surgery – which amounted to 39 studies that involved around 7,000 women – and concluded that the science couldn’t confirm that it increased survival. It may also be too much too soon – women who elect to have a mastectomy “may overestimate their breast cancer risk,” the researchers observed.3

But there’s more

But there’s another option for women with faulty BRCA genes. As women with BRCA mutations have, on average, a 60 percent increased risk of cancer, other factors – such as environment and lifestyle choices – could also be playing a part. In fact, adopting a healthier lifestyle – and especially taking up regular exercise – can reduce the chances of cancer ever developing in women with the gene mutation, say researchers from the Radboud University Medical Centre in Nijmegen, Holland.4

In a study of 270 women carrying mutated BRCA genes, the researchers found that a surprisingly high number had unhealthy lifestyles. Nearly half were physically inactive – defined as taking part in any sport less than once a week – and 40 percent were overweight, 27 percent smoked and 70 percent drank alcohol. Around 40 percent had two or more of these risk factors.

Physical activity seems to play a key role in determining whether faulty BRCA genes ever develop into cancer. Women who are active reduce their risk by 25 percent, say researchers at the Comprehensive Cancer Center in Munich, and activity in adolescence also has a protective effect. The chances of the cancer coming back – or of being lethal – are halved by regular exercise. Overall, breast cancer risk is “considerably influenced by physical activity, nutrition and body weight,” the researchers say.5

They point out that gaining more than 44 lbs in weight after the age of 18 doubles the risk for breast cancer – and that’s true for women with and without faulty BRCA genes. Depression, a pessimistic outlook and problems coping with stress also play a part in cancer risk.

In a separate study in which they analyzed the lifestyles of 68 women with the BRCA mutation, the researchers found that, not surprisingly, smoking was another big risk factor.6

Other researchers are even more emphatic, claiming that all our DNA and faulty genes can be over-written by healthier lifestyle choices. Epigenetics – the outside influences on our genes – trumps genetics every time, say researchers at the Institute for Me
dical Research in Belgrade. The single biggest change agent is our diet, and especially eating bioactive foods, also known as functional foods, such as fruits, vegetables, nuts and oils (also see page 25).7

When you know you have a faulty BRCA gene, hitting the panic button is understandable – especially if your own mother died from her cancer – but Angelina Jolie had more time than her doctors suggested. And a double mastectomy isn’t the only response: there were plenty of lifestyle changes that could have reduced her risk. But, then, her doctors never told her that.

Encourage your OPGs

Diet, exercise . . . and controlling your menstrual cycle can all reduce your chances of developing breast cancer if you have faulty BRCA 1 or 2 genes.

There’s a link between the hormones that regulate the menstrual cycle and the BRCA genes, researchers at University College London have discovered.

The genetic mutations in the genes affect organs that control the menstrual cycle, which, in turn, play an important role in the development of ovarian and breast cancers. In a study on mice, the researchers found that those with a BRCA mutation had fewer molecules in their blood that block the start of breast cancer.

Instead of having a double mastectomy, which the researchers say is a last-resort measure, women could be given a drug or supplement that encourages the generation of the molecules, known as OPGs. The OPGs block a protein known as RANKL that is a trigger for breast cancer.1

References

1

BMJ 2016; 355: i6357

2

Lancet Oncol, 2018; 19: 169-180

3

Cochrane Database Syst Rev, 2010; 11: CD002748

4

J Genet Couns, 2017; 26: 785-91

5

Trials, 2016; 17: 368

6

Arch Gynecol Obstet, 2017; 296: 1135-44

7

Nutrition and Cancer, 2013; 65: 781-92

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Article Topics: Cancer, mutation
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