Andy Ho, Senior Writer

Angelina Jolie was right to take preventive surgery

In 2013, Hollywood actress Angelina Jolie wrote in The New York Times about carrying "a faulty BRCA1 gene" that she said gave her a 65 per cent risk of getting breast cancer as well as a 50 per cent risk of ovarian cancer.

The BRCA1 is a gene that suppresses the development of these cancers. When it becomes "faulty" because of mutations, it might not be able to perform its role properly.

Given the risk level and her strong family history of breast cancer, the Oscar winner and wife of actor Brad Pitt decided to have her healthy breasts removed on her doctors' recommendation. That cut her risk to 5 per cent, they said.

Her decision made news worldwide.

Recently, Jolie, now 39, revealed she had just had her ovaries and fallopian tubes removed too. She chose to keep her womb as she has no family history of womb cancer.

Again, news of her surgery grabbed headlines.

Some might question the wisdom of prophylactic or preventive surgery to remove perfectly healthy organs. However, the medical consensus is that such surgery for carriers of high-risk BRCA1 mutations is well advised.

Here's why.

First, BRCA1 and its sister gene, BRCA2, are tumour suppressor genes. They keep DNA stable, so cell growth remains orderly.

The BRCA1 gene codes for a protein that repairs breaks in DNA. If it has a mutation that makes it unable to repair such breaks, the risk of cancer developing is increased.

The BRCA2 gene encodes a protein structurally different from that made by the BRCA1 gene. But the BRCA2 protein, like the BRCA1 protein, also repairs DNA.

Mutations in BRCA genes impair their ability to repair DNA breaks, which can then proliferate. Thus, in people with BRCA mutations, there is always a chance of cell growth becoming disordered, in which case cancer could develop.

Second, there is more than one possible mutation of the BRCA genes. There are many, and some raise cancer risks considerably.

Third, BRCA mutations tend to be population-specific, so the spectrum of mutations could differ in Chinese populations compared with, say, Caucasian ones.

A 2013 study in Hangzhou and a 2012 study in Hong Kong of ethnic Chinese both found BRCA1 mutations to be less prevalent in these Chinese populations than in Caucasian ones.

Moreover, BRCA2 mutations were more common than BRCA1 mutations in these Chinese populations - a reverse of the pattern found in Caucasian ones. This reversal was seen again in a 2007 National Cancer Centre study of Chinese families in Singapore.

Finally, studies by an international collective called the Breast Cancer Linkage Consortium confirm that when BRCA2 mutations are factored in as well, a woman with BRCA mutations has about three to seven times the breast cancer risk as well as eight to 30 times the ovarian cancer risk of a woman without them.

These heightened risks are why preventive surgery of the type Jolie underwent is considered reasonable for a woman with BRCA mutations.

Studies show such procedures reduce the woman's breast cancer risk by 90 per cent and her ovarian cancer risk by 95 per cent.

So the surgery seems rather a worthwhile wager to make. Yet, the risk reduction is less than 100 per cent. This is because not all breast tissue can be removed surgically - it is found widely on the chest wall, even just under the skin, as far down as the lower rib margins, in the armpits and just above the collarbone.

This breast tissue is still prone to cancer in a patient whose BRCA mutations give her a genetic predisposition to the malignancy.

Likewise, if any ovarian tissue is inadvertently left behind during preventive surgery, it remains prone to cancer.

While preventive breast removal creates some body image issues for women, who might do well with reconstructive breast surgery later, prophylactic ovary removal brings on menopause, which Jolie did highlight.

Thus, how to time the procedure for a young woman is a delicate issue. Jolie said she was advised to have the ovaries removed about a decade before the age at which her female family members had their earliest onset of cancer. "My mother's ovarian cancer was diagnosed when she was 49. I'm 39," she wrote.

However, even that might have been a tad late. A study in the Journal of Clinical Oncology last year reported that the procedure is optimally done before age 35.

This came after a large international study that began in 1995, which followed 5,787 women until 2011. It found that, in women with BRCA1 mutations, removing both ovaries by age 35 lowered their ovarian cancer risk the most, to nearly the 1.4 per cent risk faced by women without BRCA mutations.

If the procedure was delayed until age 40, the ovarian cancer risk rose to 4 per cent. It rose further to 14.2 per cent if surgery was delayed until age 50.

However, the study also found that women with BRCA2 mutations could wait until their 40s as these mutations play less of a role in ovarian cancer than BRCA1 mutations do.

For many women, the ovaries, fallopian tubes and also the womb, if need be, can be removed without open abdominal surgery. Instead, a flexible laparoscope with surgical instruments is introduced through the vagina and, in this manner, the procedure can be done under anaesthesia without making a big incision in the tummy.

To stave off menopausal symptoms after surgery, a young woman with no ovaries would need to take female hormones until the age that menopause is expected to set in.

Still, better late than never for Jolie, or any woman with such a cancer risk profile.

andyho@sph.com.sg