Screened to be believed

PUBLISHED : Tuesday, 17 April, 2012, 12:00am
UPDATED : Tuesday, 17 April, 2012, 12:00am


In a span of four years, three of six siblings in the Wong family were diagnosed with either breast or ovarian cancer. All three carried a hereditary mutation in the genes known as BRCA, which increases the risk for both diseases - although BRCA is named after the first two letters of 'breast' and 'cancer'.

BRCA genes are present in everyone, says Dr Ava Kwong Hoi-wai, chairwoman of the Hong Kong Hereditary Breast Cancer Family Registry. BRCA1 and BRCA2 are known as tumour suppressors because they help repair damaged DNA in cells that have divided improperly. However, when either of those genes mutate, the repair process can go awry.

According to the National Cancer Institute in the United States, the risk for breast cancer in the general population is 12 per cent, but those who are BRCA-positive carry a 60 per cent risk of developing breast cancer in their lifetime. The risk for ovarian cancer goes up from 1.4 per cent to anywhere between 15 and 40 per cent.

Ethnicity and geography may play a role, as BRCA mutations appear more frequently in the Ashkenazi Jewish, Norwegian, Dutch and Icelandic populations. In Chinese populations, the prevalence and impact of BRCA mutation are not well understood.

To begin with, cancer rates in Chinese communities are different from those in the West, says Kwong. Asians have a 6 per cent risk of breast cancer in the general population. Women in Hong Kong have a 0.8 per cent risk of ovarian cancer, says Dr Tam Kar-fai, a specialist in obstetrics and gynaecology at the Hong Kong Sanatorium & Hospital. Kwong says BRCA mutations increase those risks, but it is not known by how much.

Recognising a need to address this knowledge gap, Kwong established the registry in December 2007 to further research BRCA mutations in the Chinese population and provide genetic counselling, testing and support to high-risk patients.

Starting this Thursday until June, the registry will run a public education campaign to raise awareness about hereditary breast and ovarian cancer. Medical specialists, such as Kwong and Tam, and genetic counsellors will be on hand to speak to the public; proper breast self-examination techniques will also be taught. The roving exhibition, held from noon to 7pm each day, kicks off at Times Square (April 19-21) and heads to Tuen Mun Town Plaza (May 26-27) and Lok Fu Plaza (June 2-3).

The genetic tests are not cheap. Testing the first family member, usually the cancer patient, costs HK$18,000, as the entire gene must first be mapped out. Subsequent tests on other family members cost less, from HK$6,000 to HK$9,000, as the lab can zoom in on the site of the mutation.

For underprivileged women, the registry will subsidise the cost of the tests, says the charity's operations director, Agatha Hu.

There are other genes linked to breast cancer. Recent research by investigators at the University of Utah in the United States and the University of Melbourne in Australia has added the XRCC2 mutation to the list of genes that increase breast cancer risk. Mutations in other genes such as TP53, PTEN, STK11/LKB1, CDH1, CHEK2, ATM, MLH1 and MSH2 have also been linked to hereditary breast and ovarian cancers.

Of all these acronyms, BRCA is the main one to pay attention to - its mutations account for most hereditary breast cancers. It can also increase the risk of other cancers, such as prostate, cervical, uterine, pancreatic, stomach, gall bladder and bile duct cancer.

When the eldest Wong sister, then in her late 40s, was diagnosed with ovarian cancer in 2007, she was living in Canada and was tested for the mutation and found to be BRCA1-positive.

She informed her siblings in Hong Kong that they might be at risk of inheriting the gene defect and recommended that they be tested. But little was known about BRCA genes in Hong Kong at the time.

The second Wong sister, Carmen (whose name has been changed for patient confidentiality reasons), recalls: 'We discussed the issue but there was no information on BRCA at the time. We didn't even know where to get the test.'

Three years later, during a routine annual health check, a lump was found in Carmen's breast. She had breast cancer. Given her eldest sister's medical history, Carmen, then 48, was referred to the registry for the genetic test. She, too, came back BRCA1-positive. Unfortunately, even though a second family member now had the gene mutation, her siblings delayed being tested.

Last August, the third-eldest sister, also in her late 40s, was diagnosed with ovarian cancer. She was also found to be BRCA-positive.

This time, the remaining siblings went for the genetic test. Thankfully, all were BRCA-negative.

Kwong says that while BRCA mutations may be hereditary, there's only a 50 per cent chance of children inheriting the mutation. Having BRCA mutations does not mean one will definitely develop cancer, but one's risk for cancer is greatly increased, she adds. 'All we know is that the mutation predisposes one to cancer, but there are other factors that may trigger it,' says Kwong.

Being aware of the risks can help one make informed decisions about management options and lead to early detection and effective treatment, she says.

Hence, BRCA-positive patients are strongly recommended to be screened more intensively for breast cancer. Ninety per cent of breast cancers that are detected early are treatable, says Kwong.

In Kwong's studies, under an intensive screening protocol, four out of 76 BRCA carriers were found to have breast cancer. This is high compared to standard population screening, where cancer is picked up in two to four out of 1,000 women. Kwong says her studies show a pick-up rate of about 4 to 5 per cent in BRCA-positive patients.

Ovarian cancer, however, is notoriously hard to detect. Its symptoms are usually vague, and so it is often at an advanced stage when diagnosed, says Tam. Moreover, it is not yet clear whether regular screening using ultrasound, physical examination and a blood test for the CA125 tumour marker are cost-effective.

A more drastic option for BRCA carriers would be prophylactic surgery - removing healthy organs as a means of prevention. The surgery is popular in the West, but Kwong has found that Chinese women generally prefer to stick to screening. BRCA-positive patients who do have cancer, however, are slightly more likely to opt for prophylactic surgery (22 to 32 per cent).

In Carmen's case, it could have saved her life. After her breast cancer diagnosis and treatment, she weighed in on her risk of developing ovarian cancer like her two sisters. She opted for prophylactic salpingo-oopherectomy - the removal of the ovaries, fallopian tubes and uterus. Kwong's research shows that this surgery reduces the risk of ovarian cancer from 6 per cent to between 1 per cent and 2 per cent.

During surgery, doctors found microscopic cancer cells in the lining of Carmen's abdominal cavity. She was placed on another round of chemotherapy.

'If I had not known about the mutation, I would not have opted for the prophylactic surgery. Those cancer cells would probably not have been detected,' says Carmen. 'My sisters and I count ourselves lucky that we know about our risks.'

A third option for BRCA carriers would be to take chemoprevention drugs. However, Kwong's studies have found the take-up rate for this option is very low (between zero and 15 per cent), as most patients want to avoid the potential side effects.

As for non-carriers of BRCA, it doesn't mean you're in the clear. Kwong cautions that being BRCA-negative only means that one carries the same risk of developing cancer as the general population - keeping healthy is still imperative.


-The cost, in Hong Kong dollars, of getting a genetic test to screen for the BRCA mutation, which is hereditary.