Genes can be remarkably loose-lipped. Mutations can expose hidden disease processes, and the products that emerge from the DNA code they spell out — enzymes, hormones, proteins and the like —are also giveaways of what’s going on in the body.
These molecular motor mouths are particularly useful when it comes to pinpointing diseases like cancer. At the most basic level, it’s possible to identify certain genes, or aberrations in genes, that people inherit from their families and confer a higher risk of developing the disease.
That’s the case with BRCA1 and BRCA2, two genes that normally work to keep cells from growing abnormally. Some mutations in the DNA that encodes them, however, give tumours relatively free reign to divide out of control. Women like Angelina Jolie, who inherited the harmful mutations, can have anywhere from a 40 per cent to 90 per cent increased risk of developing breast cancer in their lifetime (not all BRCA mutations are created equal; some are more dangerous than others). That’s a fivefold increased risk of cancer compared to women without the mutations. This 90 per cent risk is a lifetime risk i.e. at age of 38 the risk is 34 per cent and in US this would mean four times higher than a normal women. However, not all women who have BRCA mutations get breast cancer.
So for the one per cent of women with breast cancer who test positive for a BRCA mutation, doctors say it’s not unreasonable to consider something as radical as a double mastectomy — before they even find any signs of cancer. It’s one of the truly unique situations where most medical professionals would say if a woman chose to have both breasts removed, it’s a pretty reasonable thing to do.
Prophylactic double mastectomies, as they are called, are one of the most common options that women in the US choose if they are diagnosed with BRCA-based breast cancer. Nipple sparing mastectomy reduces risk by 60 per cent. However, though it’s a way to prevent the disease, but it’s not the only strategy available to patients. Women can opt to have regular MRI screenings to detect the first signs of a tumour and then decide whether they want to remove their breasts entirely or just a portion of breast tissue at that time. They can also take tamoxifen, a synthetic anticancer drug that recent studies showed can cut the risk of developing breast cancer by 40 per cent to 50 per cent.
There’s also a surgery which seems completely unrelated to breast cancer but can have a dramatic effect on prevalence of the disease, particularly for women who are BRCA-positive. Not only do the mutations increase the risk of breast cancer, but they can also boost the odds of ovarian cancer from 1.5 per cent among women without the aberrations to anywhere from 15 per cent to 40 per cent for women who do. It’s this risk that’s of greater concern to cancer doctors since there are no effective ways of screening for ovarian tumours, and most women who are diagnosed with the disease have already progressed to advanced stages. Surgically removing the ovaries and fallopian tubes can significantly lower the risk of both breast and ovarian cancers. Three per cent of women undergoing the oophorectomy surgery developed breast cancer after about two years compared with 11 per cent of women who did not undergo the procedure.
Removing the breasts, however, does not seem to have an impact on the incidence of ovarian cancer. Hence, most doctors recommend surgery to remove the ovaries first to address the more pressing need of lowering a woman’s risk of developing ovarian cancer. There is no good screening strategies for ovarian cancer, so it makes sense to be aggressive in preventing the development of the disease.
But Jolie, like many women, decided to be proactive and remove her breasts first, and that decision may be driven largely by social and cultural factors. Living with the spectre of cancer goes against the American take-action mentality for which watchful waiting is anathema, and that could be why the US and Canada lead the world in preventive double mastectomies as a treatment for breast cancer. In certain parts of Europe, however, very few women, even those who test positive for BRCA, choose to have the prophylactic surgery. If you go to Paris and the Institute Curie and you have a BRCA mutation, the chances of having preventive breast surgery are almost zero.
In the US, about 36 per cent of women who test positive for BRCA choose to get prophylactic double mastectomies, according to a recent study by researchers at the Women’s College Research Institute in Toronto. Without any additional information to help them gauge exactly what their chances of developing cancer are, the peace of mind that comes from lowering their risk by any means possible may be worth losing their breasts. Jolie said her surgery dropped her chances of developing cancer from 87 per cent to five per cent.
Offit, who discovered the BRCA2 mutation, is hoping to refine that decision making process with some stronger scientific data. He recently zeroed in on an additional genetic test that could narrow the 40 per cent to 90 per cent increased risk that the BRCA test confers.
Such objective criteria, however, may not be able to sway women’s perceptions and decisions about cancer care, which are heavily influenced by the experiences of their relatives with the disease. Losing sisters or a mother at an early age to breast cancer might make a patient more likely to decide to remove her breasts prophylactically, whereas having a mother or an aunt who opted to remove the lump and a small area of breast tissue tend to bias patients toward less radical therapies. Meanwhile, those who do not test positive for the BRCA mutations but are diagnosed with breast cancer may choose to have mastectomies in order to avoid any possibility of developing a tumour.
This is frustrating for many cancer doctors since recent research suggests that a lot of these mastectomies may not be necessary. European scientists found that among a group of 701 breast-cancer patients, survival for 20 years after diagnosis was the same for women who chose to have only the tumour and a small portion of breast tissue removed as it was for women who decided to have a mastectomy.
Jolie’s experience, and her decision, while certainly not novel, is likely to raise awareness about genetic testing and its role in diagnosing and treating cancer. There will be an increase over the next months for sure in genetic testing for breast cancer. But what’s important to know is that it’s not appropriate to test everybody.
For women like Jolie who have not had breast cancer yet doctors will consider family history to determine how likely it is that she carries a BRCA mutation. Red flags include having relatives with breast cancer, or unusual cancers, as well as those who developed the disease at an early age. Only then will doctors write an order for the test, which establishes its medical necessity since the woman is likely to be at higher-than-average risk of developing cancer, and refer the patient to a genetic counsellor. The counsellor is likely to do a more thorough investigation of the patient’s family history to determine whether the test would help guide treatment or not be of much added value.
Making that decision will become increasingly challenging for genetic counsellors, since new tests that can prompt tumour genes to spill their secrets will continue to flood the clinic. For women with the BRCA mutations, the path forward is relatively straightforward; their genetic make-up puts them at increased risk of developing breast and ovarian cancers, and they have defined strategies for lowering that risk. For the vast majority of women, however, their risk will fall somewhere between the average risk of the disease and the higher vulnerability afforded by the BRCA mutations. What is coming down the pipeline are a range of additional tests that will increase the panel of genes to be explored and looked at. For most women, their breast cancer is not caused by BRCA but does run in families, so what genes are responsible? We will slowly unfold what those genes are. And that information could guide more women toward treatments that are appropriate for them — and help them to preserve their breasts where possible.
So what do we do in India?
In India, where 110,000 cases of breast cancer are diagnosed every year, with most of the victims lacking access to even basic cancer care, let alone a gene test that costs $3,000 or roughly Rs 1.8 lakh, it makes even more sense to frame a public health policy around cancer prevention and early detection rather than investing in ever more expensive diagnostic tools and treatment procedures that would at best cater to a minuscule proportion of cancer victims.
- < So till we become a ‘Developed Country’
- < Be aware of your breast, breast health and breast self-examination
- < Go for clinical breast examination to your doctor
- < Change your lifestyle- no smoking, no more than five drinks in a week. Walk briskly for 20 minutes and exercise daily, avoid fatty food, have vegetables and fruits, keep your BMI at 18 to 23
- < Avoid unnecessary use of hormones
- <Breast feed your child
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