No woman wants to be diagnosed with breast cancer.
But when she is further told she has triple negative breast cancer (TNBC), the news can leave her shattered.
TNBC is the most aggressive form of breast cancer, and tough to treat and beat as it grows and spreads faster, has limited treatment options and a worse prognosis.
This diagnosis means that the cancer cells do not have oestrogen and progesterone receptors, and do not make too much of the protein called human epidermal growth factor receptor 2 (HER2).
Doctors diagnose the type of breast cancer by identifying which receptor is present.
They run a series of tests for each of the three receptors, and these will return either positive or negative results.
In TNBC, these cells test negative on all three receptors, thus giving rise to the name “triple negative breast cancer”.
Early and aggressive
In Malaysia, TNBC accounts for about 18-20% of all breast cancers and usually strikes women below the age of 40.
“Malaysian women generally present at a younger age compared to our Caucasian counterparts, where the median age of breast cancer is about 55.
“Our median age is about 35-48, and with TNBC, it’s about five to 10 years younger because our population is younger.
“In terms of aggressiveness, most patients with TNBC will be diagnosed with at least stage 2, which means they have a 2cm tumour or the cancer has spread to the lymph nodes in the armpits, but not to other parts of the body,” says consultant clinical oncologist Dr Mastura Md Yusof.
Researchers say breast cancer in younger women tends to be aggressive because it’s often diagnosed later and is farther along when found.
Since TNBC cancer cells do not have the three receptors, hormone therapy and targeted drugs do not work.
If the cancer has not spread to distant sites (i.e. distant metastasis or cancer that has spread from the original tumour to distant organs or lymph nodes), surgery is an option.
Chemotherapy is often given first to shrink a large tumour before surgery.
It might also be given after surgery to reduce the chances of the cancer coming back.
Radiation or radiotherapy might also be an option, depending on certain features of the tumour.
“We have to treat it aggressively. During the movement control order (MCO), I saw a patient whose tumour grew from 1cm to the size of a goose egg in two months!
“So, even if the patient comes at stage 1 and is 70 years old, we will offer chemotherapy.
“TNBC likes to relapse, and when it comes back, it comes back early – not after 10 years, but usually within the first two to three years.
“It returns by sitting on distant organs such as the brain, liver and lungs.
“If I have patients with the hormone positive type of breast cancer, they can be treated with drugs to try to prevent a relapse, but for TNBC, there are no such drugs,” she says.
She adds: “Unfortunately, it has the worse prognosis among all breast cancer types.
“So, the behaviour (of the cancer) is bad from the word go due to limited treatment options.”
Dr Mastura has no idea why Malaysian women are getting breast cancer at a younger age.
She says, “Maybe it’s to do with our Asian genes. Our women take on too much and carry a heavier responsibility on their shoulders.
“Most breast cancer patients are working women who are actively contributing to society and the family.
“They have little time to look after their overall well-being.
“Our statistics capture more Chinese getting breast cancer, but then again, Chinese patients are more likely to go to the hospital when they are sick!
“So, our statistics are a bit lopsided. They don’t take into account racial distribution.”
Genes and hormones
No one knows why certain women get TNBC, although it is associated with the BRCA1 or BRCA2 genetic mutation.
BRCA is an abbreviation for breast cancer gene.
Every human being carries both the BRCA1 and BRCA2 genes, and despite what their names might suggest, these genes do not cause breast cancer.
In fact, they normally play a big role in preventing breast cancer as they help repair damaged DNA that can lead to cancer and the uncontrolled growth of tumours.
Hence, BRCA genes are also known as tumour suppressor genes.
However, in some people, these genes do not work properly.
When a gene becomes altered or broken, it is unable to function correctly and is considered to be mutated.
These mutations can be inherited from either parent and can increase the risk of developing breast cancer in both men and women.
You can test for these genes, however, a positive result doesn’t mean that you are doomed to get cancer.
Mayo Clinic points out: “The results of genetic testing aren’t always clear.
“A positive result means you carry a gene mutation that increases your risk of cancer and you can work with your doctor to manage that risk.
“A negative result may mean that you don’t have the mutation or that you might have a gene mutation doctors haven’t discovered yet.
“Your test might also identify a gene variant that doctors aren’t certain about.
“In these situations, it’s not always clear what the results mean for your cancer risk.”
Among the factors that lead to cancer formation include genetics and environment.
Dr Mastura says, “In terms of genes, those born with defective genes have a higher risk for cancer, but that’s only about 5-10% of patients.
“The other 90% is due to environmental factors, with one of the predisposing factors being obesity.
“Women who start their menses early, e.g. at age nine, are also at risk. You are already producing hormones at that age and your breast is starting to grow.
“You might go on with life, get married at 35 and have a child at 38.
“So, from the ages of nine to 38, your breasts are exposed to hormones and that can induce cancer formation.”
When breast cells are made in adolescence, they are immature and very active developmentally until a woman’s first full-term pregnancy.
Immature breast cells respond to the hormone oestrogen, as well as hormone-disrupting chemicals in products.
A woman’s first full-term pregnancy makes the breast cells fully mature and grow in a more regular way.
This is one reason why pregnancy helps protect against breast cancer.
Being pregnant also reduces the total number of lifetime menstrual cycles, which may be another reason why earlier pregnancy seems to offer a protective effect.
When a woman has her first baby at an older age or if she never has a full-term pregnancy, her breast cancer risk goes up because she is exposed to more oestrogen over her lifetime.
Her breast cells also take longer to fully mature.
“Other risk factors for breast cancer include having few child-ren, stress, high intake of alcohol and late menopause, but for TNBC, we don’t know.
“If I have a mutated BRCA1 gene, it increases my risk of TNBC, but that doesn’t mean I’m not at risk of getting other types of breast cancer,” she explains.
Treatment and survival
The survival rate for TNBC depends on the stage during diagnosis and type of treatment received.
For those who have BRCA-related TNBC, less than 5% can be treated with PARP (poly-ADP ribose polymerase) inhibitors, a kind of protein found in our cells that targets the DNA repair process.
The other 95% cannot be treated with PARP, but have the possibility of being treated with immunotherapy, combined with standard treatment (i.e. chemotherapy, radiotherapy and/or surgery), to get the cancer to shrink or not worsen, provided that they are suitable for it.
“How to find out if a patient is suitable for immunotherapy?
“We have to ensure that you have the immune cells surrounding the tumour, so we test the tumour (using the PDL1 test) to see if it has the proper characteristics.
“If at least one cell is positive, then we can do it.
“Patients often ask if one positive cell is enough to make the treatment successful, and the answer is yes.
“The test is expensive so we only do it if the patient can afford it.
“Once we have gotten a satisfactory response, we will continue you on maintenance immunotherapy so that the cancer doesn’t progress further.
“For advanced TNBC, there is no time limit as to when we should stop (the treatment),” says Dr Mastura.
She explains that the immunotherapy basically beefs up the immune system and puts a “blanket” over the cancer cells to keep them from spreading.
A small number of patients can stop the treatment once their immune system “wakes up” and takes over the work of containing the cancer cells.
For example, one of her TNBC patients who was on immunotherapy for three years, stopped the treatment eight months ago and still remains clear of the cancer.
“I also have another patient who has survived stage 4 breast cancer for 12 years.
“It’s not TNBC, but the cancer has metastasised to the brain, bone, liver and lungs.
“I see her every four months and she is doing very well – now, that’s a miracle!” she says.
Don’t give up
Women with TNBC are less likely to survive the first five years after diagnosis, compared to those with other forms of breast cancer. But all is not lost.
“From my experience, cancer patients are often those who are under duress, looking after a sick person, worrying about what others think, etc.
“There was an initiation process that took place and caused the cells to be damaged.
“The cells try to repair themselves, and if your body system is good, they can be fixed, but if it is not, the body will say, ‘Hey look, you are damaged, please die’, but something goes wrong.”
“For TNBC patients, I tell them they’re lucky because they are in my clinic!
“We are no longer treating cancers like before and have advanced so much that we can identify who is suitable for what treatment,” says Dr Mastura.
She advises TNBC patients not to confuse themselves by discussing treatment options with patients who may have other cancers and are treated differently.
“Talk to your doctor. Don’t dismiss the cancer either.
“After diagnosis, 10% don’t turn up again, preferring to leave it to progress naturally, so they miss the opportunity to find out about options.
“Another 10-15% do not return due to finances.
“What is positive in our country is that we are participating in many clinical trials (for new TNBC treatments), so do ask about them.”
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