From a physical point of view, breasts are one of the defining features of a female.
It is also the tissue that tends to develop cancer the most in not just Malaysian women, but Malaysians as a whole.
According to the latest Summary of Malaysia National Cancer Registry Report 2012-2016, breast cancer ranks as the most common cancer in our country at 19%, maintaining its top spot from the previous 2007-2011 report.
As with any type of cancer, the survival rate for patients is much higher if they are diagnosed and treated when the cancer is in the early stages, i.e. stages 1 and 2.
In fact, according to the 2018 Malaysian Study on Cancer Survival (MySCan), stage 4 breast cancer patients have a 7.52 times higher risk of dying compared to patients at stage 1.
This is not good news, considering that just under half (48%) of Malaysian breast cancer patients were diagnosed at the advanced stages of 3 and 4.
This means that the cancer has spread beyond the breast and its immediate lymph nodes, and is no longer curable.
However, while patients may have to live with the cancer, it is not necessarily an immediate death sentence.
Treatments for advanced, or metastatic, breast cancer have progressed over the years to not only give patients longer survival time, but also help to maintain their quality of life.
Treatment according to type
According to consultant medical and breast oncologist Dr Kiley Loh, there are three main markers whose presence play a crucial role in determining the type of treatment an advanced breast cancer patient receives.
These are the receptors for the female sex hormones oestrogen and progesterone, as well as the human epidermal growth factor.
Each of these three proteins can stimulate the breast cancer cells to grow faster, if the cells have the appropriate receptors.
When a breast lump is biopsied and confirmed to be cancerous, it will also be tested to see if the cells have these receptors via an immunohistochemical test.
From the test, the cancer can be classified as oestrogen receptor positive or negative (ER+ or -)*, progesterone receptor positive or negative (PR+ or -) and human epidermal growth factor receptor 2 positive or negative (HER2+ or -).
For treatment purposes, breast cancer can be classified simply as hormone receptor positive (HR+) if either or both receptors for oestrogen and progesterone are present.
Dr Loh notes that the most common types of breast cancers according to this classification are HR+/HER2-, triple negative (ER-/PR-/HER2-) and HER2+.
Gamechanging therapy
“About 70% of breast cancers are HR+ and HER2-,” he says.
“What’s special about them is that these breast cancers are driven by oestrogen, and by knowing this, it helps us tailor the right treatment for patients.
“These patients will usually have an anti-hormone approach to help control their cancer and to help them live longer.”
The anti-hormonal therapy is usually combined with a targeted therapy called a CDK4/6 inhibitor.
Short for cyclin-dependent kinase 4 and 6, CDK4 and 6 are enzymes that are important in cell division; hence, the inhibitors help to interrupt the growth of the cancer cells.
According to Dr Loh, this targeted therapy has been a real gamechanger for HR+ breast cancers since it was introduced about eight years ago.
“Firstly, because we are able to control the cancer for a fairly long period of time.
“Usually in the past, when we gave the anti-hormonal treatments alone, the duration of controlling the cancer was only about 10 to 12 months before the cancer starts growing again.
“With these CDK4/6 inhibitors, we were able to double that to about two years, and for some patients, even up to three to five years,” he says, adding that the patients only have to take two pills a day.
The other gamechanging reason is that the treatment works quickly, with Dr Loh noting that the cancer in many patients can be seen shrinking as soon as four to five weeks after starting treatment.
And the last reason, he says, is that it has been proven to make patients live longer.
“And it had been quite some time since we’ve had such a treatment that could extend life for patients with HR+ advanced breast cancer,” he observes.
The key element about the combined anti-hormonal therapy and CDK4/6 inhibitors is to “kick the chemotherapy can further down the road”, as Dr Loh says.
This is as many women are fearful of undergoing chemotherapy due to the debilitating side effects.
“Life extension is one thing, but actually living a life where they are mostly quite well and are able to do their normal activities ... that’s a gift for many women,” he says.
While this combination therapy does have side effects, they are usually deemed to be more manageable.
For example, the side effects of the anti-hormonal treatment mimic those of menopause due to the low oestrogen levels they induce.
Meanwhile, the most common side effects of the CDK4/6 inhibitors are known as “paper effects” as test results often show low blood counts, but patients themselves do not experience any direct symptoms.
Some though may have tiredness, gassiness, diarrhoea and nausea, among others.
Dr Loh says however, that the patient’s body often adjusts to counter these symptoms.
In addition, the dosage for the CDK4/6 inhibitors can often be adjusted to minimise side effects, while maintaining effectiveness in fighting the cancer.
Poorer prognosis
Unfortunately for women with triple negative advanced breast cancer, not only is their prognosis poorer, but chemotherapy also remains the first line of treatment.
“For triple negative advanced breast cancer, we are looking at a couple of years (survival) alone, because these cancers are a lot harder to treat and are more aggressive,” says Dr Loh.
However, he shares that there are other treatments for certain groups of patients, alongside chemotherapy.
Around 30-40% of triple negative breast cancer patients have a marker that indicates immunotherapy can work for them too.
Meanwhile, those who have a mutation in their BRCA (BReast CAncer) genes have the additional option of a targeted therapy called a PARP inhibitor.
Known as poly-ADP ribose polymerase in full, PARP is an enzyme that helps damaged cells repair themselves.
The inhibitor stops PARP from doing this in cancer cells, thus accelerating their death.
Another treatment is the antibody-drug conjugates (ADCs), which Dr Loh describes as “smart chemotherapy”.
“The chemotherapies are bound to an antibody that targets a specific marker on the cancer,” he says.
He adds that there are different antibodies – which target different markers – that can be utilised for this approach, including one that targets a marker 90% of breast cancer patients have.
ADCs are not currently approved for usage in Malaysia, but they can be brought in on a case-by-case basis under the Application for Medicines of Special Approval or Application to Import Product for the Treatment of Life-Threatening Illnesses, which is processed by the Health Ministry’s Pharmaceutical Services Programme.
However, he hopes that the ministry will approve the usage of ADCs in Malaysia by next year (2024).
According to him, each treatment gives the patient a few more months of life on average.
“We are trying to push that two years out even more,” he says.
Targeting the Achilles heel
Triple negative and HER2+ cases comprise about 15% each of advanced breast cancer patients.
HER2+ patients also often face chemotherapy as their first line of treatment.
However, Dr Loh shares that HER2+ advanced breast cancer also had its own gamechanging therapy introduced in the late 1990s.
“They have actually transformed a breast cancer with very short survival – we’re talking about triple negative type of two years – to patients who are living beyond five years,” he says.
“These anti-HER2 therapies, most of them are actually antibodies that are targeted against the HER2 receptor, which is amplified in these HER2+ breast cancers.
“So it’s like HER2 is the driver of the cancer cells and these treatments target the Achilles heel of the cancer cells.”
He explains that chemotherapy and the anti-HER2 treatment are usually given together, but chemotherapy is only given for a short period until the cancer stops growing.
After that, the patient is maintained on the anti-HER2 treatment, the most common of which is usually administered once every three weeks.
Dr Loh shares that these patients have a good quality of life due to the manageable side effects, and can, in fact, go to work after they receive the drug, either via an intravenous (IV) line, an injection under the skin or a pill.
A good relationship
Beyond the actual treatment, he stresses that it is important for doctors and patients to have a good partnership.
“We have to work hand-in-hand to deliver the best outcome for the patient.
“So patients need to communicate; doctors also need to communicate.
“Patients shouldn’t be afraid to speak up about what is really important to them.
“And us doctors, we have to make life work for patients; it’s not just about coming to the hospital for treatment, there is more to life than that.
“When we extend people’s lives, we try to encourage patients to do what is important to them.
“We buy more time, but more time for what?” he says.
The doctor-patient relationship is also important as sensitive matters are involved.
“When it comes to the end of life, when it’s time to say, ‘Having more treatment will not help you further; in fact, it may actually hurt you’ – having these difficult conversations, you must have a relationship.
“Doctors have to earn the right to speak about such sensitive matters,” he says.
He adds: “You have to try to go beyond all the pantang (taboo) things, because in Asian culture, unfortunately, there is a lot of taboo about death and all that.
“But death is going to happen to all of us, and I think we need to break that taboo and be open about it.
“And at least communicate with our family what we really want.”
Likewise, doctors in Asia must also have a relationship with their patient’s family members, he notes, as close relatives are often significantly intertwined in the woman’s life.
Dr Loh knows of this firsthand not only as a doctor, but also as someone who has lost loved ones to cancer.
His own mother passed away from colorectal cancer just before he entered medical school.
“Going through that experience with my mum from diagnosis, having treatment until the end of life, I think I can truly tell my patients I’ve been through that, so I kind of know what it’s all about.
“And also, what are all the traps to avoid,” he shares.
He adds: “Having cancer sharpens the focus on what’s important in life.”
The few more months of life afforded by each different treatment might not seem significant to healthy people, but can be extremely meaningful for the patient to achieve their final goals in life.
But similarly, there might be a point when the side effects of the treatments are so bad that it is not worth living such a poor quality of life for the patient.
Says Dr Loh: “By being open and honest, we’re able to do things that really matter for the patient.”
*Editor’s note: The short form is ER as it follows the American spelling for oestrogen, which is estrogen.
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