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new hope for patients with breast cancer that has spread to the brain

'when you have a cancer diagnosis, your life is kind of put on hold.'

by karen hawthorne
published oct 25, 2022
last updated nov 03, 2022
read time 7 minute read
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read time 7 minute read
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care is improving for her2-positive metastatic breast cancer
tucatinib is a game-changer in terms of improving overall survival in patients with brain metastases. getty
a breast cancer diagnosis is terrifying – and gets even worse when it’s her2-positive metastatic breast cancer, a very aggressive form that is lethal when it spreads to the brain. it involves tumours with high levels of a protein called human epidermal growth factor receptor 2 (her2), which promotes the growth of cancer cells. about half of these patients develop brain metastases. dr. jonathan noujaim, is a hematologist, medical oncologist and assistant clinical professor at the faculty of medecine of université de montréal, and is on the frontlines of patient care. he talked to healthing about the promise of new cancer drugs that hold out hope for people with her2-positive metastatic breast cancer, a diagnosis which counts for about 20 per cent of breast cancer cases each year and is more likely to recur after treatment.

how common is breast cancer in canada, and how are medical advancements making a difference?

the fact is that one of nine women is affected by breast cancer throughout their lifetime. so for women, it’s one of the most common cancer diagnosis. luckily, it’s not the most lethal, with lung cancer still being the top one. that’s due to better screening and detection of breast cancer very early, which has a huge impact on survival. currently the number of drugs coming to market really improve the centre of care, helping prevent future relapses for patients there. overall, breast cancer patient care is improving.

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we have so much talent in canada in terms of drug research and development, but it seems like we’re lagging behind the u.s. in terms of drugs being approved. why is that? 

in canada, the minute that a drug comes out, [the developers need to submit study results to back up the drug’s safety and effectiveness.]. so the request is put into health canada, and then it goes through study and approval, and then into the health ministry where each province has to individually negotiate a price for the cancer drug [to be added to the formulary so canadians can access the drug and be covered for it]. that whole turnaround time is around 19 months. so we’re a little slower in approving drugs here, and that’s why as clinicians, we’re always thankful that pharmaceutical companies knowing that there’s such a delayed lag, offer compassionate access to drugs [for practitioners].

what is her2-positive metastatic breast cancer, and why is it so challenging to treat?

the most frequent subtype of breast cancer is the hormone receptor positive cancer — the breast cancers that feed off estrogen and progesterone. then you get to the her2-positive metastatic breast cancer, the second most common subtype, where a surface protein is over expressed in breast cancer cells. and that’s the true driver of the tumour progression and cell proliferation. so it’s really a singling pathway that’s overactivated. then you have finally what we call the triple negative breast cancer that is defined by a lack of expression of hormone receptors, as well as a lack of expression of her2, representing roughly 10 per cent of breast cancer patients.
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biologically speaking, her2-positive breast cancers tend to be more aggressive in nature, where it’s to be expected that a patient could say, “well, i just noted a little lump in my breast,” and in a matter of a month, it triples in volume. so that’s either her2 overexpressing or triple negative breast cancer that could be that aggressive in terms of the progression. these types of breast cancers tend to rapidly try to get to the lymph nodes. that’s how we differentiate stage one, two and three, depending on how quickly they’re going to the lymph nodes surrounding the breast. unfortunately, her2 enriched breast cancer sometimes manages to generalize, causing what we call metastases to bone, lungs and unfortunately the brain as well.

why are brain metastases so problematic?

brain metastases in oncology in general are difficult to treat because of something called the blood brain barrier – which is usually used by your body to protect against viruses and bacterial infections so they don’t infect the brain. but unfortunately that barrier also prevents drugs, like chemotherapy and targeted therapy, to cross the brain barrier to affect the metastases. so until recently, especially for her2 breast cancer, once we had brain metastases, our go-to was always radiation therapy. those who don’t respond to radiation therapy presented a big challenge in practice, but now we have some new drugs that are quite effective.
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is surgery an option for people with brain metastases when radiation fails?

surgery for brain metastases is very rarely done, because it’s rarely just a solitary metastasis. usually when it occurs in the brain, we see multiple metastases, and not every location is easily operable in the brain. that’s why most often we go toward either what we call cyberknife, which is targeted radiation to certain lesions, or if there’s a number of brain metastases, then we have to go through whole brain radiation. this approach is usually less effective in controlling brain metastases in the long-term. so the great majority of these patients unfortunately have died from their cancer in the year following the diagnosis of brain metastases.

how have new drugs helped with patient outcomes?

the good news is now we have at least two effective drugs to help control the brain metastases, and they’re effective to a point where in certain cases where there’s multiple small brain metastases, we prefer starting with the drug systemic treatment before even considering radiation therapy.
tukysa [generic name tucatinib] and the antibody drug conjugate trastuzumab deruxtecan [also known as t-dxd] both show really impressive control and tumour size reduction of the brain metastases. current studies show roughly between 40 to 60 per cent reduction of tumour size.
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that’s been the big change in paradigm because we know radiation therapy, especially whole brain radiation therapy, comes with a certain degree of toxicity. if we could avoid that toxicity because of better drugs, then we prefer going that route. for patients who still have lesions that are easily targeted through cyberknife, we still go that route and then change the therapy

are there any side effects that people have difficulty with?

my experience, through compassionate access because the drugs are still waiting for approval, is that they’re somewhat more difficult to tolerate. there are side effects, the most cumbersome being diarrhea, that affects quite a number of patients, and after that is nausea.

when tucatinib comes to market in the coming months, what will it mean for canadians?

this drug is a game-changer in terms of improving overall survival in patients with brain metastases. once we had a diagnosis of multiple brain metastases in her2-positive patients, we usually gave them less than a year to live. now we expect life expectancy to go beyond that year. i do have some patients who are demonstrating good control past that year, but i do have other patients who unfortunately after six months, we started to see progression of cancer in the brain. as the years go on, we’ll learn more on the activity and true outcome of patients. but what’s interesting is that as we use these new drugs earlier in our lines of therapy, we’re going to prevent patients from having brain tumour recurrences down the line, so that’s exciting.
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how has your experience working in breast cancer research compared to the leading work that you also do in sarcoma, the rare cancer that develops in bone and connective tissue?

i kind of wear two hats. i do breast cancer research and i also specialize in sarcoma, on the other end of the spectrum, which is a very rare cancer that unfortunately doesn’t have the limelight like breast cancer does. compared to breast cancer in the last five years having a great number of drugs, sarcoma hasn’t had new drugs in the last 50 years. it has to do with the prevalence of the cancer, but also working with patient advocacy groups who help push the signs forward in fundraising and awareness. they’re very structured and have good support groups.

what do you find most rewarding about the work you do?

it’s seeing patients continue living their lives. when you have a cancer diagnosis, your life is kind of put on hold. especially if it’s stage four breast cancer, where the intent of treatment is palliative – there’s no cure. but [there are] patients who, despite having a cancer diagnosis that was initially deemed terminal or deadly, are now living with cancer. i have patients who are still working despite being chronically on treatment. they’re still living their lives, enjoying their vacations, their families and, for, my younger patients, seeing their kids grow. that’s what’s most rewarding for me.
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karen hawthorne is a toronto-based writer.
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karen hawthorne
karen hawthorne

karen hawthorne worked for six years as a digital editor for the national post, contributing articles on health, business, culture and travel for affiliated newspapers across canada. she now writes from her home office in toronto and takes breaks to bounce with her son on the backyard trampoline and walk bingo, her bull terrier.

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