The Importance Of Genetics In Breast Cancer

An individual’s genetic makeup is becoming increasingly important in how certain breast cancers are treated.

New treatments and prevention strategies are now being tailored to specific genetic make ups, especially those who have a known genetic mutation.

Associate Professor Judy Kirk is a Cancer Geneticist at the Familiar Cancer Service at Westmead Hospital.

She says there are two ways genetics will become more important in cancer genetic testing and personalising treatment.

“When we talk about genetic testing, sometimes we are talking about testing of the tumour to find the genetic changes in the tumour that have caused that cancer and to target the therapy for that cancer.”

“So that’s quite different to a fault in the gene that’s in every single cell in the blood that causes a higher risk of cancer.”

“Our understanding of both of those aspects of genetic testing is changing over time.”

She said what researchers know about how genetics affects cancer risk and treatment, has come a long way over the past couple of decades.

“We know when our clinic first started in 1994, we didn’t really know much.”

“We knew about two genes only at that point,” she said.

“We had very rudimentary testing, but it cost an awful lot of money and it took a long time to do.”

“Now the sequencing of these genes is much cheaper. So, it’s more available.”
She said now more funding and time is spent on interpreting the data found through testing.

“The more testing we do, the more we find changes in genes that are called unclassified variance.”

“They’re small changes that probably mean nothing but we’re not sure about that yet,” she said.

“The more genes you test the more you find and you can find in some studies, where they’ve tested lots of different genes in women with breast cancer, up to a third will have slight variations in genes that may or may not mean something.”

“So, there’s still uncertainty about some aspects of genetic testing. There’s a lot left to learn.”

Genetic Testing For Targeted Therapies

Associate Professor Kirk said that the information researchers already know about genetic abnormalities and mutations has helped to inform treatments in those with known BRCA1 and BRCA2 gene mutations.

“It’s already been shown that individuals who have a germline mutation or mutation in every single cell, a mutation in BRCA1 or BRCA2, certainly respond well to specific PARP inhibitors.”

“Now that also could be found by testing their tumour. Some people don’t have a mistake in every single cell, but there is a mistake in their tumour.”

Breast Cancer Trials currently has a clinical trial open for the prevention of breast cancer in women who have the BRCA-1 gene mutation.

You can find out more about BRCA-P and sign up for the BRCA-P mailing list here.

What Are the BRCA1 & 2 Gene Mutations?

Approximately 5-10 per cent of breast cancers are due to a strong family history or genetic mutation such as the BRCA1 or BRCA2 gene mutation.

The discovery of these gene mutations was revolutionary for those with a strong family history of breast and ovarian cancer.

It has allowed for these women to take preventative measures or engage in screening earlier therefore reducing their risk of being diagnosed with these diseases.

Cancer Geneticist Associate Professor Judy Kirk from the Familiar Cancer Service at Westmead Hospital said the discovery of the genes was a breakthrough in the cancer field.

“It was in about 1990 that Mary-Claire King, in the United States, realised that there was certain a little position on chromosome 17 that members of these families sort of shared a chunk of and so found the location of the gene.”

“But she didn’t find the gene,” said Associate Professor Kirk.

“Then there was a huge amount of work that went on all over the world, really a race to find this gene.”

Eventually researchers at Myriad Genetics in Utah in the United States published the finding of the BRCA1 gene mutation.

“It’s a really critical gene, in fact if you’re born with two faulty copies of that gene, you mostly don’t survive as an embryo.”

“So, it’s critical in early development as well.”

“But the people that we usually see have one good copy and one faulty copy of that gene. Angelina Jolie is one those people.”

You can inherit the BRCA1 and BRCA2 gene mutation from either parent.

Additionally, if you have the faulty gene, there is a 50/50 chance that your children will have it.

Preventative Options For Those With The BRCA1 or BRCA2 Gene Mutation

Those who have confirmed they have the BRCA1 or BRCA2 gene mutation can make the decision to have preventative measures to significantly reduce their chances of being diagnosed with breast and ovarian cancer.

Associate Professor Kirk said it is a decision that is completely dependent on an individual’s circumstance.

“The mastectomy is a very big operation, usually done with reconstruction.”

“Whereas if somebody finds out about this gene fault at the age of 70 and they’ve never had breast cancer, we would never advise a double mastectomy at that point.”

“So, it does depend on age, but overall, Professor Kelly-Anne Phillips has done a study in the Australian population that indicates that about 30% of women take up the opportunity of bilateral mastectomy.”

“This may be because it is a very big operation and we do have good breast cancer screening but there is no screening test for ovarian cancer. And so the uptake of risk-reducing salpingo-oophorectomy, that’s the tubes and ovaries, the uptake of that is very high.”

“It would be over 90% of women would take up the opportunity of that surgery.”

Associate Professor Kirk did stress that it was not an easy decision for these women to make.

“If you do have that surgery under the age of 40 you induce menopausal symptoms.”

“If we have women who haven’t had breast cancer in the past and are quite happy to use hormone replacement therapy in the safest form up until the age of about 50, the quality of life for those women should not be significantly altered by having their surgery to reduce their cancer risk.”

Breast Cancer Trials currently is conducting research to give these women another option.

The BRCA-P clinical trial  is open to women aged between 25 – 55, with a known BRCA1 gene mutation, with no current or previous breast cancer diagnosis, and are not planning to have, or have not already completed surgery to remove both breasts.

This breast cancer clinical trial hopes to find if using a drug called Denosumab is a safe and effective way of preventing breast cancer.

The Angelina Jolie Effect

Awareness around the BRCA gene mutations was thrust into the headlines in 2013 thanks to actress Angelina Jolie undergoing a double mastectomy after testing positive for the BRCA1 gene mutation.

Associate Professor Kirk said she did a great job of helping to raise awareness and understanding of the gene mutation and its risks.

“I think she did it in the very best of ways,” said Associate Professor Kirk.

“She had a mother with ovarian cancer.”

“Her mother was tested, so the affected family member tested as is standard procedure.”

“If they found nothing, there would be no test for Angelina. But they found a mistake in BRCA1 and so she was tested”

“She had a 50/50 chance of having it, and because she had it, she chose to have her risk reducing surgery. Both for the breast tissue, with a reconstruction, and also, a little further down the track she had the ovaries and fallopian tubes removed.”

Associate Professor Kirk said Angelina Jolie has been a positive role model for how genetic testing and risk reducing surgeries should be conducted.

“She took her time to decide what would be best for her and not everyone will make the same decisions.”

“A 70-year-old who finds out that she’s got a BRCA mutation should not make the same decision as Angelina, but if she’s really healthy, she should think about having her ovaries removed and have breast screening.”

If you would like to keep up to date on the BRCA-P clinical trial, you can subscribe to our BRCA-P newsletter here.

The Impact Of A Diagnosis

A breast cancer diagnosis is an incredibly traumatic event in a person’s life.

The psychological impact of a diagnosis can be significant if a patient’s mental health is not looked after.

However, there is no one-size fits all approach to mental health in this area as everyone will react to their diagnosis differently according to Dr Lisa Beatty, a clinical psychologist and Cancer Council South Australia Senior Research Fellow.

“It might be that it’s stopping them from going out and socialising, it might be that it’s stopping them from working and this is on top of the impact of the cancer itself.”

“We also know there can be huge issues with body image, we know that there are big issues with feeling shock and anger. And also one of the big things we’re hearing a lot more now is that women might not necessarily feel like they’re being particularly well supported, that some of the people that they thought would be their core support people would just disappear and other people that they hadn’t necessarily expected to be involved, really put their hands up.”

Unfortunately demand for mental health services far outweighs the supply in the cancer space.

Dr Beatty said access to cancer specific mental health services can be very dependent on the institution or hospital you are receiving treatment at.

“Some of the big metro-based hospitals with big cancer services will have a lot of funding for psycho-oncology, so you might have a team of people there that you can be referred to.”

“The hospital where I work, I am the only psychologist that works in cancer and I’m funded to do one day per week.”

“So, as you can imagine, it can mean that there are really long wait lists.”

“The demand is very much exceeding the available supply.”
Dr Beatty said because of this, it is not always routine for patients to be referred to these services.

“I think in some hospitals where there isn’t any (services), it leaves a bit of an ethical dilemma for some of the clinicians.”

“Do they screen for distress when they don’t have anywhere to send people afterwards?” she said.

“So, we try and work in a very integrated fashion as part of the multi-disciplinary team.”

How Poor Mental Health Can Affect Cancer Treatment And Recovery

Dr Beatty said psychology is increasingly being seen as a core component to a patient’s overall health.

“So, it is being increasingly recognised that we need to actually screen and address distress.”

“It’s not an optional extra.”

“It’s a core component.”

Dr Beatty said there can be a significant impact upon a patient’s response to treatment if their mental health is not considered during their diagnosis and treatment.

“We do know there is a three-fold reduction in adherence to their anti-cancer treatment for people who have untreated distress and that can also lead to some of the recent meta-analysis which has shown there is a 17% increase in mortality rates when people have untreated depression.”

How To Get Mental Health Help When You’ve Been Diagnosed With Breast Cancer

Dr Beatty said if the hospital or institution you are being treated at has a psychologist, you can be referred there directly.

“So, if there is a psychologist associated with the hospital, there won’t be any out-of-pocket costs for it.”

“They will actually just get a referral through their oncologist directly to that psychologist.”

However, if there is no psychologist at your treating hospital, you are still able to get help.

Dr Beatty said they are working to upskill community-based psychologists to treat cancer related mental health issues.

“One of the challenges and something we’re trying to work on here in Australia, is actually up-skilling the community based psychologists in how-to-treat depression and anxiety in cancer, so that we can actually make use of that Medicare funded system, the Better Access system, and get people treated by some of these community based psychologists as well.”

“However, there can then be out-of-pocket costs in this system.”

Dr Beatty said there are many things an individual can do to help ease their own burden.

“I think first of all, it’s really normal to struggle.”

“So, recognise that it is perfectly normal, it doesn’t make it enjoyable while you’re stuck in it.

But, it will, over time, reduce in severity.”

She also said its important to speak up and ask for help if you can.

“Make sure you are an advocate and speak up, if you feel comfortable doing so, to your treatment team.”

“There are a lot of other allied health options.”

“Also, some of the basic things you can do to really look after yourself, both your physical and your mental health is exercise,” she said.

“Don’t underestimate the role of that, that’s a very affordable and effective treatment for both your mental and physical health after your diagnosis.”

De-Escalation: Reducing Breast Cancer Treatments

Breast cancer researchers are often focused on finding new and better treatments and prevention strategies for the disease.

However, some breast cancer research has another goal: to reduce the amount and intensity of treatment patients receive, while maintaining equally good cancer outcomes.

This is a research area for Professor Julia White.

Professor White is a tenured Professor of Radiation Oncology and Koltz Sisters Chair for Cancer Research at The Ohio State University.

“I think it’s important for us as providers to clarify that de-escalation doesn’t mean we’re backing off on therapy,” said Professor White.

“For so long, breast conservation has automatically meant you’re going to get surgery, a lumpectomy and breast radiation.”

“But from our knowledge of breast cancer biology, certain patients can be cured, or their cancer control is completed by just having the surgery portion.”

Professor White said de-escalation can be incredibly beneficial for certain patients, but the issue is identifying those patients who can benefit from this ‘right-sizing’ of treatment.

However clinical trials which use multi-gene assays or genomic tests of breast cancer tissue, can help to identify biologically which patients are going to have a low event rate in the breast after breast conserving surgery.

This means some patients could safely avoid radiation therapy.

“You’ll always get a lower reduction in breast risk when you radiate.”

“But if your likelihood of recurrence is so low then adding the radiation for women might not give a meaningful difference to them.”

“So, as we de-escalate or right-size breast conservation, we’re going to see who needs both lumpectomy and radiation and who is OK with just a lumpectomy.”

“So, de-escalation is really for breast cancer that is hormone sensitive, stage one. Meaning the lymph nodes are negative, in women who are post-menopausal and committed to taking their endocrine therapy.”

Current Research Into The De-Escalation In Breast Conserving Therapy

There is an increasing number of de-escalation clinical trials, including the Breast Cancer Trials EXPERT clinical trial.

EXPERT is investigating whether a genomic test of breast cancer tissue can be used to identify women with early breast cancer who can safely avoid radiation therapy after breast cancer surgery and the potential side effects of this treatment.

Professor White said in the US, where she practices, there are two groups of de-escalation trials.

“One is really for post-menopausal stage one breast cancer, in patients who are between the ages of 50 and 70.”

“Over age 70, the approach is de-escalation.”

“Under the age of 70, between 50 and 70, the trials are really focused on using a multi-gene assay, using an immunohistochemistry assay or using recurrence score.”

This is how researchers can determine if a patient needs further treatment after surgery, like radiation therapy.

Why De-Escalation Research Is Important

Professor White said de-escalation trials are about investing in patient’s wellbeing.

“It’s maybe not the most scientifically sexy clinical trials, we’re not identifying a new targeted agent, but we need to know how to take care of women.”

“When you look at breast cancer screening studies, the most common breast cancer stage that is picked up at breast cancer screening is stage one.”

“So, over 50% of newly diagnosed breast cancers are stage one and most of these occur in post-menopausal women and most of them are hormone sensitive,” she said.

“So, the impact is tens of thousands of women annually.”

“So, it’s really incumbent on us right now to run clinical trials that we can guarantee the next generation that we’ll know how to take care of them and that’s what we’re doing by investing in de-escalation trials.”

Breast Cancer Patients Have An Increased Risk Of Cardiovascular Disease

If you have received a breast cancer diagnosis you are at a higher risk of cardiovascular disease than those without.

According to Professor Bogda Koczwara, there are a number of reasons for why this is.

Professor Koczwara is a medical oncologist and Senior Staff Specialist at Flinders Medical Centre.

She said a key reason is the risk factors for both diseases overlap to a significant extent.

“So, the same risk factors that give you cancers also give you cardiovascular disease,” she said.

“We know if you have cancer, you’re more likely to develop cardiovascular disease.”

“And we’ve just recently learned that if you’ve got cardiovascular disease, you’re more likely to develop cancer.”

Professor Koczwara said researchers suspect that the mechanisms for development of cardiovascular disease and cancer are likely to be overlapping.

“I think that requires further research, but it relates to tissue damage, premature aging, and perhaps cancer and cardiovascular disease are somewhat different manifestations of very similar overarching processes.”

“The final thing is cancer treatments seem to impact on the body in such a way that they may accelerate cardiovascular disease, either through direct impact on the heart muscle or through impact on vasculature.”

“But more anti-cancer drugs for breast cancer than not, have some form of side effect that relates to cardio-vascular health.”

How You Can Help Protect Your Heart Health

There are important considerations practitioners should take when treating breast cancer patients to protect heart health according to Professor Koczwara.

“The first thing to do is to recognise that patients with cancer also have other conditions and to recognise there is maybe an interaction between those conditions.”

“That would mean, taking sufficient history to recognise patients risk factors and comorbidities, and factoring that into decision making process.”

Professor Koczwara said breast cancer patients should consider if they have any modifiable risk factors to protect their health.

“We know already that common risk factors for cardiovascular disease which also adversely impact breast cancer outcomes are obesity, inactivity, smoking, and they need to be managed.”

“Their management would be beneficial in terms of improving breast cancer outcomes, but it would also be beneficial in terms of improving cardiovascular outcomes.”

Professor Koczwara said if your oncologist or treating physician is concerned about your heart health or risk factors, there is services and programs available which you can be referred to.

She also said it is important for your physician to revisit these issues on a regular basis.

“Sometimes patients might not be in the right headspace to deal with those issues at the beginning, at the time of the initial diagnosis, and they may wish to return to those issues later.”

“Sometimes they might be eager to do something that is good for their health at the beginning and that should also be accommodated.”

“So, I think the key message is that the vision for supporting women with breast cancer and patients with breast cancer, goes beyond just providing anti-cancer treatment.”

Am I More At Risk Of Heart Issues If I Have Breast Cancer In My Left Breast?

Professor Koczwara said this is not a silly question to ask.

“The answer is yes, because you’re quite likely to have radiation treatment on the left side and the left sided radiation treatment would increase the risk of potential complications, in contrast to the right sided treatment.”

“If you don’t have radiation treatment, if you don’t have local treatment, then the risk is not magnified.”

However, Professor Koczwara said this is only one risk factor, that is safely managed, and patients should focus on how to best manage risk factors related to overall health.

“I think you should be more concerned about your cardiac health if you’re obese, if you have high blood pressure, if your lipids are elevated, if you’re inactive etc.”

“The site of radiotherapy is only one part of that story and these days with appropriate precautions for radiation treatment, a radiation oncologist would argue that the risk is not that great but I think you need to consider all the risk factors and manage them, because many of them are modifiable.”