Liesl’s story
"Patrick my baby boy was in the process of weaning off breast feeding over December 2012. He would turn three in May. All a natural process so, that must be a blocked milk duct I feel. A few months later and it had not gone away and I had a sneaky ache under my right arm. Having to sort out my father’s UK Visa in Port Elizabeth, I decided to go for a mammogram."
Liesl is a family friend, she was 45 at the time. Thus began her journey with cancer - and the cancer was fairly nasty. Invasive ductal carcinoma, stage 2 (spread to one lymph gland), grade 3 (poorly differentiated, aggressive). What we would call an advanced “Intermediate".
There was one redeeming feature, however. Genetic testing showed that her cancer was Her2 positive[1], and therefore, targetable. She was treated with a mastectomy, chemo, radiation and a targeted drug called Herceptin.
She is now approaching 10 years with no evidence of disease, effectively cured. Can we say that Herceptin saved her life? We will never know for sure, maybe a mastectomy may have been sufficient? But being an invasive cancer increased the probability it had spread. So rather safe than sorry, and the targeted therapy could well have played a critical role.
Targeted therapy has been little short of revolutionary in the
Her2+ subset of breast cancers. At the time Liesl was diagnosed, Hope S Rugo MD,
Director of Breast Oncology and Clinical Trials Education at the University of
California, said[2]: "From the
initial discovery of the HER2 family of receptors in the mid-1980s to the
present, a ‘wealth of riches” has been uncovered in terms of agents that can
target pathways relevant to this aggressive breast cancer type. We have seen
HER2-positive breast cancer go from being the worst type of breast cancer to
one in which we can offer a lot of hope to our patients.”
An aside on Herceptin
Targeted therapies are not a panacea for all cancers. Many cancers are simply not targetable; and even if there is a druggable target, the targeting of an advanced cancer is often prone to substantial treatment resistance. But, given the right circumstances, they can be very effective[3].
In the previous blog we saw Janet's story and the successful targeted treatment of a lung cancer in a never smoker. Now, let us explore Her2 breast cancers a bit.
The NCI cancer dictionary defines Her2 as: “A protein involved in normal cell growth. HER2 may be made in larger than normal amounts by some types of cancer cells, including breast, ovarian, bladder, pancreatic, and stomach cancers. This may cause cancer cells to grow more quickly and spread to other parts of the body.”
Herceptin was the first drug used to target Her2-positive disease. It is a manufactured (so-called monoclonal) antibody which can lock onto the Her2 receptor and block it from receiving growth factors.
But there is more, Herceptin can also help fight breast cancer by alerting the immune system to destroy cancer cells onto which it is attached.
So, it has a double-whammy effect, not only does it act as a
normal targeted drug, it also acts as an immunotherapy.
Genetic Profiling
We now have a second example of an excellent result with a targeted therapy.
Is targeted therapy an option for your cancer too? To find out you need to get your cancer genetically profiled.
Also known as biomarker testing, an excellent overview of
what is involved in genetic profiling can be found in the article Biomarker
Testing for Cancer Treatment which is included in the National Cancer
Institute website. Here is an outline based on this article:
The testing looks for genes, proteins, and other substances
that may help in the treatment of your cancer. It is based on either a sample taken
from your surgery, a biopsy or a blood draw (liquid biopsy).
It is done routinely to select treatment for people who are diagnosed with certain types of cancer—including non-small cell lung cancer, breast cancer, and colorectal cancer.
But it is not yet part of routine care for most patients[4].
There is also no guarantee that it will help; for example:
- It may not find any biomarkers in your cancer that match
with available approved therapies, or
- it may identify a driver mutation which has an approved drug
for another cancer type, suggesting possible so-called ‘off label’ usage, but which
may not be supported by your health insurance, or
- it may lead to a possible clinical trial, but which may then not accept you as a participant.
But if it does help it can be very powerful. In Janet’s
case, in the previous blog, it led to the discovery of the ROS1 mutation. And in Liesl’s case it led
to the discovery of Her2 overexpression. In both cases, the profiling played a very
significant role in their successful treatment.
But there are issues
(i) Not used by some oncologists:
A recent survey tabled at the World Conference on Lung cancer showed that fewer
than half of community oncologists in the US use biomarker testing to guide
patient discussions about treatment, which compares with 73% of academic
clinicians.[5]
And in a similar finding, Dr Jack West found “two new
analyses reveal that we're still doing a woefully poor job of offering
molecular testing to our patients with advanced non–small cell lung cancer”.[6]
Why is this? West
proposes several likely reasons for these shortcomings in testing including
limited tissue availability, pressure to initiate treatment, and cost.
He proposes liquid biopsy as a possible way out of this
problem saying “although testing for circulating tumor DNA is not a substitute
for tissue-based molecular marker testing, it can be done immediately from any
oncologist's clinic and provide results for a broader array of potentially
targetable biomarkers — and does so faster than tissue testing.”
(ii) May not be covered by your health insurance
The cost of biomarker testing varies widely depending on the type of test you get, the type of cancer you have, and your insurance plan.
As things stand at the moment, private insurance providers often cover the cost if there is enough proof that the test is required to guide treatment decisions.
Tests without enough proof to support their value, on the other hand, may be considered experimental and are likely not covered by insurance.
Many clinical trials involve biomarker testing. If you join
one of these clinical trials, the cost of biomarker testing might be covered.
What do these issues mean for you, the patient?
Genetic profiling may not automatically be done as part of your initial diagnostic work-up. If it is not done, then it is an important discussion you should have with your doctor.
If it was not offered, then ask why not? There may well be a valid reason (though note again the recent consensus statement in the UK referred to above), but make sure you are convinced.
If you are not convinced, then seriously consider getting a second opinion, preferably from an academic or research cancer center. This is particularly important if your cancer is more advanced.
And do all you can to take your health insurance along with you in this process as well. Here, Liesl sets us an example:
In Liesl's case the testing was not an issue. It was part of the standard of care for breast cancer and was done as part of her diagnostic work-up. But even so, she had to work hard on her health insurance to get the Herceptin she required:
"The Herceptin was not covered by our medical aid. We
had to jump up to the most expensive plan and then I would get the biological,
designer drug for 3 months. Recommended plan of treatment was 6 months. A
Swedish study said 3 months was enough so we decided to stick with that. If I
had been living in India, I would have paid a fraction of the cost for the drug
but because I live in South Africa and have a medical aid it cost an enormous
amount. My medical aid made a concession and helped us financially to be able
to afford the treatment. This was a financial setback for our family, but hey,
this family still has a mom".
So, you may have to push for it
I must admit, my personal preference is that I would want to know as much as possible about my enemy, especially if it were an advanced cancer. And that would very definitely include genetic profiling.
Not just for the initial treatment choices, but also to serve as an important and on-going backdrop in my search for future opportunities, the ‘next new things’.
Indeed, I would push hard, both with the health care
providers and my health insurers; and would even, if necessary, pay for liquid
biopsy testing myself, as an investment in my future well-being.[7]
[1] About 1 in 5 breast cancers are Her2
positive.
[2] Treatment
of HER2-positive Disease in 2013, A Conversation with Hope S. Rugo, MD - The
ASCO Post, February 2013
[3] We talk about “stupid” and “smart” cancers in the book (chapter 3): “stupid” cancers are targetable, whereas the more advanced “smart” cancers are highly prone to treatment resistance.
[4] Though
the momentum is building. See, for example, this recent consensus statement
published by the Cancer Research Institute in the UK: All
patients’ cancers should be genetically profiled to improve care, say leading
health experts. Their primary recommendation is that “All people with
cancer should have their cancers molecularly profiled as standard within the
NHS to identify mutations and guide their treatment – helping them access more
personalised and effective treatments, both as part of standard care and by
taking part in clinical trials”.
[5] Most Community-Based
Oncologists Skip Biomarker Testing - Medscape - Sep 23, 2021.
[6] Oncologists Still Failing 'Woefully'
at Molecular Testing in Lung Cancer - Medscape - Sep 14, 2021
[7] As
of 2022, a test is in range $3000 to $5000.