Hello from my chemo chair! Today is my 10th round and it’s a long cycle with Taxol, Herceptin and Perjeta. I can’t believe we are already in the double digits!

Since today is my last Herceptin+Perjeta before coming back for maintenance after the surgery and radiation portions of my treatment are completed, I wanted to take the opportunity to talk a bit about the subtypes of breast cancer, how doctors check to narrow down on the diagnosis and the importance of understanding the subtype. I will also cover the treatment options specifically for HER2+.

When I say my breast cancer is “aggressive”, what I mean by that is this specific subtype forms, grows and spreads faster than some of the other types.

My type of breast cancer is HER2 positive, which biologically is one of the more aggressive types, and historically has been associated with a rather poor survival prognosis. Luckily there has been a lot of advancement in breast cancer research and currently HER2+ is actually one of the most treatable types of breast cancer - as long as it is detected early enough.

Subtypes of Breast Cancer and Their Diagnosis

In this post I shared how I found out about my diagnosis - I got a call from the clinic asking me to authorise payment for immunohistochemistry tests that were required to narrow down on my breast cancer diagnosis. At this point I understood that I had breast cancer for sure, but more tests were needed to determine the subtype and how to treat it.

Immunohistochemistry tests check for the existence and extent of certain receptors on the surface of the cancer cells, specifically:

• Female hormone receptors: for oestrogen and progesterone;

• HER2 receptors.

The existence of these receptors means that they are (at least partially) responsible for fuelling the growth of the cancer cells. In some cases, the HER2 part of the test may come back as inconclusive, in which case the doctor will request a follow-up test called a FISH test. FISH stands for fluorescent in situ hybridization.

The results of the immunohistochemistry and FISH tests are used to determine the molecular subtype of a patient’s breast cancer. These are the possible combinations and the resulting subtype:

• Luminal A Breast Cancer = Hormone positive (either oestrogen positive or progesterone positive, or both) and HER2 negative;

  • These cancers tend to be slow growing, less aggressive and historically have had the best prognosis.

  • About 30-45% of breast cancers are luminal A.

• Luminal B Breast Cancer = Hormone positive (either oestrogen positive or progesterone positive, or both) and HER2 positive;

  • These cancers can be more aggressive due to the over-expression of HER2 receptors.

  • About 10-20% of breast cancers are luminal B.

• HER2 Positive Breast Cancer = Hormone negative and HER2 positive;

  • These cancers tend to be aggressive due to the HER2 receptors.

  • About 10-15% of breast cancers are HER2 positive and hormone negative. They are often diagnosed in young women.

• Triple Negative Breast Cancer (TNBC) = Both hormone receptors negative and HER2 negative.

  • These cancers are considered the most aggressive. They have fewer treatment options available, but they are known to respond very well to chemotherapy.

  • About 15-20% of breast cancers are triple negative. They tend to develop in young women more frequently and are particularly common with BRCA gene carriers.

Knowing the subtype is tremendously important, because certain treatments will only be beneficial to specific subtypes. All cancer treatments are really harsh on the body and mind, so there’s really no need to offer some of them if we know they won’t work.

Cancer Treatment

Despite all the advancement in science and medicine, the treatment for cancer is still pretty blunt: it mostly comes down to burning it (radiation therapy), poisoning it (chemotherapy) and/or cutting it out (surgery). Radiation, chemotherapy and surgery are treatment options that are usually available to all patients, regardless of their subtype. Not everybody gets chemo (depends on the staging and aggressiveness), not everybody gets radiation either (full mastectomies do not require radiation, only lumpectomies), but surgery is pretty much the default in all early breast cancer cases.

Surgery and radiation are known as local treatments, because they are given specifically to the cancerous area (i.e. the surgeon will remove the tumour and / or lymph nodes and radiation will be applied to that same area as well).

Chemotherapy is known as systemic treatment, because it impacts the entire body, not just the area affected by cancer. It’s super important, especially with aggressive cancers, because it is aimed at killing off all cancer cells, including the ones that may have escaped from the tumour and might be floating around the body, waiting to settle and start metastasizing. Metastasis is what leads to advanced, stage 4 cancer, which is incurable (I wrote about it here).

In addition to the treatments outlined above, there are also targeted treatments which might be offered depending on the subtype of the breast cancer.

For cancers that are hormone positive, endocrine therapy will be beneficial in treating the cancer and helping to prevent it from coming back. For cancers that are hormone negative, there is little benefit in endocrine therapy, since the cancer cells will not respond to this sort of treatment. Patients with luminal A and B cancers will usually receive endocrine therapy, which is aimed at stopping or suppressing the production of female hormones, so that they stop fuelling the cancer’s growth.

Similarly for HER2 positive cancers, targeted anti-HER2 immunotherapy will be hugely beneficial, but not for cancers that are not fuelled by HER2 proteins. Patients with luminal B and HER2 positive will usually receive this sort of treatment.

What about triple negative? This one is a bit more tricky, because there are few targeted treatment options for this type of cancer, since it still remains mostly unknown what fuels their growth. However, TNBC usually responds very well to chemotherapy.

(The information about types of treatment outlined above is not exhaustive. There are plenty more that might be offered depending on the subtype and certain genetic traits of either the patient and / or their cancer.)

What Is HER2+ Breast Cancer and How Is It Treated?

HER2 is a protein that exists on all breast cells (not just cancer cells). In normal circumstances, these proteins help control the growth of breast cells.

They become problematic when there are too many. With over-expression of the HER2 gene, many more HER2 proteins are created than necessary, leading to uncontrollable division and growth of the breast cells (i.e…. breast cancer). For reference, a healthy cell will have about 20 thousand HER2 receptors on its surface. HER2 over-expressing cells have over 2 million receptors each.

In the 1980s it was discovered that certain incidences of breast cancer have an “over-expression” of the HER2 protein, which can cause the disease to grow and spread more quickly. Apart from the aggressive nature of these cancers, they also have a more frequent tendency of coming back after treatment is completed (aka recurrence). Aggressive growth and a high recurrence rate contribute to an overall poor survival prognosis for HER2+ breast cancer patients. Since discovery, research for HER2+ breast cancer has been focused on developing targeted treatments that slow its growth and help save the lives of HER2+ patients.

Herceptin (the brand name for trastuzumab) does exactly that. It is an antibody which works by identifying HER2 proteins on the cancer cells and targeting only them (as opposed to chemo, which targets all rapidly dividing cells, cancerous or healthy). It attaches to the HER2 receptors, blocking them from sending the signal for growth. Patients receiving Herceptin along with their chemo have a reduced risk of recurrence by 46% compared to chemotherapy alone.

Perjeta (the brand name for pertuzumab) is also an antibody that works on the surface of the cells. It works in the same way as Herceptin, i.e. blocking the chemical signals that would stimulate the cancer’s growth, but in a slightly different way. The two of them combined together and given along with chemotherapy have shown to reduce the risk of recurrence by a further ~20%.

Pause For a Moment

I wanted to take a moment and just think about all of this. Herceptin was approved for use in early-stage breast cancer patients in Europe on May 24, 2006. This was really not that long ago. Do you know what was the #1 billboard song that day? Rihanna's “SOS”. It really feels like yesterday.

Before Herceptin, early-stage HER2+ breast cancer was treated through cutting, burning, poisoning, like the rest of them; but prognosis for HER2+ was a lot worse compared to other types of breast cancer. It came back a lot, sometimes in the same place (meaning patients had to go through the whole surgery-radiation-chemo cycle again), but other times in completely different organs, thus becoming incurable stage IV disease.

I’m 34 years old.

I should have something like maybe half my life ahead of me still, maybe more if I stop eating so much cheese.

I should be enjoying my relocation to Singapore, building my career, starting a family, waiting impatiently for the pandemic to end so I could get on with my life, and then planning trips around South East Asia. That was the plan. Instead I’m sitting in a cancer clinic for the 10th Friday in a row, connected to an IV that is feeding toxic drugs into my veins.

Perjeta has only been used in conjunction with Herceptin since December 21, 2017.

Do you remember what you were doing on that day? I had to check. Instagram stories were already a thing back then, and so looking in my archive I know on that day I was taking perfectly symmetrical photos of some trendy hipster place while chugging gluhwein, excited about coming home for Christmas. Meanwhile, a life-saving drug launch was being announced, and I didn’t even know that four years later I would be benefiting from it.

And I feel so incredibly indebted towards the universe and all its good vibrations, that I need to close my eyes and breathe very slowly. Because if the same thing had happened to me just four years ago, my outlook might have been completely different. I might not have had access to any of this. I might have not been meant to survive.

…

Obviously I have no idea what’s coming and if my treatment will be successful, and even if so, if I won’t have a recurrence somewhere distant. Cancer is a lifelong companion, even after treatment has been successfully completed. So let’s not jinx it for now. But at least I know there's a pretty decent chance that statistically, I will survive this.
Judging by the example of Herceptin+Perjeta, I am also really excited to see what other innovations in treatment will come over the following years. I hope to be able to follow the news (while sipping on some more gluhwein).