Monday, July 15, 2024

Shannen Doherty and Triple-Negative Breast Cancer

*Editing in progress 





So as I mentioned yesterday, while I was writing my post, the news alert came in that Shannen Doherty of Beverly Hills 90210 and Charmed had passed from breast cancer.  

This was very sad news, not just because she was a famous actress, but because she had been so brave and public, fighting her cancer, for over a decade, including being put on the latest and newest protocols, as well as often the harshest on the body,  for her particular type of difficult-to-treat breast cancer.  

So often, we hear of celebrity cancer deaths due to not doing the proper screening, waiting too long, but not so with Shannen - she did everything right and was right on the mark, being treated by the best, but unfortunately, she had the most difficult-to-treat breast cancer diagnosis that exists. 


So essentially, whatever else her flaws/prior feuds with other actresses were, what Shannen did was bravely sign up to be a very public guinea pig for any new treatment that came down the pike for the type of breast cancer with the poorest prognosis, with the harshest, most grueling treatments  - triple-negative breast cancer. 


Because at present - even with the new immunologics -  much like pancreatic cancer, if it recurs - and it likely will - if triple-negative breast cancer doesn't get you the first time, it will the second or third time. 

She had hoped to be the face of surviving it, with all of the new advances in cancer treatments, and though doing so did prolong her life by a few years, eventually she, too, succumbed to it.😢


So what is triple-negative breast cancer?

I get to that below, but before that ... 

So for Contract 1, I type the test-marketing interviews between pharma, insurance companies, and expert clinicians for new drugs before launch, often for cancer, and for Contract 2, I type predominantly for a respected cancer clinic.

So nearly every day, with one contract or the other, I hear encouraging stories about cancer survival, which I wouldn't have heard 15 years ago, before the new immunologics knows as "mabs" or "monoclonal antibodies" were launched.


Immunologics aren't typically used as a first-line treatment for cancer at present, because they were originally designed and studied in later-stage cancers.

In other words, they were designed such that if chemo, surgery, and radiation don't work, and your cancer progresses, then immunologics are tried - the rationale being to save the "big guns" for last as a sort of "Plan B."

The result was that they have had life-saving effects with certain types of later-stage cancers that were previously a death sentence,  including melanoma, breast cancer, lung cancer, multiple myeloma,  prostate cancer and many others, including even certain non-solid tumor cancers of the lymph and blood. 


Now, they either have been or are currently being studied in earlier stages, in either a first-line "neoadjuvant" or "just before"/presurgical setting or as first-line "adjuvant" or "along with" surgery setting, with some success, depending on the type of cancer, so that they can be used first-line with more aggressive types of cancers or cancers that have some response, but not enough response, in later stages.


Immunologics work differently than chemo, in that they target only cancer cells, as opposed to chemo, which is cytotoxic to all biological cells. 

They do come with side effects, but we've learned how to manage them, and they are often less grueling than those with regular chemo (but not always), and sometimes they are given in conjunction with chemo.


Thus, oversimplified, unlike chemo, which is cytotoxic and kills all biological cells, immunologics instead work with the body's immune system to target and recognize only the cancer cells and help attack them, like the body should, rather than bypass cancer as being a natural part of the body.

That is because up until the immunologics, our immune systems could not fully recognize cancer as a foreign body that should be attacked, because often cancer shares some of the DNA of whatever organ it grows from (except in blood cancer).


In breast cancer (and also prostate cancer), this process is helped along by hormone treatments, if the cancer is found to have hormone receptors present.


(As an aside, this is why the birth control you use or the hormone-replacement therapy after menopause is so important.  While these things can protect you from other reproductive types of cancer, with breast cancer, you can have too much of a good thing with hormones, if not in the right balance, and thus you have agreater risk of overreception or even overexpression of one hormone and not enough of the other  - which is what puts you at a 2% higher risk for breast cancer.  Some suspect an even a greater risk, but point being, there is a slight risk to keep in mind in selecting hormones to use and lab tests to check your hormone levels can help. )


Those hormone receptors are ER (estrogen receptors), PR (progesterone receptors), and the third measures gene expression of HER2/neu, a growth factor hormone-related protein related to tissue growth, found to be present in excess in certain types of breast, prostate, ovarian, esophageal, and pancreatic cancers, among others.


Thus, when your cancer is described as "triple-negative," don't let the word "negative" fool you - it means your type of cancer has tested negative for all 3 markers we currently have that are known to respond well to current treatments


In Shannen's case, she tested negative for all three or "Triple Negative" - meaning her cancer would not respond to hormone-mediated and/or genetic-expression treatments and only minimally to surgery, regular chemo and radiation.

Additionally, even the immunologics would not be able save her, just extend her life by a few years.

Also, it is important to note that men are also tested for these same genetic markers, as well hormone receptivity for their types of reproductive cancers.

Men produce smaller amounts of estrogen and progesterone, just as women produce smaller amounts of testosterone, but they are particularly tested for HER2/neu overexpression in prostate and testicular cancer, because again, HER2/neu is a tissue growth factor hormone protein.

Now, how the staging is determined ...




As most know, cancer is given initial basic overall staging from I through IV, which is based on the size of the tumor, the degree to which it has invaded the surrounding tissue, the degree to which it has invaded into the surrounding lymph nodes, and the degree to which it has already metastacized, or already been carried by the lymph and blood past the margins and into other parts of the body, typically the liver, lungs, brain and bone..

Then after overall staging based on imaging, a tissue sample is obtained, either through biopsy or surgery, and the substaging happens for greater specificity. 

This way, we can then further characterize the invasiveness into  a "T N M" format - with the "T" meaning tumor size, "N" meaning the degree to which it's invaded into the surrounding lymph nodes, and "M" meaning whether or not it has metastacized past the margins and been carried by the lymph/blood, into other parts of the body, with lots of subclass numbers regarding the degree of each of those.


We also now do genetic testing on the tissue to determine initial genetic components, as well as any mutations that have or are occurring, so we can know which protocol pathway will result in the best outcome - surgery or not,  radiation, chemo or not, immunologics or not, and whether the latter should be given neoadjuvant (before surgery or radiation) or adjuvant (along with surgery or radiation) and whether chemo/immunologics should be given concurrently or in a specific order. 


You've likely heard of BRCA carriers, which are the basics, but also whether or not your cancer is PD-L1 positive can make a difference in treatment, as well as genetic mutation testing for BRAF, KRAS, EGFR, ALK, and ROS1 mutations and many others, which can also make a difference in your treatment, what your cancer will respond to and what it won't.


As a result, although late stage breast, prostate, and lung cancers used to be an automatic death sentence, the immunologics and genetic testing has altered that, so not necessarily anymore (but mutations still happen).


HOWEVER - with all of the advances we've made with genetic testing and immunologics and hormone therapies, they all appear to still have little to no effect on certain specific types of cancer - specifically pancreatic, ovarian, certain types of breast, prostate, and renal cancers, certain brain cancers and other more uncommon forms of cancer. 


In Shannen's case, based solely on what I've read in the press, she had recurrent, Stage IV, metastatic "triple-negative" breast cancer.


This means she beat it the first time, but it came back aggressively, quickly metastacized to the brain, and her cancer did not contain the 3 known hormone receptors and growth factors that we can typically can use to treat breast cancer  - so negative for ER, negative for PR, and negative for HER2/neu.

Again, this means her cancer would not respond to hormone treatments, or much of any treatment, for that matter, and although  monoclonal antibodies/immunologics such as Kysqali can extend your life by a few years, it cannot cure you.  

Chemo is still the most effective with triple-negative breast cancer, but again, it kills all cells, not just cancer cells, and it's not a course or two, it's constant chemo, so it's rough.  

Radiation is used to control the size of the metastases to the brain, lungs, and bone for comfort, but it can't stop it, either.


(Just as an FYI, HER2/neu-positive-only cancer isn't the type of breast cancer you'd want, either, as it's also in this same boat regarding regular hormones and difficult to treat, but there is an immunologic specifically for them called "Enhertu," which has some effect for some patients, but not effective enough, and it's also dependent on the genetic mutations you might have.)


Shannen was the face of all of the new treatments for triple-negative breast cancer and tried all the new treatments, and was able to successfully live years longer than expected, but ultimately succumbed to her cancer.  😢

Super sad, but her willingness to be a very public guinea pig for any new trials and protocols was admirable, and hopefully as a result, one day we will be able to cure this type of breast cancer, too.



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