Shannen Doherty and Triple-Negative Breast Cancer

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 about her fight with cancer for over a decade, including being put on the newest protocols, as well as the harshest on the body.

So often, we hear of celebrity cancer deaths due to not doing the proper screening - waiting too long for screening or treatment -   but not so with Shannen. Shannen did everything right and was being treated by the best.

However, Shannen unfortunately had the most difficult-to-treat form of breast cancer that exists – Stage IV, triple-negative, metastatic breast cancer. 

 

Essentially, 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 and the harshest, most grueling treatments.

 

Because at present,  even with the new immunologic treatments, much like pancreatic cancer, if triple-negative breast cancer it recurs - and it likely will – if it didn’t get you the first time, it likely will the second or third time. 

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

 

So what is triple-negative breast cancer?

 

First let’s take a look at how general cancer staging is determined.

As most know, cancer is given basic staging from stages I through IV after imaging  and/or surgery.

The stage 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 metastasized or carried by the lymphatic system elsewhere,  typically to 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. 

In 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 metastasized.

 

We often also do genetic testing on the tissue to determine the 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, radiation, chemo or immunologics, as well as whether the latter two treatments 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,  but additional generic determinants are also whether the cancer is PD-L1 positive and to what degree, as well as genetic mutation testing for BRAF, KRAS, EGFR, ALK, and ROS1 mutations, as well as many others, which can make a difference as to which cancer treatment will be the most effective.

 

Then in certain reproductive cancers, there is a third method of subtyping cancers, which is related to both hormone receptors and genetic expression.

In breast cancer, 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, for the past few decades, we have also treated women with breast cancer with hormonal therapies, based on the cancer’s receptivity to it.

The newcomer to treating cancer are the immunologic or “biologic” therapies.  These are the “monoclonal antibodies” or ”MABs” – their generic names literally ending in “mab” - which are synthetic proteins which mimic our body’s natural antibodies and help the body detect and attack cancer.

Previously, we have been at a loss to understand why the body does not ferociously attack, or even recognize, cancer cells forming; however, MABs are designer antibodies that target and attack only cancer cells.   This is why they are also called “targeted” therapies.

Whereas chemotherapy is cytotoxic – or kills all cells as opposed to just cancer cells – whereas immunologic therapy targets and kills just cancer cells.

However, they were not initially designed to be first-line treatment, but to be the powerhouse drugs to come in later after all else has failed, although studies are current being done in earlier-stage settings.

 

As for triple-negative cancer?

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 was not only Stage IV or her cancer had metastasized to other parts of the body, but type of cancer could not be mediated by either genetic-expression treatments or hormone-mediated expression treatments, and only minimally to surgery, regular chemo, radiation.

As for the immunologic treatments, they can extend the life of women with triple-negative metastatic cancer for up to a year, but they cannot not cure them .

(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.