Takeaways from SABCS, Part III

Last updated: February 2021

In addition to the medication that has been approved or reviewed by the FDA, a large part of the San Antonio Breast Cancer Symposium are the discussions about what's next. Some trials have started, are recruiting, or have preliminary data. Some trials are ideas that need funding or more support or streamlining. However you describe it, there are some exciting ideas out there. It may take a lot of time for these ideas to become available to patients, but knowing that many avenues are being studied gives me a lot of hope.

Categories of medication for MBC

There are five (5) key categories of medication that will be examined and studied for the possibility of prescribing to those of us with Metastatic Breast Cancer (MBC) and are described below.

1. Oral SERDs

Currently, the sole Selective Estrogen Receptor Degrader (SERD) available for hormone receptor positive MBC patients is Faslodex (fulvestrant), which is administered as two intramuscular injections in the buttocks. There are eight (8) trials going on right now:

  1. RAD-1901/Elacestrant by Radius;
  2. SAR-439859 by Sanofi;
  3. ZN-C5 by Zeno;
  4. GDC-9545 by Genentech;
  5. G1T48 by G1 Therapeutics;
  6. LSZ102 by Novartis;
  7. AZD-9833 by Astra Zeneca; and
  8. LY3484356 by Eli Lilly.

I get these lovely monthly shots, one in each butt cheek, and I'm pretty excited that an oral version might be available soon!

2. SERCAs (Selective Estrogen Receptor Covalent Antagonists)

Existing FDA-approved hormonal therapies include SERMS (tamoxifen and Fareston), SERDs (Faslodex), and Aromatase Inhibitors. SERCAS are a new series of compounds with unique modes of inhibition that target wild-type and mutant estrogen receptor alpha (ERa). SERCAs inactivate the estrogen receptor by targeting an amino acid that is not found in other hormone receptors, which produces different activity than SERMS and SERDS.

I'm still not entirely sure about this wild-type and mutant estrogen receptors. I don't have either, so I don't have personal experience with this category. If this applies to you, then the idea may make more sense. Definitely something to discuss with your medical team!

3. ShERPAs

Selective human Estrogen Receptor Partial Agonists (ShERPAs) represent a new class of drugs that mimic the effects of estradiol (a/k/a bad estrogen) in endocrine-resistant breast cancer cells. An active Phase 1 study of a ShERPA called TTC-352 is currently ongoing.

I saw a few posters about these types of medication and the science is fascinating. Just the fact that we have multiple types of estrogen and there is the ability to target the specific kinds is a revelation in and of itself. If we're able to target the "bad" estrogen only, then the menopausal symptoms we all have to deal with could be changed, maybe eliminated. This idea gets a big thumbs up from me.

4. SARMs (selective androgen receptor modulators)

The majority of hormone-receptor-positive breast tumors express the Androgen Receptor (AR), as do a moderate number of HER2 positive tumors and nearly one-third of triple-negative breast cancers. SARMs are drugs that can exert varying effects on ARs in different tissues, and there is currently one active SARM clinical trial for TNBC MBC patients whose tumors are AR-positive.

My challenge in this category as well is that my cancer doesn't express the Androgen Receptor, so I don't have a good frame of reference personally.  Bottom line is that this is just another way of attacking the cancer, just one more way in.

5. BCL-2 inhibitors

BCL-2 is a cell survival protein best known for its roles in inhibiting apoptosis (a/k/a cell death) and promoting oncogenesis (a/k/a the transformation of normal cells into cancer cells). The majority of breast cancers are BCL-2 positive, and a Phase 2 study of the BCL-2 inhibitor Venetoclax is currently recruiting.

Anything that makes the cancer cells die and inhibits the ability of normal or healthy cells from becoming cancer cells definitely has my vote as well. It will be extremely interesting to see how Phase 2 goes!

I know there are a lot of acronyms and initials in this post. If you've made it this far, congratulations!  Lots of new things coming and SABCS 2020 will likely be even more fascinating as we learn throughout the year.

Editor's Note: Here are the other articles in this series from SABC - Part 1, Part II, and Part IV.

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