Rare cancer: ovarian clear cell carcinoma

Here's an explanation of how anti-PD-1 drugs work. It's probably TMI.

PD-1 is a protein found on the surface of immune cells (not cancer cells). When the immune cell is in position to kill a target cell, PD-1 can bind to a protein on the surface of the target cell called PD-L1 and this prevents the killing. So expressing PD-L1 is one way that cancer cells escape killing by the immune system. Keytruda, Jemperli, and several similar drugs prevent the PD-1 to PD-L1 interaction and restore killing of cancer cells by immune cells.

But there's something else needed for the immune system to want to kill the cancer cells in the first place. It has to recognize the cancer cells as abnormal. The main way this happens is because the cancer has mutations, some of which cause it to make abnormal proteins. The immune system can detect these abnormal proteins.

Some cancers have thousands of mutations and so make thousands of abnormal proteins that can generate an immune response. Other cancers only have a few mutations. So using Keytruda etc. to unleash the immune system works much, much better on cancers with lots of mutations. Cancers that are defective in the DNA repair process called mismatch repair (MMR) have lots of mutations. So do cancers with mutations in the gene POLE, as well as melanomas (which have uv-induced mutations) and lung cancers, particularly in smokers. So Keytruda etc can have dramatic effects on these cancers.

Endometrial cancers that are proficient in MMR (pMMR) tend not to have many mutations, so there's not a high likelihood of a major response to Keytruda or Jemperli. They do give them to people anyway, since there is a modest improvement in prognosis with them.

thanks, i read reports of the study on jemperli and wanted to switch to it. asked my oncologist plus the second opinion doc at mayo phoenix. apparently i am pMMR though so they thought Herceptin was the better of the two. i was very impressed with the study results, however. the thing that bothers me is that i've had two medical people say, from looking at a very bad pre-surgery CT-scan and a clean one done post-fifth infusion, that it is obvious that the chemo is working. that seems like very bad logic - it seems to me that it means that either the surgery or the chemo is working. seems bad for them to base a treatment plan on bad logic. unless if i hadn't had the chemo, i would have metastasized by the second ct-scan BUT THEN WHY DIDN'T THEY SAY THAT WHEN I WAS TRYING TO DECIDE ON WHETHER TO DO CHEMO OR NOT????? these doctors are shifty little creatures -- JUST GIVE ME THE DATA!

Thank you so very very much. Not TMI at all. Just the right amount, clearly stated.
I have "mixed response," to treatment - one tumor shrinking, new ones appearing. This helps explain why. I am pMMR . Because of the way insurance works, I have to go through this step to get what I hope might be more helpful - something that will address my HER2 score of 3+.

You should be eligible to take Enhertu. This is an antibody-drug conjugate that targets cancers that express HER2. It is approved for all solid tumors that are 3+ for HER2. I expect your oncologist will recommend this tomorrow.

People on this forum who have taken it have found it to work (at least for a while) and for it to be quite tolerable.

Good luck!

So you are trying to understand if it was the surgery or the chemo that helped, is that it? I'm not quite clear on the problem. Do understand your wanting clear explanations and access to the data.

I think the idea is they use chemo to target any remaining (hiding) cancer cells after surgery.
Something is working, yes? You are winning the battle, at least for the moment. Maybe a deep breath and some gratitude?

Let me know if you are able to get the Herceptin and what insurance you have. I want to try it! I have to get rid of metastasis before I am eligible for surgery, if ever.

Do I have a solid tumor? I have clear cell carcinoma. I have lots of cancer in my uterus, inoperable now due to metastasis. I have small tumors in my abdomen. Are all tumors solid?
Sorry, I've done a lot of research but apparently I am missing some basic information. There is a patient portal and I am going to ask about Enhertu tomorrow!

Do I have a solid tumor? I have clear cell carcinoma. I have lots of cancer in my uterus, inoperable now due to metastasis. I have small tumors in my abdomen. Are all tumors solid?
Sorry, I've done a lot of research but apparently I am missing some basic information. There is a patient portal and I am going to ask about Enhertu tomorrow!

@jchantler I think @val64 can answer this question better than me.

My husband is a pathologist, now retired. He refers to these cancers that we are discussing as "tumors". Like me, you probably think of tumors as a solid sort of lump. I read that a tumor refers to a mass of abnormal cells.

Here is information from Cleveland Clinic:

What is a tumor?

-- https://my.clevelandclinic.org/health/diseases/21881-tumor

Does this help?

Yes, you have a solid tumor. (Anything that's not a leukemia or lymphoma is a solid tumor.)

I think the only issue in your eligibility for Enhertu right now is whether you have technically failed the first-line carbo/taxol/Keytruda chemo. Having some tumors that are growing doesn't sound good to me, even if others are shrinking. But I'm not a doctor. Was there a long gap between your previous scan and when you started chemo? Then maybe they're thinking that the growth occurred before you started chemo?