ER+ (luminal) to Triple Negative switch in secondary cancer

I have recently been diagnosed with triple negative mets in my lungs and mediastinal nodes. I was strongly ER+ and PR+ in my primary in 2019. I know this switch from hormone positive to negative is not *that* uncommon (I think I read something like 15% of cancers change receptors when they metastasise, usually losing their receptors). I was wondering if other people who have had this same switch between primary and secondary cancer could comments and say what treatment you have been on? I'm wondering if there is any evidence that these kinds of luminal-to-basal (or hormone positive to triple negative) tumors should be treated in a certain way, or straight up as TN.

Part of the reason I ask is that I've been taken off all hormone treatment (thank god in a way, I can't deal with that *and* chemo!) but I worry that there are cells floating around from my initial tumor that are still hormone positive, and it's only these lung/nodes tumors that have turned TN. I asked my oncologist and she basically acknowledged that is a possibility but said we fight the devil we can see in front of us at the moment. But given the hormone positive to negative switch seems to be influenced by certain gene mutations, I wonder if this also suggests that particular treatments/chemos/immunotherapys work better or worse on this kind of tumor.

Any thoughts much appreciated!

You ask a great question to which the answer is still unknown. I had a friend with TNBC MBC (whose early stage bc was hormone receptor positive like yours) who was not doing well on chemotherapy. Her oncologist prescribed letrozole as a last-ditch attempt to help her and she responded for a year!

Thank you everyone for your responses!

Moth - that's very interesting about the uncertainty regarding your hormone status. What I've read (and to be honest I have poor scientific understanding so take this in that vein...!) suggests all breast cancers may start as hormone positive but some switch almost immediately (hence primary TNBC) and some switch later. Perhaps yours half-switched and got stuck somewhere, hence the heterogeneity? I also wonder whether mine has done something similar, as my Foundation One liquid biopsy showed both genetic mutations and amplifications associated with TNBC (EGFR, RB1 mutation) *and* mutations/amplifications associated with ER+ (ESR1 mutation, FGFR1 mutation, NDS3 amplification). I wonder whether I don't have two types of cancer in there....

Bestbird - thank you! My oncologist did mention that she spoke with the endocrine-resistance guru in London (we are in UK) and he said that he has successfully treated some cancer that mutated from hormone pos to neg with CDK4/6 inhibitors and AIs, at least for a while. In my case I progress on letrozole so I'd need the CDK in there too. But my oncologist said she doesn't think that's a good move for me as my cancer has 'behaved' like TNBC - it went to my lungs not bones first (no bone involvement) and is aggressive and expresses certain TNBC genes. So we've gone straight onto TNBC SOC, but I might ask her to talk to her guru again...

Buttonsmachine - it may indeed be worth asking for another biopsy - when was your last one? I spoke to an oncologist in Italy for a second opinion (my partner is Italian and we wanted to know about the treatment landscape there) and one of his main pieces of advice was that my cancer is clearly very unstable so every time I progress he thinks I should get a biopsy of the progression. I'm proof that cancers can change their receptors very quickly (my ER+ (8/8) primary was March 2019; first sign of mets, though initially brushed off by my onc, was May 2020; properly diagnosed TNBC mets in November 2020).