Metastatic Breast Cancer 2026 UPDATE

So So first we're going to start off with ERPR-positive metastatic breast cancer.

How are we treating these ladies?

So we are thinking about frontline aromatase inhibitor.

So anastrozole, XMS, zanolestrozole, or fulvestrin with the CDK4-6 inhibitor.

So ribocyclib, palbocyclib, bemocyclib for premenopausal ovarian suppression.

And you want to start that with or before endocrine therapy.

And then ribocyclib is the only CDK4-6 with a category one OS benefit with an AI in the Fulvestrin, Ribo, or Abema are category one in the first line endocrine resistant setting.

And then endocrine and CDK4-6 is preferred over chemo, even with extensive visceral disease.

Chemo only for true visceral crisis.

This is based on the right choice trial that you can still consider getting away with hormone treatment over chemo and aggressive disease.

Absolutely.

And this is a big change from when we took boards because there were distinctions on those questions.

But now endocrine plus CDK4-6 really is the right answer regardless.

And so what about first-line PIK3CA-mutated endocrine-resistant disease?

So there's a triplet, an enavalisib, palbocyclib, and fulvestrant based on the ENAVO 120 trial for PIK3CA mutated disease with recurrence on or within 12 months of completing adjuvant endocrine therapy.

Now it's category one because of a confirmed OS benefit, 34 versus 27 months, in addition to PFS benefit, 15 versus 7.3 months.

The Serena 6 was the big thing.

Plenary in 2025 at ASCO.

And this is a ctDNA-guided switching to camisestrin to an emerging ESR1 mutation.

And I don't think we have overall survival, but this is sort of interesting to be thinking about.

MRD, just coming off those episode topics.

And then Category 1 germline BRCA1 and 2 PARP inhibitors.

So olaparib or talazoparib is an option up front.

And then in visceral crisis, chemo remains Category 1 inhibitor.

unless you're BRCA1-2 mutated where you want to think about a PrEP inhibitor.