DR LOVE: So we had another really interesting case presented. I wanted to again bring up to you a 30-year-old woman, ER-positive, HER2-negative, node-positive breast cancer who was very reluctant to receive adjuvant chemotherapy. So to get more information for this patient, a Recurrence Score was ordered, and it was high. It was 52. And as the patient was kind of finding out about this, she developed something in her right upper quadrant, went to the emergency room, got worked up, ended up having a biopsy-proven liver met.

So the question that we posed to the audience was, what kind of systemic therapy would you utilize? Here you have a patient with liver disease, but, on the other hand, maybe not that extensive at this point, ER-positive but an unusually — for metastatic disease, we know that she has a high Recurrence Score. So for whatever reason, most of the audience would give this lady chemotherapy. Some would give her hormonal therapy with palbociclib. And a couple of people, including you, would give hormonal therapy and chemotherapy. So can you kind of talk through how you think about this situation?

DR O’SHAUGHNESSY: Yes. This is one where one could really consider a variety of options. I think that we do have some data from Tari King when she looked at Recurrence Scores in metastatic disease and really did see big differences in outcomes with endocrine therapy versus chemotherapy, depending on the Recurrence Score. So the high Recurrence Score doesn’t necessarily do very well with endocrine therapy alone. So this particular patient’s case, knowing that high Recurrence Score helped me not consider endocrine therapy alone, even the best endocrine therapy, such as a BSO and an AI. I would not do endocrine therapy alone for this patient.

So before we had the CDK4/6 inhibitors, then we would be looking at cytoreductive chemotherapy followed by very optimal endocrine therapy, which, in my mind, would be a BSO and an aromatase inhibitor. However, the advent of the CDK4/6 inhibitors gives us another option for this patient. What I have done, Neil, is base it mainly on the patient’s overall tumor burden. This woman doesn’t have a large metastatic tumor burden, if you find it’s just in the liver. And it sounds like it’s smaller volume just in the liver. It’s not widespread to the bones and multiple other organs.

I think it’d be extremely reasonable, particularly since this woman is not interested in chemotherapy. But regardless of that, honestly, it would be very reasonable to just go with an LHRH agonist/letrozole and palbociclib. I think that would be an extremely reasonable option. And I wouldn’t be able to say that she would benefit additionally from chemotherapy. And the thing is, is that we put ourselves in a little bit of a box.

And I did this, Neil. I had a patient walk through the door — she was in her early forties — widespread metastatic disease, locally advanced breast cancer, very highly proliferative ER-positive, HER2-negative. And I ended up giving her chemotherapy. And I think I gave her TAC chemotherapy. She had a lot of liver disease. And she really needed immediate cytoreduction. And then she had a beautiful response, kind of the PET scan, basically — there was no further uptake. She still had some residual disease in the liver, but no further uptake. Everything went cold on PET. So went ahead and did a BSO, and she’s on letrozole.

Now I ask myself, “Hmm. Should I add palbociclib at this point?” And I thought to myself, “Nah. I don’t have any data. I don’t have any data that I would really benefit her in that particular scenario.” So if you use chemotherapy first, we don’t know what to do with the palbo after that. So I think that in this particular case, I would go by the amount of tumor burden. And I have found that the responses that occur with endocrine therapy and CDK4/6 inhibitors, they look like more akin to endocrine therapy responses than they do to chemotherapy responses with regard to the tempo of the response.

And so I wouldn’t necessarily feel I would have enough data to say that in somebody with very aggressive, heavy tumor burden that I would be comfortable just going with a CDK4/6 inhibitor. But in this particular patient’s situation, I probably would.

Adjuvant and neoadjuvant therapy for HER2-positive breast cancer (BC)

Management of HER2-positive metastatic BC (mBC)

Clinical decision-making for patients with ER-positive early BC

Management of ER-positive, HER2-negative mBC

Indications for BRCA testing in BC and ongoing investigation of PARP inhibition

Treatment of triple-negative BC (TNBC)