DR LOVE: You mentioned the issue of platinums with patients with BRCA germline mutations. How are you approaching the integration of platinums in the neoadjuvant, adjuvant and metastatic setting in patients with BRCA mutations?

DR RUGO: I think that the data is conflicting. If you give optimal neoadjuvant therapy, as was done in the CALGB neoadjuvant trial 40603, there was no difference in disease-free survival in patients with triple-negative disease. And that suggests 2 things: Overall, patients did very well. Secondly, that even though you have an increase in pathologic complete response rate, that the chemotherapy alone, even in patients who had minimal residual disease, seems to be very effective at allowing some patients to be free from recurrence.

So it’s difficult. It means that everybody with triple-negative breast cancer does not need a platinum. The German trial showed an improvement in outcome, but they used a different backbone, which is not a common one, and there was less doxorubicin dose intensity. So where that leaves us is, in patients who have BRCA mutations, if I have a trial for them to go on, I put them on our I-SPY trial.

If they don’t have a good response — and this is also the case of in a patient who has a sporadic triple-negative breast cancer. If their tumor is not shrinking by 3 or 4 weeks on paclitaxel that I start with, then that’s not a good sign. And I consider either going to an anthracycline-based regimen then or adding in platinum to the chemotherapy to try and see if I can enhance response.

If a patient’s gone all the way through neoadjuvant therapy and they end up on the other side without a pathologic complete response and with high-risk disease, I consider giving a platinum after surgery. And there actually will be an interesting cooperative group trial that will look at giving a platinum and comparing that to capecitabine based on the CREATE-X trial. And Ingrid Mayer from Vanderbilt is running that trial, which I think is really fascinating and incredibly important.

And then if I have a patient in the adjuvant setting who has a BRCA mutation, I generally do include platinum, because there’s no way to know how things are working. We have to be aware of the fact that platinum increases toxicity and reduces marrow tolerance. And a patient who has sporadic triple-negative breast cancer I tend not to add the platinum, because we just don’t have data on survival outcome.

We saw very interesting data from Joanne Blum in the ABC trials that suggested that, in triple-negative disease in particular and higher-risk breast cancer, that we really do need to keep our anthracycline. And that suggests that the anthracycline in and of itself is a critical component of this treatment.

Genomic assays and (neo)adjuvant treatment decision-making

Early-stage breast cancer in the adjuvant and neoadjuvant settings

Management of metastatic breast cancer (mBC)

CDK4/6 inhibitors for the treatment of breast cancer

Checkpoint inhibitors and other novel immunotherapeutic approaches to breast cancer

Triple-negative and BRCA mutation-positive breast cancers