Triple-Negative Breast Cancer: Expert Perspectives On Recent Advances - Episode 2
Joyce A. O'Shaughnessy, MD: I want Sara Tolaney to have the last word on this, with regard to use of platinum and maybe even the node negative patient, the T1c N0. What do you do, Sara, if they don’t have a pathologic complete response [pCR]? How do we define pathologic complete response and what do we do if we don’t have one?
Sara Tolaney, MD, MPH: I think in terms of the platinum issue, I feel very similarly to others that I generally tend to use ACT [doxorubicin, cyclophosphamide, paclitaxel] for the larger tumors. I only use platinum if someone is not having a good response generally to the upfront AC [doxorubicin, cyclophosphamide]. Then sometimes I’ll tack on the platinum because I have been concerned about the toxicity. We saw in the CALGB 40603 trial that the people who got platinum, if they had to not complete all their taxane, actually did worse. I do worry about adding on toxicity when we don’t have data that are sufficiently powered for long-term outcomes.
In the T1c tumors, I think like others have expressed, if they’re usually under 1.5 cm, sometimes I’ll do TC [docetaxel, cyclophosphamide] times 4. Whereas, if they start getting over 1.5 cm, closer to 2 cm, then I start giving them ACT [doxorubicin, cyclophosphamide, paclitaxel] therapy. I tend to use size to help me judge how much treatment to give them. I think generally speaking, we do tend to approach most of our patients with larger tumors with preoperative therapy, with the reason being that we can tailor their therapy based on response to that preoperative treatment. That tailoring of treatment is really going to change their long-term outcomes.
What we’re looking for is are they achieving a pathologic complete response to their preoperative treatment, meaning is there no invasive residual disease found within the breast or lymph nodes at the time of surgery? We know that those patients who achieve pCR have better long-term outcomes, whereas we know that those patients who have residual disease do have a higher risk of recurrence. As Kevin had alluded to, we do have data to suggest that we can alter those long-term outcomes for those patients with residual disease based on data from CREATE-X.
We know that in patients with residual disease who are randomized to get capecitabine vs no capecitabine, we saw that giving the capecitabine had a statistically significant improvement in disease-free and overall survival. We saw that that control arm with no capecitabine actually doesn’t do very well with the 5-year disease-free survival that’s around 55%. Again, there was a significant improvement to their outcomes by giving them capecitabine. I do offer all my patients with residual disease the 6 months of adjuvant capecitabine.
Joyce A. O'Shaughnessy, MD: Thank you. That’s a nicely put summary of that data. It highlights that if patients don’t get a pathologic complete response with triple negative breast cancer, their outcome is poor. It’s thankfully improved with the capecitabine, both disease-free and overall survival, as you strongly pointed out. Still, patients recur in spite of the capecitabine, and then patients still have a poor outcome if they don’t get a pCR. The pCR rates, correct me if I’m wrong, I would estimate that with an ACT [doxorubicin, cyclophosphamide, paclitaxel]-like regimen preoperatively, were in the 40%, 45% range. Then if you add the carboplatin, you’ll be in the 50%, 55% range, that’s probably pretty right, OK?
You get a little bit, 10% improvement, 13%, 16% in some of the studies specifically, but round numbers, it’s about 10 %. We’re pushing up around 55% with where we are, so that’s really good for those patients. But we have 45%, the number you said, who don’t get a pathologic complete response at 5 years; only 55% disease free is very concerning. We know what a huge issue this is in the practice. We’ve got an unmet need.
I think we’re all agreed that we would definitely have an unmet need. There is no question we have to do better in the curative setting.
Transcript Edited for Clarity