DR SLEDGE: MA17R was based on a previous trial that randomized patients who had received prior adjuvant tamoxifen at the 5-year point to receive either a placebo or to receive an aromatase inhibitor. And that was a positive trial, particularly in lymph node-positive patients, and then led to MA17R, which was a trial that then randomized patients at the 5-year point, with some sway on either side to either another 5 years of aromatase inhibitor therapy or to a placebo. And these are long-awaited results. We have many patients with ER-positive breast cancer receiving adjuvant aromatase inhibitor therapy who, when we get them to the 5-year point, we want to know: Do we continue or do we stop?

So this trial asked that basic question: Do we continue or do we stop? And the answer, I would say, was a mixed one for a plenary session lecture. And that is to say that there was a statistically significant improvement in terms of disease-free survival for continuing therapy, but the benefits, one would have to say, are modest, and in particular in terms of distant relapse, quite modest, with only about a 1% difference in terms of distant relapse rate and, unsurprisingly, given such a tiny difference in terms of distant relapse rate, no difference in overall survival at this point.

Now, I think this is probably a little bit early to come to a final conclusion on this study. And that is to say that if we look at the longer-term versus shorter-term tamoxifen trials, such as aTTom and ATLAS, the survival differences weren’t seen until out at year 15. So maybe it’s a little bit premature to answer a survival question here. But certainly this is a modest difference rather than a huge difference. And much of the benefit that’s attained appears to be benefits that are not associated with differences in distant relapse rate but rather differences in terms of second primary tumors, such as contralateral breast cancer.

DR LOVE: So to some extent being chemoprevention. On the other hand, in terms of individualizing it and maybe coning down on it, what about the higher-risk patients, node-positive patients? Any thought about that?

DR SLEDGE: Yes. I think when I sit down in clinic with my patients and have this discussion, many of the risk factors in the first 5 years are risk factors in the second 5 years. So if a patient has either a big tumor or has a bunch of lymph nodes, that is the patient who is at highest risk and, therefore, from a proportional reduction standpoint, that’s the patient who’s likely to get the greatest absolute benefit. So if I had a patient with a 5-cm tumor with 4 positive lymph nodes, that’s a patient I’m likely to encourage to continue therapy with an aromatase inhibitor.

Early-stage breast cancer (BC) in the adjuvant and neoadjuvant settings

Genomic assays and (neo)adjuvant treatment decision-making

Management of metastatic BC (mBC)

CDK4/6 inhibitors for the treatment of BC

Novel approaches under investigation in BC