Post-Conference Perspectives: RxPONDER, SABCS 2020 - Episode 4

NCCN Guideline Updates for HR+ Operable Breast Cancer


Experts in breast cancer comment on NCCN guideline recommendations as they reflect the outcomes of the RxPONDER trial for HR+ early breast cancer.

Priyanka Sharma, MD: These results have, in my opinion, established for us that postmenopausal women with 1 to 3 positive nodes with hormone receptor-positive, HER2-negative disease who have a recurrence score of less than 25, would not benefit from chemotherapy. It spares a lot of these women toxic treatment, and we can safely forgo chemotherapy in postmenopausal women. Whereas, in premenopausal women, we do see a benefit of chemotherapy, with an absolute difference ranging from 3% to 6.5%, depending on the different subgroups in the premenopausal subset. I think that led to the adoption of this in the NCCN [National Comprehensive Cancer Network] guidelines, which now recommend use of this assay in women with 1 to 3 positive nodes. It was already recommended for chemotherapy decision-making for women with node-negative disease.

For postmenopausal women with a recurrence score of less than 25, chemotherapy can be omitted. I think it’s the premenopausal subgroup where people have a lot more questions. We see the benefit of chemotherapy when it’s added to endocrine therapy from the SWOG-1007 trial. It is not known whether that benefit is totally or partially driven by the ovarian function suppression effect of chemotherapy, and whether the same benefit would have been observed if all patients received ovarian function suppression in this trial. I think this is a question that will have to be addressed in another prospective randomized study. We do know from the SOFT and TEXT trials that the absolute benefit of the addition of ovarian function suppression to endocrine therapy was much larger in women who received chemotherapy, from 5% all the way up to 15%, based on the risk. It was much lower in women who did not receive chemotherapy, so who had clinically low-risk disease. That benefit from the addition of ovarian function suppression in SOFT was about 1% to 2% in women who did not receive chemotherapy.

In our clinical practice, we are using both treatments, not necessarily using one instead of another, in our highest-risk patients. I think there are positive data for premenopausal women with lymph node-positive disease, looking at efficacy of ovarian function suppression in isolation, without chemotherapy. SOFT included only about 10% of patients who had lymph node-positive disease who did not receive chemotherapy. The majority of patients in SOFT who had lymph node-positive disease ended up receiving chemotherapy as part of their standard management, and similar treatment was noted in TEXT. I think this is a question that all of us would like to have an answer to, and it will require another prospective trial. That goes back to the NCCN guidelines, where for the premenopausal subgroup, for those with node-positive disease, 1 to 3 positive-nodes, and a recurrence score of less than 25, the guidance is a little more, I would say, “wait.” So, you can do chemotherapy or ovarian function suppression; we don’t yet know how much of the benefit of chemotherapy in SWOG-1007 was derived from ovarian function suppression. I don’t think that trial will provide us that answer.

We know the Oncotype DX recurrence score is prognostic. We see that from TAILORx. We also see it from SWOG-1007, that the higher the score, the higher the risk. We also see from 1007 that in premenopausal women, those randomized to chemotherapy plus endocrine therapy did better than those who weren’t randomized to chemotherapy and just received endocrine therapy. What 1007 showed was the benefit of chemotherapy was not tied to the actual recurrence score value. Higher value did not translate into more benefit, and vice versa. The clinical utility of the assay is still totally there, and I do not think the SWOG-1007 results question that aspect.

Lajos Pusztai, MD, PhD: The wonderful thing about medicine is that you see changes that are continuously happening. What is the current consensus about the use of adjuvant chemotherapy in lymph node-positive disease? This consensus is changing as we speak. The most recent NCCN guidelines remarkably, effectively, and efficiently already incorporate the RxPONDER results. They recommend that for many women who have ER-positive, 1 to 3 lymph node-positive, invasive breast cancer, the recurrence score could be used or should be used to help guide the value of adjuvant chemotherapy.

Transcript Edited for Clarity