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In this exclusive virtual roundtable video from 口袋女优, three expert leaders in the field of breast cancer discuss the latest emerging and potentially practice-changing data from the virtual San Antonio Breast Cancer Symposium.

Moderator , is joined by , and in this final of four episodes, discussing studies presented at the meeting on genomic tests to improve the quality of treatment decisions in higher risk, node-positive early breast cancer: the RxPONDER, ALTERNATE and ADAPT trials.

Episode 1: Immunotherapy Options

Episode 2: Adjuvant Anti-CDK4/6 in Early, HR-Positive Breast Cancer

Episode 3: Emerging Novel Therapies Presented at SABCS 2020

Following is a transcript of their remarks:

Hope Rugo, MD: Hello and welcome to this virtual roundtable where we will be discussing some of the key data that emerged from this year's San Antonio Breast Cancer meeting. I'm Hope Rugo, professor of medicine at the University of California San Francisco's Comprehensive Cancer Center, and I'm joined today by two expert leaders in the field of breast cancer and great colleagues, Dr. Jennifer Litton from the MD Anderson Cancer Center and Dr. Jo Chien from the University of California San Francisco's Comprehensive Cancer Center. Thanks for joining me today.

Now, we're going to talk about a really interesting set of presentations at San Antonio that I think really do have direct implications for clinical practice on Monday and this is the use of genomic tests -- and in some of the studies, Ki67 -- in order to try and inform us about how to treat our patients who have higher risk node-positive disease.

The RxPONDER trial presented its first data -- Kevin Kalinsky presented this information -- looking at patients who have 1-3 positive nodes and a lower recurrence score, randomized to chemotherapy and endocrine therapy or endocrine therapy alone.

Then the ADAPT trials from the West German Study Group trial looked at patients who had 0-3 positive nodes and tried to use the neoadjuvant exposure to 3 weeks of endocrine therapy and Ki67 response, as well as the recurrence score, to try and determine whether adjuvant endocrine therapy or potentially preoperative chemotherapy would be a better approach.

Then lastly, we had a little bit of an update on the chemotherapy arm of the ALTERNATE trial, which randomized postmenopausal women to different endocrine therapies, and then in patients who didn't have a great Ki67 response after 4 to 12 weeks, they actually went on to receive chemotherapy. Cynthia Ma presented data on PCR. Jennifer, do you want to tell us a little bit about RxPONDER?

Jennifer Litton, MD: Sure. RxPONDER is a trial sponsored by SWOG and randomized patients who had 1-3 positive lymph nodes and a recurrence score by Oncotype DX of 0 to 25. What was really interesting, and still debating as we speak, is in the group that was postmenopausal there was really no benefit for chemotherapy in this group and I think likely to be very practice-changing for patients to not have to have chemo.

But what remains very controversial is that in the premenopausal women we were not seeing that same... we were seeing actual differences in those 0 to 25. At this point, it did continue to show a difference if you were premenopausal, but postmenopausal women looked like they could avoid chemotherapy.

Rugo: Really fascinating information. I know we'll see a lot more data on this going forward, including which endocrine therapy regimens were used in the patients getting hormone therapy alone since premenopausal women were included. What about the ADAPT trials, Jo?

A. Jo Chien, MD: The ADAPT trials were actually quite elegant. This is a trial that took patients who had hormone receptor-positive disease. They did baseline oncotype and Ki67s on everybody. For those that had oncotypes between 12 and 25, they gave them a 3-week course of preoperative hormone therapy, and that could be either tamoxifen or AI. Then after 3 weeks they repeated the Ki67. For those that did not drop their Ki67 to 10% or lower, they were eligible for the chemo portion of this trial, where they could be randomized into a neoadjuvant chemo trial. Then for the patients who did drop their Ki67 and the patients who had recurrent scores under 12, they were able to just stay on hormone therapy.

What they showed was that their 5-year invasive disease-free survival was quite excellent. I think when we put this in context with RxPONDER, which is suggesting that at least in premenopausal women chemotherapy is beneficial, in ADAPT, where a third of patients were premenopausal and about a quarter were node-positive, there may be a subset within this group that will do well without chemotherapy.

It's hard to know and I agree with Jennifer that based on RxPONDER chemotherapy seems to benefit these young women. But I think that question of how much of this is ovarian suppression versus direct chemo benefit is still unknown, and unclear, and not addressed and answered in these trials.

Rugo: Yeah. It's really interesting and that was a great summary. The ALTERNATE trial, which took patients who didn't have a Ki67 response between 4 and 12 weeks and then went on to give chemotherapy showed a very low PCR rate in the patients who had ER-positive disease, were postmenopausal, and had a lack of Ki67 response, which is really fascinating. This is a different biology of disease and we clearly need to improve our therapy in the hormone receptor-positive setting in patients who have low proliferative disease. Where are you going to take this to the clinic on Monday, Jennifer?

Litton: I think that I feel very comfortable for patients who are postmenopausal and have a 0 to 25 recurrent score that we can forgo chemotherapy for. The premenopausal women, so far I think that this data doesn't completely support withholding chemotherapy. It's going to be a conversation discussing this percent benefit and I think the study that has to be done is doing this in premenopausal women with ovarian suppression and see. I think that just like Jo said, these trials neither answered that question or gave us the tools to answer that question, so I think that's probably the next likely study if we're going to really find out that answer.

Rugo: This is really interesting data and I think it's nice to hear how you're going to apply it to the clinic. It's also we use 1-3 positive nodes and 4 or more positive nodes because we do staging this way, but in fact in these trials the number of patients with 3 positive nodes was small and it did appear that they had a worse outcome. Do you think we should be using this 1-3 nodes in sort of a global decision or should it really be based on the number of nodes?

Chien: I think you really still need to take into consideration the clinical pathologic data in combination with oncotype and other molecular tests. Certainly in patients who had 3 nodes, they were very much underrepresented in this trial and did do worse, and so I would pause a little bit for the 3 nodes. I think for 1 and 2 I feel very comfortable in the postmenopausal patients, and premenopausal I think this data would really lead us to think about chemotherapy.

Litton: I think one thing to add there is that this trial did have an amendment in the course of it where originally N1, if it was microscopic, was allowed. There was a large number of women that may have entered because they did change the inclusion to exclude N1 microscopic, so I think it'll be really interesting when we see this written up the percentage of N1 that was really microscopic too.

Rugo: I think that the bottom line is that in postmenopausal women we can spare a lot of people chemotherapy, maybe the 3 nodes not so much. For premenopausal women, the role of ovarian suppression is incredibly important to understand, particularly in patients who have low-risk clinical pathologic features, one node or microscopic involvement of a node, and not all of those patients require chemotherapy based on this data.

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