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Breast cancer patients who paused their endocrine therapy to try to get pregnant experienced short-term breast cancer recurrence rates similar to women who did not pause therapy for pregnancy, and many went on to conceive and deliver healthy babies, according to results from the POSITIVE trial presented at the San Antonio Breast Cancer Symposium (SABCS).

In this final of four exclusive roundtable videos from 番茄社区, moderator , of the University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, is joined by , of Baylor University Medical Center, Texas Oncology, and U.S. Oncology in Dallas, and , of the University of Texas MD Anderson Cancer Center in Houston, to discuss the clinical impact of the POSITIVE trial.

Following is a transcript of their remarks:

Rugo: Hello, I'm Hope Rugo from the University of California San Francisco's Comprehensive Cancer Center. I'm here at San Antonio Breast Cancer Conference 2022 with my colleagues, Dr. Joyce O'Shaughnessy and Dr. Jennifer Litton. And we are going to have a roundtable and discuss some of the really exciting new developments and updates on certain studies that were presented here at the meeting. And we hope that you enjoy our discussion.

Just to wrap up our discussion, we saw really the results of an amazing trial. I think it pulls at all of our heartstrings and we all were so excited to see Ann Partridge present the , and then even more excited to see your discussion and putting that into context. Tell us a little bit about the POSITIVE trial, Jennifer, and what it means to our patients and to us.

Litton: Absolutely. So the POSITIVE study was an international collaboration, really tackling one of the biggest questions for our young breast cancer patients, which is fertility concerns and having children after they've been diagnosed with breast cancer. And as we look at what's been happening over the last 15+ years, a lot of women have been having to make this very difficult choice with very limited knowledge. We have some information about maybe waiting 2 to 3 years, mostly because those people are going to have really aggressive recurrences [that] tend to happen during that time.

But for our patients with hormone receptor-positive breast cancer, it's really hard with 5 or 10 years. So what do you do? And then people may not be able to have a child if they haven't already done freezing of eggs or freezing of embryos. And so the POSITIVE trial prospectively looked at really what was already happening in the clinic, it was holding endocrine therapy, giving patients 18 to 30 months to get pregnant, and then going ahead and resuming.

Now, this was the very first look and when compared to the , because obviously we can't have a randomized clinical trial to get pregnant or not, which I thought was a very excellent design to try to answer this hard question. And we're really not seeing an early sign at all that we're having worse survival. There was a high rate of patients who did go on and get pregnant and then resumed their endocrine therapy. And at the end there was only about 15% that hadn't resumed yet.

I think it's really helpful to also know that 94% were early, early stage -- stage I, stage II, really different. I think that we can't just say, okay, the POSITIVE trial is out, every premenopausal woman can get pregnant at 18. I think we really have to look what is their personal risk of recurrence? How old are they? Someone who's 25, maybe the 10 years is really a good thing for them versus someone who's 38 and node negative, that kind of thing.

So it's still really, really individual, but I think this was just a glimpse of hope that this practice that we're doing is still really safe and it'll be important to follow it out.

Rugo: And I think we definitely have the message that trying to preserve fertility for our young women is really important. I always feel so sad when women aren't given the 2 weeks they need to harvest their eggs, because people say you should start treatment tomorrow. But I think it's perfectly safe to have that time to harvest eggs and either freeze eggs or embryos. And we usually use ovarian suppression during the chemo. I think there are things we really need to be doing to support our patients, and this data was incredibly helpful.

And I thought it really intersected well with data that Laura van't Veer presented from the . They looked at extended-duration endocrine therapy and found that the patients who had MammoPrint, the 70-gene assay low-risk, benefited the most. And so that helps you because you think, okay, you could take a break and you really need maybe a little longer therapy for those low-risk patients, genomically low risk. I think it was interesting.

O'Shaughnessy: That was good. That was very interesting. It makes biologic sense because the MammoPrint high-risk, those are the patients we give chemotherapy to, they're generally more risk insensitive or resistant. And then the ultra-low risk, they don't need more than 5 years. But it was that sweet spot that's very helpful.

I was making note to self that I need to check that before I take some of my patients off, those who I know who still have residual risk. To really see if they're in that low. There was a good delta there. And that was the ideal was 5 years of previous endocrine therapy, whether it be AI for 5 years or tamoxifen for 5 years, or [tamoxifen] followed by AI and then randomization to 2 versus 5 years of letrozole. And you wouldn't think that would make a huge difference, but it made a huge difference, in the low risk, the MammoPrint low-risk patients.

Rugo: Yeah. It was really big. And I thought that was really interesting.

I have so enjoyed talking to both of you and learned so much. And I think and I hope that our audience also has learned something about the really exciting data that was presented at San Antonio, and how we're thinking about applying this to our clinical practice and to the next couple of years. So thank you for joining us and thank you, Joyce and Jennifer, for joining me.

Litton: Thank you.

O'Shaughnessy: Thanks, Hope.

Watch episode 1: New Developments in HER2-Positive Breast Cancer at SABCS 2022

Watch episode 2: Anti-CDK4/6 in Metastatic Breast Cancer Showed Further Benefits at SABCS

Watch episode 3: Promising Phase III Results in HR+/HER2- Breast Cancer

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