Matteo Lambertini, MD, PhD: Maybe, if I can ask you, [Virginia,] in this regard, which is something that I discuss a lot with the patients [in my practice], for those women who receive chemotherapy, I have your same approach. Chemotherapy [has a] higher risk of this recurrence. So [it’s a] clear indication to [start] ovarian function suppression [OFS]. In that case, would you start OFS before initiating chemotherapy as in the TEXT trial [NCT00963417] or [after chemotherapy] as in the SOFT trial [NCT00066690],…only in those patients resuming menses? This [is for] oocyte fertility, so this goes back to our 48-year-old [woman patient example].

Virginia G. Kaklamani, MD, DSc: Typically, I won’t give a GnRH [gonadotropin hormone-releasing] agonist during chemotherapy. I will only do that for fertility preservation in those women, and the 48-year-old [woman patient example], I think that’s actually a very important point. We were talking about this yesterday with some colleagues, because the majority of these women will become postmenopausal with the chemotherapy. Giving them OFS for another 5 years while they may already be menopausal, to me, is hard, especially since this is a monthly injection. What I do—and I struggle with these patients—is I will give them the chemotherapy, and then I will put them on tamoxifen for a year. And while on tamoxifen, I will be checking their estradiol and FSH [follicle-stimulating hormone], and if they’re postmenopausal, then I’ll switch them to the AI [aromatase inhibitor]. If they’re premenopausal, I will add OFS, and then switch them to the AI. But how do you approach those patients who you’re confident that, with chemotherapy, will become menopausal?

Matteo Lambertini, MD, PhD:It is a very complex situation. For those women who are young, I tend to use a TEXT trial approach, because the risk of chemotherapy-induced amenorrhea in patients under the age of 40 is quite low. In these cases, I also want the ovarian function protection effect in the long term, so I tend to go for the TEXT approach. For those women who are closer to the natural age of menopause, as you have mentioned, I give chemotherapy and then I give tamoxifen later on. I think what’s important to stress is to avoid giving an AI alone to those patients with chemotherapy-induced amenorrhea. Even [for] women around the age of 50 years with chemotherapy-induced amenorrhea, I will never start an AI alone after chemotherapy because we have data from the postmenopausal setting that giving AI alone in these women can have the [opposite] effect. So the patient will resume ovarian function, even those women older than 50 years .

Virginia G. Kaklamani, MD, DSc: That’s why our fertility specialists use AI, to induce fertility, which is so important. Thank you for mentioning that.

Matteo Lambertini, MD, PhD:Moving on to the discussion on the use of oversuppression during chemotherapy…what’s your approach in terms of the different options available and also the every month vs the every 3 month administration?

Virginia G. Kaklamani, MD, DSc: Typically what I’ll do if I give ovarian suppression, I will pair it with an aromatase inhibitor. As with you, I will risk stratify. I think, obviously, based on the TEXT and SOFT data, that the AI is superior to tamoxifen, but as we’ve seen with all of these adjuvant trials, not by a lot, it’s just by a little bit, and in most of these trials, we don’t really have a survival benefit of giving the AI vs giving tamoxifen. If a patient has a lot of symptoms, obviously, I will switch them to tamoxifen, but I will start with the AI. There was a nice University of Oxford overview that looked at all of these trials and compared the AI to tamoxifen and did find a small benefit, a 2.8% benefit in disease-free survival [with] the AI compared to tamoxifen, but no difference in mortality. We’re starting to add aromatase inhibitors [and] all of a sudden we start having issues with increased bone fractures. That’s something that we always have to keep in mind, and one of the things that we worry about [with] tamoxifen…is uterine cancer, in younger women. We don’t see it as much as we do in women over the age of 50. To me, even though it’s part of my counseling, it’s more of a reassurance that the rate of uterine cancer in younger women is much lower than it is in an older woman. I’ll use the monthly approach as well, which becomes an issue with compliance, because these women have to come every 28 days for their injection, and life gets in the way of that. I’m not sure how you deal with that as well. Are there some women who [you] will switch to the [every 3 months] approach or are you sticking completely to the monthly approach?

Matteo Lambertini, MD, PhD: In the adjuvant setting, so far, I stick to the monthly administration. I think we need to have more data for the 3-month administration.We have phase 3 trial going on that, but particularly, for those women receiving the combination of OFS plus and AI, where I’m a bit more concerned about the need to have a complete ovarian suppression, so far, I’m more comfortable [with] the monthly administration.

Virginia G. Kaklamani, MD, DSc: Yes, and I was going to also say, the trial is also showing an increase in pregnancy rates in those women, which is really our end result, right?

Matteo Lambertini, MD, PhD:Yes, indeed. If we look at a different randomized trial, even if pregnancy desire or 40 years of age were not inclusion criteria, because it was premenopausal women, and in some cases, even [patients] beyond 50 years of age could be included in these studies, still we see that there is a significantly higher number of pregnancies for those women who received a GnRH agonist during chemotherapy compared with those who did not receive a GnRH agonist. However, I want to go back to my comment that cryopreservation is not an alternative. Of course, if there is no other option, and we may have different problem [in] practice, because I work in a public health system, oocyte cryopreservation can be offered for free to my patients. So it is not a concern, but if there is this additional concern, of course, [it is] much better [to do] ovarian suppression during chemotherapy than chemotherapy without any procedure. We have data also in terms of cryopreservation potential there, but it’s not an alternative. So the optimal [option] will be still to go for oocyte cryopreservation.

Transcript edited for clarity.