Evolving Concepts in Treatment for Advanced Breast Cancer - Episode 6
Joyce A. O’Shaughnessy, MD: I wanted to mention the updated data on TAILORx that Joe Sparano, MD presented at ASCO [American Society of Clinical Oncology annual meeting] that is now online in the New England Journal of Medicine, so we can all get that article and read it in some depth. It was an important study that looked, in this node-negative population, at pre-, peri-, and postmenopausal ER [estrogen receptor]-positive patients with recurrence scores between 11 and 25. In addition, it looked at tumor size and grade, and used the MINDACT criteria for low-risk versus high-risk to see what the interaction might be with regard to the recurrence score and how much benefit from chemotherapy patients had.
The clinical parameters were definitely prognostic, as you would fully expect. Interestingly, they’re not predictive of chemotherapy benefit, as we also know. You can have an indolent but very node-positive breast cancer, but that doesn’t mean you’re going to benefit from chemotherapy, unfortunately. Nonetheless, where I think it’s going to be helpful is, for example, in patients who are premenopausal in whom we know there’s some benefit from chemotherapy, between ages 16 and 25. That’s precisely where I’m going to think, “OK, let’s think how the clinical risk layers into this.” If it’s a low clinical risk, the study actually showed very little chemotherapy benefit in that premenopausal group. It was really those with the higher clinical risk between 16 and 25 who had more benefit from chemotherapy, just because they had a higher numerical risk. I think that’s where it may be useful for us.
The other piece of information that was quite interesting was that the benefit from chemotherapy was dependent on the age of the pre- and perimenopausal woman, with women who were over 50 in the pre- or perimenopausal range not getting benefit from chemotherapy. The benefit is in women between 41 and 50, probably because chemotherapy would have some ovarian ablation effects. Interestingly, those 40 and under did not get a benefit from chemotherapy in that age group, with the hypothesis being that it’s because they didn’t get that much ovarian ablation from chemotherapy. They had recovery of menstrual function, and only 13% of patients in TAILORx were treated with an LHRH [luteinizing hormone-releasing hormone] agonist in the pre- and perimenopausal cohort. That’s an interesting hypothesis.
I would say, for myself, that if I had a younger woman—40 or under—with a clinical higher risk whose recurrence score was on the higher end—16 to 25—I would still probably be inclined to give her chemotherapy, because we really don’t know for sure that the LHRH agonist would completely take the place of the chemotherapy in these patients. Does anybody have any comments on it? It’s a really important paper. Thank goodness it’s in the New England Journal of Medicine. We can all go read it.
Debu Tripathy, MD: Yes, I think it’s complicated to analyze all of these moving parts, but I do agree that if someone is of higher risk, and we’ve been doing this already from the TEXT and SOFT trials, that ovarian ablation should be considered. We’ve traditionally been using higher risk if they get chemotherapy, then we suppress the ovaries. There may be that group of patients where you might not use chemotherapy, but they’re borderline, and they’re younger. They can have their ovarian suppression and it may only be temporary for them, because for a 40-year-old, you obviously don’t want lifelong suppression. That might be a group of patients in whom, even if you decide not to use chemotherapy, you might want to consider ovarian suppression.
Joyce A. O’Shaughnessy, MD: It did give more of a focus to optimal endocrine therapy per the updated analysis of SOFT and TEXT. For higher-risk individuals, LHRH agonist plus AI [aromatase inhibitor] is the preferred way to go. For patients with more moderate risk, LHRH agonist plus tamoxifen is preferred. For those patients who have intermediate clinical risk or not very high clinical risk, that could be a substitute for chemotherapy in those patients.
Sara A. Hurvitz, MD: I think this is a very rich study. We’re going to continue to see really important data come out of it, and I still have to digest what was presented and published today. I do think that there’s another layer. When we render a patient postmenopausal with the use of a GnRH [gonadotropin-releasing hormone] analog, that makes them eligible to receive bisphosphonate therapy, which has been shown to reduce the risk of mortality at 10 years in postmenopausal women. It’s now in ASCO guidelines. It opens up another therapy that’s less toxic than chemotherapy and may additionally reduce a woman’s risk, so that’s another reason I’m using more of the GnRH analogs in my practice.
Transcript Edited for Clarity