Gene Expression Testing and Targeted Therapies in Breast Cancer Care

Gene expression testing helps determine the necessity of chemotherapy in hormone receptor-positive breast cancer, optimizing treatment and minimizing unnecessary toxicity.

Breast cancer treatment continues to evolve with advancements in gene expression testing and targeted therapies, helping to refine treatment decisions and improve patient outcomes, according to an expert.

To discuss these developments, Dr. Sara Tolaney, a breast medical oncologist and chief of the breast oncology program at Dana-Farber Cancer Institute in Boston, shared insights on the latest approaches in breast cancer care.

In the interview at the 42^nd Annual Miami Breast Cancer Conference, Tolaney discussed the role of gene expression testing in determining the need for chemotherapy in patients with hormone receptor-positive breast cancer, the use of CDK4/6 inhibitors in adjuvant therapy and the significance of professional forums in keeping oncology professionals informed about rapidly changing treatment options.

CURE: How does gene expression testing help determine whether chemotherapy is necessary for a patient with this disease or grade 2 invasive ductal carcinoma?

Tolaney: So, we've been really fortunate to have the availability of gene expression assays to help us figure out which patients are going to benefit from chemotherapy and which patients are not. So in general, most of the time, what I do is I send an Oncotype DX test in patients who have early-stage hormone receptor-positive breast cancers. And if the score comes back, generally speaking, over 25, it suggests that the patient has a cancer that is going to be sensitive to chemotherapy, and that that chemotherapy is going to reduce their chances of having a recurrence from cancer.

So usually in those scenarios, we would recommend giving chemotherapy and then following that up with endocrine treatment, whereas if someone has a score under 25 it suggests that patient is not going to gain benefit from the use of chemotherapy. And so that's super helpful, because it really spares that patient treatments that have toxicities that aren't providing benefit. The challenge, though, is it's not quite as clear how to interpret the assay if someone is premenopausal and has a score under 25. So that's where there's a little bit of an unknown where it seems like these premenopausal patients who have scores under 25 are benefiting from chemotherapy, which is the opposite of what we just said for postmenopausal women who have scores under 25 or there is no benefit to chemo.

So the controversy that we're debating, actually at this meeting is, if someone's premenopausal and has a score under 25, should you give them chemo or not? And my personal view on this is that I think that the chemotherapy probably isn't providing very much benefit here. I think it's more that we're seeing the effects of the chemotherapy on patients’ ovaries, that it's making these premenopausal patients go into menopause, which is why we're it looks like it's having benefit because we know shutting off ovarian function is beneficial, whereas I don't think it's probably the cytotoxic effects of the chemotherapy on the cancer cells themselves.

What is the role of these inhibitors in adjuvant therapy for patients with breast cancer? What should patients with breast cancer know about this treatment option?

So CDK4/6 inhibitors are oral pills that in essence stop the cell cycle. So it takes a cancer cell and in essence puts it to sleep, and we found that these drugs are highly effective in women who have metastatic hormone receptor positive breast cancer, where, in fact, it was doubling the duration by which their cancer was controlled and allowing them to live longer. So clearly, huge benefits. So it seemed natural to think, “Well, if it's helping patients who have metastatic breast cancer, could it actually help us cure more patients who have early stage breast cancers?” And so now we actually have two different CDK4/6 inhibitors that are actually FDA approved for patients who have early-stage hormone receptor positive breast cancers. So the question then arises is, well, which one do you choose? You have [Verenzio (abemaciclib)] and you have [Kisqali (ribociclib)], and I don't think there's a clear wrong or right answer here, but in fact, I think it's a little bit more nuanced. But generally speaking, what we're seeing is that these drugs reduce risks of recurrence on the order of about 30%.

So that's a relative reduction that translates somewhere around 5% to 8% absolute benefit across these two drugs. So clearly reducing risk a lot. The [Verzenio] is given for two years, and it's given with the hormone therapy that patients are receiving, whereas the [Kisqali] is dosed for three years, so a little bit longer, and also given with the hormone therapy. Although with [Kisqali], you cannot take it with tamoxifen, it has to be given with an aromatase inhibitor. So again, incredible to have these two options available, because I do think it is allowing us to potentially be curing more early-stage breast cancer patients.

What’s the importance of hosting events such as the Miami Breast Cancer Summit for people in the oncology community?

I think breast cancer therapies are changing so quickly in a good way, that we've seen so many new drugs become [Food and Drug Administration (FDA)] approved over the last few years. It's at a pace that I've never seen in my career before. It's really amazing, and it is changing patient outcomes, but it also means that it's kind of hard to keep up with because things are evolving so quickly, and there's so many new treatments that are available for patients. So I think forums like this are really nice, because it gives an opportunity to show what our current thinking is at this point in time of what therapies are available and how we should think about utilizing them. And so I think it's a nice opportunity for patients to really feel like they have their finger on the pulse with what's going on right now with treatments.

Transcript has been edited for clarity and conciseness

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