MULTIGENE ASSAYS IN YOUNG WOMEN

“We know that chemotherapy is very effective and it certainly reduces the risk of cancer returning. In women that have hormone-receptor positive early-stage breast cancer, we also give endocrine therapy. And that is very effective also in reducing the risk of the cancer returning.”

“So, if someone has a very high-risk breast cancer, they will typically get both chemotherapy and endocrine therapy. Whereas other women whose cancer is not as risky will be able to have the endocrine therapy alone without the chemotherapy.”

“One of the challenges we face in treating hormone-receptor positive breast cancer is knowing who really needs the chemotherapy. So, we need to work out who are the people that have got a high-risk of the cancer returning, and the chemotherapy is going to help reduce that risk, and who are the people that we can just give the endocrine therapy to and not have to give them chemotherapy because chemotherapy has a lot of side effects.”

“Those side effects can be quite short-term, so things like hair loss, nausea, tiredness, infections, but there are also some serious long-term side effects. So, it can cause peripheral neuropathy, there is also a small risk of heart damage and secondary cancers. So, we need better ways of really working out who are the people that really need the chemotherapy and who doesn’t.”

“And so that’s where these multigene assays have come into the picture, because they’re sort of RNA tests. They look at tumor samples predominantly in ER-positive, HER2-negative tumors. And they look at a whole lot of different genes that predict for the risk of recurrence.”

“So, there’s several of these assays and they’ve all been shown to be effective in classifying tumors into low and high-risk. And that means if you’ve got a low-risk cancer, it’s less likely to return and less likely to need chemotherapy. Whereas a high-risk cancer is the one that we really want to make sure we’re doing what we can to reduce the risk of it returning, which would mean giving it chemotherapy.”

Do these Assays differ from young women to post-menopausal women?

“So, most of the research that’s been done on these assays has been in predominantly post-menopausal women. So, a lot of the early retrospective validation studies were mainly in studies where the women were post-menopausal.”

“There have been three large prospective studies that have been completed with different assays. And in each of those studies, about one third of the women were pre-menopausal. So again, most of the women were post-menopausal.”

“There’s less data on the pre-menopausal women, but certainly when we look at the results of these prospective studies, what they showed was that you could select a group of patients who had hormone-receptor positive, HER2-negative breast cancer, and these studies were done in women who were lymph node negative or had up to three involved lymph nodes.”

“And the assays were able to look at a group who had a low genomic risk of recurrence. And overall, in each of these studies, they showed that in that group with low genomic risk, the group that, if they received endocrine therapy alone, they did just as well as if they received chemotherapy and endocrine therapy.”

“So, there was no benefit from adding chemotherapy. However, when you look at just the one-third of patients who were pre-menopausal in these studies, again, when you pulled out the patients with low or intermediate recurrence scores, the women that got chemotherapy did better.”

“So, there was a clear benefit in the chemotherapy in reducing the risk of these cancers returning. For some reason we’re seeing the post-menopausal women not getting a benefit from chemotherapy and the pre-menopausal women with the same recurrence scores getting a small benefit from chemotherapy.”

“When we look at the reason why we might be seeing this difference between the pre-menopausal and post-menopausal women and the benefit of chemotherapy, it’s very likely that the chemotherapy is causing an early menopause in the pre-menopausal women and that’s what the benefits coming from.”

“So, we’ve known for some time that giving ovarian function suppression to young women with hormone-receptor positive breast cancer, reduces their risk of the cancer returning. And so, we know in women who are close to the age of menopause when they get chemotherapy, they’re likely to go into an early menopause.”

“And in the studies in young women, where we looked at the gene expression assays, the women who were benefiting the most from chemotherapy were those over the age of 40, who were more likely to go into menopause. So, I think the next big question really is yes, there’s a benefit from chemotherapy in these women, but is it from ovarian suppression or is the chemotherapy having an effect independent of ovarian suppression?”

“Unfortunately, in the studies that have been conducted so far, we can’t answer that question because in all these trials, the endocrine therapy that was given in those young women was suboptimal. Most of it was tamoxifen only, and it was less than 20 percent of women across those studies that received ovarian function suppression.”

“So, if you’re giving maximal endocrine therapy in a young woman, which is the ovarian function suppression and aromatase inhibitor, we don’t really know if there is any benefit to chemotherapy. And that’s why we need more research to answer this question.”

What are your hopes for the future of breast cancer research?

“My hopes for the future of breast cancer research are further along this same line. I hope that we get better at firstly giving targeted therapies, and therefore have less reliance on chemotherapy, and that we become better at working out who really needs the chemotherapy. So that the people we’re giving it to we know are really benefiting from the treatment, and we’re not giving it to a whole lot of people that are not going to benefit chemotherapy and all the unwanted side effects.”

“So, I think that for the future I’m hoping we see a lot less chemotherapy use, and a lot more targeted therapies and therapies with less side effects.”