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Expert Expands on Decision-Making Impact of Genetic Testing in Breast Cancer

Chelsea LoCascio
Published: Wednesday, Nov 01, 2017

Laura J. van't Veer, PhD
Advancements in gene therapy are changing how breast cancer experts understand the risk of recurrence and treat their patients to avoid overtreatment, according to Laura J. van’t Veer, PhD.

on Breast Cancer, van't Veer, director of applied genomics at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, discussed determining more accurate methods of treatment for patients with early- and late-state breast cancer based on advances in genetic testing, specifically the 70-gene prognostic signature.

OncLive: Can you touch on some of the current guidelines for genetic testing?

van't Veer: If we look [into the] guidelines in genetic testing, for instance, for women who are diagnosed with breast cancer and who have a family history of breast cancer, their recommendation is to get tested if you have 2 first-degree relatives with breast cancer or 1 at a really young age and you’re [young]. Those guidelines for genetic testing are quite clear if it also involves family history, but what is becoming more and more a practice is that the information of genetic risk is relevant for every woman, regardless of her family history.

Perhaps some women can [do it] every other year; some women who have a very high risk need [a mammography] every 6 months. For women under age 40, more than two-thirds have such a low risk that screening doesn't give any benefit. It does more harm because of false negatives and biopsies. You can much better understand who needs what frequency of screening and the age for somebody to start screening.

Where are we now with testing in late-stage or high-risk disease?

Once somebody is diagnosed, there's another way of using the word "risk" just to make that clear. We look into the biology of the breast cancer. We can recognize if that tumor actually would foretell a high risk of recurrence or a low risk of recurrence. There are a couple of genomic tests available, in which you do your test on the tumor material and you assess whether it is a fast-growing tumor or a slow-growing tumor. That would help determine whether therapy by systemic chemotherapy would be good advice.

These tests, such as Oncotype DX, MammaPrint, and PAM50, can all distinguish these subgroups. It depends how they have been tested in clinical trials. MammaPrint is one I’ve been working on for a long time. We also set out to understand [what it means if] somebody is clinically high risk, but the tumor is biologically low risk. Can we derive enough evidence that maybe such patients do not benefit from chemotherapy? That was a large clinical trial among 7000 patients, where we showed that those women [who are] clinically high risk and biologically low risk do not benefit substantially from chemotherapy.

It actually does more harm than good. We start to learn more and more how to apply biology for screening and frequency of mammography in a healthy woman. We start to understand by looking into the biology of the tumor. If that tumor displays factors of high risk of recurrence or low risk of recurrence, we use [that] to guide and advise “yes” or “no” [to] chemotherapy.

Can you expand on the utility of the 70-gene prognostic signature, or MammaPrint, entails?

[This was] established 15 years ago on patients whom we had the tumor material [from] that was being “banked” as we call it, so it was saved. We knew after their diagnosis what their disease course had been. Some women had developed a distant recurrence in metastases and other women, for the longest time, had remained disease free, so our scientific question was “Can we actually understand why, and can we recognize why some of these tumors have the capacity to metastasize and others do not?”

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