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Old 05-18-2015, 11:22 PM   #1
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Thumbs up knowing which tumors will/will not metastasize 1-3 yrs before they do!

needs to be repeated on larger numbr\ers of women, but very hopeful to help optimize treatment, prevent overtreatment

A blood test for early detection of breast cancer metastasis

The chances of being cured of breast cancer have increased in recent decades, however if the tumour has metastasised, the disease remains essentially incurable. One reason for this could be that the metastases are detected late, after they have grown enough to cause symptoms or be seen on a radiological scan. If they could be found sooner, it might be possible to treat the new tumours. Research findings from Lund University in Sweden now provide new hope for a way of detecting metastases significantly earlier than is currently possible.

The discovery was made by a research team led by Lao Saal, M.D. Ph.D, and is based on what is known as cell-free circulating DNA -- small fragments of genetic material from different cells which circulate in the blood. It is normal to have low amounts of such DNA material in the blood, but in the case of diseases such as cancer, these amounts can increase. Furthermore, in cancer patients, the circulating DNA contains the genetic mutations which are specific to the tumor.

Lao Saal and his colleagues used previously gathered material from a breast cancer study which has been underway in Lund since 2002. The material contained samples from surgically removed tumours from patients with non-metastatic disease as well as blood samples taken from the patients at regular intervals during the years in which they were followed up.

The tumour samples contained many genetic changes, which constituted a "fingerprint" specific to each tumour. Researchers then looked in the blood samples for circulating tumour DNA (ctDNA) with the same fingerprint. Although the study is fairly small -- it is based on material from only 20 women -- the results are striking.

"For 19 of the 20 women, the ctDNA in the blood samples gave a clear indication of how things would turn out. The women who never got a relapse had no detectable ctDNA, whereas all women who had tumour DNA in their blood eventually had symptomatic relapses that were diagnosed in the clinic", said Lao Saal.

The metastases were also reflected in the blood samples at an early stage. There it was possible to find signs of the new tumours many months before hospital investigations revealed that the patients had suffered a relapse.

"The circulating tumour DNA values in the blood samples identified the metastases on average 11 months before they were diagnosed by standard clinical procedures. In some cases, the blood test detected the metastasis three years earlier. If we could find the cancer recurrences that much earlier, we might be able to treat them more successfully", said Lao Saal.

The study must be followed by investigations with more participants, so that researchers can be sure that the results are sustainable. If they are, ctDNA testing could become a way of detecting breast cancer metastasis much earlier than is currently possible.

In addition to the possibility of treating the women who are about to get metastases, the a potential future use of the new method could be to determine which women do not need to be treated so aggressively. If we know that women with no ctDNA in their blood are not going to get a relapse, less aggressive treatment could be sufficient in their case. Currently, most breast cancer patients are treated not only with surgery, but also radiation, hormone therapy or chemotherapy.

"It is believed that many women with breast cancer are being overtreated, which entails considerable side effects and costs. But as long as we do not know for certain which women will survive without additional treatment, physicians are hesitant to skip the additional therapies. The monitoring of ctDNA could help address that question", says Lao Saal.

If supported by further studies, he believes that the monitoring should be carried out at regular intervals after the breast cancer surgery. The quantity of ctDNA, as well as the emergence of specific gene mutations, could be used in the future to steer therapy in a more precise manner. The Lund researchers have already started new studies in which a larger number of women will be monitored from breast cancer diagnosis and onwards, as well as testing ctDNA methods in other cancer types.

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Old 05-19-2015, 01:06 PM   #2
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Re: knowing which tumors will/will not metastasize 1-3 yrs before they do!

This sounds like a great way to treat without over-treating. Hope it continues and becomes a standard of care. I had a local recurrence in 2010 and after surgery and radiation I have been on Herceptin for 5 1/2 years. It would be great to know it that is really something I need to continue doing.
Diagnosed June, 2006 HER2+++, ER- PR-, Grade 3, Stage IIB. Modified radical mastectomy, radiation, chemo, Herceptin, Tykerb 1 year. [*]In remission until 2/2010. Small tumor detected on chest wall during routine scan. 2/2010 surgery to remove tumor, started Herceptin/Tykerb, follow up radiation. [*]12/26/2010 - Off Tykerb due to allergic reaction[*]12/16/2014 - Have continued on Herception for almost 5 years now and remain NED. Discussion with onc re adding Perjeta to the Herceptin as another way of preventing recurrence. Still in discussion phase. 12/26/14 Onc applying for approval for Perjeta.
Perjeta approved and I received one infusion. It had an immediate impact to my lungs and I experienced difficulty breathing so.....I'm going to be sticking with just Herceptin. Still looking for a good vaccine program to enroll in.

Debbie K
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Old 05-19-2015, 01:32 PM   #3
Debbie L.
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Re: knowing which tumors will/will not metastasize 1-3 yrs before they do!

Lani, you beat me to it, I saved this yesterday, intending to post it. Here's a link to the full text .

A big caution, discussed by the authors, is that this was a very small study (20 women). For example, all but 1 of the 20 cancers were ER+, and only two were HER2+. All the women who didn't recur had negative nodes (6 of the 14 who recurred had negative nodes). Not a particularly representative sample. I think they are showcasing the potential of the technology, without (yet) knowing much about how it might actually be used. Still, the results are intriguing. I especially like that it might someday be possible to identify those who abolutely will not recur, and spare them toxic treatments.

However, I see several issues with the potential use of it to detect a recurrence. First of all, it would be a huge paradigm shift, and require much evidence of actual benefit (chance of cure or improved OS), to treat someone who, by our current standards, is NED. Acquiring that evidence would take quite awhile, not to mention the cost. There is no mention that this test assesses response to treatment -- so we wouldn't even know if we'd hope for the test results to change (indicating response?), plus there would be no other way to monitor response -- talk about being in limbo! How would treatment decisions (changes, stopping, etc) be made?

Secondly, it is possible that these women would simply endure treatment (toxicities and decreased QOL) for more years than their counterparts whose mets were detected by current means, without actually living any longer. As the authors note, there is not even a hint, so far, that catching mets "earlier" improves OS.

I'd label this one as interesting and hopeful but (sadly) far from being of use in the trenches. But maybe I'm missing something? Much of the genomic discussion and detail was (way) over my head.

Debbie Laxague
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