TAILORX trial results Monday, September 28

TallnTerrific

I am pretty new to this, no genetic assay testing yet, but my MO seems to prefer MammoPrint instead of OncoType testing. Any thoughts? Also what is actually involved in doing the testing, blood work or a more significant piece of the tumor? Finally can they use these tests if you have either metastasis or two separate cancers

Anonymous

My MO now uses both MammoPrint and Oncotype. He is big into research.

Anonymous

Hi Molly, I took the BCI test and it showed 10 years of AIs would be of benefit to me.

muska

I am under the impression that the Oncotype test is for early-stage, estrogen-receptor-positive breast cancers that haven’t spread to the lymph nodes and the purpose of the test is to help with the chemo/no chemo decision. Is this understanding correct? 

keepthefaith

My MO said she would do the mamma-print since I was a 21 on the onco-score, to possibly help with my chemo decision. I am not sure how the insurance co's treat that. I think it is 'available' to intermediate scores. From what I understand, the mamma-print looks at more genes than the onco. I never had it done, bc I didn't want to wait any longer to start treatment. I have read a few posts that indicate that the mamma-print did not coincide with their onco-score. But, as we all know, cancer is very complex!

farmerlucy

Yes muska - that is correct.

VR - whoa there - this is something new for me Some of the benefit of extended adjuvant treatment is derived from prevention of in-breast recurrences and/or second cancers.9,18–22 Women who have undergone bilateral mastectomy are not at risk for these occurrences, reducing their likely benefits from extended therapy. (from the lancet reference above)

I'm quite surprised to read this in black and white, though it makes sense intuitively. One thing I learned from my last MRI report is that the radiologist noted very little breast tissue remaining. One would hope so but good to know. Of course I know there is always a risk of local recurrence, but stopping AIs at five years sounds like a great plan to me! Less than a thousand days to go!

BarredOwl

Hi Muska:

While the recent Tailorx trial results related to a subset of node-positive patients, the test is more broadly applicable. Oncotype DX for invasive cancer can also be used for certain node-positive patients as explained at this link:

http://breast-cancer.oncotypedx.com/en-US/Professi...

Note that there is a distinct Oncotype DX for a different purpose and with different cut-off values that is used in women with ductal carcinoma in situ (DCIS) treated by local excision:

http://breast-cancer.oncotypedx.com/en-US/Professi...

BarredOwl

muska

Hi BarredOwl, thank you for the links. Is it fair to say that the test is of value to Stage 0 to 2? Or only 0 to 1?

BarredOwl

Hi Muska:

I think one needs to make a distinction between the test being offered to patients ("eligibility") and the potential "value" to patients with different presentations. The value would depend on the strength of the data regarding the test in a particular defined sub-group, and it is not the same for all sub-groups.

The test for DCIS does not appear to be broadly offered to DCIS (stage 0), but only to DCIS patients treated by local excision according this link:

http://breast-cancer.oncotypedx.com/en-US/Professi...

For invasive disease, according to the website, it is offered to certain Stage I, II and IIIa patients who are: "early stage", ER positive, HER2 negative, either node-positive (1 to 3 nodes) or node-negative (0 nodes), and who will receive endocrine therapy. Half-way down the first page of this link for invasive, there is a chart which provides a breakdown of eligible ER positive, HER2 negative patients by stage, tumor size and nodal status. (Stage IIIa should see the footnote.) There are some citations to guidelines and some prior studies deemed pertinent to the sub-groups:

http://breast-cancer.oncotypedx.com/en-US/Professi...

Additional information about the various studies that support the value of the test in various settings can be found under the "Impact on Treatment Decisions" tab at the above link.

I note the chart at the above link does not include the recent Tailorx study results, which found the test particularly robust or valuable in a particular subset of patients scoring 0 to 10, with ER and/or PR positive, HER2-negative, node-negative invasive breast cancer who received endocrine therapy defined here:

http://www.nejm.org/doi/full/10.1056/NEJMoa1510764...

"The study included women 18 to 75 years of age with axillary node–negative invasive breast cancer that was estrogen-receptor–positive or progesterone-receptor–positive (or both) and that did not overexpress HER2. Patients had to meet National Comprehensive Cancer Network guidelines for the recommendation of adjuvant chemotherapy, including a primary tumor size of 1.1 to 5.0 cm in the greatest dimension for a tumor of any grade or a size of 0.6 to 1.0 cm in the greatest dimension for a tumor of intermediate or high histologic grade or nuclear grade (or both)."

While the link at the Oncotype DX site above refers to "ER positive", the new study group included "estrogen-receptor–positive or progesterone-receptor–positive (or both)". I don't know the implications of that for the sub-group of ER-negative/PR-positive patients. The conclusion is that one should always consult the MO to ask if you may be eligible for the test, since it is a rapidly changing field.

BarredOwl

[Edited to add: Also ask the MO what current consensus guidelines provide regarding the use of the test in patients with your particular presentation.]

voraciousreader

muska...Not to confuse the issue but to answer your question.....the TailorX trial was designed to answer the question whether or not those patients with "early stage invasive" breast cancer who had "intermediate" scores could forgo chemo. Let's be clear....Stage 0 is NOT invasive. So TailorX would NOT be including those with Stage 0.

That said, since the TailorX trial commenced, another trial is under way to see if those sisters with invasive cancer with 1-3 nodes can safely avoid chemo. That trial is still on going.

Now....with respect to Stage 0 NON-invadive cancer, those ER +, HER 2 negative sisters can have a DIFFERENT Oncotype DX test to see if they can forgo radiation.

Now....the reason why I asked everyone to read the discussion section of the NCCN guidelines is because if you read it very closely, there is NOTHING in the guideline that differentiates one early stage sister from the other except with respect to menopausal status. So.... categorizing early stage sisters, if one sister had a 5cm grade 1 node negative tumor and another had a 3 cm, Grade 3 tumor, they would be clustered together! However, the OncotypeDX test was a milestone because there was no need to split hairs in trying to figure out whose pathology score was "better" or "worse.". Instead, based on a number, physicians had a better feel for a tumor because it was the genomics of the tumor that was a better representation of its aggressiveness. No longer was traditional pathology studies necessary.

Now.....if you look at the ATLAS and ATTom studies....again, we are faced with a quandary. When the studies commenced, genomics were first being discovered. So....physicians and patients had no definitive info regarding who these cohorts of patients were...except to say they were early stage, pre or post menopausal. I remember when ATLAS was released and the physicians were in a tizzy in trying to figure out who EXACTLY should be recommended 10 years of endocrine therapy AND how many years of which kind!

Again, if you read the NCCN's breast cancer treatment guideline's discussion section, you will see there is no answer to that question! We do know that 10 years of Tamoxifen is better than 5 years for many patients, but we don't know for whom precisely! What is also interesting is that for some, what endocrine therapy did was help patients avoid a breast cancer in the other breast. Again, it is not clear who avoided getting a new breast cancer, but THAT was a very interesting finding!

My oncologist made a point of telling me that THAT was the reason why he wanted me on endocrine therapy for 10 years. He thought my risk of getting another breast cancer was greater than my chance of distant recurrence in the breast that was already diagnosed.

I hope I answered satisfactorily the muddy details of all of the current studies...

The take away message is that hopefully these trials will ultimately yield more personalized info that will help all of us make informed choices about treatment.....

Chris13

And for some of us with multiple tumors, like lobular cancer is known for? I had no chemo after a mast and DIEP reconstruction. One tumor's oncotype was 8 and the other 15. And furthermore, everyone was surprised that one node was involved.

Lobular being "slow growing" -- recurrences if any are more likely to be AFTER five years. There is no one size fits all here!

voraciousreader

http://investor.genomichealth.com/releaseDetail.cf...

Here is some more great news coming out of the European Cancer Congress!

"In an analysis of medical records of 930 patients across four medical centers within Clalit Health Services, the largest Health Maintenance Organization inIsrael, Oncotype DX was used to identify patients for treatment with hormonal therapy alone or with hormonal therapy plus chemotherapy (abstract #1963). Women with low Recurrence Score results less than 18 showed very low distant recurrence rates (0.5 percent) after five years of follow-up.

Women with high Recurrence Score results (greater than or equal to 31) and intermediate Recurrence Score results (between 18 and 30) had a 4 percent and 2.3 percent risk of distant recurrence, respectively, after five years of follow-up. The selection of patients for chemotherapy treatment was consistent with the Recurrence Score results as recommended in treatment guidelines."

123JustMe

That is really great news!

Golden01

Amazing news. Thank you.

muska

BarredOwl, Voraciousreader, thanks a lot for the details. VR, I am a bit confused by your statement about traditional pathology studies. Are you seriously suggesting Oncotype test is a replacement of pathology testing?

.

voraciousreader

muska...I'm not implying that genomic testing is going to usurp traditional pathology testing. HOWEVER, traditional pathology testing can differ from lab to lab because visual testing can be subjective. Often you hear of sisters taking their specimens to different labs! Visiting the Rare Breast Cancer Lab at Sloan Kettering, I specifically asked the question....Why do different labs describe mucinous BC differently? That led to a very interesting discussion. Our sister Golden knows what they told me and it was quite sobering. Our researchers told me that depending on where a pathologist trained and by whom they were trained by, you will get different descriptions. Furthermore, depending on the day of the week might also affect the descriptions. Mistakes are more likely at the end of the week and Mondays aren't a good time to look at a specimen because it might have been held over the weekend and degraded. I've researched this issue and there are a few studies addressing the differences among pathologists. The takeaway is that traditional pathology reports are subjective. Genomic tests are not! And therein lies the difference. You have an objective number giving you a feel for a tumor and that is a HUGE milestone! As Eric Topol, MD, explains in The Creative Destruction of Medicine, future studies will be genomic driven. What does that mean? That means, you will know your genomic number and compare it directly with a genomic study's score. Isn't that what the OncotypeDX test is all about? Hopefully soon, with genomic driven studies, we will no longer be scratching our heads and saying to ourselves, what the heck does this study mean to me????

voraciousreader

http://psqh.com/marapr06/pathologist.html

voraciousreader

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC421932...

voraciousreader

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC339175...

Moderators

Hi all, we wanted to share with you about the questions you had for us. This is the response from our editorial team and medical adviser:

Thank you for your questions and concerns.

First, we double checked with our medical adviser, who is a practicing oncologist, about the interpretation of the Oncotype DX Recurrence Score numbers. The information we have on our site and in our story about the TAILORx trial is correct.

The graphs and information that Doxie posted are on the Oncotype DX site, yes, but the information comes from the NSABP B-14 trial. In that study, the researchers set their own cut-off points for interpreting the Recurrence Scores into risk categories, which are slightly different than what we have on the Breastcancer.org site. The researchers in the TAILORx trial also set their own definitions of risk categories: low risk was a recurrence score of 10 or lower and intermediate risk was a Recurrence Score of 11 to 25. This is much different from what we have on our site.

You also asked about modifying our TAILORx story to include information about the lack of recurrence events in the intermediate risk group. We understand that the lack of events is very exciting and promising news. Still, this is unofficial information because the data hasn't been analyzed and published yet. The women with intermediate risk scores are still being followed -- while the results so far may look good, the data available is only short-term and may underestimate any benefits from chemotherapy. For us to report on this now with no published data would be very irresponsible and a huge disservice to our visitors.

Also, please remember that the researchers in the TAILORx trial are using their own definitions of recurrence categories based on Recurrence Scores. Most doctors would interpret intermediate risk as a Recurrence Score of between 18 and 31. But the TAILORx trial researchers are saying that intermediate risk is a Recurrence Score of 11 to 25. So it seems likely that women with scores in the lower end of this category (11-17) will do well with hormonal therapy alone because most doctors would classify them as having a low risk of recurrence.

We thank you for your concerns and suggestions and always welcome your feedback.

--The Breastcancer.org Team

katcar0001

Thank you, Moderators, for this clarification. I must be thick-headed--so, has Genomic Health changed the Oncotype DX ranges officially? If one were to get a 17 score today, would the Oncotype graph show they are in the intermediate range? Doctors may use the "old" numbers, but is that really correct and current? I would think that doctors and researchers would need to synch up at some point. Now I am really second-guessing my decision not to have chemo based on my recurrence score :-(.

39andhip

The clinical guidelines for Oncotype DX have not changed. It's just that different studies may choose different cutoff points.

katcar0001

Thank you, 39andhip. That was what I thought originally, but then I found the last posting confusing.

doxie

Moderators,

My issue is with the repeated statement by BC.org that intermediate scores are between 18-31. Please go to the Oncotype DX site and you will see it repeatedly stated as 18-30, not 31. I understand that the TAILORx trail has their own parameters for intermediate.

I'm fussy about this misstatement because I am a 30. It matters to me as I expect it would to someone at 31.

BarredOwl

Hi Doxie:

I agree with you.

I sent a private message to the Moderators on Oct. 6 in support of your post, and after today's reply, I have sent them a second more detailed private message.

Best,

BarredOwl

voraciousreader

Moderators....the lack of recurrences for the "intermediate" group WAS "official" news.The folks from Genomic Health were quoted saying it. Despite not publishing the data, they made it EXTREMELY clear that as of now, there haven't been enough recurrences to be statistically significant and that they will continue to monitor that group. That was very big news that should have been reported. With respect to those patients in the 10 or less cohort, that really wasn't big news at all. There was an expectation that those patients had excellent prognostics and that the benefit of endocrine therapy was favored over chemo.

Moderators

Doxie and all,

We wanted to let you know our editors have reviewed the language around the definition of recurrence score, and have adjusted the text on our website to reflect your changes:

• Recurrence Score lower than 18: The cancer has a low risk of recurrence. The benefit of chemotherapy for is likely to be small and will not outweigh the risks of side effects.
• Recurrence Score of 18 up to and including 30: The cancer has an intermediate risk of recurrence. It's unclear whether the benefits of chemotherapy outweigh the risks of side effects.
• Recurrence Score greater than or equal to 31: The cancer has a high risk of recurrence, and the benefits of chemotherapy are likely to be greater than the risks of side effects.

Thank you for bringing this to our attention, it's much appreciated!

--The Breastcancer.org Team

doxie

Moderators,

Thank you for following through with these changes. It shows your responsiveness to this community.

Moderators

Of course! Our Community is a treasured asset to our site. We thank everyone who weighs in and of course are always open to making any appropriate changes as necessary!

As a side note, you all might be interested in reading our latest blog from our medical adviser, Dr. Wojciechowski, What My Patients Are Asking: What Do the TAILORx Trial Results Mean For Me?, October 30, 2015

Happy reading!

--The Mods

voraciousreader

Thanks for the perspective. Well balanced!