Breast Cancer Index or Prosigna Assay?

Peregrinelady

I honestly do not know the difference in the numbers either. I am hoping Beesie or someone else comes along with more info. I am glad seeing my report was helpful to you. I am interested to hear about your report and hope it helps you feel better about stopping at 5 years.

windingshores

The report wasn't in my mailbox so I called Biotheranostics. My score was 5.6 and my risk of recurrence was 5.7%, with low benefit from continued AI's. They explained that in two weeks they are going to get rid of the "low risk, high risk" classification. That makes sense. She said that some patients feel 5.6% is low, and some react to it as high, that it is individual..

I also asked about the low benefit part and the scientific basis for that. When I get my report I will call back and talk to someone who knows about this, because patient support folks don't

My Oncotype was 8, and my 12% risk was decreased by 6% with Femara.

I imagine that continuing would get me down under a 5% risk, but only by, say, 2% which doesn't increase overall survival even if there is a very slight reduction in breast cancer recurrence risk. That is what I am guessing. With osteoporosis and atrial fibrillation, thin skin and joint pain, I would still argue for continued meds if my risk reduction was over 4%.

I am still going to consider the idea of going off for two years, then doing two years, for a total of 7.

Peregrinelady, your risk reduction is dramatic, which is both good and bad.

ps I have also read that continued meds helps a lot with preventing local recurrence and contralateral breast cancer, and with double mastectomy that is another argument for me against meds I don't know how that figures into your decisions though- I see you have had a BMX too.

Peregrinelady

Thanks for the info, Windingshores. I so wish I had little benefit after 5 years because I am pretty sure the Arimidex is causing my high blood pressure. I am happy for you and I would not hesitate to stop if I were you, especially with the afib and osteoporosis.

It makes sense about getting rid of the high, low classification. It sure freaked me out since my oncologist ordered the test 2 months after diagnosis. I had started to feel optimistic with the low Oncotype and then seeing “high risk” shocked me. I called the company about the discrepancy and they replied with something to the effect that high and low are subjective, similar to the reasoning you gave for no longer classifying them.
I also have a 2nd page to my report that is included for tests done upon diagnosis and it says 16% risk recurrence for years 1- 10. I didn’t even want to think about that number.

Thanks again for starting this topic and let us know if you pursue further testing.

windingshores

Got the whole thing in the mail today. My score of 5.6= risk of 5.7% in years 5-10 and is currently categorized as high risk. No benefit from continued meds but at the bottom it says risk is 13 without meds and 9 with meds,which doesn't seem negligible to me. I have a call in to the company to explain the discordance between numbers on the report.

On the second page, at time of diagnosis, the risk would have been 10/4% for years 0-10 with low benefit of extended meds after 5 years.

windingshores

I have not heard back yet from Biotheranostics though the patient support person has contacted someone in the company who can answer my questions and will get back to me on Monday.

In the meantime, this is the best article/study I have found yet: https://www.futuremedicine.com/doi/full/10.2217/bm...

" The BCI Prognostic is based on the algorithmic combination of the HoxB13/IL17BR (H/I) ratio, a set of proliferation-based genes and the molecular grade index, comprised of BUB1B, CENPA, NEK2, RACGAP1 and RRM2) with four reference genes and it reports individualized risk of late distant recurrence and a risk category [15]. Notably, the BCI test report initially reported a low, intermediate or high-risk category; however, the report was modified in April 2015 to bin intermediate and high risk results into a single high risk category (based on time-dependent analysis of three validation studies [13,15] showing similar late distant recurrence rates in intermediate and high risk patients). The BCI predictive component is based on the H/I biomarker alone and reports a prediction of high versus low likelihood of benefit from EET. "

So, from this, I would understand the numbers at the bottom of the page for with and without extended therapy to be from the H/I ratio alone, not the other genomic factors included in evaluating risk of recurrence. So while my risk of recurrence in years 5-10 is 5.7%, the reduction in risk from extended endocrine therapy is 4 %, from 13" to 9%. They consider 3-5% risk reduction with extended therapy to be "modest" and not worth the side effects. And overall survival isn't longer which must mean side effects also cause risk of not surviving (bones, heart?).

They got rid of the intermediate score because they found intermediate and high risk folks ended up with the same rate of recurrence. I would have been in the intermediate range before that change. Intermediate was 5.0825 to 6.5025, kind of a narrow range and I am right in the middle Now, this week or next, there will be no categories at all.

I feel a little uncomfortable with the ambiguity of my results.

My late recurrence score (H/I ratio, proliferation genes, molecular grade index) is on the low end of "high risk" and actually lower than my "low" Oncotype risk. But BCI considers it fairly high.

My benefit from extended therapy (H/I ratio score only) without meds is kind of high at 13% and the reduction in risk with meds if 4% which seems high to me but they count it as low.

Hmmmmmm. There are 4 categories wit BCI results. The high-high group, like you, peregrinelady, have a clear path if they can tolerate it. The low-low folks have a clear path and a happier one. The high-low people like me don't all follow the BCI recommendations, and the low-high ones probably don't either (that may be the most confusing result).

I am going to investigate taking that two year break, helping my bones, and then doing my 6th and 7th year of Femara. One oncologist suggest that and I'll see what my other one says.

In the meantime I have sent paperwork for the Prosigna Assay to my regular oncologist!

windingshores

One other nugget among many: In patients treated with endocrine therapy, MGI and HOXB13:IL17BR modified each other's prognostic performance. High MGI (molecular grade index) was associated with significantly worse outcome only in combination with high HOXB13:IL17BR, and likewise, high HOXB13:IL17BR was significantly associated with poor outcome only in combination with high MGI.

I would surmise from all this that my proliferation results were low, despite having grade 3 or grade 2 (different hospitals), LVI (focal) and a ki67% of 20. I have some ideas about why this discordance that I won't go into here.

DebAL

very helpful thread. I know I'm late to the party and may have missed it but is this a test that is done closer to the 5 year mark? And is it on the original tumor send to oncotype?

I definitely want to have this done. I'm PR neg, ( lower ER 60ish % on oncotype but 100% positive on staining...never fully understood that part) I have a sneaky feeling I will be high risk for recurrence but low benefit. Who knows. I will cross that bridge as I get closer to the 5 year mark.

Winding shores I think you mentioned a subtle psychology in one of your posts. So very true.

I see why there is non adherence to these drugs. Oddest thing for me is that I feel 20 years younger during the day but in the evening 20 years older. From 6pm- 9pm its rough. Deep random pulsating bone pain. ( I take arimidex at 8pm so symptoms start b4 I take it) I go go go all day, exercise daily , feel great but when I stop its like a whole different world. I'm too scared to change meds etc since feeling good 20/24 hours is not too shabby. Thanks for letting me vent!

The thought of a vacation from this drug would be a dream but I just don't know if I could do it

Again, super helpful thread. I tend to drop on and off the boards but this is a keeper. Best luck to all navigating this shitty disease.

windingshores

Yes the BCI is helpful closer to the 5 year mark (though the test also has a recurrence rate if done at the time of diagnosis...glad I didn't do that because it is twice my Oncotype risk!). I got the paperwork from the company (Biotheranostics) and gave it to one of my oncologists. I also called pathology because I am superstitious and wanted this test done on the same sample block as all my other testing (my tumor was heterogeneous). Genomic Health told me that the genetic make up is the same in the whole tumor but with parts lobular and parts ductal and parts close to HER2+, I just felt better having the same block tested.

What was your Oncotype Dx score? You did chemo so I guess it may have been high or high end of intermediate.

I take Femara in the morning but like you am sooo tired in the evening. My daughter is moving in with me for a bit and I had to tell her, after 8pm, no talking about big issues and I need to lie on the couch and watch tv and snooze.

For me, there has been psychological benefit to doing the BCI because I feel like I looked things in the face after 5 years of trying not to think about it. I don't need to continue looking at the realities of cancer but pausing for a moment at my 5 year mark has been oddly helpful. Scary but worth it for me. (I am quite sure Prosigna will classify me as high risk but what the heck...)

DebAL

thanks for the info! Oncotype was 27. Subtle psychology played a huge part in my chemo decision too. I would be more excited to take an AI if I was strongly positive but I'm determined to hang in there

april1964

I’m curious, does insurance pay for the Prosigna Assay test?I wonder if my MO will order the test now since my diagnosis was a while ago (2015). What paperwork do you give the MO? Thank you!!

windingshores

I'm on a Medicare Advantage plan with BC/BS and they pay for the BCI and the Prosigna. For the Prosigna you have to be stage 1 (I think),

HER 2 - (I think( and ER+. I actually have not been working so based on my income, I got the BCI for free and didn't involve insurance at all.

These tests are geared to people who are approaching 5 years on meds so 2020 would be your year, just like mine.

Paperwork for BCI is at Biotheranostics. Call the patient support for more info (number is on website). Biotheranostics does their own test.

Paperwork for Prosigna is on their site too. I printed out the application from the website. The Prosigna can be done in other labs as long as they have the Nanostring equipment, and I can let you know about that.

In both cases I filled out what I could. For BCI I sent oopies of my insurance card and I should probably have done that with Prosigna but my doctor can do it too.

Hope that helps!

Even with my 5.7% ("high" but okay with me) risk and "low benefit" I am still considering doing an extra 2 years of Femara, but after a break.

Prosigna will tell me if I am Luminal A or B. I know that test puts a lot of low Oncotypes into a high risk group based on being Luminal B but at this point I just want to know all the tests results I can. If I could I would do the Endopredict too!!!! I am not sure if any of the tests that use pathology results like grade, take into account that fact that lobular always gets a high tubular score within the grade. There are lots of details like that but, you know, whatever, I consider everything "ballpark."

windingshores

Insurance coverage for the Prosigna assay

Some insurance companies will pay for the total cost of the Prosigna assay, while others may pay a portion of the cost.

If you and your doctor are considering the Prosigna assay, talk to your insurance company to find out if it's covered.

NanoString, the company that makes the Prosigna assay, offers the Prosigna Patient Support Program to help with insurance and payment issues. If you don't have insurance or your insurance company doesn't cover the Prosigna assay, NanoString may be able to help. Call 1-855-4-PROSIGNA to speak to a program counselor.

ps Prosigna is FDA approved, BCI is not.

Hopeful82014

Re: Payment/Expense of genomic tests -

FWIW: My MO used the EndoPredict for me, as it's validated for node+ women. It doesn't offer prediction of the benefit of continued ET but otherwise is quite similar to the others.

My insurer declined to authorize it, characterizing it as "experimental." However, I spoke with Myriad customer support who assured me that they would appeal to the insurer and that, regardless of insurance payment, I would NOT be held liable for any portion of the cost. The lab also went ahead and processed my tumor sample without waiting for insurance authorization, so results weren't delayed at all.

IF you have trouble getting authorization, you might simply call the company and ask about their policies.

(I think I've mentioned this elsewhere but some members may have missed it.)

april1964

thank you all for this information.... what does the Prosigna test actually show... what is it for? thanks again!!

windingshores

The Prosigna is apparently the best at separating out risk groups for years 5-10 (better than Oncotype). Breast Cancer Index comes in second but also give info on whether or not to continue hormonal meds.

Prosigna tells us whether we are Luminal A or B, and this risk stratification:

• node-negative cancers are classified as low (0-40), intermediate (41-60), or high (61-100) risk.
• node-positive cancers are classified as low (0-40) or high (41-100) risk.

My low Oncotype conflicted with high grade, highish ki67% and LVI. My Breast Cancer Index seems murky as well (5.7% risk is considered "high" by BCI and my risk reduction with meds is 4% which seems significant to me but they say 3-5% is still low). So I have asked for a Prosigna as a sort of tie breaker.

april1964

Thank you Windingshores for that very helpful information! It’s sounds as though the Prosigna test is more comprehensive.

windingshores

It uses more genes. But if you are trying to decide on continuing hormonal meds, the BCI is the only one to evaluate that.

The hard part of all this is that the various tests, Oncotype, Prosigna, BCI, Endopredict, and traditional pathology tests, don't agree. There is a high degree (50%+) of discordance! I am not going to rely on any one test but an overall ballpark gut feeling after seeing the ones I can manage to get.

I may also talk to the three oncologists I talked to 5 years ago for second and third opinions!

april1964

windingshores, are you mostly doing this because you want to know how long to be on anti hormonal meds? thank you again for providing all of this useful information!! I will be looking into the Prosigna more closely.

windingshores

Yes, mainly because I am almost at the 5 year point and need to decide (with my oncologist) about whether or not to continue meds. Also, I have read that the Oncotype doesn't really give us a good risk estimate for years 5-10.

Rennasus

I took the BREAST CANCER INDEX test at my 5-year anniversary in 2016. I was 52 when diagnosed in 2011 with ER/PR+, HER2- breast cancer. My Oncotype score was 16, so I did NOT have chemo; I had a bilateral mastectomy. I took Tamoxifen for 2.5 years, then switched to Femara for another 2.5 years. In February 2016, I took the Breast Cancer Index (BCI) test at my oncologist's suggestion. (I had never heard of it before.) My insurance company initially denied paying for the BCI test, saying it was "investigational" for me. However, Biotheranostics (creator of BCI) worked with me to appeal, and we eventually got it approved. My BCI results came back LOW RISK (1.8%) of late recurrence between years 5-10, and LOW likelihood of Benefit from extended endocrine therapy. Based on these results, my oncologist said I could stop taking Femara, as it would have little benefit to me. So I stopped taking it in April of 2016. Without the BCI test, I would not have been comfortable stopping endocrine therapy. I highly suggest taking the test.

windingshores

You were fortunate to have such clear results and I hope you are doing well!

Mine are a little murky so I have asked my other oncologist to do the Prosigna Assay. My pathology and Oncotype were not consistent and now I am going to do the same thing at year 5 that I did at diagnosis, gather a lot of information and get a third opinion if I have to!

Good luck and glad you were able to comfortably stop hormonal meds

windingshores

Insurance has approved my Prosigna Assay and my main oncologist is ordering it at Quest or LabCorp. Unlike the Breast Cancer Index, it can be done at any lab that has the equipment. Biotheranostics never got back to me on my questions about the bottom half of the report, regarding benefit from continuing meds.

No matter what I am going to take 12-18 months off to take Tymlos to rebuild bones. When I go back on meds, if I do, I will then do Reclast to counteract any effects on my bones, I would then do a year or two more of Femara.

The main question is the effect of all this on my heart: I already have paroxysmal atrial fibrillation (once or twice a year) and the a fast heart beat from Tymlos may be a problem. We'll see. But at least I have a plan.

If Prosigna comes back low risk I will consider not doing Femara. If it comes back high risk I will try to do the extra two years.

I am seeing two oncologists, the ones I talked with at the time of diagnosis, and might even see the third one who I saw then too. Until I am sure of my path. I saw an osteoporosis guru yesterday, two hour drive each way but worth it.

Peregrinelady

Thanks for the update, Windingshores. I am curious to see how your Prosigna test comes out. I had some high blood pressure issues in December. Ended up in the emergency room twice. Angiogram showed no blockages, but I have left branch bundle block, but have yet to find out if that is causing the high blood pressure. I took a month off Anastrozole in case it was a contributing factor. Latest test was an ABI to check for peripheral artery disease. (I did have a blood clot after revision surgery in 2016.). I am now on 2 blood pressure meds and see the cardiologist next week. I will say that it felt great to be off the AI for that month. So wish my BCI had come back low.

windingshores

Pergerine Lady, can you do two more years rather than five? I have read that two is as good as five in some studies. Sorry you also have heart and bp issues. I will keep you posted. There is low correlation among all of these tests which is disturbing. What if you got a low risk score from the Prosigna?! I don't think any test will make us feel safe but unfortunately doing the most (more meds)suggested by these tests rather than picking one test that indicates no meds, seems to be the way to go.

ctmbsikia

Oncotype test is only for yr 1 thru 5? I wasn't clear on how that is weighing on your current situation? I too am interested how you do with the test., winding....

I am unsure of what my protocol will be, which test they will do. I do imagine there will be one at the 5 yr mark. I hate thinking about it coming back but how can one not? My Onco was a 17 so no chemo, I believe I am luminal A-also had a mixed type tumor which has better prognosis. I may have scored even better if not for the size of my tumor and 0.3mm micro met in my sentinel node. I am hopeful to get off the AI at yr 5.

Good luck to you....

windingshores

The Oncotype has a graph for 10 year risk of distant recurrence. It is used mainly to decide about chemo.

The BCI is, in some studies I have seen, more accurate for years 5-10 and is the only test that gives likelihood of benefit of continuing hormonal meds for five (or two?) more years.

The Prosigna Assay, I have read, is #1 for accuracy and distinguishes Luminal A and B and low/high risk of recurrence, more reliable for years 5-10 than Oncotype. I haven't figured out another way to determine Luminal A vs B and ki67% is unreliable.

I also had a mixed ductal and lobular tumor.

I am not a doctor and am only relying on what I read. I make an effort to read only good studies, and of course many of them conflict. The test themselves conflict for most of us. I'm just going to get a gut feeling and sort of average them out to make a plan.

I didn't realize we could take a year or two off Femara et al. One oncologist told me that I could do that while building my bones back up. MGH does 9 months on, 3 months off, so we'll see what they say.

I have gone down to Femara every other day after reading that is as effective as daily, while I wait for a plan, and with my doctor's okay- but am having more hot flashes so I am wondering if this dosing really is equivalent!!!

Hopeful82014

I've not been online here for a while but have been following this thread and thought I'd jump in on the topic again.

I finished my 5 years of letrozole in October and while my MO strongly recommended another five years of treatment, he was fine with me taking a 3-month vacation from ET and then switching to tamoxifen to give my system a break from letrozole.

I very happily took my 3 months off and was sad to face the reality of needing to go back on treatment, especially with a new drug with potentially new side effects. I was warned in no uncertain terms about the potential for depression as well as the other SEs, mostly because my GYN wanted me to get in touch right away if that occurred and not be taken by surprise. (Good thing she said something, as my MO had not.) However, I've been on tamoxifen a month now with only one minor, non-bothersome SE. I've not had any hot flashes, new joint pain, depression, insomnia, etc. At the rate things are going, I am definitely o.k. with staying on it as needed.

I was fortunate enough to have received Teva brand tamoxifen (without even remembering to ask) and that may help account for the lack of SEs. Or it could be that after 5 years of letrozole switching to tamoxifen is just easier on the body. I realize it's early days yet but I'm cautiously optimistic at this point.

I am a bit concerned given the superior efficacy of letrozole over tamoxifen in studies. However, I'm rationalizing that switching drugs may limit the likelihood of any remaining cancerous cells developing resistance. Who knows - I might switch back to letrozole for a year, then alternate between the drugs. That's a decision and discussion for another day.

Endopredict's results were pretty quite sobering for me so it would have felt stupid and irresponsible to quit ET altogether. Moving to tamoxifen feels like a good alternative to me. It might be something to discuss with one's MO.

Regarding intermittent letrozole, that issue was addressed in part in the SOLE trial. The link below discusses that and links to additional discussion in the sidebar. I hope some of this is helpful in one way or another.

https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.503

Peregrinelady

Windingshores, I may only end up doing the 7 years. That is what I was thinking when that study came out but I think there have been studies since then saying 10 is still better. I will be discussing this with my oncologist on next visit later this month. Unfortunately, I have had a difficult time with keeping an oncologist. Long story, but latest may have moved out of state, depending on her husband’s job, and since there aren’t any here who specialize in just breast cancer, I feel like I know more about BCI, etc. just form reading on this site. As far as getting the Prosigna, I don’t know that I would trust the results if they came back low since BCI was high. I will just keep on keeping on and hope I can make it a few more years on the pills without major side effects. Good luck to all of us!

windingshores

Hopeful8201 I am so glad that you are finding the Tamoxifen easier than expected. After reading your link and a couple of other articles, it seems like a switch might even be beneficial in terms of avoiding resistance (I was surprised to read that 4-=50% of us develop resistance to our meds). There is a reason I cannot take Tamoxifen, possibly related to afib and clots, or maybe because the lobular part of my mixed cancer would not respond-? I'll have to check. But happy for you that you have this option. (I remember you writing about your Endopredict.)

Peregrine Lady I hear you about the Prosigna not being useful when your BCI was high. If my results weren't so murky I would feel the same. Your path is certainly clear but not very pleasant Good luck with it.

I'll post my results for the Prosigna just fyi.

My main problem right now is my bones- and my heart- and how best to proceed with those in mind. I think at a certain risk level, the risks associated with these other problems looms larger. That is why overall survival may not be better on meds, but cancer free survival is.

Peregrinelady

Exactly. Do we risk recurrence or watch our overall health decline from the meds? What a conundrum. Looking forward to hearing the results of your Prosigna.