Breast Cancer May Return Even 20 Years Later, Study Finds

cp418

https://www.nbcnews.com/health/health-news/breast-...

Breast Cancer May Return Even 20 Years Later, Study Finds

Anonymous

Just saw this and I believe it. Reason to consider extending AIs.

wallycat

would be nice if treatment improved exponentially. The thought of having to pick a different set of diseases to spare one from recurrence just seems so cruel. Not that anyone asks.

AIs and tamoxifen can increase uterine cancer risk, osteoporosis, heart disease, dementia, quality of life while you're waiting....just off the top of my head.

Lindissima

https://www.medscape.com/viewarticle/888191#vp_3

Here's a more detailed Medscape article on the topic.

besa

https://medicalxpress.com/news/2017-11-breast-canc...

http://www.nejm.org/doi/10.1056/NEJMoa1701830

abstract of original article in above NEJM link

ElaineTherese

OY. With my large tumor and compromised node, it looks like I'll be on Aromasin forever at this point.....

KathyL624

Are the numbers in the article without extended hormonal therapy? So if tamoxifen or A.I.s are continued the risks would be lower? Why not keep us on these drugs forever

besa

During a quick read of the original article the authors discuss the fact that they don't know how many women in their study quit tamoxifen early (not taking it for the full five years) which could have skewed their results.

wallycat

The cancer drugs have their own issues, so simply saying stay on them forever is not possible for everyone. And there are gals here that had recurrences even on the meds. The article did say that some of these statistics are older......

Meow13

I just keep hoping for better medicines today and in the future.

ksusan

This meta-analysis (the type of study this is--a statistical review of other studies) lists a number of limitations to their method, including those you've given above. It looks like it's more a study of those who started treatment, but the researchers acknowledge that they don't know whether people stayed on it. What's being measured, then? Some mishmash of people who were prescribed anti-hormonal treatment and didn't take it, plus people who took one dose, plus people who took it for x length of time, plus people who started and stopped, plus people who took it for 5 years. That's a very heterogeneous group and a very dubiously defined variable that omits only those participants who didn't receive a prescription.This is a really significant wrench to throw into this study, and I'm surprised it was accepted at this journal with the claim that its findings represent anything solid about the recurrence rate for participants who had 5 years of anti-hormonal treatment. I'm not going to plow into their analysis, but just based on their own description of the limitations, I'm not at all convinced that their stats mean anything since they weren't able to constrain their variable meaningfully.

Let's say I'm studying whether birth control pills prevent pregnancy. I do a statistical analysis of a large group of previous studies. I can't tell from those previous research reports whether the women in each study were just prescribed the pill, or took one dose and stopped, or took it for awhile and stopped, or started and stopped, or took it but because of something like a medication interaction became pregnant anyway, or took it for 5 years. Although I can state what percentage of the research participants got pregnant during 5 years, why on earth would I claim that the pregnancy of a participant who may not even be taking the medication represented a failure of the medication?

ErenTo

To add to what Susan said above, one main challenge of long-term studies like this is accounting and adjusting results for newer treatments. This result is based on treatments available at the time. Widespread use of AIs, ovarian suppression among younger patients, newer chemo agents, HER2 targeted therapies, increasing emphasis on the importance of exercise are all variables that may not make these numbers from decades ago as predictive as we think they may be.

Denise-G

My Oncologist, Dr. Daniel Hayes from the University of Michigan, was the Senior Study Author of this Study. He is one amazing Oncologist. His credentials are staggering. I am beyond fortunate to have him as my doctor, my mom's doctor, and my sister's doctor. Dr. Hayes has been telling me almost since diagnosis back in 2011 that I will need to stay on AIs probably "until the end of your very long life or 15 years as long as your bones hold out." I'm now in year 6 of Anastrozole and thankfully my bones are still fine. His encouragement helped me get through the side effects I had to endure for the first 2 years. Suddenly, they got considerably better about Year 3.

.

Outfield

ksusan, research done like that, where the inclusion criteria is something like anyone who was given a prescription, is "intention to treat" and may be more valid in the real world than studies that only look at people who were able to stick to a treatment perfectly. It's definitely valid in medical research to look at things this way. If there were a drug that was 100% effective but that only 10% of people prescribed it could tolerate, then in terms of combating a disease it wouldn't be a magic bullet and that's important to know. We know we don't have a magic bullet for breast cancer, and if women who couldn't tolerate any of the drugs were included in the final outcomes, then that's the best description of what a group of patients receiving their first prescription can expect over time. You're right - it's not the answer for specific subgroups or one specific person.

I'm not at all surprised by these results, I'm surprised that they were big news. My initial reaction is "Duh!". This was a really big meta-analysis, but their finding could not have been unsuspected after a gazillion smaller studies showing that the cumulative disease-specific recurrence and death rates never level off (leveling means that after some point, no more patients have recurrences or die from the disease).

ksusan

I don't think they've conveyed their findings that way, though. I do agree with you about the "duh" factor.

Outfield

ksusan, for the audience of the NEJM, they don't have to say all that stuff as plainly as I did. Medical training includes training in reading the medical literature, so a level of expertise in the reader is assumed. Also, this was a meta-analysis including intention-to-treat studies, not a trial using an intention-to-treat method itself. Intention to treat is a trade off: answers closer to "real world" population results vs. best case scenario with the intervention.

Traveltext

Is this really news? I've read enough studies over the past few years to understand that 20-30 percent of Stages I-III will move to Stage IV of this disease. Now, of course, individual cohorts have a more or less chance of progressing, but since the effectiveness of hormone blockers have been proven so effective in prolonging life, it stands to reason that our individual survival odds are improved by staying on them for as long as we can tolerate any side effects they cause.

Bounce

What about developing resistance to hormonal (anti hormone) treatment?

My breast surgeon didn't seem to think it was a bad idea for me to stop Tamoxifen after 4 years even though I am high risk (as per family history - intermediate Oncotype)- she said I would probably become resistant to it over time anyway! Scared the hell out of me and made me depressed.

I don't think she is a bad doctor who doesn't care about me. I think she is talking from her experience with breast cancer patients.

dtad

Hi everyone...I agree with Meow13. I'm happy for anyone who does well on anti hormone treatment. I do believe its effective however due to the side effects the compliance rate is just not high enough for it to be the end all treatment. I would love to see new treatment options that more of us could tolerate. Good luck to all.

Anonymous

I would love to see more efforts directed at re-designing AIs so that they create less negative side effects than they do now. I did fine on Aromasin for 2 years, (terrible on Arimidex before that--that's why I switched) but I'm finding a few more joint aches in my hands than before, and my moods are more volatile than they once were, too. How about some kind of test to find out whether they are indeed protecting us or not before we recur? I'd like to know if indeed I am protecting myself by taking this drug every single day, instead of just hoping I am. If I'm not getting benefit from it, I'd like to know so I can stop taking it. I'm able to manage the side effects but they aren't fun and are sometimes pretty horrible.

And how about research on making our bodies less resistant to these drugs over time? If these drugs are indeed an important factor in protecting us from recurrences, then let's make it easier for our bodies to use them over a lifetime without becoming resistant to them.

No matter how the research is carried out, sometimes I am frustrated that these findings about bc, bc drugs, etc. wind up being research for the sake of research and not truly hands-on helpful for millions of us who are in active treatment or are doing what we can to live long enough to die of something that isn't BC.

Claire in AZ

Traveltext

Because our physiologies are all different, we can all have different reactions to hormone blockers. And Bounce is correct, bc can work around these drugs and suddenly you find yourself with a recurrence. My male bc pal went four years on Femara, then went stage 4. I know people who have been on tamoxifen for nearly 10 years and all is well. Some oncs will recommend changing from one drug to another after five years.

Since there is such a variation in responses and side effects to these drugs, we all just have to make our individual decisions and run with them.

BarredOwl

Pan published preliminary results based on a subset of patients (46,138 patients) in a 2016 meeting abstract, per an earlier post of mine.

A few differences between this study (Pan (2017)) and others come to mind. Prior studies with long-term follow-up, such as Colleoni (2016) were much smaller as compared with this study (Pan (2017)). For example, there were 4,105 patients in Colleoni (2016). In contrast, Pan (2017) included 74,194 women entered at year 0 plus 10,200 added later, with a total of 62,923 patients who were event-free and followed at year 5. Pan notes, "Although a persisting recurrence risk among women with ER-positive breast cancer is well recognized,[13-17,34] our study quantifies the 20-year risk more reliably than previous studies, since it is large and has long follow-up."

Colleoni (2016) included patients with ER+ or ER- disease, so the patient population was more diverse in hormone receptor status. In Pan (2017), all patients were ER+.

Another difference is that none of the patients in Colleoni received modern endocrine therapy regimens. Per the accompanying commentary to Colleoni, the regimens would have been one (1) year of tamoxifen with or without prednisone (no longer in use). In contrast, in Pan (2017), patients were enrolled in various EBCCTG clinical trials and were assigned to receive 5 years of endocrine therapy (Tamoxifen, an aromatase inhibitor, or switch regimens). It looks like around 65% of patients received Tamoxifen in Pan (2017).

As noted above re Pan (2017), although trial participants were assigned to five years of endocrine therapy, some may have discontinued treatment early. Pan notes, "All the patients were scheduled to receive endocrine therapy for 5 years then stop, regardless of actual adherence. Most of the patients entered the study at the time of diagnosis, but some entered later, having already received 2 to 5 years of endocrine therapy, but were scheduled to stop therapy at 5 years."

Regarding adherence, they note: "First, the recurrence rates reported here are in women who were scheduled to receive 5 years of endocrine therapy, not in those who completed treatment. Only a few of the trials in our study provided detailed data with respect to adherence, but a substantial minority of women in trials of 5-year endocrine therapy did not complete their treatment. [Reference 2]" I note that it has been suggested elsewhere that clinical trial participants differ from the general population, in that the former may have increased motivation to adhere to assigned therapy in view of their role as trial participants, receipt of trial support, and reduced treatment costs.

Pan (2017) includes assessment of the association of various factors with distant recurrence during the first five years and beyond. The factors assessed in Pan (2017) included tumor diameter and nodal status, as well as age, grade, Ki-67, PR status, and HER2 status (although "only 2% of the women in our study received trastuzumab.")

Regarding the particular recurrence rates, keep in mind: "However, long follow-up means that most of the patients received the breast-cancer diagnosis well before 2000. Since then, the prognosis for women in particular TN categories has somewhat improved owing to earlier diagnosis, more accurate tumor staging, and better surgical, radiation, and systemic therapies."

BarredOwl

Moderators

Hi all -- we wanted to share BCO's take on this study with you:

Distant Recurrence Risk of Hormone-Receptor-Positive Breast Cancer Steady 20 Years After Initial Diagnosis
November 13, 2017
After 5 years of hormonal therapy, the risk of distant recurrence is still sizable, even 20 years after the initial diagnosis, and the risk of distant recurrence is strongly linked to cancer size and number of positive lymph nodes. Read more...

Traveltext

Thanks Mods this was a useful summary of his study. Because bc men were excluded, we're left to guess how these results might extrapolate to us. That said, likely we'd be wise to assume our recurrence risk was similar and keep taking hormone blockers past the five-year mark.

besa

Barred Owl- I just want to thank you for a wonderful post!

gentianviolet

What ever happened to the trials of tamoxifen in a trans dermal base? I once read, can't remember where, that this was tried and side effects were greatly reduced. Has anyone read anything recent?

runor

Gentian, I think I read something to that effect, applying tamoxifen as a topical cream rather than pill. As best I was able to determine, and I admit that I'm on shaky ground here because reading these things confuzzles me, the skin application seemed to have some positive effect in preventing a LOCAL recurrence. But I was not able to determine if this approach was expected to prevent DISTANT recurrence too. Women who had a high risk of it coming back in the breast were able to target the breast with the skin application, but this did not exactly address the need to help prevent distant mets.

I hope someone else has a better understanding. Barred Owl?