determining which patients benefit from more than 5 years of antihormonal therapy--
 

her2 may be involved. It is unclear if it is just because her2+ bc usually is less endocrine sensitive or if there is some other mechanism coming into play

from MedPage Today website:

Some Breast Cancers Require Longer Tx

Published: Mar 21, 2014
By Charles Bankhead, Staff Writer, MedPage Today



Breast cancers with high-level estrogen sensitivity had a significantly greater risk of late recurrence, possibly indicating a need for more than 5 years of adjuvant hormonal therapy, British investigators reported.

HER2-negative tumors with a high score on the estrogen panel of a genetic test had a recurrence rate of 13.6% during years 5 to 10 after diagnosis, more than double the recurrence rate during the first 5 years.

In contrast, women with HER2-positive, highly estrogen-sensitive tumors did not have an increased risk of recurrence beyond 5 years, as reported at the European Breast Cancer Conference (EBCC) in Glasgow, Scotland.

"Our data suggest that these patients, who are those that appear to benefit most from the current standard 5 years of endocrine treatment, may also benefit from adjuvant hormone treatment that extends beyond 5 years," Mitchell Dowsett, PhD, of the Institute for Cancer Research in London, said in a statement.

The results add to the longstanding recognition that estrogen receptor-positive tumors have a higher risk of late recurrence compared with ER-negative tumors, added Jack Cuzick, PhD, of Queen Mary University, also in London.

"This work makes it clear that even within ER-positive cancers, the level of expression is important," said Cuzick. "Further work is needed to see if genetic expression profiles are better at doing this than more conventional quantitative immunohistochemistry."

The findings came from a new analysis of the landmark Arimidex, Tamoxifen Alone or in Combination (ATAC) randomized trial, which showed improved survival in breast cancer patients who received 5 years of adjuvant hormonal therapy with an aromatase inhibitor instead of tamoxifen.

The analysis included 1,125 ATAC participants whose tumors were evaluated by the OncoType DX 21-gene test, which assesses the risk of distant recurrence in patients with ER-positive breast cancer. Gene expression evaluated by the test includes four genes involved in estrogen signaling (the E-module), one being the estrogen receptor.

The subgroup included 1,009 patients who had HER2-negative tumors.

The analysis showed 215 recurrences during 10 years of follow-up. Overall, the recurrence rate was similar during years 0 to 5 and 5 to 10. However, the recurrence rate and pattern varied markedly according to HER2 status and E-module score.

HER2-positive tumors had a higher recurrence rate during years 0 to 5. HER2-negative tumors had a higher recurrence rate during years 5 to 10.

Further analysis showed that the recurrence pattern of HER2-negative tumors varied by E-module score. A low E-module score was associated with similar rates of recurrence during years 0 to 5 and 5 to 10. The combination of HER2-negative status and high E-module scores was associated with more than a twofold increase in recurrence during years 5 to 10.

"Similar overall recurrence rates between years 0 to 5 and years 5 to 10 hide substantial and therapeutically important subgroup differences," the investigators concluded. "Importantly, HER2-negative cases with high estrogen signaling are generally considered relatively low risk but showed increased recurrence after 5 years, coincident with cessation of treatment and may be candidates for extended endocrine therapy."

The ATAC analysis was one of several noteworthy studies reported at the EBCC.

Primary source: European Breast Cancer Conference

Source reference: Dowsett M, et al "Estrogen module of 21-gene recurrence score predicts increased late recurrence for ER+ HER2- breast cancer" EBCC 2014; Abstract O-216.

Re: determining which patients benefit from more than 5 years of antihormonal therapy
 

Um... Maybe I should rethink how long to be on Arimidex. I was highly Her2+ but PR negative and only ER+ (50%). I have been on almost 9 years and was first on Tamoxifen 3 months.

Thanks for posting Lani (as always)

Re: determining which patients benefit from more than 5 years of antihormonal therapy
 

I am thinking similarly, Becky. I have 2 years of Tamoxifen and 3 years of Femara under my belt and was urged to continue on an anti-hormonal another 5 years. I was highly ER and PR positive as well as highly Her-2. Hope there is some follow up data to support these findings for those who are triple positive. For now I will continue on the Tamoxifen since it is not bothering me.

Re: determining which patients benefit from more than 5 years of antihormonal therapy
 

Hi Becky like you this is my 9th year on AI (Femara)
being Estrogen 90%
highly Her2 positive
OncotypeDX was high also ....so for me it was not requiring brain surgery to continue on Femara past 5 yrs.
My concern is next year....after yr.10

http://www.medicalnewstoday.com/releases/274300.php?tw

From article:

"We are about to start a trial called IBIS-3 of extended therapy with aromatase inhibitors in long-term survivors with ER+ breast cancer with other unfavourable characteristics, and also adding new drugs used in other conditions that show promise in preventing breast cancer recurrence - a bisphosphonate (bone sparing drug) and metformin (diabetes drug). Hopefully, this biomarker work will help to pinpoint more accurately which patients need additional treatment."

I am thinking I woud like to take part in this trial.
I am seeing my onc. early April and will discuss this but I am fairly certain i will hear that "we just don't know"
What are your thoughts Becky?
Hugs dear sister,
Jean

Re: determining which patients benefit from more than 5 years of antihormonal therapy
 

I'm only 5% ER+, but my new oncologist put me on Exemestane after he found out I'd had a combined 5 years worth of Tamoxifen. There were studies (I'd dug it out before) validating the 10 year schedule.

Re: determining which patients benefit from more than 5 years of antihormonal therapy
 

Jean

There are things to consider in the trial. For example, will they test you for the biomarker? This would be an interesting piece of information. I guess they would have to test your tumor for the biomarker. Secondly, you have to look at the potential side effects of the test drugs. You also have to try to find out if there are additional side effects of taking these drugs together too. Is there a time frame for the trial participants - you may be too far out from treatment to participate. I am really thinking more on your quality of life here as you are almost 9 years out right now.

Also, can Metformin's side effects be more intense for a person taking it who is not diabetic or even pre-diabetic? Will you have to eat more to not lower your blood sugar too much? We all know that medications can be used for other diseases than they were intended but find out the facts. If you can try to get into a trial, you can at least talk to the trial folks and make a decision from there.

Re: determining which patients benefit from more than 5 years of antihormonal therapy
 

Thanks Lani, I'm similar to Jean in that I'm highly triple positive so nine years out this summer (hopefully!) and this will be my eighth year taking Arimidex as I only took Tamox for six weeks before having an Ooph. I think my Onc will be happy to leave me on this drug until we get more info and certainly up to ten years, that trial sounds interesting Jean, although I already get a once yearly iv of Zometa for bone loss.

Re: determining which patients benefit from more than 5 years of antihormonal therapy
 

My first experience with breast cancer - her2+' er+/pr-, no herceptin or chemo (not approved for early stage). Tamoxifen for 4.5 years, Femara for 5 years. 2.5 years after stopping Femara, new primary with same pathology. Details are in my signature.

I have always wondered if I had stayed on Femara would I have suppressed the 2nd occurrence. In other words, which characteristic was stronger, her2 or er?

Bottom line, I expect to stay on an anti-estrogen for the rest of my life. I've been osteopenia for years, even before cancer. I will do zometa every year as long as it helps.

Janis

Re: determining which patients benefit from more than 5 years of antihormonal therapy
 

Lani,

Keep up the good work. I am trying to help Genentech turn out more doses at their facility in California. Also looking at how to get more Brain mets treated.

Paul