finally...a basic question is being looked @:her2+ER+s have differnt relapse pattern

Lani · 12-05-2009, 09:08 AM

and pattern of metastatic spread

Cancer Chemother Pharmacol. 2009 Dec 3. [Epub ahead of print]
Patterns of relapse and metastatic spread in HER2-overexpressing breast cancer according to estrogen receptor status.
Park YH, Lee S, Cho EY, Choi YL, Lee JE, Nam SJ, Yang JH, Ahn JS, Im YH.

Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.

PURPOSE: The primary aim of this study was to compare the relapse patterns of estrogen receptor (ER)-positive and ER-negative patients with HER2-overexpressing breast cancer. A secondary aim was to distinguish the preferential primary site of metastases in HER2-overexpressing breast cancer. METHODS: Out of 886 patients treated for metastatic breast cancer (MBC) between January 1995 and December 2006, 269 patients with HER2-positive tumors were identified. Of these, 198 patients with relapsed breast cancer following surgery were included in this study. Rates and patterns of relapse and metastatic spread in HER2+/ER+ and HER2+/ER- patients were analyzed. This analysis was evaluated by the validation patients' cohort of our institute prospectively. RESULTS: Median relapse-free survival was longer in the HER2+/ER+ group than in the HER2+/ER- group (32.0 vs. 19.5 months, p = 0.0012). The peak of recurrence occurred at 12 months after surgery in the HER2+/ER- patients. The peak of relapse was later and the level was lower in the HER2+/ER+ patients (66 and 78 months following surgery) than in the HER2+/ER- patients (33 and 39 months following surgery, respectively). This result was reproduced by the validation cohort with great similarity. Young age [hazard ratio (HR) 1.59, p = 0.002], TNM stage 3 (HR 1.51, p = 0.005), and ER-negativity (HR 1.68, p < 0.0001) were identified as independent risk factors for relapse. Severe bone metastasis (HR 4.48, p = 0.028) and massive hepatic metastasis (HR 5.24, p = 0.043) were identified as independent risk factors for early relapse. CONCLUSIONS: Our study shows that HER2-overexpressing breast cancer displays characteristic patterns of relapse and metastatic spread depending on ER status.

PMID: 19956951

I have often warned against articles that talk about the behavior of breast cancer as if it were one entity, or putting too much value on basic science
articles on the behavior of breast cancer cell cultures made up of cell lines that are not her2+--here we see that even talking about her2+ bc as if it is one entity may be comparing apples and oranges! And it looks quite possible that there are subtypes of her2+ER+, as this abstract infers there were two peaks of recurrence within the her2+ER+s.

Still trying to access the whole article.

Rich66 · 12-05-2009, 11:45 AM

I hope focus gets put on shared vulnerabilities across the cancers. Otherwise it seems like it will be endless incrementalism.

Sandra in GA · 12-05-2009, 01:21 PM

Lani,
Am I correct? The results of this study indicates that those of us who are ER neg have recurrances earlier in the bones and liver than those who are ER positive. The status of progestrone was not included in this study.

I know that there are studies looking at benefits gained from adding drugs that strenghten bones to HER2 patients' treatments. Wouldn't it be wise to ask for this treatment even if you are ER neg. and not given estrogen suppression therapy?

Thank you so much for posting this information. This is a question I will have for my onc whom I will be seeing next week.
Sandra

tricia keegan · 12-05-2009, 02:11 PM

Lani, do you know of any similar studies done for triple positive's???

Becky · 12-05-2009, 03:50 PM

It seems studies and research in general fail to separate out the progesterone receptor which is very, very key.

There have been presentations and posters in regard to those (like me) who are ER+ but PR neg. One such study was interesting. It looked at the molecular assay of ER+PR+ vs ER+PRneg and ERnegPRneg. This study did not take Her2 or any other marker into consideration. The interesting thing is that ER+PR+ and ERnegPRneg cancers have a certain "look" to them on a molecular assay "picture". When studying ER+PRneg cancers they found 3 things. Some of these tumors look like ER+PR+. Some look like ERnegPRneg. But there are a few ER+PRneg cancers that look very different from either. (Interestingly, some ER+PR+ cancers look like ERnegPRneg cancers and vice versa).

The point of the presentation is that a few ER+PRneg cancers are really what they are - different. But many are really in a more common category.

The study Lani posted is interesting but I bet they didn't separate out PR so some of these women are PR+ and some are negative. However, if a woman is ER+ she also tends to be PR+ as well as the ER+PRneg is quite rare. Even on this board, there are only a few of us in this category.

For Tricia Keegan - I would take the data as most are triple positive but I would bet my bottom dollar that there are a couple of PRnegs in there.

Becky · 12-05-2009, 03:53 PM

I also want to add separately that this study shows that Her2+ER+ tends to recur late much like those who are ER+PR+ but not Her2+. Plain old "vanilla" bc tends to recur around 6-7 yrs from surgery (if you recur - please remember, many do not even if Her2+).

tricia keegan · 12-05-2009, 05:07 PM

Thanks for the tip Becky!

Jean · 12-05-2009, 08:33 PM

Becky,
Well I always knew we were rare! lol....I am now wondering just for the heck of it....how many of us on the board are ER+ PR-

I know you are and so am I (love to be in your company).

How many more of you are out there?
Jean

Margerie · 12-06-2009, 10:52 AM

What about herceptin?? If these patients "had relapsed following surgery" in the time period '95-'06, how many had been previously treated with herceptin? Adjuvant herceptin started in '04/'05??

Maybe not many.....

Lani · 12-06-2009, 12:19 PM

Margerie--I have now read the entire article and the only ones ,in their original group of those treated during those years, who got herceptin anytime in their treatment were excluded from the group they reported on as their "semi-natural history" would have thrown off the the statistics, which were for those who got the standard (at the time) treatment. I use the term "semi-natural history" for the results of what happens WITH the best treatment for the era.

These sorts of information I think might help people make decisions--ie, as there are few stats on the true natural history of the disease without treatment (they weren't doing her2 testing at the time, eg the 1960s) they wonder what their chances of recurrence may be and when it might peak/occur. Although this study looked only at those who DID recur and didn't biopsy their mets to see if they were her2+ (other studies have done so and the majority, but not all, are), it gives some sort of inkling as to what might be expected if one did not get herceptin. Since herceptin doesn't work for everyone, one might view these figures as the "worst case scenario"

In that way, someone might, depending on their risk aversion level, decide to stay on antihormonals past 5 years(something for which there is not yet any information for her2+ bc patients, nor definite answers for ANY bc patients yet), might decide whether late herceptin might be worth it, etc

The numbers in this patients were large ie, lots of patients, so the stats are more likely to mean something.

Hope some of you found this useful.

Margerie · 12-06-2009, 07:47 PM

Thanks Lani, and thanks for posting about this article.

I am always interested in info for the her2+er+ world. On one hand, my onc feels my aggressive her2+ cancer would have recurred by now if it was going to at 4 years out. But at the same time, he has said he will probably recommend that I take Arimidex for more than 5 years.

There are always more questions than answers.

Hopeful · 12-07-2009, 08:41 AM

Here is a link to the full article: http://www.springerlink.com/content/...5/fulltext.pdf

And the graphs:http://www.springerlink.com/content/...MOESM1_ESM.ppt

One paragraph in particular stands out to me:

"These findings suggest that ER-negativity interacts with Her2-overexpression to cause a more aggressive clinical behavior, and that the acquisition of of ER-positivity in Her-2 positive disease affects the disease course of Her2-positive breast cancer and ameliorates the aggresiveness of Her2+/ER- diseases. There is increasing evidence that HER2 amplification may be the biological driver of Her2-positive diseases, overriding the influence of HR, and that acquisition of ER expression may be a late event in pathogenesis. However, maintaining ER-positivity independent of HER2 status may be more closely related to intrinsic dormancy, which is regulated by the microenvironment of the host and could be part of later events in tumorigenesis. This elucidation was supported by relapse curves according to HER2 status in the ER-positive and ER-negative patients. Apparently, favorable outcomes of ER-positive patients are not only due to hormonal therapy, but also from the less aggressive biologic behavior of the tumor, irrespective of the presence or absence of HER2."

This is a very strong statement. I am wondering how this can be reconciled with the concept that "biology drives treatment," and also with the high Oncotype scores seen for hormone positive, Her2 positive patients.

Thanks, Lani, for posting this interesting article.

Hopeful

SuThorn · 12-07-2009, 10:19 AM

Thanks for posting this article Lani!

Jean and Becky, I am also ER+/PR-.

WolverineFan · 12-07-2009, 06:49 PM

Great article, Lani. Thanks so much for posting. Very, very interesting.

Barbara2 · 12-14-2009, 12:23 PM

Lani said "In that way, someone might, depending on their risk aversion level, decide to stay on antihormonals past 5 years(something for which there is not yet any information for her2+ bc patients, nor definite answers for ANY bc patients yet), might decide whether late herceptin might be worth it, etc."

Very true. Current articles and information proveded in them certainly influence our decisions.

I have followed the advice of my onc and have spent much time on this board reading,reading, reading, all of which has certainly influenced the choices we've made.

As a result, I did have late herceptin; 26 months after chemo, and am now taking Arimidex past 5 years. As of this coming March, I will have completed 7 years of Arimidex, and plan to continue until my onc wants to discontinue that med. Counting my blessings...

weety · 12-21-2009, 03:18 PM

Okay, one more possible theory to throw into the barrel:

In some early lab (not human) experiments, Herceptin caused ER- tumors to change to ER+ tumors. I pretty much dismissed this at first because of it not being tested in actual humans. However, in doing more research the other night, I found a trial that is actively recruiting right now to see if this actually happens in real people. The trial is giving one dose of Herceptin to ER negative gals before their surgery and then rechecking estrogen receptors after surgery to see if hormonal status has changed. I don't have the exact link to the study, but I think I found it on the clinicaltrials.org or .com? site.

Thinking through it, though, I don't know if this could explain much in the study we're discussing, because as someone else pointed out, herceptin wasn't standard during the years they looked at.

Laurel · 12-21-2009, 09:28 PM

Well, actually Weety, that's an interesting study you have shined the light of exposure on for us. Just think, if Herceptin converts ER- to ER+ what that may mean in terms of follow up post Herceptin tx. Out come the A.I.s and Tamoxifen for everyone! It may change the course of treatment and the recurrence patterns.

Chelee · 12-21-2009, 11:28 PM

Weety, I know I was weakly Er. (5% I believe?) when 1st dx back in 2005. At that time I did finish a yr of herceptin back in 07. Then I recurred this last Sept so I am back on herceptin. The recent bone biospy path report from femur shows now I am highly Er positive now...60%. So maybe there is something to it?

Laurel, Very good point you made about AI's for everyone. It would be interesting to see the results from this study once it's done.

Chelee