HER2 Support Group Forums - Pattern of recurrence of early bc differs by intrinsic subtype & proliferation index

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- - Pattern of recurrence of early bc differs by intrinsic subtype & proliferation index (https://her2support.org/vbulletin/showthread.php?t=59367)

Hopeful

10-23-2013 06:59 AM

Pattern of recurrence of early bc differs by intrinsic subtype & proliferation index

http://breast-cancer-research.com/co...df/bcr3559.pdf

Hopeful

'lizbeth

10-23-2013 09:09 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

Here you go Linn65:

Quote:

Based on genomic-defined luminal tumors, it has been possible to establish a value of Ki-67 with prognostic utility and useful to distinguish between both classes of luminal tumors, A and B [12]. Moreover, several studies have confirmed the prognostic usefulness of these intrinsic subtypes defined by four [6-10] or six immunohistochemical markers [8,13-15].

However, it is not clear the value of Ki67 as a prognostic marker in the other intrinsic subtypes such as triple negative and HER2-enriched.

In our study, only the luminal population demonstrated significant differences in actuarial BCFS according to Ki-67 value.
No significant differences were found in triple negative and HER2-enriched tumors.

It is possible that these findings occurred because we use a Ki-67 cutoff
obtained in luminal tumors. Nevertheless, Aleskandarany et al. also failed to detect a significant difference in actuarial survival, despite using different cutoffs defined specifically for both triple negative and HER2-enriched tumors

This study shows that the KI-67 score might not be as big of a factor in Her2 positive cancers.

Only 25% of the patients had received a taxane, and only 18 patients in this analysis received Herceptin. Since the patient information is prior to 2009.

It is good information from a historical perspective. I can't wait to see how Herceptin has changed Her2 from what is so obviously the worst diagnosis to one of the luckier and more treatable breast cancer.

'lizbeth

10-23-2013 09:49 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

I'm still digging out nuggets from the article and found a couple more interesting pieces. The first is about Her2, margins & early recurrence:

Quote:

The first peak of early relapses has been associated with surgery because the removal of the primary tumor could trigger the growth of clinically unapparent dormant micrometastatic foci[42].

Surgery could promote the growth of micrometastatic disease through several processes as an alteration in the angiogenic balance [42,43], surgical stress-induced neuroendocrine activation [44] or alteration of the immune response [45,46].

These mechanisms could influence particularly the disease course in intrinsic subtypes with a high expression of proliferation pathways such HER2 or basal-like tumors.

An increase of proliferation has been reported in HER2-positive patients with positive margins after conservative surgery between the first and the second tumor samples, as determined using Ki-67 immunohistochemistry; this was not the case with HER2-negative cases [47].

Hopeful

10-23-2013 09:57 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

What I found interesting was this:

Quote:

In addition, those other patients with Luminal-HER2 subtype could benefit from a second treatment with trastuzumab in order to decrease the second peak of recurrences.

I recall discussion here from way back, that perhaps triple positives could do with a "booster" of Herceptin at the 5 or 7 year mark.

Hopeful

'lizbeth

10-23-2013 09:58 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

This shows a novel shift in the management of preventing recurrence and not just treating intial cases or recurrences. The suggestion is to use Herceptin in the future to prevent many Her2 positive cancers that recur in the 5-6 year range.

Quote:

The information provided from the study of the patterns of recurrence in early breast cancer would benefit to the patients in different ways. In this regard, our results could generate several hypotheses that, if confirmed in prospective randomized trials, would have noteworthy practical value. First of all, the surveillance after initial treatment could fit to the expected recurrence pattern depending on each intrinsic subtype. But more importantly, the adjuvant treatment could be tailored more accurately according to each intrinsic subtype.

Patients with tumors with high proliferation rate such HER2-enriched or basal-like would benefit from more aggressive chemotherapy schedules (e.g. dose-dense). Such type of chemotherapy could avoid some of the recurrences appeared during the first peak. Also in these cases with high expression of proliferation pathways, it could be especially useful the treatment with novel inhibitors of cell cycle (e.g. palbociclib).

In addition, those other patients with Luminal-HER2 subtype could benefit from a second treatment with trastuzumab in order to decrease the second peak of recurrences.

'lizbeth

10-23-2013 10:01 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

That is just too weird Hopeful. We are on the same page!

'lizbeth

10-23-2013 10:09 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

Has anyone done a clinical trial with the triple positives and a second round of Herceptin? I think prior to the 5 year mark, 48 to 50 months would be the safest strategy for prevention. (and I personally would want more than 1 booster, maybe 1 per month for 6 months.)

I also wonder what affect the E75 or AE37 vaccines are having on the late recurrence rates.

This is just such a change in thinking from the wait and see, and let a huge percentage of women recur. I would love changes to the standard of care.

'lizbeth

10-23-2013 10:17 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

Triple positive recur about the 5-6 year mark, isn't that about the time the 5 year treatment of Tamoxifen is up? This might also be a factor.

SusanN

10-23-2013 04:11 PM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

WHEW Mister Sister...VERY, VERY INTERESTING...!!! I usually do try & read what is posted in some of these articles (when I have time...) just don't comment, what can I say, except that this information is beyond me...knowledge is power!! :)

'lizbeth

10-23-2013 07:59 PM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

I'm not fond of the wait & see, and try to find symptoms system of cancer surveillance. If we can find a way to prevent or some less invasive testing to screen survivors - I'm waving my pom poms!

JennyB

10-24-2013 12:19 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

I wonder how many oncs/insurance companies would prescribe the booster shots though? I for one would love a top up in 18 months - would seriously pay out of pocket too - but would need the doc to go with my wish and probably some data!! Great topic though thank you xx

Hopeful

10-24-2013 06:46 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

The "booster" would be easier, now that Herceptin is becoming available in forms other than infusion (i.e., subcutaneously). It would be less expensive than having to go to an infusion center. I do think that this would need to be tested before it becomes standard practice.

Hopeful

Hopeful

10-24-2013 06:51 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

In re: booster, look here: http://her2support.org/vbulletin/sho...ter#post224894

Hopeful

SusanN

10-24-2013 08:04 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

Hopeful & 'lizbeth, thank you so very much for extracting so much valuable information...as to "wait & see, symptoms...!!" I'm going to share this article with my oncologist, he always tells me IF I can find anything that would convince him, he would be willing to take a look at it...hmmm...(yeah, right?!?!)...

I find some articles of interest from "PracticeUpdate", Oncology Daily Digest...I'm sure others of you read that as well.

Kinda off the subject...very, much...anyhow, a year ago this month is when I found my "pea"...NOT from a mammogram or ultrasound...and today I go for my yearly mammogram, the only one I still have...trust me, I've called them already & explained "where I'm coming from..."...makes no difference as we know "dense breasts"...

Okay...didn't mean to go there...I'm with you JennyB...all over this "Booster"...it just may be adding up...hmmm...

'lizbeth

10-24-2013 10:53 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

I like the idea of the booster.

After looking at Hopeful's prior conversation I see perhaps two higher risk times, one about a 2-2 1/2 year interval, another at 5-6 years with ER+, Her2+.

I love the idea of the Herceptin injections as boosters. Do we really need a clinical trial? Almost all have had an entire year of Herceptin infusions. For stage 1-3 who remain as NED this has been for prevention. To receive an injection booster at 18 months, then 24 mths, 48 mths and 60 mths for ER+, Her2 patients should be something left to the discretion of the oncologist and patient.

"Modern" medicine will never achieve personalized care if the FDA has to approve & micromanage everything based on clinical trials for the good of the group, and not the individual.

jaykay

10-24-2013 01:15 PM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

I'd do a booster in a heartbeat and I still have one more Herceptin to go (next Wednesday, Oct 30th).

But would it just be one "loading" dose or a couple of doses? I know there are no answers...

Susan - your mammograms now should be diagnostic vs. screening and you should get the results before you even leave the facility. Prescription should be written that way.

Best
Janis

Laurel

10-24-2013 06:48 PM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

Smart People than I,

I am a bit confused by this study and think I must be reading it wrongly. Please, if anyone can, help me to wrap my brain around this. On page #14 in table #9 I see that the hazard ratio for recurrence in Luminal Her2 is actually declining annually through years 5-7. It appears that Her2 Enriched does spike around year 5, however. Isn't Luminal Her2 that which is Er or Pr (or both) positive and Her2 positive (Er/pr+, Her2 +) while Her2 Enriched is Her2 positive, but hormonally negative (Er/Pr-, Her2 +)? I must be reading that table wrongly because according to my interpretation Luminal Her2s would not require a booster, but Her2 Enriched would qualify.

Anyone?

'lizbeth

10-25-2013 09:34 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

Laurel,

We picked it up off of page 4 - from other studies:

Quote:

Different authors have described the maximum peak of recurrence risk at 12-24 months after surgery [16-22] and the occurrence of a second peak at approximately the fifth year in some cases [17,18,20,22].

I did find the same confusion - about the terminology.

From prior reading I was under the impression that Her2 positive, hormone negative cancers recurred within the first 2 years then dropped. Recurrences with Her2 Positive ER Positive cancers had a tendency to occur more frequently beyond 2 years.

I think this brings us back to the prior discussion: Who is recurring? and the fact that SEERS does not track this type of data.

I will take another look . . .

'lizbeth

10-25-2013 10:13 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

Just so we understand for the purposes of this study Luminal Her2 is defined as:

Quote:

Luminal-HER2 (ER + and/or PR+, HER2+, any Ki-67, any CK 5/6, any EGFR

from page 3

'lizbeth

10-25-2013 10:43 AM

Re: Pattern of recurrence of early bc differs by intrinsic subtype & proliferation in

If you look at page 12 under: Analysis of recurrence prognostic factors and variations in recurrence risk over time

Quote:

For the HER2-enriched subtype, the first peak occurred at approximately the same time, nearly 20 months for both groups, but the maximum risk was 1.0% (95% CI: 0.5%-2%) in patients with Ki-67 <14% and 1.3% (95% CI: 0.9%-3.1%) in those cases with Ki-67 ≥14%. A second risk peak at 72 months appears for both HER2 populations, but interestingly the magnitude in this case seems to be higher in the HER2-enriched with Ki-67 <14% (0.75%; 95% CI: 0.3%-1.8%) than with Ki-67 ≥14%

Here they state for both Her2 populations there is a peak at 72 months and it was higher for the lower KI67 scores.

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