Topic: How large does Tumor gets chemo and herceptin

Forum: HER2+ (Positive) Breast Cancer — Testing, treatment, side effects, and more.

Posted on: Jan 21, 2012 02:05PM

Posted on: Jan 21, 2012 02:05PM

ccjj wrote:

Curious... my step mom had BMX due to high grade DCIS in left and suspicious area of concern in right.  After surgery, pathology came back with invasive ILC Her2+ in right breast. Very small, less than 1/2 cm. Sentinel nodes were clear.  Surgeon thought no chemo would be needed.  I thought all Her2+ invasive tumors were treated with chemo and herceptin.  What size warrants chemo and herceptin?

Dx 7/7/2011, ILC, 2cm, Stage IIA, Grade 2, 1/9 nodes, ER+/PR+, HER2+
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Jan 24, 2012 04:16PM - edited Jan 24, 2012 04:21PM by Hindsfeet words...My school, Christian School, sent out a prayer request for my upcoming BC surgery. In the past I've kept it quiet...but for a few close friends who knew. It was nice because after the mx, they brought over meals, and so much more. I haven't been on the receiving side so it was indeed a different experience...humbling, but appreciate the support of so many good friends.

I live in an area where alternative and holistic is preferrable...the great N.W. Even a lot of the medical professionals here are alternative supportive.

Another comment in regard to "read the threads here and see all who are surviving"...actually,one of the reasons, I fear tamoxifen, rads and chemo. I see how so many of them are struggling, and the pain they have been through. I know there are a few who stay here on bco who continue to do well...but too many others, who shared side effects have scared me away from it.

I feel tried. I guess I'm getting tired of explaining myself and having to defend my choices and etc. After reading your post VR...although you are a very supportive to those going through BC, I realize, not so much you, but others here too, who do not consider everything in my health that needs to be taken into consideration before "standard" treatment is administered. 

Hope the best to all of you. ((((hugs)))) Evebarry 

Dx 6/13/2014, IDC, 1cm, Stage IV, Grade 3, mets, ER+/PR+, HER2+
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Jan 24, 2012 05:04PM voraciousreader wrote:

Eve... You may recall my niece is a medical oncologist and did her residency and several years of practicing in Portland! I know exactly what you are talking about! I am sorry that she has moved on to Denver... Otherwise I would have had you get in touch with her...

I hope you get all your questions answered fully. I would hate to see you make a decision as important as this when you are confused. Furthermore, once you receive answers, perhaps you will have a change of heart.

Without a doubt it can be comforting to be enveloped by folks who are concerned for you. But Eve, at the end of the day, no one should be angry with your treatment decisions. Everyone should support your decision....


Doctor told me regarding my prognosis that I WASN'T on the Titanic! Hmmm...Really?....Okay! 02/2010 Pure Mucinous Breast Cancer, Oncotype DX 15, Stage 1, Grade 1, 1.8 cm, 0/2 nodes, ER+ 90% /PR+ 70% HER2- (+1)
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Jan 25, 2012 08:13AM bluedasher wrote:

Bessie, regarding your 3), the MD Anderson study wasn't looking at all stage I. They looked only at tumors less than 1 cm without chemo and  the HER2+ group in that study had 77.1% 5 year disease free survival so about 23% recurrence. The 95% confidence interval was 67% to 84.5% (i.e. if one gets that result looking at a random group of that size, the real probability of recurrence is probably somewhere between 15  and 33%).

In the article that VR posted, they also said that they didn't see a significant difference in recurrence rate between the T1a and T1b HER2+ tumors. With these small tumors, your logic of twice the number of cells meaning it is more likely that some have gone beyond the breast doesn't seem to hold true. Perhaps that is because the women also had cancer cells in varying amounts of non-invasive tumors (e.g. a combination of DCIS and IDC). Or perhaps something is happening when the cancer goes from non-invasive to invasive that sometimes means that the cells go wondering.

The whole world is a narrow bridge and the main thing is to not fear. Dx 9/2008, IDC, <1cm, Stage IB, Grade 2, 0/5 nodes, ER-/PR-, HER2+ Targeted Therapy Herceptin (trastuzumab) Surgery Lumpectomy: Left Radiation Therapy Chemotherapy Cytoxan (cyclophosphamide), Taxotere (docetaxel)
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Jan 25, 2012 04:29PM wrote:

bluedasher, the results you quoted are correct but you have misinterpreted what I was saying. As you said, the study that VR quoted shows that "The 5-year recurrence-free survival was 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively"  Note that they are referring to "recurrence-free survival" which therefore includes both local recurrence and distant recurrence.  

The comment made here (more than once) that I challenged was that there is "a 25% chance of the HER2+ cancer spreading through the blood without lymph node involvement....when first undergoing staging, there is a 25% chance that BC will be found outside the breast with no involved lymph nodes." This refers specifically to distant recurrence.  So here is the next sentence in the study report, which refers to this: "The 5-year distant recurrence-free survival was 86.4% and 97.2% in the 2 patient groups."  So this says that for those with HER2+ tumors that are less than 1cm in size, the risk of distant recurrence (over 5 years) is 13.6% - not 25%. 

I understand that all HER2+ cancer are more aggressive than non-HER2+ cancers, whatever the size. That is what these studies are telling us. I also agree with VR that treatment standards for smaller HER2+ cancers (including T1a tumors) are likely to become more aggressive in the future as more data about these small HER2+ tumors becomes available. These recent studies certainly suggest that even small HER2+ can be concerning, particularly as compared to HER2- cancers of the same size.

However while I understand all that, what I don't see anywhere in these studies is any statement that says that the distant recurrence risk for a T1a HER2+ tumor is the same as the distant recurrence risk for a T1b HER2+ tumor. (If I missed that, I would appreciate someone pointing it out.) The studies in fact seem to group all patients with T1a and T1b (i.e. 1cm or smaller) tumors together, and therefore they draw their conclusions for this group as a whole.  But saying that those with T1a/b HER2+ tumors face a greater risk than previously understood and saying that T1a/b HER2+ patients may need to consider treatments such as chemo and Herceptin, is not the same as saying that the risk is the same for those with T1a and T1b tumors.  The studies have simply grouped both sizes of tumors together to reach a single conclusion; they have not compared the results of each group and determined that they are the same.

I have tried to see if I can find any studies that actually compare HER2+ T1a and T1b tumors. The study linked below did group the two tumor sizes together however they reference the results for the T1a tumors, as well as providing total results.  Therefore, by subtracting the T1a numbers from the total numbers, it leaves the results for the T1b tumors.  Here's the finding (over a 41 month follow-up period):

- HER2 T1a tumors:  3 recurrences among 36 patients who did not receive Herceptin & chemo, therefore an 8.3% recurrence risk.

- HER2 T1b tumors: 9 recurrences among 76 patients who did not receive Herceptin & chemo, therefore an 11.8% recurrence risk.  This is 42% higher rate of recurrence.  I don't know if the results are statistically significant - they possibly aren't due to the small sample size. 

So back to my earlier point, it is my understanding that, all other factors being equal (grade, ER status, PR status, HER2 status, etc.), a larger tumor will present a greater risk.  

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Jan 25, 2012 05:27PM bluedasher wrote:

Bessie -

Quotes from the article that VR posted in the second to last post on the first page of this thread:

"There was no significant difference in the risk of recurrence or distant recurrence in patients with Stage TIb vs Stage TIa disease."


"The M. D. Anderson study, which showed no significant difference in recurrence rates between women with Stage TIa and TIb HER2-positive tumors, suggests that even the smallest tumors may benefit from trastuzumab, Dr. Rakkhit said."

I haven't seen the numbers published - I'm just going by those statements. 

They did show the DFS survival and Distant Recurrence Free Survival for the whole group in the San Antonio poster. 

It was (95% confidence interval in parenthesis):

DFS for all patients in the study:

1a     92.5% (88.9%, 94.9%)

Ib      91.8% (89.3, 93.8%)

Distant recurrence  Free Survival

1a   96.6%   (93.8%, 98.2%)

1b   95.9%  (94%, 97.3%)

In both cases, while there is a small advantage in the actual number for Ia vs Ib, there is  considerable overlap in the confidence intervals - the difference might be random variation. I wish they had broken out the numbers for the two parts of the HER2+ group so that we could compare for ourselves and to see if those were closer than for the whole group, but they didn't.

I understand that as tumors get larger, the risk that they have spread gets greater if all other factors are equal. But it is possible that the difference between a T1a and a T1b tumor isn't enough for that to be a significant factor and other variations may overwhelm it. 

The whole world is a narrow bridge and the main thing is to not fear. Dx 9/2008, IDC, <1cm, Stage IB, Grade 2, 0/5 nodes, ER-/PR-, HER2+ Targeted Therapy Herceptin (trastuzumab) Surgery Lumpectomy: Left Radiation Therapy Chemotherapy Cytoxan (cyclophosphamide), Taxotere (docetaxel)
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Jan 25, 2012 08:28PM orange1 wrote:

No statistically significant difference between recurrence rate of T1a and T1b does NOT mean that the recurrence rates are similar.  It means in the population studied, that a statistically significant difference wasn't demonstrated with 95% confidence.  There could still be a real (even statistically significant difference) in the recurrence rate in  the overall population of Her2+ T1a and T1b tumors - it may just be a matter of doing a larger study.  Due to huge variation, with a sample size of < 100 women, its pretty hard to demonstrate a difference unless the difference was huge.

Dx 8/2007, IDC, 1cm, Stage I, Grade 3, 0/3 nodes, ER+/PR-, HER2+
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Jan 25, 2012 08:38PM wrote:

bluedasher, thank you!  I read VR's posts on this page and the previous page but I missed the one that you referenced. I too really wish that we had the raw data because it's hard to know what's actually going on without having the data.  Saying that there was "no significant difference" means only that there was no difference that was certain at a 95% level. So maybe there really was no difference at all, or maybe there was a difference but it was only significant at the 80% level (just as an example).

Looking at the numbers quoted, part of the issue may be sample size.  It's mentioned that there were 965 patients, of whom 10% were HER2+ - let's say that's 96 women.  Of those, 2/3s had T1a tumors and 1/3 has T1b tumors.  So that's roughly 63 patients with T1a tumors and 33 patients with T1b tumors.  

Of the 96 women who were HER2+, 77% were recurrence-free and 86% were distant recurrence-free over 5 years. Personally I don't think that the recurrence-free numbers are relevant to this discussion because that includes local recurrence. Tumor size may be a bit of a factor in local recurrence but other factors such as margin size are much more critical.  So it's only the 14% who had a distant recurrence - approx. 13 women out of the 96 - that's relevant to the question as to whether tumor size makes a difference or not.  So it's all a question of how that small group of 13 women was split between the T1a and T1b tumors.  

I pulled up a statistical significance calculator, and discovered that with the sample size split the way it is between T1a and T1b tumors, you need some pretty extreme results in order to reach the 95% statistical significance level. For example, if only 6 of the 63 T1a women had a distant recurrence (9.5%) while 7 of the 33 T1b women had a distant recurrence (21.2%), the results would only be 89% significant and therefore the conclusion would be that there was no significant difference in the risk of distant recurrence in patients with Stage TIb vs Stage TIa disease.  We only reach the 95% statistical significance level when no more than 5 of the T1a women (7.9%) and no fewer than 8 of the T1b women (24.2%) have a distant recurrence.  So to me this suggests that the statement that there was no statistically significant difference between the T1a and T1b results really holds no meaning, given the small sample size in this study. 

The other important point is that the study did not distinguish between other important factors such as grade and ER/PR status.  I understand that a larger lower grade ER+/PR+ tumor might present less risk than a smaller high grade ER-/PR- tumor - even if both are HER2+.  In this study (and most of the studies discussed here) all those other factors were blended together so there is really no way to measure the effect of tumor size, in isolation of everything else.  

There has been a lot of discussion in this thread that seems to suggest that all HER2+ tumors present an equal risk, regardless of size. People have presented "average" risk numbers and suggested that they apply to someone who has a smaller than average tumor. I believe that this is misleading and wrong.  I was not suggesting that other factors such as grade and ER/PR status are not also important, nor was I suggesting that tumor size is a more important than any of these other factors. What I simply was saying is that when all other factors are equal, the bigger the tumor, the greater the risk.

orange1, just saw your post as I was reviewing mine.  We are thinking the same thing! 

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Jan 25, 2012 10:43PM suzieq60 wrote:

Ladies - I've posted this study before and still find it very interesting. It may be helpful to ccjj - the original poster. A lot of us HER2+ve girls who had chemo/herceptin were very happy to read this when it was first posted on this site.

2nd diagnosis October 2010 - IDC 5.8mm node negative - missed on mammogram in October 2009 Dx 10/13/2009, ILC, 1cm, Stage I, Grade 3, 0/5 nodes, ER+/PR+, HER2+
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Jan 26, 2012 05:35AM voraciousreader wrote:

Susieq58...Thanks for posting the letter to the editior indicating these authors retrospective analysis of T1a and T1b HER2 + tumors.  IMHO the most important paragraphs are the following:

"In addition to the retrospective                     nature of our study, other limits are the small number of patients and the short follow-up, which may have led to an underestimation                     of the benefit of trastuzumab-based therapy. As chemotherapy was associated with trastuzumab in most occurrences, it is difficult                     to ascertain the respective impact of each therapy. However, our results are strikingly close to those presented by McArthur                     et al13 at the 2009 ASCO breast meeting.                 

Adjuvant trastuzumab combined with chemotherapy is now a standard of care for HER2-positive breast tumors that exceed 1 cm                     and/or pN+. We believe it should also be considered for T1ab, pN0, HER2-positive tumors, especially in the presence of other                     poor prognosis factors (ie, high grade, high MI or HR negative). Of course, the incremental gain in absolute benefit observed                     by adding trastuzumab-based therapy in this series cannot be predicted, and long-term toxicities should be carefully considered                     on an individual basis during the decision-making process. As trastuzumab has proven its efficacy in the adjuvant setting                     exclusively when combined with chemotherapy,5-10 we would recommend the administration of adjuvant trastuzumab along with chemotherapy when considered. We also propose that                     patients with T1ab, pN0, HER2-positive breast tumors have access to current adjuvant trials of HER2-targeted agents."

It is important to note that THIS study was a retrospective analysis of patients. The downside of the study was that they were NOT able to base their conclusions on clinical trials and that the sample populations in the studies were very small.     The researchers all would welcome a clinical trial  to answer the question as to whether or not the benefits of aggressive treatment for very small HER2+ tumors would outweigh the risks.  Again, it seems that in retrospective analysis, the answer is there.  With the latest Lancet study, I think it is just a question of time before the NCCN guidelines will be updated WITH A FOOTNOTE because the level of evidence is NOT as certain as it would be had there been a clinical trial.     

Doctor told me regarding my prognosis that I WASN'T on the Titanic! Hmmm...Really?....Okay! 02/2010 Pure Mucinous Breast Cancer, Oncotype DX 15, Stage 1, Grade 1, 1.8 cm, 0/2 nodes, ER+ 90% /PR+ 70% HER2- (+1)
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Jan 26, 2012 08:26AM - edited Jan 26, 2012 08:43AM by bluedasher

Susieq, While I was really happy to see that letter when I first skimmed it - especially the graph with the flat 100% line for those who received Herceptin, the short follow up period (25 months median) makes the results not terribly useful. Is Herceptin preventing or merely delaying recurrences? Only 11 Herceptin treated cases had 3 years of follow up and only 2 had 4 years.

In BCIRG, with over 600 node negative cases (with larger tumors) getting Herceptin, almost no recurrences had occurred by 24 months of follow up and DFS at 5 years was 93% for AC-TH and 90% for TCH. If one looked at only 11 of those cases at 3 years or 2 cases at 4 years in that study, one would be likely to see zero recurrences too (if DFS was 94% and one randomly chose 11 cases there would be a 50% probability of finding 100% DFS).

I'd like to see at least 5 year follow-up numbers but Herceptin hasn't been given for women with such small tumors for long enough to build up that data I guess.

The whole world is a narrow bridge and the main thing is to not fear. Dx 9/2008, IDC, <1cm, Stage IB, Grade 2, 0/5 nodes, ER-/PR-, HER2+ Targeted Therapy Herceptin (trastuzumab) Surgery Lumpectomy: Left Radiation Therapy Chemotherapy Cytoxan (cyclophosphamide), Taxotere (docetaxel)

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