Understanding the impact of HER2 on progosis/survival

rozem

dancermom - I think this study should give you comfort not getting pCR and being triple positive - AND from my understanding getting pCR in the nodes is great and having some residual breast tumor is not as big a deal - I remember my MO telling me that.  Ditto on the tamoxifen!

BlueFox

Here is a paper that shouldn't worry anyone.  It is a useful overview of the different ways of classifying breast cancer including the different multi-gene systems (Oncotype Dx, MammaPrint, PAM50) that I kept hearing about.

http://www.mlo-online.com/articles/201209/breast-cancer-prognostic-markers-where-are-we-now.php

BlueFox

This is an interesting report.  http://www.breastcancer.org/research-news/20140326

What I think it implies is:

if you had 1-3 positive nodes AND you had a Mx with radiotherapy, your survival might be significantly better than predicted by the online tools such as Predict and Adjuvant Online. These models are based on historical data, so their estimates already reflect the benefits of radiotherapy only to the extent to which the study population had radiotherapy.   

But if it wasn't routinely given in those days to women with 1-3 positive nodes (is this assumption reasonable?) then the online tools effectively assume no radiotherapy.  

Patients with greater number of positive nodes also benefit from radiotherapy, but this is probably already built into the predictions if patients normally received it in the past.

jennid1

As I finished my last herceptin treatment in May 2006 as part of a clinical trial these geek facts where just a prayer. 8 year's later and still cancer free but I still love seeing these charts.

yensmiles

hi BlueFox, i'm following this post to know more and perhaps get to "understand" why "i need chemo"... struggling to come to terms with it..or make a concrete decision on treatment, because on predict, my risk is fairly low.. 90% chance of survival without doing anything... doing the works just increase the chances by another 5% or so.. arghghghgh!!!

suzieq60

yensmiles - you have been mislead - the chance of recurrence for triple positive bc is 23% - chemo and Herceptin halves that - so about 11%

yensmiles

Which tool did you use suzieq60? or was the stats provided by your oncologist? I used Predict (the one bluefox shared right at the top of the post), and i've played around with it a bit. My prognosis would be worse if it's Grade3, though the tumour i had removed was a grade 2, so it could be these little distinctions, that or the tool predict has given me a very rosy picture!

suzieq60

My oncologist gave me the figures - I personally would not trust those tools.

SpecialK

suzieq - wouldn't that 23% be your individual risk?  Even though we are all Her2+ some of us are node positive or negative or had larger/smaller tumors - so differing stages, differing grades, differing ages at diagnosis  - all of this would affect our recurrence rates.

suzieq60

Yes, stage 1 node negative. I quoted that because yensmiles has a similar diagnosis except her tumour is a wee bit bigger.

AlaskaAngel

A difference could be due to Susieq having a history of both IDC and ILC, perhaps.

If oncs are not up front in discussing the risk of chemo causing cancer (whether involving other types of cancers such as leukemia, or recurrence of a patient's past or current cancer), the question I have is this:

If one patient, for example, has a 20% prediction, and another patient has a 10% prediction for recurrence of bc, the amount of each of those predictions presumably would include the percentage of risk posed by the chemotherapy itself. Would that portion of risk percentage be the same for each of the two patients? In other words, if for example the percentage of risk for chemo-caused cancer is 2%, is the patient with a 20% prediction for bc recurrence dealing with a 2% out of 20%, whereas the 10% patient dealing with a 2% out of 10% due to chemo-caused cancer?

suzieq60

No AA - those figures were given to me at the first diagnosis - the IDC was a year later and not HER2

AlaskaAngel

Kayb,

So... if one's risk is 10% for recurrence not due to chemo, then one also has an additional percent risk for chemo-induced cancers (including recurrence due to the chemo)?

As for family risk... there are some known of course, like BRCA, and some that are yet to be determined, but because I too have a LOT of family members on both sides with a history of bc (but no such dx as BRCA), I just look at whether any of them recurred or died of bc. For me, only one out of the bunch ever died of it, none recurred, and the one who died of it was diagnosed "late", back in the 1950's when detection, evaluation, and intervention were lousy in comparison. My sister's IDC has never recurred but she did later develop IBC, which has remained NED following her treatment. Hope that is reassuring.

AlaskaAngel

kayb, I think there has to be an additive value to that 2%, because that risk incurred is directly due to doing the treatment. If one doesn't choose to do the treatment, one has not incurred any secondary risk.

AlaskaAngel

I don't know if it is possible one way or the other, but since chemotherapy can cause cancers of various kinds, have researchers done the homework to show conclusively whether or not recurrence can be facilitated by chemotherapy? 

yensmiles

hmm... AlaskaAngel, referring to your last most, i don't think anything conclusive is in the near future, I'm thankful that there's tools such as oncotype and mammaprint (and a tad disappointed that it is not in my country). Was earlier asking one of my oncologist questions concerning why for some individuals who have no circulating cancer cells, they get cancer cells after chemo. . he didn't really answer my question.. cancer research is a very wide field..and i think a lot of the studies that oncologists refers too are mainly the ones regarding drug trials and efficacy..  and less on immunology and pathology.

Suzieq, after what you said, I did ask my oncologists as to why some others in my support group (this site here) reports higher risks than what I found in the tool, predict. He sent me a study, which i think clarifies this to a certain extent. Here are 5year mark recurrence free survival for HEr2+ vs HEr 2- (without adjuvant chemo+herceptin) 77.1% vs 93.7%  and distance recurrence free survvival for HEr2+ vs HEr2-   86.4% vs 97.2% It is of course a concern. This is just one study! Gosh, i don't know why i can't paste links here?!?? Does anyone know how to paste links to webpages?

and i don't quite understand the maths/stats you ladies have been discussing, though one thing for sure is chemo does increase chances of cancer (maybe not recurrence.. though leukemia is one possibility and different drugs have different risks). 

While I am quite, in a way feeling defeated at the moment (because i really think chemo sucks and i still have hopes of having my own kids), though i'm sure i will swing back to my positive self once chemo commenced because it's a choice that i'd have taken and i don't believe in regrets...until then, i'm eating turmeric/curcumin at almost every meal, heaps of fresh veg+fruit juices, snacking on nuts and fruit, even going on mecomin (a vit b that'd help prevent nerve damage), snake gourd (an Asian plant, proven to kill cancer cells yet research is not quite there yet in terms of dosage), eliminated processed food and heavy carbs/starches. 

AlaskaAngel

Thanks, yensmiles. When science is approached with an open mind, previously unquestioned assumptions can provide surprising avenues for more effective treatments. In part, that is what happened with trastuzumab.

Figuring out the plusses and minuses involved in treatment for those with early stage bc means keeping a lot of different causes and effects in mind all at the same time, to be able to find the best balance among them all for your own situation. It is also difficult because the information gathered to date is not yet long-term for trastuzumab, with only small populations having had use of it until it was approved for adjuvant use in 2005.

The questions about the use of trastuzumab without chemo exist because of the restrictions imposed by the original trials, which for the most part did not permit those with either tumors under 2 cm or those having negative nodes to participate. The rationale was that they did not want to expose patients with lower likelihood of recurrence to the unknowns of trastuzumab. However, it also may be true that the primary reason was because when a population at lower risk is included in studies like that, the outcomes are not as dramatic or impressive, since most early stage patients would not recur anyway, even if all they had was surgery.

The net of that is that for early stage HER2 positive bc, the risks and benefits for using BOTH chemo and trastuzumab have not been documented, particularly for long-term. The concerns about potential damage to the heart when combined with the additional damages posed for some by chemotherapy have no long-term answer yet, for example. That safety margin is higher for those who chose trastuzumab alone and are able to get it, because of the lack of documentation long-term about chemo plus trastuzumab, due primarily to the restrictions imposed that limited participation in the original trials for early stage bc patients.

AlaskaAngel

kayb, my thoughts on the how and why are the same as yours, but because of the huge amount of suffering and the expense that is attached to recommending chemotherapy and all the support drugs and labs and doctor visits and patient time and disfigurement for a group in which most patients would never recur, I wonder if they may have done some kinds of investigations to try to find out whether possibly some patients are recurring due to the chemo treatments -- perhaps by comparing that with other cancers caused by chemo in some way, or comparing patients from each of those groups to see if there are commonalities. I just wonder why that kind of investigation and information is not more well-known.

suzieq60

If Herceptin causes heart issues, it is not permanent. Also the only chemo drug found to have caused any other cancer diagnosis is Andriamycin - might cause leukaemia. I told my onc I did not want AC-TH. AC-TH is given usually to node positive patients TCH for node negative.

http://www.breastcancer.org/research-news/20111005

 

SpecialK

suzieq - it is important to qualify your statement regarding cardiac issues and Herceptin - there are BCO members permanently on cardiac meds after having to discontinue Herceptin early and before finishing the year of infusions.  For most, any drop in ejection fraction does improve over time, but this is not true for all.

BlueFox

In relation to some of the recent posts raising concerns and questions about the risks of chemo, my layperson's understanding is as follows:

1/  The risk of bladder cancer and leukemia that exists for some chemo drugs is very small compared with other risks from chemo.  The biggest risk from chemo by far is infection (which is a temporary risk as once you are post chemo the white blood cells recover).  

Chemo is unpleasant but most people find it very doable and are really glad they did it.  Most recurrences are metastatic cancer, so well worth going through a few months of unpleasantness to avoid,

2/  There is strong evidence for the efficacy of adjuvant chemotherapy.  Trials and studies would have been done when chemotherapy was first widely introduced as adjuvant treatment in the 1980s/90s. 

3/ Higher risk patients get the most benefit from chemotherapy, partly because their recurrence risk is higher to start and partly because the response to chemo is bigger for more aggressive cancers.  This is why it is not recommended for all patients and low risk patients are often advised that they don't need it.

3/  The NHS predict tool should only be used as a general guide - if you want accurate figures for the risks and benefits of different treatments, ask your onc.

yensmiles

Thanks BlueFox, things seem clear when you put it out that way! Checked out your blog, and sorry to hear about the infection! Hope all's going well in your treatment.

BlueFox

Thanks guys,

It definitely was an evil infection 

I'm now out of hospital with a vac dressing and oral antibiotics, and being followed up as an outpatient.

BlueFox

Herceptin (with chemo) remains that gold standard for adjuvant treatment of HER2 positive cancer. 

ALLTO results show that there is no survival advantage in combining Herceptin and Lapatinib, despite it improving pCR rates, casting doubt on the validity of complete response rates in predicting recurrence risk - see: 

http://www.newswise.com/articles/altto-test-of-dua...

http://www.medpagetoday.com/HematologyOncology/Bre...

ben50

Interesting and thanks for the post. Forgive my ignorance, but I am slightly confused on how the ALTTO results negates the value of achieving a pCR neoadjuvantly. The ALTTO demonstrated that there is no clinical benefit for dual target therapy in the adjuvant  setting, but there is still a plethora of past studies showing improved DFS, EFS, and OS with a pCR. So, because Tykerb/Herpcetin  post-surgery is no better then just Herceptin, the value of pCR is reduced? I think I'm just missing the connection.

rozem

i have to take this thread off my favorites. Depressing. I thought pcr was predictive   I think this is the second time i posted about my disappointment

Whats the point of neoadjuvant if not to get an idea of how your tumor is responding to rx. Why do they do it then ( other than cases where it makes surgery easier ) 

ben50

Thank you, kayb!! You cleared things up for me and reading the articles again, I was able to interpret the points much easier with your great explanation.  

ben50

My wife did indeed. I'm happy to say TCHP was very effective for her and the tumor/lump was gone by about the fourth day after the first infusion. All our doctors hailed the pCR as huge triumph at the time of surgery, so it's good to know we can still hold on to that=). 

And funny enough (and quite topical), we are actually getting dual targeted therapy for our adjuvant treatment -- excecpt it's Herpcetin/Perjeta and not Herpceptin/Tykerb. Soooo hopefully our adjuvant combo is more effective than the one researched...? After the release of this study, you have conclude probably not, but logic aside - it still gives us additional peace of mind. Furthermore, the study did demonstrate there was not much additional cardiac risk with duel inhibition, so I predict we'll stay the course. 

And of course, congrats on your pCR  

Girlstrong

hi Ben50, can I ask how you got approved for the combo of Herceotin/per jets for early stage breast cancer in the adjuvant setting? I thought it was only approved in the neoadjuvant settng for early breast cancer? 

BlueFox

Kayb is right.  

All that has been shown so far is that despite the Lapatinib Herceptin combo significantly increasing the proportion of patients with pCR, this has not translated across into decreased recurrence risk.  The researchers were very surprised by this and work needs to be done to understand why.

The results of other Herceptin combo trials will be eagerly awaited to see they follow a different or similar pattern.  No one knows which way they will go at this stage.

In terms of patients deriving a significant advantage from pCR from standard treatments (eg chemo), there is good evidence that it makes a big difference for triple negative and HER2+ non luminal cancers