for Jean and others-Topo2a identifies those patients needing anthracylines

[Lani]

1: J Clin Oncol. 2006 May 8; [Epub ahead of print] Links

Topoisomerase II{alpha} Gene Amplification Predicts Favorable Treatment Response to Tailored and Dose-Escalated Anthracycline-Based Adjuvant Chemotherapy in HER-2/neu-Amplified Breast Cancer: Results From the Randomized Scandinavian Breast Group Trial 9401.

Tanner M, Isola J, Wiklund T, Erikstein B, Kellokumpu-Lehtinen P, Malmstrom P, Wilking N, Nilsson J, Bergh J.

Laboratory of Cancer Biology, Institute of Medical Technology, and Department of Oncology, Tampere University and Tampere University Hospital, Tampere; Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland; The Norwegian Radium Hospital, Oslo, Norway; Department of Oncology, Lund University Hospital, Lund; and Cancer Centre Karolinska and Radiumhemmet Karolinska Institute and University Hospital, Stockholm, Sweden.

PURPOSE: Amplification of the HER-2/neu and topoisomerase IIalpha (TOP2A) genes has been linked to the effects of anthracyclines. Their role in predicting the outcome of anthracycline-based adjuvant chemotherapy for breast cancer patients has remained controversial. PATIENTS AND METHODS: The present substudy of the Scandinavian Breast Group trial 9401, in which an epirubicin-based regimen (nine courses of tailored and dose-escalated fluorouracil, epirubicin, and cyclophosphamide [FEC]) was compared with three or four courses of standard FEC followed by bone marrow-supported high-dose chemotherapy (cyclophosphamide, thiotepa, and carboplatin), included high-risk breast cancer patients (with eight or more positive axillary lymph nodes or at least five nodes with additional poor prognostic indicators). Amplification of HER-2/neu was determined retrospectively in paraffin-embedded tumor tissue sections by chromogenic in situ hybridization. TOP2A was tested only in HER-2/neu-amplified tumors. RESULTS: HER-2/neu amplification alone, which was present in 32.7% of the tumors, was a strong prognostic factor for short relapse-free (P = .0034) and overall survival (P = .0008) but showed no direct association with treatment assignment. TOP2A coamplification, which was present in 37% of HER-2/neu-amplified tumors, was associated with better relapse-free survival in patients treated with tailored and dose-escalated FEC (hazard ratio [HR] = 0.45; P = .049). A statistical multivariate Cox's regression analysis confirmed the predictive significance of TOP2A coamplification (HR = 0.30; P = .020) in HER-2/neu-amplified tumors. There was no such association in patients with HER-2/neu-amplified tumors without TOP2A gene amplification. CONCLUSION: Coamplification of HER-2/neu and TOP2A may define a subgroup of high-risk breast cancer patients who benefit from individually tailored and dose-escalated adjuvant anthracyclines.

PMID: 16682728 [PubMed - as supplied by publisher]

[Jean]

Lani,
Just received my TOPO 11 results late last night from Calif.
I am negative therefore I will not be getting A/C chemo. Dr. Slamon
has recommended another. Will meet with the onc. next week out
here and my journey will begin.

I know of onc. that are giving A/C without having the TOPO 11 test performed.
This is unfortunate for their trusting patients. Once again great post!
A big thank you!

Jean

[al from Canada]

TOPO II testing is relatively new and therefore most oncs will not be aware of it, unless they go to conferences as we do. That said, the TOPO II test is also a predictor of who might suffer LVF problems in the future which is probably even a better reason for having that test. If my memory serves me well, the TOPO II test may also be used as a predictor of who will respond favourably to herceptin without cardio problems therefore may be used by some countries in a herceptin cost / benefit analysis. Dr. Slaman mentioned that this can be done with the FISH therefore needent be costly. When I talked to our onc last Dec. he hadn't heard of the marker.

I would be interested in how many members or their oncs are aware of this test.


Al

[Lani]

What you are receiving is AHEAD of state of the art care. The article was just listed with the Library of Medicine of the Library of Congress today! The talk by Dr. Slamon in December at San Antonio regarding topo II testing and potentially withholding Anthracycline treatment from all but those who tested topo IIa positive was his preliminary results that were not yet published--they got their WORLD PREMIERE THERE. Most oncologists don't even know they have access to topo IIa testing and it was not until today that the paper was published for them to peruse if they didn't make it to San Antonio. What I find interesting is that a very large number of oncologists who presented papers in San Antonio did not necessarily stay to hear the talks of others. The abstracts were available in a book to them and a CD ROM later, but not the whole papers and not the whole meeting unless they paid over $1000 for the CDs of all the talks.

You must remember that after they learned H pylori caused the vast majority of ulcers about five years passed before they stopped doing stomach surgeries to treat ulcers and placing patients on various medicines and diets for ulcers.

Breast cancer is an area too important to let things go slowly so if we educate patients through this site they can prod their oncologists to find out more--remember doctors are always worried about malpractice cases and malpractice cases are based on the fact that a doctor cannot be found guilty if practicing the "standard of care in the community" a fact which makes oncologists hesitant to change to new ways even if they look like they will be superior until their professional society sanctions and endorses the new way of treating patients.

Why don't you post where your topo II testing was done, how many (unstained) slides had to be sent in (vs a whole block),and how you arranged it so others can take advantage of this. Let's move the treatment of breast cancer forward. TMD lists it as topoII was yours listed as topo IIA?

You might want to ask your oncs about radiation recall dermatitis. It is usually described with an anthracycline, but can happen with other chemos when given AFTER radiation therapy I think. Always better to think preventatively when possible.

According to the studies I have read, you will have decreased your chances of cardiotoxicity tremendously by not taking the anthracycline before the herceptin. Was your tumor on the left side (ie radiation therapy may have involved the heart)?

Congratulations on getting to skip an anthracyline. Let's hope with more exact molecular diagnoses of individual's tumors many individual patients get to skip toxic treatments that would not even be effective in their case.

Good luck!
Lani

[Jean]

Lani,
The arrangments for the TOPO 11 test were done by Dr. Slamon, at USC.
I had returned back from LA and contacted my New York hospital to send
five slides in parafin to USC for testing. It took five days to test and two
days for the slides to be sent.
My radiation was on my right side.
Radiation had gone extremely well and I had no side effects or negative
reactions during the treatment.
I am very fortunate that the test was done since the dr. here in New York
was set to go forward with A/C.
Lani- also to note many times when patients inform their onc. with current
updated information they are reluctant and hold off - (as you mentioned in the post) it appears that it takes time for new trt or test to take hold.
I would like to think that some onc. would at least take some moments out of their busy work days to investigate the information that their patient has reseaarched. There is a change occuring in medicine with paitent care in that patients are taking (as it should be) a team role in their treatment. Gone are the days where patients sit and just listen to the doctor's orders. I am always concerned for the group of patients that come from the old school, that my doctor knows best. I have had many dicussions with close family and friends who during my dx. did not understand questioning the dr. esp. with a disease such as cancer. Believe me there are many patients who DO NOT
question the trt or the dr. When I was receiving radiaiton most of the women did not even know the type of cancer they had, often times they said, "Oh my dr. said I was lucky I had the good kind." I could not understand this at the time. I have come to understand that many women are so frightened in those early months they are almost paralysed. This is noted in a certain age group, I would like to think the younger women are more prone to push and ask questions. I do believe that education in patient awarness is vital to women who are facing this disease (esp. 55- and up age group). This site is a GIFT
and I hope more women learn of it.
Many thanks for your well wishes!
Jean



Regards,
Jean

[Barbara2]

Al, sorry, but what does LVF stand for?

Thanks

[saleboat]

LVF- Left Ventricular Function (the little gate between the heart chambers, I believe)Jen

[Carol.hope]

I for one had not heard of this test. Do you think there would be any value in having it "after-the-fact" - after I've taken Herceptin for 5+ months and just found out my LVEF is too low (35%)? Would it help in the decision to re-start Herceptin if (I mean ASSUMING) my heart recovers?

I would guess insurance would not cover something so new, right? Any idea of the cost?

Thanks so much for posting all this great information!

-Carol