Clinical Use of Herceptin Explored

[tousled1]

http://www.cancerpage.com/news/article.asp?id=11076

The Clinical Use of Herceptin Explored


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By Rachael Myers Lowe, Cancerpage
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(ffice:smarttags" /><?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-comJuly 6, 2007</st1:date>) – Up to 30 % of women with invasive breast cancer have disease that over-expresses the HER2 growth factor. HER2 both promotes cell proliferation and puts the breaks on cell death – a hallmark of cancer. HER2 over-expression pointed to a cancer that, until recently, was harder to treat and had a poorer prognosis. With the development of the targeted therapy, trastuzumab (Herceptin), came real hope of prolonged survival for these patients.
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Trastuzumab clogs up the signaling apparatus of HER2, blocking its over-expression and putting the breaks on HER2 dependent cancers. Yet, clinical trials have demonstrated a downside to trastuzumab treatment. Depending on the chemotherapy given with it, between 13% and 27% of the patients developed heart problems. It appears the HER2 performs an important function in helping repair damage to the heart caused by the chemotherapy.
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Writing in this week’s New England Journal of Medicine, Dr. Clifford Hudis, of the Memorial Sloan-Kettering Cancer Center, examines the research and concludes trastuzumab does have a role to play in managing some late and early stage breast cancers and that the clinical trials to date show how important it is to refine how cancers are biologically categorized. In the case of HER2 positive breast cancers, Dr. Hudis believes the evidence supports trastuzumab use in the following circumstances:
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Recurrent metastatic breast cancer – Patients with high-risk aggressive (HER2+, Estrogen - ) cancer should be seriously considered for chemotherapy with trastuzumab because the risk of the cancer far outweighs the potential risk of toxicity to the heart. It’s still a matter of debate whether patients with HER2+ and Estrogen+ cancers benefit from adding trastuzumab before, during, or after hormone therapy.
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Newly diagnosed metastatic breast cancer – Trastuzumab can be considered as mono-therapy before chemotherapy since a small non-randomized trial demonstrated the drug was effective alone and spared the patient the side effects of chemotherapy for as long as six to 18 weeks. Once a cancer has progressed on trastuzumab, however, there’s no evidence to suggest continued use of the drug, even with chemo, is helpful.
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Early stage breast cancer - Trastuzumab might benefit women with early stage HER2+, estrogen- breast cancer and should be considered. But women with small tumors that are HER2+, estrogen+ with no node involvement, the benefits seem” quite modest,” requiring more attention to the potential toxic effect of the trastuzumab on the heart.
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In a letter to the editor in the same NEJM issue, two Canadian researchers report on their trial of 155 women treated for early stage breast cancer between July and December 2005. Of those, 102 received sequential treatment (chemo then trastuzumab), and 53 got concurrent treatment for 52 weeks.
In the sequential treatment group, 22 of the patients experienced heart trouble that required temporary or permanent stopping their trastuzumab. Four women in this group developed suspected or confirmed congestive heart failure.
In those who got concurrent treatment, one woman developed a decline in a measure of how well the heart is pumping blood. She had to stop treatment but then was able to resume. One other woman had congestive heart failure.

[Lani]

This seems to go against all the findings of the HERA and No. American combined studies which showed in the adjuvant setting that herceptin decreased the incidence of recurrence when combined with chemo by almost 50% IRRESPECTIVE of whether the her2+ bc was ER+ or ER-

From my attendance at various bc meetings and listening to the audiotapes of other meetings, Dr. Hudis seems to be someone who is very hesitant to give up the "gold standard" treatment of carpet bombing breast cancer with non-specific chemotherapies in this age of "smart bomb" targeted therapies.

He may or may not end up being right, but publishing these opinions as guidelines as he does in the New England Journal of Medicine gives ammunition to insurance companies wishing to deny treatment to patients. He may just be publishing what he believes to be state of the art, but dollars to doughnuts (ooh, I love these old sayings) I bet this "state of the art" will change in less than six months, but insurance companies will hold onto this article for years, citing it as a reason not to pay for "variations from the theme" If those who published these articles took a few minutes to think of the consequences to individual patients, they might phrase their "findings" or "conclusions" differently

Until we can dissect the different types of breast cancer and better detect which have metastasized early eg with isolated tumor cllls in bone marrow or Circulating tumor cells in peripheral blood to better decipher which subtypes respond best to which treatments, such blanket statements serve as a disservice, I think, by pressuring oncologists NOT to offer treatment options which might be the best for an individual patient.

A lot of lip-service has been paid to individualizing treatment, then articles like this seem to back-track by producing the same "cookbook" formulas to be followed unquestioning as these "pronouncements" come from one of the meccas of cancer treatment.

Sorry about editorializing, but at least I identify what I am doing.

[Lani]

" Trastuzumab MIGHT benefit women with early stage HER2+, estrogen- breast cancer and should be considered"
(where has he been? Virtually all adjuvant trials of herceptin, whether HERA, No. American combined trials, the TCH trials, and Fin Her trials came to the same conclusion-- isn't an ALMOST 50% reduction in recurrence , even if the absolute risk of recurrence may be a larger or smaller number (based on various clinical and immunohistochemical factors), which has proven to hold out over 4 years as the trial data has matured, worthy of of a word stronger than MIGHT?

He sounds like a representative of a national health service parsing his words trying to avoid giving an expensive drug to those it might benefit.

I don't think he has the data to support his statement regarding the "small", her2+ ER+ TUMORS WHICH WERE node negative, as they were not included in the studies. So more patients will be treated or denied treatment based on "but the New England Journal says"...

Sorry for more ranting and raving.

[Gerri]

I always look forward to your take on these things. Today, after reading that article I wondered about the validity of Dr. Hudis' "recommendations". Thanks for your "editorial" - it was much appreciated.

[Hopeful]

I read Dr. Hudis' article in the NEJM, and learned some intereting information, for example, that one of the Phase II trials to establish dosing of Herceptin actually showed better results in metastatic patients who had NOT had prior chemotherapy. A few days ago, I posted this article in the Articles forum: http://www.medwire-news.md/46/67774/..._activity.html The researchers posit that Herceptin may work better in an uncompromised immune system (i.e., one not yet exposed to chemotherapy) as Natural Killer cells are more plentiful before chemo and radiation, and one of the mechanisms of action of Hercetin is to work with the body's immune system to identify and kill Her2+ cells.

I chose to forgo chemotherapy as I though the toxicity did not justify the benefit, but I certainly wanted to receive Herceptin, and was fortunate to find an onc who would treat me with Herceptin and an AI. If Dr. Hudis was setting the standard for my care, I don't think that treatment would be available to me.

My biology is 1.3 cm IDC, ER+ (80%) PR+ (50%), Her2+++ by IHC, Node Negative, BR Score 7, Ki-67 11%, postmenopausal at dx.

Hopeful

Always good to get the other perspective. Congestive heart failure was the family curse until I broke the mold by getting breast cancer. I wonder sometimes if I should toss a coin!

[Jean]

Dr. Hudis....this is why I flew out to see Dr. Slamon....I truly believe that
Sloan is NOT the Mecca it once was believed to be. They are doing
some wonderful research (trials etc) but when Lani mentioned goling by
the OLD gold standard...this is hitting the OlD nail on the head.

Jean
PS Shame on Dr. H....for writing that article he has now caused set backs
for many woman who may be denied Herceptin.