her2 and anthracyclines--deserves posting on the main board

[Lani]

did not topo2a test to see which her2 tumors really needed the anthracyclines, but this is big as it might save a lot of her2- patients a lot of toxicity and save governments/insurance companies money leaving them more able tto afford herceptin. Dr Piccarts comments at the end are particularly welcome! Joe, if you disagree with this posting, just move it to the articles!



HER2 Overexpression Linked to Breast Cancer Response to Anthracycline

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NEW YORK (Reuters Health) May 17 - Amplification of the human epidermal growth factor receptor type 2 (HER2) gene and overexpression of its product are associated with clinical responsiveness to anthracycline-containing chemotherapy, Canadian investigators report.

According to their report in the New England Journal of Medicine for May 18, previous studies have demonstrated that the combination of cyclophosphamide, epirubicin and fluorouracil (CEF) used to treat breast cancer led to increased survival compared with a regimen of cyclophosphamide, methotrexate and fluorouracil (CMF). CEF is more toxic and more expensive, however.

Lead author Dr. Kathleen I. Pritchard, from the University of Toronto in Ontario, and her team theorized that CEF preferentially benefited tumors that amplified HER2. To test their theory, they examined tumor specimens from women who participated in the Mammary.5 randomized trial involving premenopausal women with node-positive breast cancer.

They examined the HER2 status of 639 tumor specimens four ways, with immunohistochemical analysis using CB11 antibody and TAB 250 antibody, fluorescence in situ hybridization (FISH), and polymerase-chain-reaction (PCR) analysis.

Immunohistochemical analysis showed that 18% to 20% amplified HER2, while PCR was positive in 31% and FISH in 26%.

According to FISH results, women with HER2 amplification had decreased relapse-free and overall survival compared with those without HER2 amplification.

However, cancers that amplified HER2 had a superior response to CEF than to CMF (hazard ratio for relapse, 0.52, p = 0.003; HR for death, 0.65, p = 0.06).

In contrast, tumors that did not amplify HER2 did not differ significantly in their response to chemotherapy with CEF or with CMF.

After adjusting for age, nodal status, estrogen-receptor levels, type of surgery, and tumor size, the hazard ratio for the interaction between treatment and amplification remained significant for relapse-free and overall survival.

Dr. Pritchard's group advises that "patients whose tumors do not exhibit amplification or overexpression of HER2 could be treated with the less toxic regimen of CMF, whereas those with tumors that show amplified or overexpressed HER2 should receive dose-intensive anthracycline-containing regimens such as CEF."

While acknowledging that these findings "represent a step forward in anthracycline tailoring," Dr. Martine J. Piccart-Gebhart, from Universite Libre de Bruxelles, Brussels, points out that, with the advent of the anti-HER2 monoclonal antibody trastuzumab, anthracyclines may not even be required.

She concludes, "The time has come to divide breast cancer into clinically relevant molecular subgroups, to prioritize the clinical questions applicable to each subgroup, and to strengthen collaboration between clinicians and laboratory scientists in identifying molecular signatures that can predict the success or failure of treatment." She writes that the use of genomics and proteomics may be particularly beneficial in this process.

N Engl J Med 2006;354:2103-2111,2177-2179.

[Lani]

Research identifies most effective chemotherapy treatment for premenopausal women with HER2 positive breast cancers [Sunnybrook Health Sciences Centre]
A study led by Canadian Cancer Society researchers has found that premenopausal women with HER2 positive breast cancers have better overall survival and lower cancer recurrence rates when they are treated with an anthracycline-based chemotherapy. The findings are published in the May 18 issue of The New England Journal of Medicine.

The findings mean also that the two-thirds of premenopausal breast cancer patients whose tumours are not HER2 positive can be treated just as effectively with a less toxic chemotherapy regime.

"The results of this study are encouraging because they suggest that we can fine tune cancer treatments for specific groups of patients," says Dr. Barbara Whylie, CEO of the Canadian Cancer Society. "Because of these findings, we will be able to offer many breast cancer patients a treatment that is just as effective, but that has fewer side effects. That means a better quality of life for these women."

Dr. Kathleen Pritchard, chair of the breast cancer site group and head of clinical trials and epidemiology at Toronto Sunnybrook Regional Cancer Centre, the comprehensive cancer program at Sunnybrook Health Sciences Centre and the study's lead author, says, "This research suggests that we can target treatment and give each woman only the most effective treatment for her particular situation. If we begin by identifying certain factors, such as HER2, it helps us to make a clearer selection of the treatment that is needed."

In previous studies involving premenopausal women with lymph node-positive breast cancers who were treated with CEF, there was an 18 per cent increase in overall survival and a 30 per cent lower cancer recurrence rate over women who were treated with CMF. CEF is an anthracycline-based chemotherapy that is a combination of cyclophosphamide, epirubicin and fluorouracil. CMF is a combination of cyclophosphamide, methotrexate and fluorouracil. Dr. Pritchard and her team analyzed data and tissue samples from more than 700 women from one of these studies - a clinical trial funded by the Canadian Cancer Society - to clearly show that the survival benefits of CEF are actually limited almost entirely to patients whose tumours are HER2 positive.

Because CEF has more significant side effects, including increased rates of hair loss, nausea, vomiting and a small increase in the risk of congestive heart failure, doctors prefer to use CMF, if they can. HER2 breast cancers test positive for a protein called human epidermal growth factor receptor-2, which promotes the growth of cancer cells. One out of every three breast cancers produces an excess of HER2 due to a gene mutation. HER2 positive breast cancers tend to be more aggressive than other types of breast cancer.


ABSTRACT: HER2 and Responsiveness of Breast Cancer to Adjuvant Chemotherapy [New England Journal of Medicine; Subscribe]
Background: Amplification of the human epidermal growth factor receptor type 2 (HER2, also called HER2/neu) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens.

Methods: In the randomized, controlled Mammary.5 trial, we studied 639 formalin-fixed paraffin-embedded specimens obtained from 710 premenopausal women with node-positive breast cancer who had received either cyclophosphamide, epirubicin, and fluorouracil (CEF) or cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant chemotherapy. HER2 amplification or overexpression was evaluated with the use of fluorescence in situ hybridization, immunohistochemical analysis, and polymerase-chain-reaction analysis.

Results: Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment. In patients whose tumors showed amplification of HER2, CEF was superior to CMF when assessed on the basis of relapse-free survival (hazard ratio, 0.52; 95 percent confidence interval, 0.34 to 0.80; P=0.003) and overall survival (hazard ratio, 0.65; 95 percent confidence interval, 0.42 to 1.02; P=0.06). For women whose tumors lacked amplification of HER2, CEF did not improve relapse-free survival (hazard ratio for relapse, 0.91; 95 percent confidence interval, 0.71 to 1.18; P=0.49) or overall survival (hazard ratio for death, 1.06; 95 percent confidence interval, 0.83 to 1.44; P=0.68). The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival (95 percent confidence interval, 1.15 to 3.36; P=0.01) and 2.04 for overall survival (95 percent confidence interval, 1.14 to 3.65; P=0.02).

Conclusions: Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy.

[R.B.]

10/10

Good find.

Keep asking those difficult questions.

RB

[R.B.]

Here a link to another article on tailoring BC chemo and relation to HER 2.

I know very little about chemo. There is some comment on HER 2 alternatives at the end. I suspect it is another take on Lani's news item above.


RB



http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/3319

ABSTRACT

MedPage Today Action Points

* Explain to interested patients that a tumor's HER2 status is increasingly important for treatment decisions.

* In particular, note that this study suggests that women without HER2 over-expression can be treated with a less-aggressive form of adjuvant chemotherapy.

* Note that the trial described here reflects treatment before the availability of Herceptin (trastuzumab) for HER2-positive breast tumors.