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Breast cancer combination trial offers favourable results


Women with a particularly aggressive form of breast cancer seem to do better if treated with a combined anthracycline and taxane chemotherapy regimen before surgery, together with trastuzumab (Herceptin®) before and after surgery, according to results from the largest multicentre trial to investigate this treatment.

Professor Michael Untsch  told the 6th European Breast Cancer Conference (EBCC-6) in Berlin that the women in the trial suffered no serious side-effects from the treatment, such as severe heart problems.

These results are challenging, as both trastuzumab and anthracyclines are associated with cardiac toxicity.

Prof Untsch  said: “When we started this trial it was considered very courageous to give patients anthracyclines plus trastuzumab, but we wanted to expose patients to trastuzumab for as long as possible before surgery to make it as effective as possible.

“To minimise the risk, we excluded patients with any previous heart problems and excluded patients with ejection fractions of below 55%.

“However, our results showed no increase in toxicity for the combination chemotherapy plus trastuzumab compared with chemotherapy alone.

“There were no cases of congestive heart failure or cardiac-related deaths, and other cardiac-related symptoms were not severe.

“The combination chemotherapy plus trastuzumab proved to be the most effective combination, but at the same time we have to keep an eye on the heart.

“Therefore, cardiac monitoring every three months is a must for patients treated with this regimen.”

Of 1,510 breast cancer patients recruited to the GeparQuattro trial in 2006–7, 453 had tumours that overexpressed the HER2 receptor – a particularly aggressive form of the disease.

Before surgery the patients received four cycles of epirubicin/cyclophosphamide (EC) and were then randomised to receive either four cycles of docetaxel (D) or four cycles of D-capecitabine (DX), or a combination of both D and DX, or four cycles of D followed by four cycles of DX.

Women with HER2-positive tumours also received trastuzumab at the same time as the neoadjuvant chemotherapy, and then continued with it after surgery for up to one year.

Both the chemotherapy and the trastuzumab were given via three-weekly infusions.

When the researchers analysed the data 15 months after the start of the trial, they found no evidence of any cancer remaining in the breast in 41.3% of women with HER2-positive tumours who had received both chemotherapy and trastuzumab, whereas the pathologic complete response rate (pCR, complete disappearance of cancer cells from the breast) was 19.5% in women who had not received trastuzumab.

Prof Untsch  said: “Previous studies have shown that HER2-positive women who do not receive trastuzumab never have a pCR rate that exceeds 20%.

Our study has shown that it is possible to combine trastuzumab with anthracycline/taxane chemotherapy regimen without any significant adverse effects on the heart, thereby significantly increasing the pCR rates for these women to 41.3%.”

The researchers are continuing to follow the women to see whether the pCR rates translate into improved overall survival.

They have also started a further trial, the GeparQuinto study, which will compare the combination of chemotherapy plus trastuzumab with lapatinib (a tyrosine kinase inhibitor) as a preoperative treatment.

GeparQuattro was run jointly in more then 100 breast cancer centres by the German Breast Group and the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), the two major German cooperative research groups for the treatment of gynaecological malignancies and breast cancer.


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