Trastuzumab with neoadjuvant chemotherapy before surgery improves response rates for HER2 positive breast cancer

A particularly aggressive form of breast cancer may be tackled 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 multi-centre trial so far.

Professor Michael Untch told the 6th European Breast Cancer Conference that the women in the trial did not suffer from any serious side effects of the treatment such as severe heart problems. The results are significant as both trastuzumab and anthracyclines are associated with cardiac toxicity.

Prof Untch 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."

A total of 1510 breast cancer patients were recruited to the ‘GeparQuattro' trial between 2006 and 2007; 453 of them with tumours that over-expressed the HER2 receptor. Before surgery they received four cycles of epirubicin/cyclophosphamide (EC) and were then randomised to receive either four cycles of docetaxel (D), four cycles of D-capecitabine (DX), 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 they analysed the data 15 months after the start of the trial, the researchers found that there was no evidence of any cancer remaining 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 Untch 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 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. In addition, they have started a further trial, the GeparQuinto study, which will compare the combination of chemotherapy plus trastuzumab with lapatinib as a pre-operative treatment.

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