A new study suggests that the superior benefits of anastrazole over tamoxifen already shown in clinical trials are maintained long after treatment is finished.
The study is published on Saturday 15th December in the early online issue of The Lancet Oncology and is the work of a large team of researchers from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. The study writing team was chaired by professor John F Forbes, who also chaired the ATAC steering committee. Forbes is from the University of Newcastle, Calvary Mater Newcastle Hospital, Newcastle, NSW, Australia.
Anastrozole, trade name Arimidex, from AstraZeneca, is an aromatose inhibitor used to treat breast cancer in postmenopausal women with hormone sensitive breast cancer. It is used after surgery (adjuvant therapy) and in the treatment of breast cancer that has spread to other parts of the body (metastatic). Aromatose inhibitors reduce the amount of hormone (estrogen) by damping down its conversion from androgens. Estrogen sends signals to breast cancer cells to grow.
The ATAC trial, which was carried out in collaboration with AstraZeneca, compared the effect of Arimidex (anastrozole), tamoxifen, or both, given for 5 years, on the recurrence and survival in postmenopausal women with hormone-sensitive, operable, early breast cancer. Altogether the trial recruited over 9,300 women from 21 countries who were randomly assigned to each of the three treatment groups.
A number of studies have been published at various stages of the ATAC trial, but this is the first to show ATAC results at 100 months of follow up, and, according to the authors, it “is the longest follow-up to date after 5 years of upfront treatment with aromatase inhibitors”.
A previous study published in the Lancet in 2005 (365: 60-62) after 68 months of follow up showed that patients in the anastrozole group had increased disease free survival by about 15 per cent compared to the tamoxifen only group. They also had a higher time to disease recurrence that was 25 per cent longer than the tamoxifen only group, less cancer spread (time to distant recurrence was 16 per cent less), and fewer new cancers in the other breast (over 50 per cent fewer), compared to the tamoxifen group.
Another report on the same follow up period, published in the journal in 2006 (7: 633-43) showed treatment with anastrazole was linked to fewer serious adverse events than treatment with tamoxifen.
The results of these, and other studies, led to aromatose inhibitors being recommended for adjuvant therapy for postmenopausal women with hormone receptor positive early breast cancer.
But, the jigsaw was not complete. The missing piece was whether the benefits and lesser side effects of anastrozole remained long after treatment was finished.
In this study the authors report, that after nearly 4 years of follow up, the disease free survival reported in the earlier studies was maintained after treatment was finished. The mean age of the participants at this point was 72 years.
Also, the time to recurrence differences between the anastrazole and tamoxifen groups increased over time (from 2.8 per cent after 5 years to 4.8 per cent after 9 years), and recurrence rates after treatment had finished stayed significantly lower in the anastrazole group. The effect on distant recurrence was maintained.
The researchers also found no significant differences in the risk of disease or death from cardiovascular causes between the treatment groups.
They concluded that:
“The findings of this report extend the previously reported superior efficacy of anastrozole over tamoxifen at 68 months of follow-up to 100 months. We also show a carryover benefit for recurrence in the hormone-receptor-positive population which is larger than that previously shown for tamoxifen.”
Breast cancer is the most common type of cancer in women and the most frequent cause of death linked to cancer.
Worldwide, over 1 million women are diagnosed with breast cancer every year, with over 400,000 deaths every year.
About 75 per cent of breast cancers diagnosed in developed countries are in postmenopausal women, of which 8 in 10 are of the hormone receptor positive type addressed by aromatose inhibitors.
“Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial.”
The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group.
The Lancet Oncology, Published Online, December 15, 2007
DOI:10.1016/S1470-2045(07)70385-6
Written by: Catharine Paddock