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Long-term treatment superiority of anastrozole over tamoxifen in early breast cancer "carries over" years after treatment has stopped

17 Dec 2007
Long-term treatment superiority of anastrozole over tamoxifen in early breast cancer "carries over" years after treatment has stopped New data from the landmark ATAC (Arimidex, Tamoxifen, Alone or in Combination*) trial have revealed that the benefits of managing hormone-sensitive early stage breast cancer (ESBC) with anastrozole, a 3rd generation aromatase inhibitor (AI), are maintained for up to 4 years after the end of a 5-year course of treatment.

Details of the 100-month ATAC follow-up were presented at the 2007 San Antonio Breast Cancer Symposium (San Antonio, Texas, US, Friday December 14th) by lead investigator, Professor John Forbes (University of Newcastle, New South Wales, Australia).

These latest ATAC findings confirm that the “carry over” benefit favouring anastrozole over tamoxifen, the previous ‘gold standard’ adjuvant hormonal therapy, actually increases with time.

Meanwhile, the data also indicate that the excess fracture risk associated with active anastrozole therapy – a continuing concern for physicians considering AI therapy in this setting – completely disappears within a matter of months of stopping treatment.

Professor Forbes commented: “In my opinion, these new data show that there is no longer any rationale for using tamoxifen over anastrozole in women with postmenopausal early breast cancer.

“ATAC is a ground-breaking study. It has already led to a significant change in breast cancer treatment strategies, with anastrozole now replacing tamoxifen as the standard of care in many centres.

“In countries where this has yet to happen, these new data will seriously challenge the status quo, as they show us that the protective effect of anastrozole is present well beyond completion of treatment. It provides an indisputable reason for starting with anastrozole to give women the best chance of staying cancer-free.”

He reported that the efficacy gap between anastrozole and tamoxifen (first established at 68 months) widens still further at 100 months – up to 4 years after ATAC patients had stopped taking either drug.

Specifically, he noted that compared to tamoxifen, treatment with anastrozole in women diagnosed with hormone receptor-positive ESBC:

• reduces the risk of breast cancer recurrence by 24% (hazard ratio 0.76, p=0.0001)

• improves disease-free-survival by 15% (HR 0.85, p=0.003)

• reduces the risk of distant metastases by 16% (HR 0.84, p=0.022)

• reduces the risk of contralateral breast cancer by 40% HR 0.60, p=0.004)

Professor Forbes said this represents an overall 25% “carry over” benefit for anastrozole over and above tamoxifen in the years following completion of adjuvant hormonal therapy (HR 0.75, p=0.01).

Importantly, the absolute difference in terms of time to recurrence, favouring anastrozole over tamoxifen, nearly doubled over time - from 2.8% at completion of treatment to 4.8% at up to 4 years following completion of treatment. The same was true of time to distant recurrence (an absolute difference of 1.3% rising to 2.4%) and risk of contralateral breast cancer (0.8% rising to 1.7%).

Although breast cancer deaths were marginally fewer with anastrozole than with tamoxifen (245 vs 269), there was no difference in overall survival (HR 0.97) – possibly because patients on adjuvant hormonal treatment are living longer and dying of other causes.

Previously published 68-month data from ATAC had suggested that while anastrozole is significantly more effective than tamoxifen in preventing disease recurrence and is better tolerated, it is also linked to a higher risk of fractures on treatment. This was reflected in an annual fracture rate of 2.62 with anastrozole compared to 1.77 with tamoxifen.

However, at 100 months, this difference had disappeared: an annual fracture rate of 1.15 with anastrozole vs 1.02 with tamoxifen.

Other safety benefits with anastrozole were maintained during the 100-month follow-up – in particular for endometrial cancer (an annual rate of 0.014