Aromatase inhibitors produce a greater reduction in the risk of breast cancer recurrence compared to tamoxifen in premenopausal women
The use of aromatase inhibitors leads to a greater reduction in the risk of breast cancer recurrence in premenopausal women with ovarian suppression compared to tamoxifen. This was the key finding of a meta-analysis of individual patient data from randomised trials undertaken by a team from the Early Breast Cancer Trialists’ Collaborative Group, based in Oxford, UK.
In a 2011 analysis of 20 trials which included over 21,000 women, it was concluded that 5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. Moreover, aromatase inhibitors such as anastrozole, exemestane or letrozole, which block the conversion of androgens into oestrogens, have also been found to reduce recurrence rates of breast cancer by about 30% compared with tamoxifen in postmenopausal women. However, whether this class of drugs produce a similar and greater reduction in risk among premenopausal women with early-stage oestrogen receptor positive breast cancer and ovarian suppression is unclear.
In the present study, the UK team undertook a meta-analysis of individual patient data from randomised trials in which an aromatase inhibitor was compared with tamoxifen for between 3 and 5 years in premenopausal women and who were receiving ovarian suppression with goserelin, triptorelin or ablation. Data were collected on patient’s baseline characteristics including age, use of chemotherapy, body mass index, tumour grade, involvement of lymph nodes etc. The the primary outcome was recurrence of invasive breast cancer, breast cancer mortality, death but without cancer recurrence and all-cause mortality. In addition, they set pre-specified investigations for any recurrence, distant recurrence and mortality during years, 0 – 1, 2 – 4, 5 – 9 and greater than 10 years.
Aromatase inhibitors and breast cancer recurrence
The analysis included data from 7230 premenopausal women with oestrogen-receptor positive tumours.
Among these women, 888 (12.6%) experienced a breast cancer recurrence and 418 (5.9%) deaths occurred of which 54 were unrelated to breast cancer. When compared to women receiving tamoxifen, use of aromatase inhibitors led to a significant reduction in the rate of breast cancer recurrence (ratio ratio, RR = 0.79, 95% CI 0.69 – 0.90, p = 0.0005). Interestingly, the main benefit from aromatase inhibitors on the risk of recurrence was only seen in year 0 – 4 of follow-up (RR = 0.68, 95% CI 0.55 – 0.85, p < 0.0001). Between years 5 – 9, there was no further benefit (RR = 0.98, 95% CI 0.73 – 1.33, p = 0.89). The authors calculated the 5-year absolute risk of breast cancer recurrence to be 3.2% which was lower for aromatase inhibitors compared to tamoxifen (6.9% vs 10.1%). There was also a significant reduction in the risk of distant recurrence with aromatase inhibitors (RR = 0.83, p = 0.018) compared to tamoxifen but again this benefit was lost over time.
There was no difference in the risk of breast cancer mortality compared to tamoxifen (RR = 1.01, 95% CI 0.82 – 1.24, p = 0.94), death without recurrence (RR = 1.30, 95% CI 0.75 – 2.25, p = 0.34) and all-cause mortality (RR = 1.04, 95% CI 0.86 – 1.27, p = 0.68). Interestingly, women experienced a higher incidence of fractures with aromatase inhibitors (6.4% vs 5.1%).
The authors concluded that compared to tamoxifen, use of an aromatase inhibitor, reduced the absolute risk of breast cancer recurrence by 3% at 5 and 10 years. They also called for future studies to examine the effect of endocrine therapy and ovarian suppression on women’s quality of life alongside the reduced risk of breast cancer recurrence.
Early Breast Cancer Trialists’ Collaborative Group. Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials Lancet Oncol 2022