Aromatase inhibitors reduce breast cancer recurrence vs. tamoxifen for certain women
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Use of an aromatase inhibitor instead of tamoxifen reduced the risk for breast cancer recurrence among premenopausal women with ER-positive disease who received ovarian suppression, according to a study published in The Lancet Oncology.
Longer follow-up is needed to assess the potential impact on breast cancer mortality, researchers wrote.
"Overall, the risk was reduced by an average of a fifth. The main benefit was seen in the first 5 years, when the treatments differed, whereas the risk of recurrence was a third lower in the aromatase inhibitor group," Rosie Bradley, BSc, MSc, medical statistician in the clinical trial service unit at University of Oxford's Nuffield Department of Population Health, told Healio.
Background
Bradley and colleagues of the Early Breast Cancer Trialists’ Collaborative Group (EBCTG) initiated the study with the knowledge that for women with early-stage, ER-positive breast cancer, 5 years of tamoxifen has been shown to reduce the risk for breast cancer death at 15 years by about one third. Additionally, they knew aromatase inhibitors are even more effective than tamoxifen for postmenopausal women, yet ineffective for premenopausal women in the absence of ovarian suppression.
EBCTG identified four randomized trials comparing aromatase inhibitors with tamoxifen in premenopausal women receiving ovarian suppression.
“There were conflicting findings published from these trials — some showed benefit, whilst some did not show benefit,” Bradley said. “This provided the motivation to look at the totality of the evidence to assess the benefits and risks of aromatase inhibitor compared with tamoxifen in premenopausal women receiving ovarian suppression.”
Methodology
The analyses included 7,030 women (60.2% node-negative cancer) with ER-positive tumors enrolled in the trials between June 17, 1999, and Aug. 4, 2015, with median follow-up of 8 years (interquartile range, 6.1-9.3).
Bradley and colleagues performed a meta-analysis of individual patient data, comparing aromatase inhibitors (anastrozole, exemestane or letrozole) vs. tamoxifen for 3 or 5 years. They collected data on baseline characteristics, dates and sites of any breast cancer recurrence or second primary cancer, and dates and causes of death.
Breast cancer recurrence (distant, locoregional, or contralateral), breast cancer mortality, death without recurrence and all-cause mortality served as primary outcomes.
Key findings
Results showed a lower breast cancer recurrence rate among the 3,528 women who received an aromatase inhibitor compared with the 3,502 women assigned tamoxifen (11.5% vs. 13.8%; RR = 0.79; 95% CI, 0.69-0.9).
Researchers observed the main benefit in years 0 to 4 (RR = 0.68; 99% CI, 0.55–0.85), the period when treatments differed, with a 3.2% (95% CI, 1.8-4.5) absolute reduction in 5-year recurrence risk (6.9% vs. 10.1%). Additionally, they reported no further benefit, or loss of benefit, in years 5 to 9 (RR = 0.98; 99% CI, 0.73-1.33) or after year 10.
Bradley and colleagues also reported a rarity of nonbreast cancer deaths (30 vs. 24; RR = 1.3; 95% CI, 0.75-2.25) and endometrial cancer (7 vs. 15; RR = 0.52; 95% CI, 0.22-1.23).
Additional findings included:
- reduced distant recurrence with aromatase inhibitors (RR = 0.83; 95% CI, 0.71-0.97);
- no significant differences between treatments for breast cancer mortality (RR = 1.01; 95% CI, 0.82-1.24), death without recurrence (RR = 1.3; 95% CI, 0.75-2.25) or all-cause mortality (RR = 1.04; 95% CI, 0.86-1.27);
- aromatase inhibitors being just as effective among women aged younger than 35 years, who have a higher risk for recurrence than older women; and
- more bone fractures with aromatase inhibitors than with tamoxifen (227 vs. 180; RR = 1·27; 95% CI, 1.04-1.54).
Implications
Researchers reported no differences in breast cancer mortality between aromatase inhibitors and tamoxifen.
“Distant recurrence invariably results in death from breast cancer several years after the occurrence,” Bradley told Healio. “Given the significant reduction in distant recurrence seen with aromatase inhibitors here, it would be too early to conclude that survival is not improved with aromatase inhibitors. There is great need for longer-term follow-up of these trials to fully assess any impact on breast cancer mortality.”
References:
Early Breast Cancer Trialists' Collaborative Group (EBCTG). Lancet Oncol. 2022;doi:10.1016/S1470-2045(21)00758-0.
Aromatase inhibitors are better than tamoxifen at reducing the risk of breast cancer recurrence in premenopausal as well as postmenopausal women. www.ndph.ox.ac.uk/news/aromatase-inhibitors-are-better-than-tamoxifen-at-reducing-the-risk-of-breast-cancer-recurrence-in-premenopausal-as-well-as-postmenopausal-women. Published Feb. 3, 2022. Accessed Feb. 17, 2022.
For more information:
Rosie Bradley, BSc, MSc, can be reached at Department of Population Health at the University of Oxford, Richard Doll Building, Old Road Campus, Headington, Oxford OX3 7LF, United Kingdom; email: rosie.bradley@ctsu.ox.ac.uk.
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