This article is more than 5 years old. Information may no longer be current.
Aromatase inhibitors improve recurrence rates, survival in early breast cancer
Click Here to Manage Email Alerts
The use of an aromatase inhibitor reduced breast cancer recurrence rates approximately 30% compared with tamoxifen, according to the results of a meta-analysis.
Further, use of an aromatase inhibitor for 5 years reduced 10-year breast cancer mortality rates approximately 15% compared with 5 years of tamoxifen, equating to an approximate 40% reduction compared with no treatment.
“Aromatase inhibitors, given either for 5 years or for 2-3 years after 2-3 years of tamoxifen, produce greater reductions in recurrence than 5 years of tamoxifen alone, but the effect on breast cancer mortality, and the optimal way to schedule aromatase inhibitors and tamoxifen in the treatment of early breast cancer, remain uncertain,” Mitch Dowsett, PhD, head of biochemistry and professor of biochemical endocrinology at The Royal Marsden Hospital and Institute for Cancer Research in London, and colleagues of the Early Breast Cancer Trialists’ Collaborative Group wrote. “To help clarify the relative benefits of aromatase inhibitors and tamoxifen and the effect of different scheduling during 5 years of endocrine therapy, we undertook collaborative meta-analyses of individual patient data from the trials of aromatase inhibitors versus tamoxifen.”
The meta-analysis included data from 31,920 postmenopausal women with ER-positive early breast cancer who participated in randomized trials evaluating:
- 5 years of an aromatase inhibitor vs. 5 years of tamoxifen (n = 9,885);
- 5 years of an aromatase inhibitor vs. 2 to 3 years of tamoxifen alone followed by an aromatase inhibitor to year 5 (n = 12,779); or,
- 2 to 3 years of tamoxifen followed by an aromatase inhibitor to year 5 vs. 5 years of tamoxifen (n = 11,798).
Primary endpoints included any breast cancer recurrence, breast cancer mortality, death without recurrence and all-cause mortality.
In the two trials that compared 5 years of aromatase inhibitors vs. 5 years of tamoxifen, aromatase inhibitors significantly reduced the risk for recurrence during years 0 to 1 (RR = 0.64; 95% CI, 0.52-0.78) and 2 to 4 (RR = 0.8; 95% CI, 0.68-0.93). However, the effect was nonsignificant thereafter.
Further, aromatase inhibitors significantly lowered the rate of 10-year breast cancer mortality (12.1% vs. 14.2%; P = .009).
Results of three trials that compared 5 years of aromatase inhibitors vs. 2 to 3 years of tamoxifen followed by an aromatase inhibitor to year 5, aromatase inhibitors reduced the risk for recurrence years 0 to 1 (RR = 0.74; 95% CI, 0.62-0.89), but not during years 2 to 4 — when both groups received aromatase inhibitors — or thereafter.
Patients in these trials who received 5 years of aromatase inhibitors experienced fewer recurrences overall (RR = 0.9; 95% CI, 0.81-0.99); however, the breast cancer mortality reduction did not achieve statistical significance (RR = 0.89; 95% CI, 0.78-1.03)
In the six trials that compared 2 to 3 years of tamoxifen followed by an aromatase inhibitor to year 5 vs. 5 years of tamoxifen, aromatase inhibitors reduce the risk for recurrence during years 2 to 4 (RR = 0.56; 95% CI, 0.46-0.67), but not thereafter. The rate of 10-year breast cancer mortality appeared significantly lowered among patients who switched from tamoxifen to an aromatase inhibitor compared with patients who remained on tamoxifen (8.7% vs. 10.1%; P = .015).
When the researchers aggregated all three comparisons, recurrence data favored aromatase inhibitors during periods where treatment differed (RR = 0.7; 95% CI, 0.64-0.77) but not significantly thereafter. However, reduced breast cancer mortality occurred when treatment differed (RR = 0.79; 95% CI, 0.67-0.92) and thereafter (RR = 0.89; 95% CI, 0.81-0.99), and for all periods combined (RR = 0.86; 95% CI, 0.8-0.94).
The researchers also observed a reduction in all-cause mortality (RR = 0.88; 95% CI, 0.82-0.94).
Fewer endometrial cancers occurred with aromatase inhibitors compared with tamoxifen over 10 years (0.4% vs. 1.2%; RR = 0.33; 95% CI, 0.21-0.51); however, more bone fractures occurred in women who received aromatase inhibitors (5-year risk, 8.2% vs. 5.5%; RR = 1.42; 95% CI, 1.28-1.57).
“Our global collaboration has revealed that the risk of postmenopausal women with the most common form of breast cancer dying of their disease is reduced by 40% by taking 5 years of an aromatase inhibitor — a significantly greater protection than that offered by tamoxifen,” Dowsett said in a press release. “The impact of aromatase inhibitors is particularly remarkable given how specific these drugs are — removing only the tiny amount of estrogen that remains in the circulation of women after menopause — and given the extraordinary molecular differences between ER-positive tumors. But aromatase inhibitor treatment is not free of side-effects, and it is important to ensure that women with significant side-effects are supported to try to continue to take treatment and fully benefit from it.”
Erica L. Mayer
These study findings should be interpreted in light of advancements made in the time since the trials included by the researchers in the meta-analysis, Erica L. Mayer, MD, MPH, and Harold J. Burstein, MD, PhD, both senior physicians at Dana-Farber Cancer Institute, wrote in an accompanying editorial.
Harold J. Burstein
“When the trials included in this meta-analysis were done, the standard duration of adjuvant endocrine therapy was 5 years,” Mayer and Burstein wrote. “Since then, we have learned that extending adjuvant treatment beyond 5 years out to 10 years with either ongoing tamoxifen or by switching to an aromatase inhibitor can further reduce breast cancer recurrences. These finding invite speculation that longer treatment duration with an aromatase inhibitor — longer than the 5 years studied in this meta-analysis — or a longer sequential program would be of benefit to patients. But, at present, there are no data from randomized trials assessing the efficacy of these approaches.”
Further, the potential for adverse events should be considered, Mayer and Burstein wrote.
“Those caring for women with breast cancer realize that the accompanying meta-analysis is missing a key set of data: the patient experience,” Mayer and Burstein wrote. “Women on anti-estrogen treatments endure substantial side effects, including menopausal symptoms such as hot flashes and night sweats. Aromatase inhibitors, in particular, are also associated with bone pain and arthralgias, vaginal dryness, sexual dysfunction, osteoporosis, bone fracture and hair thinning. … Ultimately, the best choice for adjuvant endocrine therapy is a treatment the patient is willing to take. For most patients, especially as we envision an era of longer durations of endocrine therapy, it will be more important to assure that they are on a tolerable medication than to be unyielding over prescribing a specific bottle that sits untouched in the medicine cabinet.” – by Cameron Kelsall
Disclosure: The Early Breast Cancer Trialists’ Collaborative Group is funded by Cancer Research U.K. and U.K. Medical Research Council grants to the Clinical Trial Service Unit. Dowsett reports grants and personal fees from AstraZeneca, Novartis and Pfizer. Mayer reports research funding from Eisai, Myriad and Pfizer. Burstein reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts