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Switching to aromatase inhibitor after tamoxifen reduces breast cancer recurrence

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May 31, 2017

Switching to exemestane after tamoxifen led to durable reductions in disease recurrence and mortality among patients with breast cancer, according to long-term follow-up data from the Intergroup Exemestane Study.

“For postmenopausal patients who had breast cancer and who have been taking adjuvant tamoxifen for 2 to 3 years, it is better for patients to switch to exemestane, an aromatase inhibitor,” Raoul Charles Coombe, MD, PhD, professor of medical oncology at Imperial College London and director of The Imperial CRUK Cancer Centre, told HemOnc Today. “By doing this, they have a reduced incidence of recurrence, which is durable and sustained over the 10-year follow-up period.”

Raoul Charles Coombe

The Intergroup Exemestane Study first showed the benefits of switching to exemestane after 2 to 3 years of tamoxifen therapy. The last update with efficacy analyses — published in 2012, after a median follow-up of 91 months —showed postmenopausal patients with early breast cancer benefited from switching therapies.

Coombe and colleagues conducted a final efficacy analysis and exploratory analyses to further investigate clinical factors that may impact a patient’s risk for distant relapse after endocrine therapy.

“The identification of patients who remain at higher risk [for] disease recurrence after the completion of 5 years of endocrine therapy ... according to clinical factors, such as nodal involvement and tumor size, will aid decision-making about the administration of additional endocrine therapy or additional therapeutic agents,” the researchers wrote.

The researchers randomly assigned patients who remained disease free after 2 to 3 years of adjuvant tamoxifen to continue tamoxifen therapy or switch to exemestane for a total of 5 years of adjuvant endocrine therapy. The analyses focused on patients with ER–positive (n = 4,052) or unknown tumors (n = 547).

Breast cancer–free survival, with censorship of intercurrent mortality, served as the primary survival endpoint.

Median follow-up was 120 months (interquartile range, 114.8-122; range, 2.9-164.1).

Researchers observed 1,111 breast cancer–free survival events, which occurred in 508 (22.1%) of 2,294 patients in the exemestane group and 603 (26.2%) of 2,305 patients in the tamoxifen group.

These data equated to an absolute difference in 10-year breast cancer–free survival of 4% (95% CI, 1.2-6.7), favoring exemestane (HR = 0.81; 95% CI, 0.72-0.92). This association persisted in multivariable analysis after adjustment for nodal status, prior use of hormone replacement therapy and prior chemotherapy (HR = 0.8; 95% CI, 0.71-0.9).

OS rates improved slightly with exemestane; the absolute difference in 10-year OS between exemestane and tamoxifen was 2.1% (95% CI, –0.5 to 4.6), with an HR of 0.89 (95% CI, 0.78-1.01). These data appeared similar in the intention-to-treat population; the absolute difference in 10-year OS was 1.6% (95% CI, –0.9 to 4.1), with an HR of 0.91 (95% CI, 0.8-1.03).


Researchers found risk for distance recurrence increased in patients with tumor sizes large than 5 cm vs. smaller than 2 cm (HR = 1.92; 95% CI, 1.28-1.9) and in those who had 10 or more involved nodes compared with node-negative patients at random assignment (HR = 6.1; 95% CI, 4.41-8.44).

Fracture incidence remains a potential concern, Coombes said. However, the number of patients who reported a fracture event in the posttreatment period was not statistically different between the groups (exemestane, 9.3% vs. tamoxifen, 8%).

“By pretreating with tamoxifen — which tends to reduce calcium loss in bones in this way — we hoped to offset the risk for fracture,” Coombes said. “This is in fact what we found; there was no overall increase in fracture rate.” – by Melinda Stevens

For more information:

Raoul Charles Coombe, MD, PhD, can be reached at Division of Cancer, Department of Surgery and Cancer, 1st Floor, ICTEM Building, Imperial College London, Du Cane Rd, London, W12 0NN United Kingdom; email:

Disclosures: Coombes reports honoraria and research funding from as well as speakers bureau roles with Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures.

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