Abstract P1-12-17: Mature data (&gt; 25 years) on 2 years adjuvant tamoxifen treatment in premenopausal women with breast cancer: Time to re-emphasize the progesterone receptor as predictive factor?
Authors: Ekholm Maria , Bendahl Pär-Ola , Fernö Mårten , Nordenskjöld Bo , Stål Olle , Rydén Lisa 
Published: May 2015

Background

In 2011 The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) reported that five years of adjuvant tamoxifen (TAM) significantly reduces the 15-year risks of breast cancer recurrence and death. Moreover, the estrogen receptor (ER) was considered the clinically most relevant predictive factor for efficacy of TAM treatment. In premenopausal patients participating in a randomized trial of 2 years of adjuvant TAM, we have previously reported on increased recurrence free survival in patients with ER- and PR-positive disease and a trend for increased overall survival in patients with PR-positive tumors. The median follow-up time was 13.9 years for patients without events. Since the effect on mortality may increase beyond year 10, we investigated more mature of data.

Aims

To investigate the long-term effect of 2 years adjuvant TAM in premenopausal patients choosing cumulative mortality (CM) and cumulative breast cancer mortality (CBCM) as end-points.

Methods

Premenopausal patients (n=564) with stage II breast cancer were included in a Swedish randomized multicenter trial between 1986-1991 and allocated to 2 years of TAM (n=276) or no treatment (n=288). The hormone receptor status of the tumor was known for 541 (96%) of the patients included, determined by immunohistochemistry or cytosol-based methods. Less than 2% were treated with adjuvant chemotherapy and they were equally distributed between the two groups. Median follow-up time was 26.3 years (22.7-29.7). Mortality data was obtained from the Swedish Cause of Death Register.

Results

Death from any cause was recorded among 312 (55%) of the patients, and 265 (47%) of the deaths were due to breast cancer. Two years of TAM decreased CM and CBCM in all patients irrespective of hormonal receptor status (n=564) (CM: HR 0.81; 95% CI: 0.65-1.02, p=0.070; CBCM: HR 0.79; 95% CI: 0.61-1.01, p=0.058), as well as in patients with ER-positive disease (n=346) (CM: HR 0.77; 95% CI: 0.57-1.03, p=0.077; CBCM: HR 0.72; 95% CI: 0.52-1.01, p=0.051), however not strictly significant. Importantly, in patients with PR-positive tumors, TAM significantly reduced CM and CBCM (CM: HR 0.73; 95% CI: 0.55-0.98, p=0.037; CBCM: HR 0.68; 95% CI: 0.49-0.94, p=0.020). Moreover, in patients with ER- and PR positive tumors TAM decreased CM (HR 0.74; 95% CI: 0.55-1.01, p=0.057) and CBCM (HR 0.69; 95% CI: 0-49-0.97, p=0.033), whereas there was no effect of TAM in patients with ER-positive and PR-negative tumors (p=0.97 and p=0.99, respectively).

Conclusions

The present study demonstrates that 2 years of adjuvant TAM as monotherapy significantly reduced CM and CBCM in premenopausal women with PR-positive tumors as well as CBCM in ER- and PR-positive tumors, after &gt; 25 years of follow-up. Five years of adjuvant TAM have been proven to reduce mortality rates at 15 years, but we herein show that also 2 years of TAM yields a survival benefit at 25 years.

In the latest meta-analysis from EBCTCG, PR did not add predictive information in patients with ER-positive tumors, but according to our results the significance of PR, as a predictive factor for TAM efficacy, should be re-emphasized in premenopausal women.

Citation Format: Maria Ekholm, Pär-Ola Bendahl, Mårten Fernö, Bo Nordenskjöld, Olle Stål, Lisa Rydén. Mature data (&gt; 25 years) on 2 years adjuvant tamoxifen treatment in premenopausal women with breast cancer: Time to re-emphasize the progesterone receptor as predictive factor? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-17.