For women receiving tamoxifen in the adjuvant setting for early stage breast cancer or as a preventive for high risk of breast cancer, the risk of developing endometrial pathology in those with negative uterine examination findings prior to treatment is very low, a study published in the journal NPJ Breast Cancer has shown.1
Despite tamoxifen’s effectiveness in the adjuvant setting for women with early stage, estrogen receptor–positive breast cancer and as a chemopreventive for women at high risk for breast cancer, many women choose to forego the therapy because of its known but low risk for causing endometrial abnormalities.
In the breast, tamoxifen has an anti-estrogenic effect; however, the agent acts as a weak estrogen agonist on the endometrium resulting in endometrial abnormalities in as many as 30% of patients receiving the drug compared with untreated patients. Higher rates of endometrial hyperplasia are also seen in healthy women receiving the drug as a preventive.
However, this risk may be reduced by adding cyclical progestin to hormone replacement therapy, hypothesized these researchers. In this study, they sought to compare the effects of adding cyclical medroxyprogesterone acetate (MPA) to tamoxifen therapy with tamoxifen alone. Endometrial pathology was assessed in both patient groups via endovaginal sonogram (EVS) and subsequent endometrial biopsy (EBM) if stripe width was 5 mm or greater at 2 years and 5 years.
The 296 eligible participants were randomized to receive tamoxifen plus MPA 10 mg for 14 days every 3 months or tamoxifen alone. Of the eligible participants, 169 (89 in the tamoxifen arm and 80 in the tamoxifen + MPA arm) were evaluable.
At year 2, 60 of 89 (67%) participants in the tamoxifen arm had an endometrial stripe width 5 mm or greater, and underwent subsequent EMB, compared with 48 of 80 (60%) in the tamoxifen + MPA arm (P =.40).
Among the 108 participants who underwent EMB, 4 cases of proliferative endometrium and 1 simple hyperplasia were seen on the tamoxifen arm (6% [95% CI, 2%–13%]) and 1 case of proliferative endometrium was seen on the tamoxifen + MPA arm (P =.11).
The overall number of participants with benign endometrial abnormalities at year 2 was 3.6% (6/169; 95% CI, 1.3%–7.6%). At year 5, only 1 new benign proliferative event was seen among the remaining 102 participants who had undergone EMB at the 2-year point.
These results were much lower than projected. However, the researchers note that the study criteria may have contributed to the low rate of endometrial abnormalities. All the women recruited underwent uterine ultrasound examinations before beginning tamoxifen. If a thickening of the inner uterine lining of more than 5 mm was seen, a biopsy was obtained. Those women whose biopsy showed an endometrial abnormality were excluded from the study.
Although these data can reassure women with a normal endometrium prior to initiating tamoxifen therapy, the researchers note that these results need to be validated in a larger trial.
1. Potkul RK, Unger JM, Livingston RB, et al. Randomized trial of medroxyprogesterone acetate for the prevention of endometrial pathology from adjuvant tamoxifen for breast cancer: SWOG S9630. NPJ Breast Cancer. 2016 Aug 10. [Epub online ahead of print]