A new study may help to reassure groups of breast cancer patients concerned that treatment with Nolvadex (tamoxifen) will increase their risk of endometrial, or uterine, cancer.
The study, “Randomized trial of medroxyprogesterone acetate for the prevention of endometrial pathology from adjuvant tamoxifen for breast cancer: SWOG S9630,” published in the Nature partner journal Breast Cancer, showed that if women found to be without uterine problems (like a thick inner lining, or endometrium) in a pre-screening are selected for Nolvadex treatment, the rate of tamoxifen-induced endometrial abnormalities is much lower than expected.
Nolvadex, a selective modulator of the estrogen receptor (ER), is one of the most frequently prescribed anticancer therapies worldwide. It is particularly effective when used in combination with surgery in women with early stage, ER-positive breast cancer, and is often used in post-menopausal women or other women at high-risk to prevent the development of breast cancer.
“However, many women who would benefit from taking tamoxifen fail to do so because they fear getting endometrial cancer,” Ronald K. Potkul, MD, chair of the department of obstetrics and oncology of Loyola University Chicago Stritch School of Medicine, and the study’s first author, said in a press release.
In fact, previous studies have reported a link between Nolvadex exposure and endometrial cancer risk. One particular study, a large Phase 3 trial called National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14, found a 7.5-fold increase in the risk of endometrial cancer in tamoxifen-treated breast cancer patients, compared to those who received placebo. Endometrial abnormalities were also found to be more common in women preventively treated with Nolvadex than in untreated women.
Previous studies have reported that progestin, a synthetic progesterone, could reduce estrogen-induced endometrial abnormalities. Therefore, the researchers hypothesized that progestin could decrease the rate of benign and malignant endometrial abnormalities in patients receiving Nolvadex.
Their randomized, controlled trial enrolled 296 post-menopausal breast cancer patients with ER-positive tumors, who were assigned to receive either Nolvadex alone or in combination with progestin. Patients who showed an inner lining of the uterus greater than 5 mm at ultrasound examination at baseline were further screened with a biopsy. Patients whose biopsies showed endometrium abnormalities were not included in the study.
After two years, results showed that 67 percent of women taking Nolvadex alone had a thickening of the uterine inner lining greater than 5 mm, compared to 60 percent of those taking Nolvadex and progestin, a difference that was not statistically significant.
Researchers then analyzed biopsies done in all patients with uterine wall thickness greater than 5 mm, and found that only 5 women in the Nolvadex group had endometrial abnormalities, compared to one women in the Nolvadex plus progestin group. Again, the difference was not statistically significant.
Only one additional benign abnormality was found at a five-year follow-up, and no cancers were detected in any patient at either time point.
Importantly, although the researchers expected that nearly 30 percent of women in the Nolvadex group would develop endometrial abnormalities, they found only 6 percent of the women actually did.
“Our study found that for women who did not have endometrial abnormalities when they began taking tamoxifen, there was a very low rate of developing pre-malignant conditions,” Potkul said.
“For women who are concerned about taking tamoxifen to treat or prevent breast cancer, our study suggests that a normal ultrasound before treatment may provide additional reassurance,” added Kathy S. Albain, MD, a professor in the Loyola department of medicine, division of hematology/oncology.