What are the next steps for a 45-year-old woman on tamoxifen (tamoxifen citrate) for breast cancer prophylaxis, who has developed vaginal spotting and has a pelvic ultrasound showing an endometrial echo complex with a thickness of 5 mm and a 1.1 cm subserosal leiomyoma?

From the Guidelines

For a 45-year-old woman on tamoxifen who has developed vaginal spotting with an endometrial thickness of 5 mm and a 1.1 cm subserosal leiomyoma, the next step should be endometrial sampling, preferably via endometrial biopsy in an office setting or dilation and curettage (D&C) if office biopsy is not feasible. This is necessary because tamoxifen increases the risk of endometrial hyperplasia and cancer, making any vaginal bleeding concerning, as indicated by guidelines for management while on tamoxifen or raloxifene therapy 1. Although her endometrial thickness of 5 mm is not markedly elevated, the presence of bleeding requires tissue diagnosis regardless of thickness. The subserosal leiomyoma (fibroid) is likely an incidental finding and not the cause of her bleeding given its location outside the uterine cavity.

After endometrial sampling, if no pathology is found, she can continue tamoxifen with close monitoring. If endometrial hyperplasia or cancer is detected, she would need to discontinue tamoxifen and receive appropriate treatment for the specific pathology. Throughout this evaluation, the risks and benefits of continuing tamoxifen prophylaxis should be discussed, considering alternative preventive options such as aromatase inhibitors if she is postmenopausal or has completed menopause. Regular follow-up, including annual gynaecological examinations and possibly gynaecological ultrasound, is recommended for patients on tamoxifen 1.

Key considerations in her management include:

• Prompt evaluation for endometrial cancer if uterus is intact, as per guidelines 1
• Annual gynaecological examination, possibly with a gynaecological ultrasound, by an experienced gynaecologist for patients on tamoxifen 1
• Discussion on the risks and benefits of continuing tamoxifen versus alternative preventive options
• Close monitoring for any recurrence of symptoms or development of new symptoms.

From the FDA Drug Label

The signs of changes in the uterus are: Vaginal bleeding or bloody discharge that could be a rusty or brown color. You should call your doctor even if only a small amount of bleeding occurs. Change in your monthly bleeding, such as in the amount or timing of bleeding or increased clotting. Changes in the lining (endometrium) or body of your uterus. These changes may mean serious problems are starting, including cancer of the uterus

The patient has developed vaginal spotting and has a pelvic ultrasound showing an endometrial echo complex with a thickness of 5 mm and a 1.1 cm subserosal leiomyoma.

• Vaginal bleeding is a sign of potential changes in the uterus, which may indicate serious problems, including cancer of the uterus.
• The patient should be evaluated for potential endometrial cancer or other uterine problems.
• Given the patient's symptoms and ultrasound results, a gynecologic evaluation is necessary to determine the cause of the vaginal bleeding and to assess the endometrial echo complex and subserosal leiomyoma.
• The patient's tamoxifen therapy should be reassessed in light of the potential risks of endometrial cancer and other uterine problems associated with tamoxifen use 2.

From the Research

Next Steps for Management

The patient, a 45-year-old woman on tamoxifen for breast cancer prophylaxis, has developed vaginal spotting and has a pelvic ultrasound showing an endometrial echo complex with a thickness of 5 mm and a 1.1 cm subserosal leiomyoma. The next steps in management should consider the potential effects of tamoxifen on the endometrium, as evidenced by several studies 3, 4, 5, 6, 7.

Consideration of Tamoxifen-Related Endometrial Changes

• Tamoxifen is known to have estrogenic effects on the endometrium, which can lead to proliferative endometrial lesions, including hyperplasia and polyps 3, 4.
• The patient's endometrial thickness of 5 mm is notable, as studies have shown that tamoxifen can cause an increase in endometrial thickness, with some studies using a cutoff of 5 mm or greater as an indication for further evaluation 5, 7.
• The presence of a subserosal leiomyoma (1.1 cm) should also be considered, although its significance in this context is less clear.

Diagnostic Evaluation

• Given the patient's symptoms and ultrasound findings, further diagnostic evaluation may be warranted to rule out endometrial pathology, such as endometrial hyperplasia or cancer.
• Hysteroscopy with directed biopsy may be considered, particularly if the endometrial thickness is irregular or greater than 3 mm, as suggested by one study 6.
• However, other studies have noted that ultrasound findings may not always correlate with endometrial abnormalities on biopsy, and that routine sonography in asymptomatic patients on tamoxifen may not be necessary 7.

Management of Vaginal Spotting

• The patient's vaginal spotting should be further evaluated, as it may be related to the tamoxifen therapy or underlying endometrial pathology.
• A thorough history and physical examination, including a pelvic exam, should be performed to assess for any other potential causes of vaginal bleeding.

Surveillance and Follow-Up

• Regular follow-up with transvaginal ultrasonography may be considered for patients on tamoxifen, particularly those with a history of endometriosis or other risk factors for endometrial pathology 3.
• However, the optimal frequency and duration of surveillance are not well established, and should be individualized based on the patient's risk factors and clinical presentation.