What are the considerations for a 55-year-old female with benign microcalcifications in the left upper outer quadrant of the breast, who is interested in starting vaginal topical estrogen (estrogen replacement therapy)?

From the Guidelines

Vaginal topical estrogen can be safely prescribed for this 55-year-old woman with benign microcalcifications on her mammogram. The most recent and highest quality study, 1, suggests that low-dose vaginal estrogen preparations are effective in treating vaginal dryness, irritation, and dyspareunia. Some key points to consider when prescribing vaginal topical estrogen include:

• Low-dose vaginal estrogen preparations such as estradiol vaginal tablets (Vagifem 10 mcg), estradiol vaginal ring (Estring), or estradiol vaginal cream (Estrace 0.01%) are all reasonable options with minimal systemic absorption.
• The patient should continue with her recommended 6-month follow-up diagnostic mammogram as scheduled, as the use of vaginal estrogen does not change this recommendation.
• Unlike systemic hormone therapy, topical vaginal estrogen has not been associated with increased breast cancer risk due to its minimal systemic absorption.
• The estrogen remains primarily localized to vaginal tissues where it effectively treats symptoms like vaginal dryness, irritation, and dyspareunia by restoring vaginal epithelial thickness and improving lubrication.
• For initial treatment, daily application for 1-2 weeks followed by maintenance therapy 2-3 times weekly is typically effective.
• The patient should be instructed to report any unusual vaginal bleeding, as this would warrant further evaluation. It's also worth noting that other options, such as vaginal moisturizers and lubricants, can be tried first, as suggested by 1 and 1. However, the most recent and highest quality study, 1, provides the strongest evidence for the safety and efficacy of vaginal topical estrogen. Therefore, vaginal topical estrogen is the recommended treatment option for this patient, with careful consideration of her individual needs and medical history.

From the FDA Drug Label

ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding Estrogens and progestins should not be used for the prevention of cardiovascular disease. The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2. 5 mg) relative to placebo. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

The considerations for a 55-year-old female with benign microcalcifications in the left upper outer quadrant of the breast, who is interested in starting vaginal topical estrogen (estrogen replacement therapy) are:

• Increased risk of endometrial cancer: Close clinical surveillance is important, and adequate diagnostic measures should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
• Cardiovascular risks: Estrogens should not be used for the prevention of cardiovascular disease, and the patient should be aware of the increased risks of myocardial infarction, stroke, and deep vein thrombosis.
• Breast cancer risk: The patient should be aware of the increased risk of invasive breast cancer associated with estrogen therapy.
• Prescription at lowest effective dose: Estrogens should be prescribed at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman 2.
• Regular monitoring: The patient and healthcare provider should talk regularly about whether the patient still needs treatment with estrogen therapy 2.

From the Research

Considerations for Benign Microcalcifications and Estrogen Replacement Therapy

• The presence of benign microcalcifications in the left upper outer quadrant of the breast is a common finding, and the majority of calcifications depicted on mammograms are benign 3.
• The American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) classifies calcifications on mammograms into three categories: typical benign, intermediate concern, and higher probability of malignancy, according to types and distribution of calcifications 3.
• Benign calcifications are typically larger, coarser, round with smooth margins, and have a scattered or diffuse distribution, whereas malignant calcifications are typically grouped or clustered, pleomorphic, fine, and with linear branching 3.

Management of Microcalcifications in Postmenopausal Women on HRT

• In postmenopausal women taking hormonal replacement therapy (HRT), the diagnostic value of clinical examination and complementary imaging in the exploration of a breast lump or microcalcifications should be evaluated based on a systematic review of the literature 4.
• A double evaluation by mammography and ultrasound is recommended, and allows the imaging to be classified into 5 BI-RADS categories 4.
• The diagnostic management of masses classified BI-RADS 4 and 5 should be based on percutaneous sampling, with microbiopsy being the first step 4.

Estrogen Replacement Therapy and Breast Health

• There is no clinical evidence to rule out cancer in the presence of a clinical breast mass in postmenopausal women, and a rigorous multidisciplinary approach is necessary for the exploration of a breast mass or microcalcifications in a postmenopausal woman 4.
• Discontinuation of HRT is necessary in cases of malignancy (in situ or invasive cancer) 4.
• The management of benign breast lesions is not different in women taking HRT, and there is no contraindication to continue HRT in the case of simple cysts or benign solid tumors 4.

Monitoring and Follow-up

• A low rate of open surgical biopsies was performed with no cancer diagnoses missed at the time of initial assessment, and none of the women in the benign outcome group developed a subsequent breast cancer arising from the calcifications initially recalled 5.
• The recognition of sedimented calcifications is important because these characteristic calcifications are an indication of benignity, and malignant-appearing microcalcifications found in the vicinity of sedimented calcifications can be distinguished and require biopsy 6.