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 used in this 55-year-old female with benign microcalcifications on mammogram, as it has been shown to be effective in treating vaginal dryness and has not been associated with an increased risk of breast cancer-specific mortality 1.

Considerations for Vaginal Topical Estrogen Use

When considering vaginal topical estrogen use, it is essential to note that low-dose preparations such as Estrace vaginal cream, Vagifem tablets, or Estring vaginal ring result in minimal systemic absorption and are not associated with increased breast cancer risk 1.

• The patient's benign microcalcifications are not a contraindication to vaginal estrogen use, as the systemic absorption is negligible compared to oral or transdermal hormone therapy.
• Vaginal estrogen effectively treats symptoms of vaginal atrophy, including dryness, irritation, and dyspareunia, by restoring vaginal epithelial thickness, elasticity, and lubrication.
• The patient should be instructed to report any vaginal bleeding that may occur after starting therapy, as this would warrant further evaluation.

Alternative Options

Other options for treating vaginal dryness and dyspareunia include vaginal androgens, such as DHEA, and selective estrogen receptor modulators, like ospemifene 1.

• However, the safety data for the use of androgen-based therapy in survivors of hormonally mediated cancers are limited, and DHEA should be used with caution in survivors receiving aromatase inhibitor therapy.
• Ospemifene has been shown to effectively treat vaginal dryness and dyspareunia in individuals with postmenopausal vulvar and vaginal atrophy, but data in the survivor population are limited.

Follow-up and Monitoring

The patient should proceed with her follow-up diagnostic mammogram in 6 months as recommended, regardless of starting vaginal estrogen therapy 1.

• Regular follow-up and monitoring are essential to ensure the safe use of vaginal topical estrogen and to address any concerns or side effects that may arise.

From the FDA Drug Label

Estrogens increase the chances of getting cancer of the uterus. Report any unusual vaginal bleeding right away while you are taking estrogens. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause. Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have or had cancer, talk with your healthcare provider about whether you should take Estradiol valerate injection, USP . Using estrogens with or without progestins may increase your chances of getting heart attacks, strokes, breast cancer, and blood clots.

The patient has benign microcalcifications in the left upper outer quadrant of the breast. The main considerations for this patient are:

• The presence of benign microcalcifications is not a contraindication to estrogen replacement therapy, but it does indicate a need for close clinical surveillance.
• The patient should be aware of the increased risk of breast cancer associated with estrogen replacement therapy.
• The patient should report any unusual vaginal bleeding to her healthcare provider.
• The healthcare provider should check any unusual vaginal bleeding to rule out malignancy.
• The patient and healthcare provider should discuss the risks and benefits of estrogen replacement therapy, including the risk of breast cancer and other potential risks, such as heart attacks, strokes, and blood clots 2, 2. The decision to start vaginal topical estrogen should be made on a case-by-case basis, taking into account the patient's individual risk factors and medical history.

From the Research

Considerations for Benign Microcalcifications

• The presence of benign microcalcifications in the left upper outer quadrant of the breast is a common finding, occurring in approximately 4% of symptomatic women undergoing mammography 3.
• The recognition of sedimented calcifications is important to avoid unnecessary workup, follow-up, or biopsy, as they are typically an indication of benignity 3.
• However, adjacent malignancies are a potential pitfall, and malignant-appearing microcalcifications found in the vicinity of sedimented calcifications can be distinguished and require biopsy 3.

Estrogen Replacement Therapy Considerations

• There is no direct evidence in the provided studies to suggest that vaginal topical estrogen (estrogen replacement therapy) would affect the benign microcalcifications in the breast.
• However, it is essential to note that the use of estrogen replacement therapy may have an impact on breast density and potentially affect the detection of microcalcifications on mammograms.

Microcalcification Characteristics

• Benign calcifications are typically larger, coarser, round with smooth margins, and have a scattered or diffuse distribution 4.
• Malignant calcifications are typically grouped or clustered, pleomorphic, fine, and with linear branching 4.
• 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 4.

Follow-up and Monitoring

• A study found that none of the women in the benign outcome group, with available five-year follow-up records, developed a subsequent breast cancer, arising from the calcifications initially recalled 5.
• The presence of microcalcifications often affects the extent of surgical intervention, and certain types of microcalcifications are associated with negative genetic and molecular characteristics of the tumor and unfavorable prognosis 6.