Is testosterone replacement therapy safe for females (females) with a history of breast cancer?

Testosterone Replacement Therapy in Females with History of Breast Cancer

Testosterone replacement therapy should not be used in females with a history of breast cancer due to potential risks of cancer recurrence and progression. 1

Rationale and Evidence

Contraindications for Testosterone Use

• Testosterone is explicitly contraindicated in patients with known carcinoma of the breast according to FDA labeling 2
• The American Society of Clinical Oncology (ASCO) guidelines specifically recommend against testosterone/androgen supplementation in patients with breast cancer 1
• This recommendation is based on the concern that testosterone can be aromatized to estrogen, potentially stimulating hormone-sensitive breast cancer cells 1

Mechanism of Risk

• Testosterone can be converted to estradiol by the aromatase enzyme present in breast tissue and adipose tissue, particularly in postmenopausal women 3
• This conversion could potentially stimulate estrogen receptor-positive breast cancer cells, leading to recurrence or progression 1
• The risk may be higher in postmenopausal women who are estrogen-depleted and have increased adipose aromatase activity 3

Clinical Evidence and Case Reports

• There have been case reports of breast cancer development shortly after initiation of testosterone therapy, including one case that became clinically manifest after only 5 weeks of treatment 4
• A systematic review identified 22 cases of breast cancer development in patients on testosterone treatment, though the exact relationship between testosterone therapy and breast cancer development could not be definitively established due to small sample size 5

Special Considerations for Transgender and Gender-Diverse Individuals

• For transgender and gender-diverse individuals with a history of breast cancer who are considering gender-affirming hormone therapy (GAHT), the decision is particularly complex 1
• Some transgender individuals (up to 35%) may choose to continue hormone therapy despite a cancer diagnosis due to the importance of gender-affirming care for their quality of life 1
• In such cases, a thorough discussion of the potential risks is essential, weighing the benefits of GAHT against the risk of cancer recurrence 1
• Recent genomic profiling studies suggest androgen receptor activation may have different effects than previously thought, but clinical outcome data are still lacking 1

Alternative Approaches

• For females with a history of breast cancer experiencing symptoms that might otherwise be treated with testosterone (such as sexual dysfunction or decreased libido):
  • Non-hormonal treatments should be considered first-line 1
  • Management of symptoms should follow similar approaches used for women without using testosterone 1
  • Consultation with both oncology and endocrinology specialists is recommended to develop a comprehensive management plan 1

Monitoring and Follow-up

• Patients with a history of breast cancer should receive regular follow-up care with physicians experienced in cancer surveillance 1
• Regular breast examinations and appropriate imaging studies should be performed according to standard breast cancer surveillance protocols 1
• Patients should be counseled about symptoms of recurrence including new lumps, bone pain, chest pain, dyspnea, abdominal pain, or persistent headaches 1

While some older research suggested potential therapeutic activity of testosterone in metastatic breast cancer 6, and some in vitro and animal studies have shown anti-proliferative effects 3, 7, current clinical guidelines and FDA labeling clearly contraindicate testosterone use in patients with breast cancer history due to safety concerns.