Are testosterone therapy or SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors contraindicated in a patient with breast cancer?

Testosterone and SGLT2 Inhibitors in Breast Cancer Patients

Testosterone Therapy: Contraindicated

Testosterone therapy is contraindicated in patients with breast cancer. 1, 2

FDA-Labeled Contraindications

• The FDA explicitly lists "known carcinoma of the breast" as a contraindication for testosterone products in the drug labeling. 2
• This contraindication applies regardless of patient sex or gender identity. 2

Guideline-Based Recommendations

• ASCO guidelines specifically recommend against testosterone/androgen supplementation in patients with breast cancer. 1
• This recommendation is based on the biological mechanism whereby testosterone undergoes aromatization to estradiol via the aromatase enzyme present in breast tissue and adipose tissue. 1, 3
• The resulting estradiol can stimulate estrogen receptor-positive breast cancer cells, potentially leading to cancer recurrence or progression. 1, 3

Special Considerations for Transgender Patients

• For transgender men (female-to-male) with breast cancer, the decision regarding gender-affirming hormone therapy (GAHT) is particularly complex. 4
• While some transgender individuals may choose to continue testosterone despite cancer diagnosis due to quality-of-life considerations and the life-saving nature of GAHT, this requires thorough risk-benefit discussion. 4
• Up to 35% of transgender individuals surveyed indicated they would continue hormone therapy even with a hormonally dependent cancer diagnosis. 4
• However, the standard medical recommendation remains against testosterone use in the setting of active breast cancer. 1

Clinical Evidence

• Limited case reports document 22 patients (4 cisgender men, 18 transgender men) who developed breast cancer while on testosterone therapy, though causality cannot be definitively established from these small numbers. 5
• In postmenopausal women who are estrogen-depleted with increased adipose aromatase activity, higher testosterone levels have been associated with greater breast cancer risk. 6

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SGLT2 Inhibitors: Not Contraindicated

SGLT2 inhibitors are NOT contraindicated in patients with breast cancer and may actually have potential anticancer effects. 7, 8, 9

Mechanism of Potential Benefit

• SGLT2 is overexpressed in breast cancer cell lines and human breast tumor tissue samples. 7
• SGLT2 inhibitors (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin) demonstrate anti-proliferative effects against breast cancer cells through multiple mechanisms:
  • Reduction of glucose uptake by cancer cells 7, 8
  • Induction of cell cycle arrest in G1/G0 phase 7
  • Promotion of apoptosis 7, 8
  • Activation of AMPK-mediated pathways 7
  • Suppression of PI3K/AKT/mTOR and MAPK signaling pathways 8, 9
  • Mitochondrial membrane instability 8

Clinical Application

• SGLT2 inhibitors can be safely used for their primary indication (type 2 diabetes management) in patients with breast cancer. 7, 8, 9
• Emerging evidence suggests potential synergistic effects when combined with standard chemotherapy regimens, though this remains investigational. 8, 9
• No contraindications exist in FDA labeling or clinical guidelines regarding breast cancer and SGLT2 inhibitor use. 7, 8, 9

Important Caveat

• While preclinical and in vitro data are promising, clinical trials are still needed to definitively establish the safety and efficacy of SGLT2 inhibitors as anticancer agents in breast cancer patients. 9
• Current use should be primarily for diabetes management, with potential anticancer effects considered an additional benefit rather than a primary treatment strategy. 8, 9