Does hormone therapy cause invasive ductal carcinoma?

Hormone Therapy and Invasive Ductal Carcinoma Risk

Menopausal hormone therapy with estrogen plus progestin increases the risk of invasive ductal carcinoma, while estrogen-only therapy may have a neutral or potentially decreased risk effect. 1

Evidence on Combined Estrogen-Progestin Therapy

• The Women's Health Initiative (WHI) trial demonstrated that combined estrogen plus progestin hormone therapy significantly increases the risk of invasive breast cancer (HR 1.25,95% CI 1.07-1.46), with approximately 8 more cases per 10,000 woman-years 1
• This increased risk was specifically observed for estrogen receptor-positive and/or progesterone receptor-positive tumors 1
• The Million Women Study and other large observational studies consistently support this association between combined hormone therapy and increased breast cancer risk 1
• Ductal carcinoma in situ (DCIS) risk may also be increased with combined estrogen-progestin therapy (HR 1.23,95% CI 0.91-1.64 in clinical trials; HR 1.65,95% CI 1.25-2.19 in observational studies) 2
• The risk appears to increase with longer duration of use, with women using combined therapy for more than 5 years showing higher risk 3

Evidence on Estrogen-Only Therapy

• In contrast to combined therapy, estrogen-only therapy in women who had undergone hysterectomy was associated with a reduced risk of invasive breast cancer in the WHI trial (HR 0.77,95% CI 0.62-0.95) 1
• This translates to approximately 8 fewer cases per 10,000 woman-years 1
• Estrogen-only therapy was also associated with reduced breast cancer mortality (HR 0.37,95% CI 0.13-0.91) 1
• The relationship between estrogen-only therapy and DCIS is less clear, with some studies showing no significant association 2, 4

Factors Affecting Risk

• Prior hormone replacement therapy use may modify the risk - women with no prior HRT showed clearer risk reduction with aromatase inhibitors than those with prior HRT 1
• The type of breast cancer affected by hormone therapy varies:
  • Combined therapy increases risk for both favorable and unfavorable prognostic features of breast cancer 5
  • Estrogen-only users were slightly more likely to develop estrogen receptor-positive breast cancers compared to non-users (RR 1.14,95% CI 1.06-1.23) 5

Clinical Implications

• The use of hormone replacement therapy for menopausal symptoms should be carefully weighed against the increased risk of breast cancer, particularly for combined estrogen-progestin therapy 1
• ASCO guidelines recommend against hormone replacement therapy in women at high risk for breast cancer 1
• For women who have already been diagnosed with breast cancer, hormone replacement therapy is generally contraindicated due to the increased risk of recurrence 1
• Regular mammographic screening is particularly important for women on hormone therapy, as it may increase breast density and potentially mask abnormalities 1

Monitoring and Risk Reduction

• Annual mammography with ultrasound is recommended for women on hormone therapy 1
• For patients on hormone therapy, especially tamoxifen, annual gynecological examinations are recommended due to potential side effects 1
• The decision to use hormone therapy should consider the patient's overall risk profile, including family history, personal history, and other risk factors for breast cancer 1
• The shortest duration of hormone therapy necessary to control menopausal symptoms should be used to minimize breast cancer risk 1