Exogenous Hormones, Tumor Intrinsic Subtypes, and Breast Cancer

Area of Science:

• Oncology
• Endocrinology
• Epidemiology

Background:

• Understanding the etiologic heterogeneity of breast carcinogenesis is crucial for developing targeted prevention strategies.
• The associations between menopausal hormonal therapy (MHT) and oral contraceptive (OC) use and specific breast cancer intrinsic-like subtypes remain poorly understood.

Purpose of the Study:

• To investigate whether the use of exogenous hormones is differentially associated with various breast cancer subtypes.
• To evaluate potential heterogeneity in these associations across intrinsic-like breast cancer subtypes.

Main Methods:

• Pooled data from 31 case-control studies within the Breast Cancer Association Consortium.
• Analysis included over 42,000 breast cancer cases and 71,000 controls.
• Breast cancer intrinsic-like subtypes were determined by immunohistochemistry; polytomous logistic regression analyzed hormone use associations, stratified by body mass index (BMI).

Main Results:

• Current estrogen-progestin therapy (EPT) use in postmenopausal women was associated with an increased likelihood of luminal A-like and luminal B-ERBB2-like subtypes, particularly in healthy-weight individuals.
• Estrogen-only therapy (ET) showed a positive association with luminal A-like breast cancer in healthy-weight women, but an inverse association with obesity.
• Recent oral contraceptive (OC) use in premenopausal women was linked to luminal B-ERBB2-like, ERBB2 enriched-like, and triple-negative breast cancer subtypes.

Conclusions:

• Significant differences exist in the associations between current EPT use and breast cancer subtypes, with a higher likelihood of luminal-like subtypes in healthy-weight EPT users.
• Heterogeneity in subtype associations was less pronounced for OC and estrogen-only therapy (ET) use.
• Further research is needed on contemporary hormone formulations, usage patterns, and administration routes to refine understanding.