MON-318 - Impact of Progesterone Receptor and COMT Gene Polymorphisms on Breast Cancer Risk

Background:
Hormonal regulation, including progesterone receptor sensitivity and estrogen metabolism efficiency mediated by catechol-O-methyltransferase (COMT), may influence carcinogenic potential in women. Progesterone deficiency is associated with hormone-dependent pathologies, and genetic variations reducing receptor sensitivity or COMT activity may exacerbate oncogenic mechanisms.

Materials and

Methods:
Four women aged 45–52 years (mean 48.25 ± 2.75) with biopsy-confirmed breast cancer were studied. Steroid hormone levels were measured using salivary steroid profiling. Genotyping was performed for the progesterone receptor (PGR, PROGINS; g.101062681 C>A; c.1486 G>T) and COMT (c.472G>A) genes by direct sequencing. Clinical histories, including premenstrual symptoms and fibrocystic mastopathy, were analyzed.

Results:
All patients had a history of pronounced premenstrual symptoms, including lower abdominal pain, breast tenderness, and mastalgia, indicating clinical progesterone deficiency. Salivary progesterone measured during the luteal phase was below the reference range (norm ≥130 pg/mL). Genotyping revealed heterozygous PGR PROGINS (C/A) with partial progesterone resistance and homozygous COMT c.472A/A associated with reduced enzymatic activity. All patients underwent surgical resection followed by radiotherapy and targeted therapy.

Discussion:
The combination of reduced progesterone receptor sensitivity and impaired COMT-mediated estrogen metabolism may trigger breast carcinogenesis by enhancing hormonal imbalance. Early fibrocystic changes observed in all patients could act as additional risk factors.

Conclusion:
Progesterone resistance combined with decreased COMT activity contributes to hormonal dysregulation and may increase breast cancer risk. Identification of these genetic factors could inform risk stratification and personalized preventive strategies.

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