THE EFFECTS OF HORMONAL REPLACEMENT THERAPY (HRT) ON MAMMOGRAPHIC BREAST DENSITY AND ABNORMAL MAMMOGRAMS PROMPTING FURTHER INVESTIGATION

AIMS: The purpose of this study was to portray and analyze the inter-relationship between the use of HRT, mammographic breast density and the finding of any mammographic abnormality that prompted further investigation such as core needle biopsy or additional imaging testing, while controlling for obstetric and relevant demographic data. BACKGROUND: Mammographic breast density has been associated with higher risk of breast cancer and decrease in its sensitivity, while hormonal replacement therapy (HRT) in turn, has been implicated in increasing mammographic density and is considered a risk factor for breast cancer by itself. The inter-relationship between HRT, breast density and any mammographic or sonographic finding requiring further investigation has not been fully investigated. METHODS: A total of 2,758 consecutive, screening mammograms performed during one year in a single academic medical center in Israel were analyzed. Each mammogram was supplemented by high resolution ultrasound. Density was measured by a visual, semi-quantitative, 5-grade scale, based on Boyd's classification and grouped into low density mammograms (LDM) (1-3) and high density mammograms (HDM) (4-5). Demographic and obstetric data, personal and family history of breast cancer, and the use of HRT were entered into the database. These parameters were correlated with breast density and any detected abnormality that prompted further investigation. Univariate and multivariate analyses as well as multivariate logistic regression were performed using SAS 9.2. RESULTS: A significant difference in density was observed between pre- and post-menopausal women (p = 0.0001). However, the use of HRT in post-menopausal women was not associated with higher incidence of HDM (18.6%, n=110/592) compared to post-menopausal women without HRT (15.4%, n=211/1370) (p=n.s). Mammographic abnormality was more likely to occur in post-menopausal women without HRT (52%, n=711/1370) compared with women on HRT (38.7% n=229/592) (p = 0.0001). This held true for solid lump (p=0.0001), tissue irregularity (p=0.016) and calcifications (p=0.0005). Menopause was associated with higher likelihood (48%) of any mammographic finding compared with 41.6% in pre-menopausal women (p = 0.0017). A total of 266 women with mammographic findings prompting histological assessment were identified, revealing 105 malignant lesions. HRT in post-menopausal women was associated with lower incidence (28%) of malignancy compared to post-menopausal women without HRT (50%). CONCLUSIONS: The present study, portraying the inter-relationship between mammographic breast density, any abnormal finding in screening mammograms, and the use of HRT has not found such treatment to be associated neither with increased density, nor with higher probability of finding malignancy. Furthermore, a lower incidence of mammographic abnormality was noted in HRT users. Albeit, further and larger studies are required to substantiate these findings. The results of this study do not support the notion that HRT increases the likelihood of malignancy or affects breast density.