Abstract P2-06-01: The effect of a subcutaneous combination of testosterone (T) and anastrozole (Ai) (HAVAHT+Ai™) on volumetric mammographic breast density (MBD); an open labelled cohort study
Authors: Birrell SN , Dougherty D , Good SB , Birrell NJ , Rolan P 
Published: May 2019

Abstract
MBD is the single greatest modifiable risk factor for the development of breast cancer; this risk can be lessened by reducing MBD. Previous studies suggest breast cancer risk is reduced in women treated with subcutaneous HAVAHT+Ai™. As well, HAVAHT+Ai™ has been suggested to be effective in managing hormone deprivation symptoms in women who have had breast cancer and in perimenopausal women with hormonal dysfunction.
HAVAHT+Ai™alters the androgen/estrogen (A/E) ratio in breast tissue by delivering more bioavailable T in the presence of Ai to tissue known to contain high levels of 5alpha-reductase and aromatase, respectively facilitating production of the potent androgen dihydrotestosterone and diminishing conversion of T to estradiol. Alteration of the A/E ratio in favor of an androgenic environment reduces MBD. This study evaluates the effect of HAVAHT+Ai™on volumetric MBD.
Methods: 652 women attending Wellend Health Clinic (a clinic that manages perimenopausal symptoms and/or high risk of breast cancer) received HAVAHT+Ai™and evaluated for MBD change as determined by a fully-automated volumetric density analysis (VolparaDensity™). Women received a HAVAHT+Ai™subcutaneous implant every 3-4 month containing 1mg/kg T and a fixed dose of Ai 1-4mg. 142 women had 2 or more mammograms within the analysis period and were included in the final analysis. A restricted analysis set (RAS) of 89 of these women were compared with a matched 65 women undergoing mammographic screening for high risk, but not receiving hormonal therapy. Safety and tolerability data were collected and analyzed.
Results:
Least squares mean estimated (LSME) change in % volumetric breast density (%VBD), by cumulative testosterone dose and time from first implant.
table 1Cumulative testosterone doseTime from first implant (yrs)LSME (%)Lower 95% CIUpper 95% CIp-value500 - &lt;700mg1-1.13-2.420.170.087500 - &lt;700mg2-1.69-3.01-0.380.012500 - &lt;700mg3-2.26-4.23-0.290.025700+mg1-1.87-3.62-0.120.036700+mg2-2.34-3.88-0.790.003700+mg3-2.80-4.66-0.950.003
LSME change in absolute mammographic breast density (AVBD), by cumulative testosterone dose and time from first implant.
table 2Cumulative testosterone doseTime from first implant (yrs)LSME (cm3)Lower 95% CIUpper 95% CIp-value500 - &lt;700mg10.3-12.312.80.965500 - &lt;700mg2-4.2-19.811.40.595500 - &lt;700mg3-8.7-34.116.70.499700+mg1-7.8-26.310.70.405700+mg2-22.0-39.5-4.50.014700+mg3-36.2-59.7-12.70.003
Comparison with control group:Analysis of RAS (n=89) versus untreated controls (N=65) revealed statistically significantly different from zero for both %VBD and AVBD between the 2 groups, respectively 2.36%, (95% CI on the difference, from 1.15 to 3.56) and 18.0cm3, (95% CI on the difference, from 4.8 cm3 to 31.1cm3).
Summary of safety: The treatment was well tolerated with no serious adverse events.
Conclusions:  HAVAHT+Ai™ therapy significantly reduces volumetric MBD with good safety and tolerability. An accumulative dose of greater than 700mg of T and 30mg of Ai over 2-3 years is required to achieve a similar reduction in MBD as that demonstrated with tamoxifen as a preventative agent for breast cancer.
Citation Format: Birrell SN, Dougherty D, Good SB, Birrell NJ, Rolan P. The effect of a subcutaneous combination of testosterone (T) and anastrozole (Ai) (HAVAHT+Ai™) on volumetric mammographic breast density (MBD); an open labelled cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-01.