Introduction: There is evidence that androgens are breast protective and that testosterone (T) therapy treats many symptoms of hormone deficiency in both pre and postmenopausal patients. However, there is a lack of data on the effect of long-term T therapy on the incidence of breast cancer.

Methods: A ten-year prospective, IRB approved study (Dayton study) was designed to investigate the incidence of breast cancer (BCA) in women with symptoms of hormone/androgen deficiency who were treated with subcutaneous testosterone (T) implants or, T combined with an aromatase inhibitor, anastrozole, implants (T+A). Breast cancer events during 'active therapy' (within 120 days post implant, i.e, clinically effective/therapeutic T levels), and 'post therapy' (240 days and 1-year post implant) were reported as incidence per 100 000 person-years. Person-days for each participant were calculated from the date of first T pellet insertion up to the date of cancer registration, the date of death, a set number of days post last implant, or the set date of 31 March 2018, whichever came first. Person-years (p-y) were calculated by dividing (total) person-days by 365.25. Bootstrap sampling distributions were constructed to determine if there were important differences in breast cancer incidence rates between our results and the SEER data. Allowing for patient aging and different cancer rates over the period of the study, the range of expected values based on SEER data was calculated from the age composition of our study patients and the published grouped age breast cancer incidence rates for two time periods, SEER 2006-2011 and SEER 2011-2016.

Results: 1267 pre (23.2%) and post (76.8%) menopausal women, mean age 52.1 + 8.6 y, were enrolled in the study March 2008-2013 and were eligible for analysis. As of March 2018 there have been 12 cases of invasive breast cancer diagnosed within one year of last T or T+A pellet implant. The incidence of breast cancer at each specified time frame is listed in Table 1. For comparison, the calculated age matched SEER incidence rate is approximately 271/100 000 p-y.

Incidence of BCA

Time frame 120 days 240 days 365 days 
P-Y 6372 6666 6960 
BCA (n) 11 12 
N/100 000 p-y 110 165 172 
Time frame 120 days 240 days 365 days 
P-Y 6372 6666 6960 
BCA (n) 11 12 
N/100 000 p-y 110 165 172 

Time frame is number of days post last pellet insertion.

Bootstrap results confirm a significant reduction in BCA incidence compared to age specific SEER data.

Bootstrap results

Time frame Dayton incidence Dayton sd Seer incidence Seer sd Ratio corrected Ratio sd 
120 d 110.26 41.72 270.73 3.10 0.41 0.15 
240 d 165.33 50.31 270.46 3.01 0.61 0.19 
365 d 172.65 49.45 270.33 2.93 0.64 0.18 
Time frame Dayton incidence Dayton sd Seer incidence Seer sd Ratio corrected Ratio sd 
120 d 110.26 41.72 270.73 3.10 0.41 0.15 
240 d 165.33 50.31 270.46 3.01 0.61 0.19 
365 d 172.65 49.45 270.33 2.93 0.64 0.18 

Bootstrap estimates of Dayton and expected SEER incidence rates (per 100 000 P-Y), their standard deviations (sd), the ratio (R) of the Dayton incidence rate to the SEER and its sd for various time frames.

Conclusion: Long-term therapy with T or T+A subcutaneous implants, used to treat symptoms of hormone deficiency, reduced the incidence of breast cancer by 59% during active therapy (p < 0.001), which continued up to one year following the last pellet implant, 36% reduction at 1-year (p < 0 .001).

Citation Format: Glaser RL, York AE, Dimitrakakis C. Reduced incidence of breast cancer with testosterone implant therapy: A 10-year 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 P6-13-02.