Methods of reducing mammographic breast density and/or breast cancer risk

• US 10,525,063 B2
• Filed: 08/06/2018
• Issued: 01/07/2020
• Est. Priority Date: 10/22/2014
• Status: Active Grant

• Current Assignee: Havah Therapeutics Pty., Ltd.
• Original Assignee: Havah Therapeutics Pty., Ltd.
• Inventors: Birrell, Stephen Nigel
• Primary Examiner(s): Gembeh, Shirley V
• Application Number:
  US16/055,588
• Publication Number:
  US 20190167697A1
• Time in Patent Office: 519 Days
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/569 substituted in position 17 alpha, e.g. ethisterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present disclosure is directed to generally methods and/or compositions for treating mammographic breast density and/or breast stiffness in a patient in need thereof, such as a pre-menopausal, a peri-menopausal or a post-menopausal patient, comprising the administration of an effective amount of androgenic agent and an effective amount of an aromatase inhibitor. The present disclosure is also directed to methods and/or compositions for reducing breast pain. The present disclosure is also directed to method and/or compositions for reducing elasticity and/or decreasing mechano-transduction on the genome of breast cells. The present disclosure is also directed to methods and/or compositions for stabilizing and/or increasing the levels of androgen receptor expression in breast tissue.

Claims

1. A method of reducing breast density in a patient in need thereof, comprising administering to the patient:

i) an effective amount of androgenic agent selected from the group consisting of testosterone, methyltestosterone, testosterone undecanoate, testosterone propionate, testosterone cypionate, and testosterone enanthate; and

ii) an effective amount of an aromatase inhibitor selected from the group consisting of;

exemestane, formestane, anastrozole, letrozole, vorozole, and fadrozole;

wherein the method mitigates the treated patient'"'"'s risk of developing breast cancer.

2. The method of claim 1, wherein the effective amount of androgenic agent is testosterone and the effective amount of the aromatase inhibitor is anastrozole and is administered by subcutaneous implant.

3. The method of claim 1, wherein:

i) the effective amount of the testosterone is 2-200 mg; and

ii) the effective amount of the anastrozole is 0.5-10 mg.

4. The method of claim 3, wherein:

i) the effective amount of the testosterone is 2-200 mg; and

ii) the effective amount of the anastrozole is 0.5-10 mg.

5. The method of claim 4, wherein the method improves breast compression during mammographic visualization or detection of the breast between one or more annual intervening mammographic detections.

6. The method of claim 4, wherein the method stabilizes and/or increases levels of androgen receptor expression in breast tissue in at least one of the patient'"'"'s breasts between one or more annual intervening mammographic detections.

7. The method of claim 4, wherein the patient is pre-menopausal.

8. The method of claim 4, wherein the patient is peri-menopausal.

9. The method of claim 4, wherein the patient has, or is diagnosed with having, a breast with an area breast density percentage (ABD %) of 7.5% or greater.

10. The method of claim 9, wherein the method reduces the ABD % or an absolute area breast density (AABD) of the patient'"'"'s breast by at least 2% over a 2 week, 1 month, 2 month, 3 month, 6 month, 9 month, or 1 year period.

11. The method of claim 4, wherein the patient has, or is diagnosed with having, a breast with a volume breast density percentage (VBD %) of 7.5% or greater.

12. The method of claim 11, wherein the method reduces the VBD % or an absolute volume breast density (AVBD) of the patient'"'"'s breast by at least 2% over a 2 week, 1 month, 2 month, 3 month, 6 month, 9 month, or 1 year period.

13. The method of claim 1, wherein the method improves breast compression during mammographic visualization or detection of the breast between one or more annual intervening mammographic detections.

14. The method of claim 1, wherein the method stabilizes and/or increases levels of androgen receptor expression in breast tissue in at least one of the patient'"'"'s breasts between one or more annual intervening mammographic detections.

15. The method of claim 1, wherein the patient is pre-menopausal.

16. The method of claim 1, wherein the patient is peri-menopausal.

17. The method of claim 1, wherein the patient has, or is diagnosed with having, a breast with an area breast density percentage (ABD %) of 7.5% or greater.

18. The method of claim 17, wherein the method reduces the ABD % or an absolute area breast density (AABD) of the patient'"'"'s breast by at least 2% over a 2 week, 1 month, 2 month, 3 month, 6 month, 9 month, or 1 year period.

19. The method of claim 1, wherein the patient has, or is diagnosed with having, a breast with a volume breast density percentage (VBD %) of 7.5% or greater.

20. The method of claim 19, wherein the method reduces the VBD % or an absolute volume breast density (AVBD) of the patient'"'"'s breast by at least 2% over a 2 week, 1 month, 2 month, 3 month, 6 month, 9 month, or 1 year period.