Methods of Reducing Mammographic Breast Density and/or Breast Cancer Risk

• US 20190167697A1
• Filed: 08/06/2018
• Published: 06/06/2019
• 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
• Granted Patent: US 10,525,063 B2
• Time in Patent Office: 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 mammographic breast density and/or breast stiffness in a patient in need thereof, comprising administering to the patient:

i) an effective amount of androgenic agent; and

ii) an effective amount of an aromatase inhibitor.

2. The method of claim 1, wherein the patient has a mammographic breast density of 7.5% or greater.

3. The method of any one of claims 1-2, wherein the androgenic agent is a selective androgen receptor modulator.

4. The method of any one of claims 1-3, wherein the patient is pre-menopausal.

5. The method of any one of claims 1-3, wherein the patient is peri-menopausal.

6. The method of any one of claims 1-3, wherein the patient is post-menopausal.

7. The method of any one of claims 1-6, wherein the reduction in mammographic breast density is in the range of between 10% to 25% after 1 year, 2 years, 3 years, 4 years or 5 years of treatment.

8. The method of any one of claims 1-7, wherein the breast stiffness reduces by at least 10% after 1 year, 2 years, 3 years, 4 years or 5 years of treatment.

9. The method of any one of claims 1-8, wherein the androgenic agent is selected from the group consisting of testosterone, methyltestosterone, testosterone undecanoate, testosterone propionate, a selective androgen receptor modulator or combinations thereof.

10. The method of any one of claims 1-9, wherein the method reduces the treated patient'"'"'s risk of developing breast cancer between one or more annual intervening mammographic detections.

11. The method of any one of claims 1-10, wherein the method provides one or more of the following:

i) enhances mammographic detection due to reduced breast density enabling the mammogram to visualize malignancy at an earlier and/or less aggressive stage;

ii) enhances the ability to achieve better mammographic compression due at least in part due to reduced pain;

iii) enhances the ability to achieve better patient compliance in having regular mammographic check-ups;

iv) enhances the ability to treat the patient and at the same time not causing perturbations in the hypothalamic-pituitary axis and/or other endocrine axis;

v) reduces breast pain in a patient;

vi) reduces breast elasticity in a patient;

vii) decrease mechano-transduction on the genome of a cell in order to reduce the risk of malignant transformation in a patient;

viii) increases ratio of fibro-glandular and adipose tissue in a patient;

ix) increases CD36 in a patient;

x) stabilizes and/or an increase in levels of androgen receptor expression in breast tissue of a patient;

xi) increases the level of GCDFP15 in a patient;

xii) reduces BPE in an MRI image of a patient; and

xiii) reduces cysts in size and/or quantity in a patient'"'"'s breast.

23. The method of any one of claims 1-22, wherein the method reduces the risk of developing breast cancer in a patient.

12. A method of reducing VBD % and/or AVBD in a patient in need thereof, comprising administering to the patient:

i) an effective amount of an androgenic agent; and

ii) an effective amount of an aromatase inhibitor.

14. The method of claim 12, wherein the patient has a VBD % and/or AVBD of 7.5% or greater.

16. The method of any one of claims 12-13, wherein the androgenic agent is a selective androgen receptor modulator.

17. The method of any one of claims 12-16, wherein the patient is pre-menopausal, peri-menopausal or post-menopausal.

18. The method of any one of claims 12-17, wherein the reduction in VBD % or in ABD % is in the range of between 10% to 25% after 1 year, 2 years, 3 years, 4 years or 5 years of treatment.

19. The method of any one of claims 12-18, wherein the breast stiffness reduces by at least 10% after 1 year, 2 years, 3 years, 4 years or 5 years.

20. The method of any one of claims 12-19, wherein the androgenic agent is selected from the group consisting of testosterone, methyltestosterone, testosterone undecanoate, testosterone propionate, a selective androgen receptor modulator or combinations thereof.

21. The method of any one of claims 12-20, wherein the method mitigates or reduces the treated patient'"'"'s risk of developing breast cancer between one or more annual intervening mammographic detections.

22. The method of any one of claims 12-21, wherein the method provides one or more of the following:

i) enhances mammographic detection due to reduced breast density enabling the mammogram to visualize malignancy at an earlier and/or less aggressive stage;

ii) enhances the ability to achieve better mammographic compression due at least in part due to reduced pain;

iii) enhances the ability to achieve better patient compliance in having regular mammographic check-ups;

iv) enhances the ability to treat the patient and at the same time not causing perturbations in the hypothalamic-pituitary axis and/or other endocrine axis;

v) reduces breast pain in a patient;

vi) reduces breast elasticity in a patient;

vii) decrease mechano-transduction on the genome of a cell in order to reduce the risk of malignant transformation in a patient;

viii) increases ratio of fibro-glandular and adipose tissue in a patient;

ix) increases CD36 in a patient;

x) stabilizes and/or an increase in levels of androgen receptor expression in breast tissue of a patient;

xi) increases the level of GCDFP15 in a patient;

xii) reduces BPE in an MRI image of a patient; and

xiii) reduces cysts in size and/or quantity in a patient'"'"'s breast.

13. A method of reducing ABD % and/or AABD in a patient in need thereof, comprising administering to the patient:

i) an effective amount of an androgenic agent; and

ii) an effective amount of an aromatase inhibitor.

15. The method of claim 13, wherein the patient has a ABD % and/or AABD of 7.5% or greater.