![Page 1: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/1.jpg)
MENOPAUSAL HORMONAL MENOPAUSAL HORMONAL TREATMENT AND BREAST TREATMENT AND BREAST
CANCER RISKCANCER RISK
PROF DR H DEPYPEREPROF DR H DEPYPERE
Gynaecologische oncologie en borstkliniek, Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, GentUniversitair Ziekenhuis, Gent
![Page 2: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/2.jpg)
Sixty procent of women have vasomotor complaints
Cochrane data base of randomised trials indicates hormonal replacement is the most effective treatment to treat vasomotor symptoms
A small increase in breast cancer will deter women from taking HRT
![Page 3: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/3.jpg)
cardiovascular disease
7%don't know
16%
other problems 16%
cancer27%
breast cancer34%
Women’s perceptions of their greatest health problems
Mosca L et al Arch Fam Med 2000;9:506-515
![Page 4: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/4.jpg)
Age No alive atbeginning ofinterval
No incidentbreastcancers
No deathfrom breastcancer
No incidentbreast cancersper 5 years per1000
No incidentbreast cancersper year per1000
0 1000 0 0 0 025-29 990 0 0 0 030-34 988 1 0 1.0 0.235-39 986 3 0 3.1 0.640-44 983 5 1 5.1 1.045-49 977 8 2 8.2 1.650-54 968 11 3 11.4 2.355-59 952 12 3 12.6 2.560-64 929 12 3 12.9 2.665-69 892 14 4 15.7 3.170-74 836 13 5 15.6 3.175-79 752 11 6 14.6 2.980-84 624 9 6 14.4 2.8>85 434 5 7 11.5 2.3
![Page 5: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/5.jpg)
Age at menarche 3 menarche before 11
age at menopause 2 menopause after 54
age at first full pregnancy 3 first child in early 40s
family history >2 first degree when young
previous benign disease 4-5 atypical hyperplasia
cancer in other breast >4
diet 1.5 high sat fat intake
BMI premenopausal 0.7 BMI>35
postmenopausal 2 BMI>35
alcohol 1.3
hrt 1.35 hers, NHS, WHI
![Page 6: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/6.jpg)
![Page 7: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/7.jpg)
Estrogen only
Safer progestogens
Serm : MORE trial
STAR trial
CORE trial
![Page 8: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/8.jpg)
Estrogens are not associated with an increase in breast cancer incidence (WHI : JAMA 2002;288:321-333; Olsson et al, Cancer, 2003, 97;1387-1392). Latest results of WHI suggest a significant reduction.
Million Women Study does suggest an increase in breast cancer in estrogen only treatment (Lancet 2003;362:419-427). This is also observed in E3N study Int J Cancer 2005;114:448-454). Dahors study indicates a very small increase.
INFLUENCE OF ET ON BREAST CANCER INCIDENCE
![Page 9: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/9.jpg)
Estrogen only WHI RR 0.77
NHS - duration ? 28 835 women with hysterectomy
BMI <25 BMI>25
never 78 1.00 148 1.00
<5 y 45 1.03 (0.69-1.52) 54 0.96 (0.96-1.33)
5-9.9 78 1.17 (0.84-1.62) 66 0.74 (0.55-1.00)
10-14.9 94 1.18 (0.86-1.62) 94 0.97 (0.74-1.28)
15-19.9 66 1.36 (0.97-1.92) 63 1.11 (0.82-1.51)
>20 80 1.77 (1.26-2.48) 65 1.25 (0.91-1.71)
![Page 10: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/10.jpg)
Estrogen only
Safer progestogens
Serm : MORE trial
STAR trial
CORE trial
![Page 11: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/11.jpg)
Hers I study (RR : 1.38 (0.82-2.31; p =0.22))
WHI (RR :1.26 (1.00-1.59))
conform : Nurses’ health study and Lancet ‘97 meta analysis (RR :1.35 (1.21-1.49))
This is also observed in E3N study for synthetic progestogens and not for natural progesterone.
In WHI only significant increase in breast cancer after more than 5 years of intake of EPT
INFLUENCE OF EPT ON BREAST CANCER INCIDENCE
![Page 12: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/12.jpg)
Prospective studyProspective study 54.584 postmenopausal women54.584 postmenopausal women 5,8 years follow-up5,8 years follow-up 29.420 HRT users (54%)29.420 HRT users (54%) 12% E2 alone12% E2 alone 88% EP combined88% EP combined 948 invasive breast cancer948 invasive breast cancer
![Page 13: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/13.jpg)
Oral estrogens
+ Synthetic progestogen
+ micronized progesteron
+ micronized progesteron
+ Synthetic progestogen
RR = 1.3(1.1-1.5)
RR = 0.9 (0.7-1.2)
RR = 1.4(1.2-1.7)
RR = 1.5 (1.1-1.9)
Cutan. estrogens
estrogens + progestatogen
•To small number to compare
![Page 14: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/14.jpg)
1,4
1,0
1,3
1,8
-0,5 0 0,5 1 1,5 2 2,5 3 3,5 4 4,5 5 5,5
Estrogens alone (57)<2 years (26)2-4 years (17)4-6 years (4)6+ years (9)Estrogens + progesterone (109)<2 years (45)2-4 years (29)4-6 years (19)6+ years (16)Estrogens + retroprogesterone (97)
<2 years (34)2-4 years (29)4-6 years (15)6+ years (18)Estrogens + other synthetic progestins (468)<2 years (174)2-4 years (123)4-6 years (87)6+ years (81)
![Page 15: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/15.jpg)
0
0,5
1
1,5
2
2,5
3
51-54 55-59 60-64 65-69
2mg E2, 1 mgNETA4mg E2, 1 mgNETA
Breast cancer risk according to progestogen type and estrogen dose
1 mg NETA 51-54 RR 1.3; 55-59 RR 2.2; 60-64 RR 2.7; 65-69 RR 3.00.5 mg NETA no significant increase in any age group;
![Page 16: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/16.jpg)
Dahors : Danish Sex Hormones Dahors : Danish Sex Hormones register Studyregister Study
4 242 334 women years4 242 334 women years12 831 breast cancers12 831 breast cancersdeaths per 100 women yearsdeaths per 100 women years
never usersnever users :: 5.95.9ever users :ever users : 4.54.5current users :current users : 2.92.9
![Page 17: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/17.jpg)
Estrogen only
Safer progestogens
Serm : MORE trial
STAR trial
CORE trial
![Page 18: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/18.jpg)
Cauley J, et al. Breast Cancer Res Treatment. 2001;65:125-134
Years
0.0
2.0
0 1 2 3 4 5
Raloxifene1.9 per 1000woman-years
Placebo5.3 per 1000woman-years
% o
f Ran
dom
ize
d P
atie
nts
RR = 0.38 (95% CI = 0.24-0.58)*
Effect of Raloxifene on Breast Cancer Effect of Raloxifene on Breast Cancer IncidenceIncidence
MORE Trial - 48 MonthsMORE Trial - 48 Months
Total Cases = 77*P<.001
1.0
![Page 19: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/19.jpg)
7705 postmenopausal women
10.5 per 1000 women in control arm.
Reduction by 76 % with raloxifen. This implicates a reduction of 2.52 breast cancers per 1000 women.
Only ER rec positive tumors are prevented.
Raloxifen
![Page 20: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/20.jpg)
3510 women receiving raloxifene 60 mg/d vs 1703 women receiving placebo from more that continue in core.
ER positive invasive breast cancers reduced 66 % (RR 0.34 CI : 0.18-0.66). No difference in ER negative cancers. Absolute numbers 1.4 cancers per 1000 women per year vs 4.2 cancers.
CORE - Continuing Outcomes Relevant to Evista
![Page 21: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/21.jpg)
Mammografie voor en na Mammografie voor en na behandeling met Livialbehandeling met Livial®®
Vrouwen onderVrouwen onderCEE/MPACEE/MPA
Dezelfde vrouwen na 1 jaarbehandeling met Livial
Valdivia & Ortega 2000 Clin Drug Invest 20:101-107
![Page 22: MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent](https://reader034.vdocuments.us/reader034/viewer/2022051819/5519231955034638428b4bc1/html5/thumbnails/22.jpg)
Practical guidelinesA small increase in breast cancer will deter women from taking HRT.
Small increase in breast cancer with EPT formulations. Importance of progestogen.
Increase with ET after 20 years. The combination with mirena is an interesting option.
Serm concept is an interesting field of new development.
Tibolone data from liberate will be disclosed next year.