Danish sex Hormone Register Study DaHoRS

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Danish sex Hormone Register StudyDaHoRS

• Hormone therapy and breast cancer
• Øjvind Lidegaard1, Ellen Løkkegaard2,
• Anne Helms Andreasen3, Lisbeth Møller3
• Carsten Agger3, Torben Jørgensen3
• 1) Rigshospitalet, Gynaecologic Clinic, 4232
• 2) Dept. Obstetrics Gynaecology, Hilleroed
  Hospital, DK.
• 3) Research Centre for Prevention and Health,
  Glostrup, DK

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DaHoRS Principal study design

• Aim
• Assess the influence of OC and HT on
• The risk of cardiovascular diseases and cancer
• Material and methods
• A National cohort of 1.8 million women
• 15-69 years old January 1, 1995
• Followed from January 1995 through 2002
• Exposures and outcomes from national registers
• Details on www.dachre.dk

Danish Sex Hormone Register Study (DaHoRS)
www.dachre.dk
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Data retrieval Registers involved

• National Register of Medicinal Product Statistics
  (NRM) assessing daily exposure of OCs and HT and
  medicine for diabetes, hypertension, and
  hyperlipidaemia
• National Register of Patients (NRP)
• assessing clinical outcomes, hysterectomy,
  oophorectomy
• Central Person Register (CPR)
• assessing education, job-status, address

Danish Sex Hormone Register Study (DaHoRS)
www.dachre.dk
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Clinical outcomes

• Cancers included, total 36,552
• Breast, endometrium, ovaries, cervix, colon,
  rectum, lymphoma, leukaemia
• Cardiovascular end points, total 63,483
• Acute myocardial infarction (AMI)
• Ischaemic heart disease
• Thrombotic stroke
• Haemorrhagic stroke
• Venous thromboembolism

www.dachre.dk
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Clinical outcomes

• Cancers included, total 36,552
• Breast, endometrium, ovaries, cervix, colon,
  rectum, lymphoma, leukaemia
• Cardiovascular end points, total 63,483
• Acute myocardial infarction (AMI)
• Ischaemic heart disease
• Thrombotic stroke
• Haemorrhagic stroke
• Venous thromboembolism

www.dachre.dk
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Hormone therapy and breast cancer

• Cohort Included women 50-69 785,397
• Exposed women (currentprev) 234,955
• Control women (never users) 550,442
• Women currently on HT with BC 3,010 2.5
• Women previously on HT w BC 1,957 1.7
• Women never on HT with BC 7,864 1.4
• Included with BC 12,831

Danish Sex Hormone Register Study (DaHoRS) www.
dachre.dk
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BC risk Influence of age, current use
Adjusted RR, 95 CI
Never Current systemic use
DaHoRS/05
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BC risk Length of systemic HTStratified by age
and duration of use (years)
Corrected RR, 95 CI
51-54 55-59 60-64 65-69
DaHoRS/05
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BC risk according to HT regimen
Adjusted RR, 95 CI
Estrogen Long cyc Cyc com Cont com
Tibolone
DaHoRS/05
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BC risk according to route
Adjusted RR, 95 CI
Oral E Oral comb TD Estrogen TD
comb.
DaHoRS/05
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The impact of progestagen doseLow 0.5mg NETA
or 2.5mg MPA. High 1mg NETA or 5mg MPA
Adjusted RR, 95 CI
All continuous combined regimens
51-54 55-59 60-64
65-69
DaHoRS/05
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BC risk acc to progestagen type and estrogen
dose. Cyclic combined regimen
Adjusted HR, 95 CI
DaHoRS/05
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Previous systemic use and BC risk
Adjusted RR, 95 CI
DaHoRS/05
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Death after BC accord to HT

• Group Wom yrs Dead deaths/100wy
• 51-54 yrs 4,098 143 3.5
• 55-59 yrs 7,635 382 5.0
• 60-64 yrs 7,301 450 6.2
• 65-69 yrs 7,658 545 7.1
• 70-74 yrs 3,164 237 7.5
• Never 29,856 1,757 5.9
• Previous 5,876 263 4.5
• Current 11,212 327 2.9

Danish Sex Hormone Register Study (DaHoRS)
www.dachre.dk
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Case-fatality rate after five years in women on
HT at diagnosis
Adjusted RR, 95 CI
Women with BC 12,831 Dead after diagnosis
2,347 (18) Five years follow-up 1,269
DaHoRS/05
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Risk of lethal BC with hormones within five years
after diagnosis
Adjusted RR, 95 CI
Women with BC 12,831 Dead after diagnosis
2,347 (18) Five years follow-up 1,269
DaHoRS/05
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Risk of incidence versus mortality
Relative risk
DaHoRS/06
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The reduced case-fatality rate and low risk of
lethal BC may be due to

• Earlier detection of BC in hormone users
• Less pathological histology
• More receptor positive tumors
• Withdrawal of hormones after detection
• More intensive screening of women on hormones
  with detection of tumours which would never have
  manifested as clinical BC

Danish Sex Hormone Register Study (DaHoRS) www.
dachre.dk
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HT-BC Conclusion

• HT in women 50-54 years old have little excess BC
  risk
• Estrogen only for any length in women below 65
  years implies only little risk of BC
• Combined HT increases the risk of BC after gt4
  years therapy or age gt55 years old
• Cyclic comb therapy confers roughly the same risk
  as cont comb HT up to 4 years of hormone use.
• gt4 years cont comb therapy confers a higher risk
  of BC than gt4 yrs cyclic comb. therapy

Danish Sex Hormone Register Study (DaHoRS) www.
dachre.dk
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HT-BC Conclusion

• Consistent association to duration of use.
• Consistent association to estrogen dose.
• Consistent association to progestagen dose.
• Older women higher relative risk on cont combined
  regimen than younger postmenopausal women.
• Risk disappears 6 months after last use
• Case-fatality rate ratio 0.5 in current users
• Risk of lethal breast cancer not increased

Danish Sex Hormone Register Study (DaHoRS) www.
dachre.dk
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HT-BC Clinical implications

• Low-dose products
• Less concern of estrogen only therapy
• Less concern about HT in women during their first
  five years after menopause.
• Advise for low-progestagen dose regimens
• - especially if long term use.
• No concern about local estrogen
• Probably no increased risk of lethal BC

Danish Sex Hormone Register Study (DaHoRS) www.
dachre.dk