hormone replacement therapy and breast cancer in postmenopausal

Hormone Replacement Therapy and Breast Cancer in Postmenopausal Women

Seminário da Licenciatura em Ciências Biomédicas

Diana Catarina Santos nº23271

Diana Catarina Santos nº23271 2

Postmenopause hormonal changes

• Degeneration of women’s last oocytes

• There is no follicular development

< [estrogens]

• FSH has a drastic increase

Ovulation does not occur

• There is no corpus luteaum development

<[progesterone]

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Vasomotor Symptoms

Hot flashes;

Palpitations;

Night sweats.

SexualUrogenitalSymptoms

Cardiovascular disease (CVD);

Osteoporosis;

Alzheimer

Anxiety;

Insomnia;

Mood change;

Poor memory.

Psychological Symptoms

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Urogenital infections;

Vagina dryness;

Loss of libido

Chronic diseases


Hormone Replacement Therapy

ET

•Unopposed estrogen therapy - women with uterus – continuous proliferation of endometrium – hyperplasia – endometrial cancer

•ET (eg: CEE) must only be used by hysterectomized women

CHT

•Combined hormone therapy uses a progestin plus estrogens to oppose them effects (eg: CEE+MPA)

•Can postmenopausal women trust in HRT? What are the risks?

•To answer the questions there were performed several randomized clinical trials (RCTs) and observational studies

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WHI clinical trialsExpectations

•Climacteric symptoms relief

•Osteoporosis prevention

•CVD prevention

Results•Climacteric symptoms relief

•Osteoporosis prevention

•Increase of stroke risk and CVD

•Increase of breast cancer risk

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Breast cancer risk depends on…

CHT ET

Duration of use

Regiment

selection (e.g.:

progestin type)

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CHT and breast cancer riskBreast cancer risk for users of CHT (CEE+MPA) is higher

than for placebo group

Women’s Health Initiative (WHI) –> HR=1,26

Heart and Estrogen/Progestin Replacement Study (HERSII) -> HR=1,30

Breast cancer risk in users of CHT is higher than in never users

Million Women Study (MWS)Collaborative Group Study –Reanalyzes of 51 studies

Shah Nirav, et al -> estimated the risk of 1,39 fold increase for observational studies

RCTs

Observational Studies

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Long of use of CHT and breast cancer risk

Breast cancer risk for users of CHT (CEE+MPA) is increased in time against placebo group

1 year – 8 more cases per 10 000 against placebo group

5,2 years – there are expected 46 more cases per 10 000 than in placebo group

Breast cancer risk for users also appeared to depend on time

MWS -> RR=1,63 (<5 years) and 2,21 (>5 years)

RCTs


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Continuous or Sequential use of CHT and breast cancer risk

Observational data:

• Studies show that women using CHT sequentially (<15 days/mo) present lower risk against continuous users;

• Others found an increased risk of 30% against non users for both strategies of use;

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After 5 years of discontinuing the hormonal therapy use, past and current users have the same relative risk.


ET and breast cancer risk

Breast cancer risk for users of ET (e.g.: CEE alone) presented no raise in the risk of breast cancer compared

with placebo

WHI –>HR=0,77 (23% decrease)

Most of studies show a higher breast cancer risk in users compared with never users

MWS -> RR=1,30Collaborative Group Study -> RR=1,34

E3N cohort study-> RR=1,29Shah Nirav, et al -> estimated the risk of 1,16 fold increase as

a review of observational studies

RCTs


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ET, long of use and breast cancer risk

Most observational studies found that:

• Breast cancer increases with the course of time for current users;

• Breast cancer has a higher risk for past users;

• After discontinuation of ET, breast cancer risk decreases;

• Breast cancer risk increase for ET is smaller than the risk that these studies presented for CHT, according with time.

Other observational studies presented similar results to WHI studies.

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Histological types of breast cancer, CHT and ET

CHT• CHT are associated with 2.0 – 3.9 fold increased risk of ILC, but generally

not with IDC.

ET• Both ILC and IDC risks remain unaltered, even after prolonged use of 25

years.

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Invasive lobular carcinoma (ILC) is more difficult to detect by mammography but have better prognosis than invasive ductal

carcinoma (IDC) [Christopher I., et al]


HRT and Animal Models Female primates – Macaca fascicularis

•Breast epithelial proliferation increases – high breast cancer risk

CEE+MPA

•Breast epithelial proliferation increases – high breast cancer risk

CEE alone

•Breast epithelial proliferation is not altered with this therapy

Tibolone

•Significant increase for both ductal and lobular epithelial proliferation

E2+MPA

•Breast epithelial proliferation (ductal and lobular) remains unaltered

E2+P4

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Breast cancer, mammography, mortality AND clinical trials

Abnormal mammogramsDiagnostic delay

6,9% raise in breast cancer densityWorse tumors and increased mortality

CHT leads to: Mammograms are

not compromised

2,9% raise in breast cancer density

ET

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Breast cancer, mammography, mortality AND observational

studies

NHS (Nurses Health Study) and the majority of observational studies showed a decrease in the risk of death for HRT users compared with never users;

These results are expected because:• Women taking HRT are more under medical supervision;• Breast cancer can be detected and treated earlier.

Although observational studies have a lot of limitations:

• They combined CHT and ET results;• Selection criteria is varied;• Difference in women’s age (WHI comprised older women)

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Conclusion Women taking CEE+MPA (CHT) have a high breast cancer risk, compared

with women taking other HRT or compared with non-users;

The risk is more apparent with continuous CHT and for ILC;

Although the differences between RCTs and observational studies ET is associated with less risk than CHT is;

Replacing MPA for other progestin may provide more safety for users;

Mortality is still a controversial.

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HRT is associated with a small but significant increase in breast cancer risk


Conclusion

Benefits Risks

Diagnostic delay/Mortality

Stroke / CVD

Breast cancer increase

CVD prevention

Osteoporosis prevention

Quality of life

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The End

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Discussion

hormone replacement therapy and breast cancer in postmenopausal

Documents

higher breast cancer

current users breast

higher risk

risk of death

observational studies

users of cht cee

users observational

fold increased risk