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Additional data for breast cancer
surveillance in women
with Down syndrome

D
aniel Satgé MD, PhD1
Clotilde Mircher MD2
Brigitte Trétarre MD3
Marie-Odile Réthoré MD2
1Pathology, University Hospital, Saint Etienne, France
and ONCODEFI Project,IURC Montpellier France
2Institut Jérôme Lejeune, Paris, France
3Hérault Cancer Registry, Montpellier, France

World Down syndrome
Congress 2012

August 14-17 Cape Town SA
Breast cancer in the general population

Breast cancer is the most frequent tumor in
women in the world.
One women on 9 will be diagnosed with breast
cancer during her life in France.

More than half of breast cancer are diagnosed
after 65 years in industrialized countries.
Breast cancer is the second cause of cancer death in the world. World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Breast cancer in women
with intellectual disability

Globally breast cancer seems as frequent in women
with intellectual disability as it is in the general
population
Patja et al Finland 2001
SIR at 0.90 (CI 95% 0.6-1.3)

Sullivan et al Australia 2004 SIR at 0.69* (CI 95% 0.43-1.06)
* Possible underestimation linked to underutilization of screening service
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Risk factors for breast cancer
in women with intellectual disability

General population
Intellectual disability

Nulliparity

Overweight (after menopause)
Sedentarity
Familial history of breast cancer
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Breast cancer risk is not similar
for all women with intellectual disability

Conditions with increased risk
Cerebral palsy
Cowden syndrome
Saethre Chotzen syndrome
Type1 neurofibromatosis

Conditions with similar risk
???
Conditions with decreased risk
Down syndrome +++
Fragile-X syndrome
World Down syndrome
Congress 2012

August 14-17 Cape Town SA
Breast cancer frequency in women
with Down syndrome

Incidence studies

Hasle et al 2000 (Denmark) 0/7.3 (CI 95% 0.0-0.41)
Patja et al 2006 (Finland) 6/15.4 (CI 95% 0.1-0.8)
Sullivan et al 2007 (Australia) 0/?
World Down syndrome
Congress 2012

August 14-17 Cape Town SA
Breast cancer frequency in
women with Down syndrome

Mortality studies
Scholl et al 1982 (USA) 1/11.7 (CI ?)
Satgé et al 2001 (France) 5/69 (CI ?)
Yang et al 2002 (USA) 25/(625) (CI 95% 0.03-0.06)

World Down syndrome
Congress 2012
August 14-17 Cape Town SA
Breast cancer in women with Down
syndrome

Published cases 1968-2012 Incidence studies Only 2 case reports provide clinical
World Down syndrome
Congress 2012

details.
August 14-17 Cape Town SA
Breast cancer in
all intellectual disabilities/ Down syndrome

Whereas breast cancer seems to occur at a similar
frequency in women with intellectual disability and in
the general population, epidemiological studies
suggest a reduced frequency in women with
Down syndrome.


This suggests that the supernumerary 21
chromosome could have a protective effect on
breast cancer occurrence.

World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Factors increasing breast cancer risk
in women with Down syndrome

- Nulliparity
- Oxidative stress
- Overweight after menopause

- Premature aging
- DNA repair anomalies (mild)
Thoracic X-rays for respiratory infections
- Immune deficiency (mild)
World Down syndrome
Congress 2012

August 14-17 Cape Town SA
Factors decreasing breast cancer risk
in women with Down syndrome


Reduced estrogen exposure

In utero: decreased maternal estriol levels
Decreased estradiol levels during cycle
Early menopause
Decreased oral contraception
Decreased menopause hormonal treatment
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Protective genetic factors
Studies of loss of heterozygosity and of comparative
hybridization suggested genes protecting against
breast cancer on 21 chromosome


ANA (BTG3)

TIAM1
ETS2
DSCR1, DYRK1A angiogenesis inhibition
S100B

And others…
World Down syndrome
Congress 2012

August 14-17 Cape Town SA

Men with Down syndrome develop less
frequently gynecomastia compared to men
with other intellectual disabilities [Sabeen et
al 1971]
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

syndrome have significantly smaller
mammary buds
compared to non-Down
syndrome fetuses [Petrikovska et al 1996]
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Experience at the
Institut Jérôme Lejeune,
Method

All women, aged 20 years or more included
years 1998-2012 (some patients since 1955)
40% from Paris 55% from other towns in France 5% from other countries
Histologically proven cancers
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Institut Jérôme Lejeune experience
Results

889 women aged 20 to 73 years

Corresponding to 4272 person-years

4 breast cancers after 1998
1 breast cancer before 1998
Expected number of breast cancer after
1998 16.45 (for 4 cases observed)
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Breast cancer in women with
Down syndrome at the
Institut Jérôme lejeune

25 years type1 neurofibromatosis + DS
59 years mother with breast cancer
53 years mother with breast cancer

menopause hormonal ttt 3 yrs
52 years oral contraception 10 yrs
40 years tuberculous pleurisy
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Note 1:
Although genetic conditions favoring breast
cancer occur in around 5-10% of women with
breast cancer in the general population 3/5
patients in this series had a family history
or a genetic favoring condition


Note 2
The mean age at diagnosis was 46 years,
whereas it is 61years in the general population
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

In the medical literature only one other
case is documented: Bernardino et al
1997. There was also a familial
predisposition to cancer
(B Dutrillaux
personal communication).
Together with our observations this
suggests that in case of familial cancer
the supernumerary chromosome 21
does not seem to protect against breast

World Down syndrome
cancer occurrence.
Congress 2012
August 14-17 Cape Town SA

1) Women with Down syndrome have a
reduced frequency of breast cancer
which
remain to be more precisely assessed

2) Women with Down syndrome are more
vulnerable to ionizing radiations
(X-rays)

3) In this series tumors occurred at a lower
mean age
compared to the general
population (to be confirmed)

4) A supernumerary 21 chromosome does
not seem to protect in case of familial-

World Down syndrome
genetic predisposition to breast cancer. Congress 2012
August 14-17 Cape Town SA
Breast cancer monitoring
in women with Down syndrome

A mode of monitoring is necessary
Palpation? Mammography? Echography
?

Which may be different from that in the
general population

An earlier awareness is warranted

For patients with familial/genetic
predisposition, women should be followed
similarly to other family members

World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Thank you for
your attention

Acknowledgments

The Fondation Jérôme Lejeune
supports the study on cancer in people
with Down syndrome
World Down syndrome
Congress 2012
August 14-17 Cape Town SA

Source: http://docs.sbs.co.za/Daniel%20Satge%20Breast%20Cancer-DS%20CTown%202012.pdf

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