Journal Reading

Reproductive Biomedicine Online 2014; 29: 573-80.

Ovarian reserve in breast

cancer: assessment with antiMllerian hormone
Anne-Sophie Hamy, Raphel Porcher,
Caroline Cuvier, Sylvie Giacchetti, MarieHlne Schlageter, Christiane Coissieu,
Hloise Gronier, Jean-Paul Feugeas, Nadir
Adoui, Jean-Marc Lacorte, Catherine Poirot,
Mohamed Habdous, Marc Espi

Introduction
Chemotherapy in breast cancer
treatment-induced ovarian failure
Present as acute amenorrhea
Maybe followed by irreversible premature
ovarian failure

No validated predictive marker of

ovarian function recovery
Studies usually report amenorrhea and
menstrual changes weak predictive
value

Anti-Mllerian Hormone
(AMH)
A glycoprotein produced in somatic cells
of gonads
Function: reproduction and in the process
of sexual development and differentiation
In ovary: expression is restricted to
granulosa cells of growing ovarian follicles
Serum concentrations correlated with
size of the non-growing primordial follicle
pool
Reflects a marker of ovarian reserve

Studies on AMH
In assisted reproductive technology
AMH is a better marker of ovarian
reserve than age or basal FSH,
oestradiol and inhibin B
Oncofertility women receiving
chemotherapy experience rapid
decline of AMH
Most studies lack long-term data
Ovarian recovery can occur up to 2 or 3
years after end of chemotherapy

Objective
Evaluate AMH patterns of changes
before, after and in the long term after
chemotherapy in a population of
women who received chemotherapy
for breast cancer
Part of the O.B.A.M.A study (Ovarian
reserve in Breast Cancer: AssessMent
with Anti-Mllerian Hormone)

Materials and methods

Study Population and

Participants
Retrospective identification of
women aged between 18 and 43
years who received chemotherapy in
Saint Louis Hospital, Paris, France
from May 1 2005 to January 31 2011
Exclusion: history of prior cytotoxic
treatment or had undergone an
oophorectomy

Blood Sample Collection and

Assay
One sample on the day of the first
chemotherapy baseline timepoint
2-4 samples during chemotherapy
samples were centrifuged at 1000 g for 15
min and stored at 20C to 30C
One post-treatment sample taken at 4 months
to 5,5 years after end of chemotherapy
ELISA was done using Immunotech A11893
kits
Lower limit of detection for AMH 0.14 ng/ml

Statistical Analysis
AMH values were log-transformed to stabilize
variance
Tobit regression models
assess association of baseline (pre-chemotherapy)
AMH with patients characteristics
correlation between measurements carried out on
the same participant

Tests were two-sided, with p0.05 considered

significant and 95% credibility interval
Used R statistical software version 2.15.0

Results
146 women initially included
12 excluded
Previous chemotherapy 1
Previous oophorectomy 1
post-treatment measurement sampled less
than 4 months after the end of treatment
6
Age over 43 years at inclusion 1
Missing sample 3

134 patients analyzed 871 samples

Patient Characteristics

Patient Characteristics

Correlation of age with AMH

Older age
significantly
correlated with a
lower AMH rate

Amenorrhea at 6 months not significantly

correlated to baseline AMH (p=0.16) (B)
Baseline AMH was 46% lower in women who
remained amenorrheic at 12 months (p=0.002)
(C)

AMH Change During and After Chemo

Black points : baseline, red points: during chemotherapy, blue

points: after chemo
Dashed line : average AMH increase after chemo
AMH fell drastically during chemo 69% AMH values undetectable
at the end of chemotherapy
A significant increase in AMH was found after chemotherapy, with

Older age, amenorrhea at 12 months and

rate of AMH decrease associated with a
lower AMH recovery rate

AMH changes over time (log scale,

slope per year), as a function of
AMH during and after breast cancer chemotherapy
patient age

des Maladies du Sein), GERM (Gro

sur les Mastopathies), Sano Aven
Chugai, Amgen, Sandoz.

In almost all
patients the
slope
of AMH
Acknowledg
ements
variation
after
We are grateful to the medical a
breast care unit for
the time they
treatment
was
pling patients. We thank Patric
positive
Cellulaire, Hopital St Louis) for th
the sera and retrieval of frozen
AMH
recovery
(Service
de Biochimie Endocr
Salptrire) for the careful man
likely
to be
surements. Finally, we thank the
O.B.A.M.A study.
constant
in our
subjects

Appendix: Supplementar

Critical Appraisal

Are the results of the study

valid? (Internal Validity)

Unclear
It was stated that the patients recruited were women aged 18-43
receiving chemotherapy, but the cancer stage or stage of
chemotherapy was not explained. Furthermore, patients were not
recruited from a primary center (Saint Louis Hospital is a teaching

Yes
The median time from last chemotherapy to last AMH assessment
was 20 months (range : 465 months)
12 patients were excluded
Previous chemotherapy 1
Previous oophorectomy 1
post-treatment measurement sampled less than 4 months after
the end of treatment 6
Age over 43 years at inclusion 1
Missing sample 3

Unclearly stated in this journal

No
There was no adjustments for important prognostic factors

How likely is the outcome over

AMH during and after breast cancer chemotherapy
time?

des Maladies du Sein), GERM (Gro

sur les Mastopathies), Sano Aven
Chugai, Amgen, Sandoz.

AMH changes
over time (log
Acknowledgements
scale,
slope
are grateful to the medical a
perWe
year),
as a
breast care unit for the time they
pling patients.
We thank Patric
function
of
Cellulaire, Hopital St Louis) for th
the sera and
retrieval of frozen
patient
age
(Service de Biochimie Endocr

Salptrire) for the careful man

surements. Finally, we thank the
O.B.A.M.A study.

Figure 3 Anti-Mllerian hormone (AMH) changes over time (log

scale, slope per year), as a function of patient age.

Appendix: Supplementar

Figure. Five year curves for three different diseases.

How precise are the prognostic estimates?
To determine the precision of the estimates we need to look at the 95% confidence intervals (CI)
around the estimate. The narrower the CI, the more useful the estimate. The precision of the
estimates depends on the number of observations on which the estimate is based. Since earlier
follow-up periods usually include results from more patients than later periods, estimates on the
left hand side of the curve are usually more precise. Observations on the right or tail end of the
curve are usually based on a very small number of people because of deaths, dropouts and late
entrants to the study. Consequently, estimates of survival at the end of the follow-up period are
relatively imprecise and can be affected by what happens to only a few people.

Can I apply this valid, important evidence about prognosis to my patient?

The questions that you should ask before you decide to apply the results of the study to your
patients are:

Because of the statistical model used (tobit longitudinal regression)

Is my patient sointerval
different towas
thosenot
in theprovided,
study that thebut
results
cannot
apply?
95% confidence
95%
credibility
Will this evidence make a clinically important impact on my conclusions about what to
interval).
offer to tell my patients

A significant increase in AMH was found after chemotherapy, with an

average increase of +1.2% per month (95% credibility interval: 0.7 to
1.6)
Centre for Evidence-Based Medicine, University of Oxford, 2010

The 95% CI is sufficiently narrow

Can I apply this valid, important evidence about prognosis to my patient?

The questions that you should ask before you decide to apply the results of the study to your
patients are:
Is my patient so different to those in the study that the results cannot apply?
Will this evidence make a clinically important impact on my conclusions about what to
offer to tell my patients

The patients in this study are not different from our patients, but
there
differentMedicine,
ethnicity
that
should
Centre forisEvidence-Based
University
of Oxford,
2010 be considered.
Knowledge on AMH changes during chemotherapy may help counsel
younger women (in reproductive age) with breast cancer who still
desire to have children and select those who are eligible for fertility
preservation.
But further studies are still needed before we can completely apply
this evidence.