Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT02311647 |
| Other study ID # |
SHEBA-14-1374-SD-CTIL |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
December 4, 2014 |
| Last updated |
December 22, 2014 |
| Start date |
January 2015 |
| Est. completion date |
February 2017 |
Study information
| Verified date |
December 2014 |
| Source |
Sheba Medical Center |
| Contact |
Shir Dar, MD |
| Phone |
97235303048 |
| Email |
dr.shirdar[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
Israel: Ministry of Health |
| Study type |
Observational
|
Clinical Trial Summary
The aim of this multi-center study is to assess the effects of Tamoxifen on the uterine
cavity and endometrial abnormalities in young premenopausal women diagnosed with breast
cancer.
The research contains two parts: a clinical study and a laboratory study.
- Clinical part: to evaluate the association between tamoxifen treatment and uterine
abnormalities.
- Laboratory part: to investigate the effect of Tamoxifen treatment on endometrial
tissue, by exploring the molecular aspect of endometrial receptivity.
Description:
Breast cancer is the most prevalent malignancy amongst women and approximately 13% of newly
diagnosed breast cancer patients are diagnosed between the ages 20-34 [1]. At this age group
women are at the peak of their reproductive years, and many have not yet completed family
planning. Moreover the age at first birth has steadily increasing in developed nations [2]
and more than a quarter of the deliveries are in women above the age of 35. Despite repeated
reports in the literature of a worse prognosis in young breast cancer patients, newer
treatments have none-the-less improved the outcome amongst young women and for some early
stage disease subtypes the outcome is similar to that of older women [3,4]. These increasing
numbers of breast cancer survivors are concerned with post-cancer quality of life issues,
such as the ability to have children after completing treatment [5-6], hence it is critical
to discuss fertility preservation and the ability to conceive when breast cancer is
diagnosed [7-9].
Treatment for early breast cancer involves local therapy that includes surgery and adjuvant
radiation therapy as well as systemic therapies including chemotherapy, biological therapy
and hormonal therapy. Chemotherapy protocols for breast cancer include different
combinations of alkylating agents, platinum derivates and taxanes that are toxic to the
ovaries, destroy primordial follicle stockpiles, which directly represent ovarian reserve
and can result in infertility and premature menopause [10-12].
Tamoxifen Citrate, a Selective Estrogen Receptor Modulator (SERM), competes with estrogen
for binding sites in the Estrogen Receptor (ER) in target tissues such as breast. The drug
has been in use for over 30 years with a proven high therapeutic index and significant
efficacy. The drug is effective in reducing breast cancer recurrence and improving patient's
survival across all age groups. The drug is effective in young pre-menopausal breast cancer
patients [13-15] . Recently, it has been reported (16) that breast cancer survivors who take
tamoxifen for ten years have half the risk of dying from estrogen receptor positive breast
cancer. Therefore the new ASCO (American Society of Clinical Oncology ) recommendations are
to increase the period of tamoxifen treatment.
However, at this period these patients cannot conceive, in order to enable pregnancy
patients should hold Tamoxifen treatment, either with complete termination, or (a more
suitable option with the new recommendations) a tamoxifen free window to allow pregnancy
should be offered. If ovarian function is preserved women can try to get a spontaneous
pregnancy. In patients that suffer from ovarian failure post chemotherapy treatments or
embryos (or eggs) that were stored at diagnosis during fertility preservation procedure can
be used.
Pregnancies post (and even during) tamoxifen treatment are reported but former breast cancer
patients achieve lower pregnancy rate when performing embryo transfer with embryos that were
frozen prior to treatment. The chances to conceive post tamoxifen treatments and even more
with prolong Tamoxifen treatments are not determined. This becomes of major importance when
a limited window of time is allowed for conception.
The risk of developing endometrial cancer for post-menopausal women taking tamoxifen is well
established as well as the incidence of endometrial thickening endometrial adhesions and
polyps (17). There is no available data whether changes in the endometrium that may be
induced by Tamoxifen further impairs the ability to conceive. Ultrasound assessments of the
endometrium in patients treated with tamoxifen are limited and often inconclusive mainly due
to sub-endometrial ultrasonographic findings that impair evaluation. The incidence of
endometrial adhesions and polyps in premenopausal breast cancer patients treated with
tamoxifen is unknown. However these abnormalities can interfere with the success of future
conception.
The human endometrium is a dynamic tissue that undergoes physiological and clinical changes
during the menstrual cycle. Adhesion of the embryo to the endometrium is possible only
during a very short period of time, during which the endometrium acquires a functional
ability and becomes receptive. This functionality is a pre- requisite for a successful
pregnancy.
It is assumed that inadequate uterine receptivity is responsible for approximately
two-thirds of implantation failure. Although many fertility disorders have been overcome by
a variety of assisted reproductive techniques, implantation remains the rate-limiting step
for the success of in vitro fertilization.
As mentioned previously, Tamoxifen may affect the endometrium, however there is no study
regarding the effects of these changes on the chances to become pregnant.
Furthermore, tamoxifen effects on endometrial receptivity have not been investigated yet.
Although to date no single, clinically relevant morphologic, molecular, or histologic marker
capable of indicating endometrial receptivity status has been identified. Few genes were
found to be associated with implantation and could act as potential markers for receptivity
and can be used to compare endometrial receptivity in patients previously treated with
Tamoxifen to normal population. The research will use several genes that have been proven to
have high correlation with implantation process and endometrial receptivity.
Aims of the study:
The aim of this multi-center study is to assess the effects of Tamoxifen on the uterine
cavity and endometrial abnormalities in young premenopausal women diagnosed with breast
cancer.
The research contains two parts: a clinical study and a laboratory study.
- In the clinical part our goal is to evaluate the association between tamoxifen
treatment and uterine abnormalities.
- The laboratory study's target is to investigate the effect of Tamoxifen treatment on
endometrial tissue, by exploring the molecular aspect of endometrial receptivity
