Role for Tamoxifen as Fertility Drug for Breast Cancer Patients?
the Cancer Headlines®
US fertility experts have
discovered a potential new role for the wonder drug tamoxifen – helping breast
cancer patients to have babies by IVF.
In a study published in
the journal Human Reproduction, researchers from New York's Cornell
University report the first IVF pregnancy to result from the use of tamoxifen as
an ovarian stimulant.
In a study of 12 breast
cancer survivors they found that stimulating the ovaries with a short, carefully
timed course of tamoxifen boosted the number of eggs they could retrieve. Every
patient had one or more embryos, either for freezing for later attempts at
pregnancy, or for immediate transfer. One patient who had two fresh embryos
transferred has already given birth to twins. Another patient conceived on her
second attempt, although she miscarried. None of the patients with frozen
embryos has yet attempted pregnancy.
Lead researcher Professor
Kutluk Oktay said that the experiment arose from a desire to find a safe way of
preserving fertility among the 15% of breast cancer patients – around 27,000
annually in the US – who were still of reproductive age when they were
ovarian failure in many patients – nearly as many as four out of five women in
the case of those given cyclophosphamide. Even those who remain fertile or don't
have chemotherapy face the problem of needing a recurrence-free period of
perhaps two to five years before trying to conceive, bringing them up against
the barrier of infertility due to aging and diminishing ovarian reserves.
"These women can try
natural cycle IVF without ovarian stimulation, but typically no more than a
single embryo can be achieved for immediate use or freezing. So, we need to find
a safe way of increasing the number of embryos to give these women a better
chance of having a baby," said Oktay, assistant professor of Reproductive
Medicine and Obstetrics and Gynaecology at the Center for Reproductive Medicine
and Infertility, Weill Medical College of Cornell University.
Tamoxifen was developed in
the UK in 1966 as a contraceptive, but found to stimulate ovarian follicle
growth and became used in Europe as an ovarian stimulant. (A related compound,
Clomiphene, is usually used in the US). It wasn't until 1976 that tamoxifen's
suppressive, anti-estrogenic effect on breast cancer was discovered. Since then
it has become the world's most successful anti-cancer drug, saving the lives of
thousands of breast cancer patients every year worldwide.
"Sometimes the best
ideas are the obvious ones and tamoxifen seemed the obvious choice of drug to
test, although, to my knowledge, no one has tried it before in breast cancer
patients," said Oktay. "We hypothesized that tamoxifen stimulation
would result in higher numbers of embryos compared with natural cycle IVF, while
theoretically shielding breast cancer cells against estrogen."
A retrospective group of
five breast cancer patients who had undergone nine cycles of natural cycle IVF
was used as a control for the 12 study patients. The 12 patients were given
40-60 mg tamoxifen for around seven days on days 2-3 of their menstrual cycle (a
total of 15 treated cycles). The tamoxifen patients produced a greater number of
mature eggs than the controls (1.6 versus 0.7) and embryos (1.6 versus 0.6). All
tamoxifen patients generated embryos compared with three out of five controls.
After a mean follow up of around 15 months, none of the study patients has had a
recurrence of cancer.
"This is a novel use
of tamoxifen to attempt to preserve fertility and treat chemotherapy-related
infertility via IVF embryo cryopreservation and embryo transfer after breast
cancer," said Oktay. "We exploited tamoxifen's dual action as an
ovarian stimulating drug and an anti-cancer agent."
Because most patients in
the tamoxifen group froze their embryos while most in the control group had
fresh embryo transfer, it has not been possible yet to compare pregnancy rates
between the two protocols or to provide long-term data on the effects of
tamoxifen on pregnancy. However, long-term experience of the drug in ovulation
induction did not suggest an embryo-damaging effect. In any case, its use was
discontinued prior to ovulation and egg retrieval and IVF embryos were never
exposed to it as fertilization took place in vitro.
Oktay said the study had
limitations with its short follow-up and its retrospective, small control group,
but a larger study was planned with modifications to the protocol to include low
amounts of follicle stimulating hormone (FSH) in addition to tamoxifen.
optimistic," he said. "Many of my patients tell me that just doing
something to address the issue of loss of reproductive function makes it easier
for them to deal with breast cancer. It connects them to their future and
underlines that because they have breast cancer it does not mean they have a
"It would be
especially fitting if a drug that has saved so many women's lives should also
turn out to be a means of preserving their fertility," he added.
He urged all breast cancer
physicians to be aware of the effect of chemotherapy on women of reproductive
age and to refer them to an appropriate assisted reproduction center as soon as
a diagnosis was made so that options for preserving fertility could be