The protective effect of tamoxifen in women with ER-positive breast cancer who opt for cryopreservation of oocytes or embryos: a prospectively controlled study.

Significant medical advances in cancer treatment have improved survival rates
in female cancer survivors of reproductive age and as a consequence, the wish
to have children has become increasingly important. Fertility preservation
techniques (e.g. ovarian, embryo and oocyte freezing) are now available to
increase chances of further childhood, and these techniques need to be
performed just prior to gonadotoxic treatment, like radiotherapy or
chemotherapy. Different centers in the Netherlands employ embryo and/or oocyte
freezing. Women who opt for embryo or oocyte freezing will receive hormone
stimulation with GnRH analogues and recombinant FSH injections during a 2-3
weeks period and subsequently undergo ovum pick up with the aim to freeze
embryos or oocytes. In women with ER-positive breast cancer,
hormone-stimulation may induce extra growth of cancer cells. The additional use
of 60 mg of tamoxifen may block the effect of high estrogen levels. Until now
it is unknown what dosage of tamoxifen is regarded as sufficient to protect
women for the high levels of estrogens that arise during ovarian
hyperstimulation. In this study we will investigate the protective effect of
tamoxifen by measuring the level of its active metabolites ( endoxifen,
N-desmethyltamoxifen, 4-hydroxytamoxifen, 4*-hydroxytamoxifen en N-desmethyl-4*-
hydroxytamoxifen). Below a certain endoxifen level (< 5,9 ng/ml) the estrogen
receptor modulation in estrogen sensitive breast cancer receptors is supposed
to be insufficient. To this aim we want to investigate if the dosage of
tamoxifen given is protective during the whole period of hormone stimulation.

The objective of this study is to investigate the relation between tamoxifen
use during COS, endoxifen levels reached during COS, and recurrence-free
survival (locoregional recurrence, distant recurrence or death from any cause)
when compared with matched controls who did not undergo COS.

Pharmacokinetic effects of tamoxifen will be studied in a prospective
longitudinal cohort study. A nested case control study will be made comparing
40 cases -women with ER-positive breast cancer using tamoxifen in combination
with COS- with 120 age matched women with ER-positive breast cancer who do not
opt for fertility preservation, but started tamoxifen as standard adjuvant
therapy. Another 120 women will be followed up by looking at recurrence free
survival after 5 and 10 years. These women will be matched by tumour
characteristics.

Except for the minor risk of a hematoma as a consequence of the venous blood
sampling, there are no risks associated with participation of the study.