It is not rare for women of reproductive age to be diagnosed with breast cancer, but a high healing rate has now been achieved for breast cancer. According to a calculation based on the cancer register of the Saar region in Germany (www.krebsregister.saarland.de), more than 440 women aged up to 34 years develop breast cancer in Germany every year, and the five-year survival rate of all age groups is 79% (von Wolff et al., Gynäkologische Endokrinologie, 2006, 4:189-96). Therefore, all women with breast cancer whose family planning is not complete should present to an experienced fertility protection centre for advice immediately after receiving their diagnosis (contacts).
Risks of therapy-induced ovarian damage
Due to limited data, it is difficult to estimate the therapy-induced ovarian damage. In the studies published, the women have been allocated into a group < 40 years and another ≥ 40 years. There is no further subdivision into an age group < 35 years, where less ovarian damage can be expected.
A good summary of the risks of therapy-induced amenorrhea in women < 40 years as a function of the type of chemotherapy applied can be found in a review by Stearns et al. www.nature.com/reviews/cancer 2006, 6:886-893:
- In the case of chemotherapy based on the CMF regimen (x 6), the rate of amenorrhea was estimated at 30-80% after analysing 7 studies,
if the AC regimen was followed (x 4), the rate of amenorrhea was estimated at 13-30% (6 studies),
if the FEC/FAC regimen was followed (x 6-8), the rate of amenorrhea was estimated at 13-35% (3 studies),
if the AC regimen was used (x 4) and followed by P x 4, the rate of amenorrhea was estimated at 35% (1 study),
if the AC regimen was used (x 4) and followed by T x 4, the rate of amenorrhea was estimated at 29-42% (1 study).
(A= Doxorubicin; C= Cyclophosphamide; E=Epirubicin; F= 5-Fluorouracil; M=Methotrexate; P=Paclitaxel; T=Docetaxel)
Possibilities of fertility protection
As the time period from the diagnosis to the beginning of chemotherapy is usually ≥ 2 weeks, all available fertility protection measures can theoretically be offered.
However, if the breast cancer is receptor-positive, ovarian stimulation or the administration of GnRH analogues must be discussed with the patient in detail.
Theoretically, accelerated tumor cell growth is possible under ovarian stimulation, so the likelihood of a relapse could be increased. However, an argument against this assumption is that the young woman will keep her menstrual cycle right up to the chemotherapy even without fertility protection measures, i.e. she will have a high endogenous estrogen level anyway. It is unlikely that a short-term increase of this estrogen level under ovarian stimulation will lead to a significant acceleration of tumor cell growth. Interestingly, the relapse risk does not seem to be increased in patients becoming pregnant directly after having breast cancer.
Administering GnRH analogues during chemotherapy reduces estrogen production and therefore decelerates the growth of receptor-positive tumor cells. Therefore, the question arises whether the chemotherapy for receptor-positive breast cancer could be less effective under GnRH therapy. There are theoretical arguments both for and against this assumption, but none of these considerations is currrently based on solid data.
So there are no sufficient studies available, neither on the risk of ovarian stimulation nor on the risk of GnRH agonist administration when there is a receptor-positive carcinoma of the breast. Therefore, any fertility protection measures in these constellations must be discussed with the patient and the treating oncologist in an experienced centre (contacts).
The following fertility protection measures are available:
A therapy especially for a receptor-negative carcinoma is ovarian stimulation and cryopreservation of fertilised or unfertilised oocytes. As an alternative particularly for women <= 35 years, ovarian tissue can be laparoscopically extracted and cryopreserved. In this case, the risk of metastases developing after retransplantation of the tissue must be discussed although there are no reports of metastases in humans after the transplantations performed so far. In addition to these measures, GnRH analogues may be administered during chemotherapy. However, there is still no clear evidence of the effectiveness of GnRH analogues. The results of the nine controlled studies published so far suggest a protective effect (Blumenfeld & von Wolff Hum Reprod Update 2008 in press).
In principle, it is also possible to greatly reduce the estrogen levels under stimulation treatment, e.g. in the case of receptor-positive breast cancer.
For example, the patient can be treated with aromatase inhibitors in addition to the gonadotrophins, which significantly reduces estrogen levels in blood. However, there is limited but very promising experience with this method (Oktay et al., 2006, J Clin Endocrinol Metab, 91: 3885-3890).
Alternatively, it is possible to retrieve immature oocytes with no or very little gonadotrophin stimulation and to mature them prior to cryopreservation (in vitro maturation, IVM). However, only a relatively small number of oocytes can be retrieved with this method, which is currently only available in a small number of centres. Therefore, this technique should not be used as the sole measure but combined with other methods such as the cryopreservation of ovarian tissue.