Breast cancer

Detailed information and a list of references can be found in Chapter 2.1 of the FertiPROTEKT book, "Indications and fertility preservation methods for oncological and non-oncological disorders", which can be downloaded free of charge.

Prognosis

The 10-year survival rate for all women and stages is approximately 86%. The prognosis is largely determined by the tumour stage and tumour cell characteristics such as hormone dependence etc. 


Damage to the ovaries caused by chemotherapy

Damage to the ovaries depends on the type of chemotherapy, the woman’s age and the so-called ovarian reserve, i.e. the number of existing follicles. 

+ Current study data

A study on damage to the ovaries depending on the chemotherapy administered and age was published in 2010 (Sukumvanich et al., 2010). From 1998 to 2002, the authors studied 466 women aged 20-45 years (see table). 111 women received the chemotherapy regimen "AC" (doxorubicin and cyclophosphamide), 143 women received "ACT" (doxorubicin, cyclophosphamide, and paclitaxel) and 76 women received "CMF" (cyclophosphamide, methotrexate and 5-fluorouracil). Other chemotherapy regimens (n = 136) were ACR, FAC, FACT and other unspecified schemes. The risk of damage to the ovaries increased with age and longer duration of chemotherapy. Women between 20-34 years of age reported amenorrhoea in only 11% of cases, i.e. an absence of menstrual bleeding as a sign of significant damage to the ovaries 6 months after the end of chemotherapy. This did not vary significantly between the different chemotherapy regimens. There are hardly any studies on other chemotherapy regimens to date.


Risk of significant damage to the ovaries from chemotherapy with the development of amenorrhoea (absence of menstrual bleeding)

Chemotherapy20-34 years, 112 woman35-39 years, 142 women≥40 years, 212 women
Amenorrhoea rate (%)Amenorrhoea rate (%)Amenorrhoea rate (%)
AC, 6 months02168
AC, 24 months0431
ACT, 6 months113775
ACT, 12 months32054
ACT, 24 months31642
CMF, 6 months17943
CMF, 12 months0943
CMF, 24 months0536
Other Chemo, 6 months112865
Other Chemo, 12 months51649
Other Chemo, 24 months11140

When deciding whether to perform fertility preservation, it should be noted that the risk of a loss of ovarian function in breast cancer patients is sometimes not particularly high; however longer hormonal treatment often follows, especially in the case of hormone-dependent breast cancer.  In the meantime, the woman’s ovarian reserve can further decrease and her age increases, so that a pregnancy is then difficult or no longer possible. Therefore, fertility preservation treatment should be considered, even if there is a low risk of any relevant damage to the ovaries.

 

Risks of fertility preservation

+ Risks of postponing chemotherapy

This risk does not generally exist for breast cancer because the time from diagnosis to the start of chemotherapy is usually sufficiently long enough to allow fertility preservation treatment to be carried out and all relevant procedures can usually be performed. Double stimulation is also possible, which allows egg cells to be collected twice if the woman is immediately referred to a reproductive medicine centre after diagnosis.

+ Risks of cryopreservation of ovarian tissue

Laparoscopy is required for the cryopreservation (freezing) of ovarian tissue and the risks of this procedure are low. Theoretically, tumour cells can be found in ovarian tissue which can lead to a relapse after later re-transplantation of the tissue. The risk of tumour cells being present in the ovaries is increased in so-called lobular carcinoma and a higher tumour stage, especially in stage IV where metastases are already found. This is taken into consideration when deciding for or against the cryopreservation of ovarian tissue. In women with a genetic predisposition for breast cancer (a so-called mutation in the BRCA1 or BRCA2 gene), there is a lifetime risk of developing ovarian cancer of 15-56%. This means that although ovarian tissue can be cryopreserved and transplanted after corresponding explanation of the risks associated with a BRCA mutation, it should be removed again later.

+ Risks of hormonal stimulation

There is a theoretical risk that hormone-dependent tumour cells could grow as a result of the high-dose hormonal stimulation used to collect egg cells. There is no evidence for or against such an effect up to now. However, for the following reasons it is very unlikely that hormonal stimulation affects the tumour:

  1. When hormonal stimulation is used, so-called aromatase inhibitors can also be given which reduce the estrogen concentration in the serum by about one half.

  2. The estrogen levels only significantly increase over one week.

  3. After diagnosis, the oncologists may allow several weeks to pass before the start of chemotherapy if the menstrual cycle is otherwise intact with estrogen production.

Although there is no evidence for a worsening prognosis as a result of stimulation, an alternative fertility preservation method such as cryopreservation of ovarian tissue should always be considered for a hormone-dependent tumour.

+ Risks of GN-RH agonists

GnRH agonists should reduce the likelihood of damage to the ovarian tissue resulting from chemotherapy by early reduction of estrogen production in the ovaries. Its use was critically discussed for a long time. Its definitive protective effect is not yet clear and it has been questioned whether the reduction in estrogen levels by GnRH agonists could lead to a reduction in the effect of chemotherapy in hormone-dependent tumours. However, initial studies show that a negative effect on the chemotherapy is unlikely. Because of this, the administration of GnRH agonists during chemotherapy has been specified by the German Society of Gynaecology and Obstetrics (DGGG) Gynaecological Oncology Working Group as an option for fertility preservation. GnRH agonists can therefore also be considered as a fertility preservation method in hormone-dependent breast cancer, when the patient is informed of the limited data available.

 

practical approach if a fertility preservation method is considered (figure)

Women should generally be referred to a reproductive medical centre early on to allow the greatest possible time frame for advice and fertility preservation measures. The procedure for breast cancer is presented in the figure above. Administration of GnRH agonists, hormonal stimulation with collection of egg cells and freezing of oocytes or ovarian tissue are all possible as individual measures or in combination.