7. Breast cancer during pregnancy and lactation, pregnancy after breast cancer, fertility preservation – Breast Cancer

 

Background 7.1 to 7.6

A subsequent pregnancy after breast cancer should not be advised against. The evidence from prospective studies is missing, these are currently being collected. Retrospective studies show that pregnancy should not be discouraged for fear of worsening the prognosis.

In a multicenter cohort study, 333 women who became pregnant after breast cancer disease were compared in a 1:3 ratio with a non-pregnant breast cancer control cohort to investigate the influence of pregnancy on disease-free and overall survival. There was no difference in disease-free survival for both ER-negative (HR = 0.75; 95%-CI, 0.51-1.08, P = 12) and ER-positive (HR = 0.91; 95%-CI, 0.67-1.24, P = 0.55) tumors. However, overall survival was significantly better for the group that became pregnant without interaction with ER status (HR = 0.72; 95%-CI, 0.54-0.97, P = 0.03; P interaction = 0.11). The outcome of the pregnancy and the interval between disease and pregnancy did not play a role.

In women with hormone receptor-positive breast cancer, if endocrine therapy has not yet been administered for 5 years, it should be continued after the desire for children has been fulfilled, but at the latest after 2 years, and continued for 5-10 years depending on the risk of relapse. For the connection between the duration of endocrine therapy and the chances of recovery, please refer to the chapter on endocrine therapy (see chapter 4.7.2. Endocrine therapy).

After breast cancer, pregnancy can be achieved with the help of reproductive medical procedures.

The chances of success for an intact pregnancy or child are lower with autologous egg cell use in breast cancer patients than in non-cancer patients.

In a retrospective study, 198 women were included, 25 of whom underwent a reproductive examination. These women were older at diagnosis, at conception and suffered more miscarriages. In both groups the rate of full-term pregnancies was equal to 77% and 75%. There was no difference in prognosis between the two groups. Necessary stimulation therapy can be used to obtain oocytes in the case of hormone receptor-positive breast carcinoma with anti-hormonal concomitant treatment (e.g. aromatase inhibitors or tamoxifen) (see also S3 guideline Fertility maintenance).

In a population-based register of 53,426 women, 441 women with a previous carcinoma were identified within the last 5 years. One third of the women had a breast carcinoma. In women with au-tologous oocytes, there were significant differences in live birth rates between women with and without cancer (47.7% without carcinoma versus 24.7% with previous carcinoma, p = 0.0001) and between the different tumor types (from 53.5% for melanoma to 14.3% for breast cancer, p = 0.0001). With donor oocytes these differences did not exist. In breast cancer patients, the probability of a live birth was only 11.7% if the ART was performed within 6 months of the breast cancer diagnosis, compared to 23% if it was beyond 6 months. Overall, only with melanoma and ovarian cancer was the probability of a live birth after ART as high as without cancer. For breast, cervical and endometrial carcinoma the probability was up to 80% lower. However, there was no difference in the birth rate after successful conception.

 

 

Background 7.7 to 7.10

Breast cancer diagnosed during pregnancy has no worse prognosis if it is treated according to its stage and biology. Surgery including sentinel node biopsy can be performed at any time during pregnancy. Chemotherapy can be administered from the beginning of the 2nd trimester. The data on anthracyclines including cyclophosphamide are better than those on taxanes. Both standard therapies can be administered during pregnancy. Due to the higher transplacental transition of platinum salts, more caution is required. The data on platinum salts is less good. Anti-HER2 therapy should be avoided during pregnancy, as the development of an oligo-anhydramnion has been described here under therapy with a fatal outcome. Likewise, endocrine therapy is not indicated during pregnancy.

Radiotherapy should only be performed in exceptional cases and then only in the 1st and beginning of the 2nd trimester.

Supportive therapy should be carried out as for non-pregnant women.

It is important for patients with breast cancer in pregnancy that the pregnancy is closely monitored ultrasonographically and clinically. This is a high-risk pregnancy and should be managed as such.

The inclusion of patients in prospective registries, e.g.: that of the German Breast Group, is recommended as this is the only source of evidence (http://www.gbg.de/de/studien/bcp.php).

 

 

Background 7.12 and 7.13

Women of childbearing age should be advised on the potential gonadotoxicity of the planned systemic therapy and any fertility-sustaining measures.

GnRH on the possible preservation of ovarian function

281 premenopausal patients with hormone receptor-positive or -negative breast cancer, were randomized to triptorelin vs. observation. Triptorelin was started at least 1 week before the start of (neo)adjuvant chemotherapy and then administered every 4 weeks until the end of chemotherapy. Twelve months after the end of the last chemotherapy cycle, the rate of premature menopause (defined as absence of menstruation and postmenopausal levels of FSH and estradiol 1 year after the end of chemotherapy) was 8.9% in the group with triptorelin and 25.9% in the group without triptorelin for chemotherapy. The absolute difference was -17% (95% confidence interval, -26 to -7.9%; P < 0,001. Die Odds Ratio zur therapieinduzierten Menopause betrug 0,28 (95%-CI; 0,14–0,59; P < 0,001).

In December 2015, the long-term data were published after a median follow-up of 7.3 years from the study. Overall, 72.6% (95%-CI, 65.7-80.3%) of the 148 patients in the GnRH group and 64.0% (95%-CI, 56.2-72.8%) of the 133 patients in the control group menstruated again (1.28 [95%-CI, 0.98-1.68]; P = 0.07; age-adjusted HR, 1.48 [95%-CI, 1.12-1.95]; P = 0 ,006). A total of 8 pregnancies occurred, 5 (cumulative 5-year incidence 2.1% [95%-CI, 0.7-6.3%]) with GnRH and 3 (cumulative 5-year incidence, 1.6% [95%-CI, 0.4-6.2%]) in the control group (HR, 2.56 [95%-CI, 0.68-9.60]); P = 0.14; age adjusted HR, 2.40 [95%-CI, 0.62-9.22]; P = 0.20). The 5-year DFS was 80.5% (95%-CI, 73.1-86.1%) in the GnRH group and 83.7% (95%-CI, 76.1-89.1%) in the control group (GnRH vs. control HR, 1.17 [95%-CI, 0.72-1.92]; P = 0.52).

The POEM study included 214 patients with HR-negative breast cancer and randomized them to standard chemotherapy with or without GnRH to maintain ovarian function. This was defined in the study as resuming menstruation 2 years after the end of therapy. The amenorrhea rate was 8% with and 22% without GnRH analogue (odds ratio, OR 0.3; 95%-CI 0.1-0.87, p = 0.03). Birth and pregnancy rates were significantly higher in the group with GnRH than in the group without (21% vs. 11%; OR 2.45 p = 0.04). The women who had a child were significantly younger than the others. They may also have been more motivated to contribute to the success of the study. In addition, the study showed a significantly better disease-free and overall survival for the GnRH group in patients with HR-negative breast cancer. Overall, the primary endpoint could only be determined in less than 50% of the patients, and the study was terminated prematurely. The study therefore has clear deficiencies.

A meta-analysis of the various studies on the subject also comes to a positive effect of GnRH therapy, at least as far as ovarian function is concerned.

As far as fertility maintenance is concerned, reference is made primarily to the methods of reproductive therapy, which will not be discussed here (reference to S2/3 guideline on this).