Successful delivery after cryopreservation and heterotopic transplantation of ovarian tissue in a patient with breast cancer

Author(s):  
Triin Tammiste ◽  
Külli Idla ◽  
Andres Salumets ◽  
Piret Veerus
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
L Eijkenboom ◽  
V Palacio-Castañeda ◽  
F A Groenman ◽  
D D M Braat ◽  
C C M Beerendonk ◽  
...  

Abstract Study question Is it possible to eradicate cancer cells from ovarian cortex by using tumour-specific designed ankyrin repeat protein (DARPin)-toxin fusion proteins, without compromising the ovarian tissue? Summary answer Purging ovarian cortex ex vivo from experimentally induced breast cancer tumour foci is possible by tumour-targeted DARPin-toxin fusion proteins trough inhibition of protein synthesis. What is known already Ovarian tissue cryopreservation and autotransplantation is a successful technique for fertility restoration in cancer patients. The procedure is not without risk since malignant cells may still be present in the graft. Procedures to detect cancer cells render the tissue fragment useless for autotransplantation. Strategies to circumvent this problem such as in vitro maturation of follicles or the construction of artificial ovaries are pursued but are still experimental. Alternatively, we have shown ex vivo purging of ovarian cortex is possible by elimination of rhabdomyosarcoma after treatment with verteporfin. This allows treatment of cortex fragments before autotransplantation without compromising ovarian tissue integrity. Study design, size, duration Human ovarian cortex fragments harbouring breast cancer tumour foci were exposed for 24 h to DARPins fused to the translocation and catalytic domain of Pseudomonas aeruginosa exotoxin A (DARPin-toxin fusion proteins) targeting EpCAM or HER2. After treatment with the DARPin-toxin fusion proteins the tissue was cultured for an additional 6 days to allow any remaining tumour cells to form foci. In addition, the functional integrity of the ovarian tissue was analysed after purging. Participants/materials, setting, methods Breast cancer cell lines expressing different levels of EpCAM and HER2 were introduced in human ovarian tissue to form tumour foci. After purging with DARPin-toxin fusion proteins, the presence of any remaining cancer cells in the tissue was analysed with (immuno)histochemistry and RT-qPCR. Possible detrimental effects on the viability of ovarian cortex and follicles were determined by (immuno)histology, a follicular viability assay and an assay to determine the in vitro growth capacity of small follicles. Main results and the role of chance Ovarian cortex harbouring EpCAM-positive breast cancer cells showed a significant decrease in the number of tumour foci after treatment with the EpCAM-targeted DARPin-toxin fusion proteins. Although exposure to the EpCAM-specific DARPin had no effect on morphology or viability of follicles, a decrease in oocyte viability after in vitro growth experiments was observed, presumably due to low level expression of EpCAM on oocytes. In contrast to the EpCAM-specific DARPin-toxin fusion protein, the DARPin-toxin fusion protein targeting HER2 had no detrimental effects on morphology, viability or in vitro growth of follicles while foci of HER2-positive breast cancer cells were severely affected as indicated by the presence of apoptotic bodies, tumour cell remnants and the absence of viable tumour cells. The histological results after purging with the HER2-specific DARPin-toxin fusions proteins were confirmed by RT-qPCR, showing a decrease to basal levels of HER2 mRNA in the ovarian cortex tissue. Limitations, reasons for caution The effect of DARPin-toxin fusion proteins depends heavily on the expression of their target on the cancer cell. The target protein should not be expressed by ovarian cortex as this may lead to tissue damage. The functional integrity of ovarian cortex after the treatment requires further investigation in vivo. Wider implications of the findings Purging metastases from ovarian cortex without harming ovarian tissue is possible by targeting tumour specific surface expressed antigens with DARPin-toxin fusion proteins. Purging ovarian cortex tissue with DARPin-toxin fusion proteins provides a feasible therapeutic strategy to prevent reintroduction of cancer by autotransplantation in case of malignancies expressing tumour-specific surface markers. Trial registration number not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Sellami ◽  
M Grynberg ◽  
A Benoit ◽  
C Sifer ◽  
A Mayeur ◽  
...  

Abstract Study question Does oocyte vitrification for fertility preservation (FP) delay the initiation of neoadjuvant chemotherapy for breast cancer? Summary answer The indication of neoadjuvant chemotherapy for breast cancer should not be considered as an impediment to urgent oocyte vitrification for FP. What is known already FP is considered as one of the most important issues to address for young breast cancer patients. Cryopreservation of oocytes or embryos may be considered after controlled ovarian hyperstimulation (COH) or in vitro maturation (IVM). Pregnancies have been reported after reutilization of oocytes frozen following both procedures. Although oocyte competence is better after COH, this strategy requires on average 13 days to be achieved. In addition, the safety of ovarian stimulation before tumor removal is currently not formally established. In case of neoadjuvant chemotherapy, the risk-benefit balance of COH is not well known. Study design, size, duration Retrospective cohort study including all breast cancer patients eligible for oocyte vitrification following COH or IVM before initiation of neoadjuvant chemotherapy between January 2016 and December 2020. Participants/materials, setting, methods Inclusion criteria were: female patients with confirmed non metastatic breast cancer, 18 to 40 years of age, with indication of neoadjuvant chemotherapy, who have had oocyte retrieval for FP after COH or IVM +/- cryopreservation of ovarian tissue. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. Main results and the role of chance A total of 198 patients with confirmed breast cancer who had oocyte retrieval following COH (n = 57) or IVM +/- cryopreservation of ovarian tissue (n = 141) for FP prior to neoadjuvant chemotherapy were included. Although women in IVM group were significantly younger as compared to patients who underwent COH (31.7 ± 4.2 vs. 33.3 ± 4.0 years, p = 0.019), ovarian reserve parameters, BMI and cancer stage did not differ between the two groups. Overall, the average time from cancer diagnosis to chemotherapy start was similar between patients having undergone COH or IVM before oocyte vitrification (37.3 ± 13.8 vs. 36.9 ±13.5 days in COH and IVM groups respectively, p=0.857). Limitations, reasons for caution The time from referral to FP consultation may have influenced the type of FP. In addition, the retrospective nature of the present analysis may constitute a limitation. Moreover, the efficiency and security of the different FP strategies used has not been analysed. Wider implications of the findings Oocyte vitrification following COH or IVM was not associated with delayed breast cancer treatment in the neoadjuvant setting, so long as there was a prompt FP referral. Young patients undergoing neoadjuvant chemotherapy should be informed of these findings to avoid unnecessary anxiety due to concern for delays. Trial registration number Not applicable


2016 ◽  
Vol 64 (3) ◽  
pp. 819.2-819
Author(s):  
I Shapira ◽  
P Daksharam ◽  
V Kremer ◽  
A Banavali ◽  
M Kopf ◽  
...  

Purpose of StudyBlack women with triple negative breast cancer have 46% lower survival rates attributed to differences in tumor biology. We analyzed presurgical plasma microRNA of white (W) and black (B) women with TNBC enrolled in our breast ovarian tissue bank between 2004 and 2014.AimsDetect microRNA patterns in pre-surgical plasma of TNBC W or B Analyze differences by integrated approach to detect pathways differentially activated in the two groups.Methods UsedBetween 2004 and 2014 we investigated patterns of plasma miRNAs collected before, after surgery, during and after chemotherapy in 67 patients presenting for surgery for breast cancer (W=44 & B=44) and 25 age and race matched normal controls. Two-sample t-test was used for all 2-sample comparison and ANOVA followed by Benjamin Hochberg post-hoc test to compare the mean response between subject factors of interest. All tests were 2-tailed and results with a p<0.05 were considered statistically significant. Coremine was used to identify datasets in breast cancer microarray with emphasis on our differentially expressed circulating miRs.Summary of ResultsMean age cancer 48 (range 35–78), control 44 (range 35–67): B patients did not express over 70% of pre-surgical plasma miRs over-expressed in the W pre-surgical plasma. Black patients had lower expression of MiRs: −16-5p, −484, −126, −150-5p, −142-3p; −30c-5p, −186-5p, 139-5p. Samples from white patients overexpressed miRs−126, −150-5p, −142-3p; −30c-5p, −186-5p, 139-5p compared to healthy controls. These miRs significantly suppressed in blacks p<0.05.Coremine text mining suggests differentially regulated microRNA are involved in mitochondrial quality control and biogenesis.ConclusionsDeregulation in circulating miRs between B and W patients point to pathways involved in mitochondrial fission and fusion. Aberrant mitochondria biogenesis was reported as mechanism for cancer stem cell survival and detrimental to innate immunity. Such pathways could explain the lower survival seen in black breast cancer patients.


2019 ◽  
Vol 35 (12) ◽  
pp. 1043-1049 ◽  
Author(s):  
Olga Bystrova ◽  
Elena Lapina ◽  
Alla Kalugina ◽  
Alla Lisyanskaya ◽  
Natalya Tapilskaya ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document