Impact of breast cancer chemotherapy on ovarian damage and recovery.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24059-e24059
Author(s):  
Shari Beth Goldfarb ◽  
Giuliano Bedoschi ◽  
Volkan Turan ◽  
Angelena Crown ◽  
Nadia Abdo ◽  
...  

e24059 Background: As societal shifts have led to more women delaying childbearing, a diagnosis of breast cancer is increasingly more likely to occur prior to the completion of family building. Therefore, understanding impact of chemo on future fertility is of the utmost importance. This study evaluates the trends in AMH over time in women receiving different chemo regimens for breast cancer. Methods: This is an IRB approved prospective study of 164 women, < 45 years old with non-metastatic breast cancer who were enrolled at time of diagnosis. Patients received chemo and had prospective serum AMH measured at baseline,12, 18 & 24 mos post-chemo. Of those, 99/164 completed 2-yr follow up. Pts were divided according to their chemotherapy regimen: ddAC-T, CMF and other (e.g. TH). Results: Mean age in ddAC-T (n = 118), CMF (n = 22) and other (n = 23) chemo groups were 37.1±4.6, 41.1±3.2 and 37.6±4.3 yrs, respectively (p = 0.001). AMH sharply declined between baseline & 12 mos post-chemo in all groups (p = 0.005). There was no difference in rate of decline between the groups, after adjusting for age. Age was an important predictor of AMH. Older age at study entry was associated with lower AMH with a decrease of 9% per life year (p = 0.0005). AMH recovered from 12 to 18 mos post-chemo in all groups. 18 mos after chemo, AMH recovery was observed in 61%, 59% & 65% in ddAC-T, CMF & other groups, respectively. In the ddAC-T arm there was a 1.9 fold increase in AMH while there was a 1.4 and 3.3 fold increase in the CMF and other arms, respectively. At 2-yrs post-chemo, AMH recovery rate reached 67%, 69% & 77% in ddAC-T, CMF & other groups, respectively. However, 12% in ddAC-T and 23% in CMF had undetectable AMH. Baseline AMH was 1.59 fold higher in pts whose AMH increased compared to those whose AMH decreased between 12 & 18 mos (p = 0.035). AMH recovery was associated with higher baseline AMH. Age, BMI & chemo type did not correlate with AMH recovery and tamoxifen treatment did not impact AMH recovery. Conclusions: Our data show that anthracycline plus taxane, taxane-based and CMF chemo regimens compromise ovarian reserve in breast cancer patients in similar fashion. As surviving ovarian follicles resume production of AMH, most of ovarian reserve recovery occurs by 18 mos post-chemo with some minor recovery from 18-24 mos. Baseline AMH level is the most important predictor of AMH recovery. Hence in women undergoing gonadotoxic chemo, ovarian reserve should be assessed by AMH before and 12 months after treatment to determine extent of damage. The novel information provided in this study is valuable for counseling cancer pts about fertility preservation. Clinical trial information: NCT00823654 .

Breast Care ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. 398-404 ◽  
Author(s):  
Michael P. Lux ◽  
Peter A. Fasching ◽  
Michael G. Schrauder ◽  
Alexander Hein ◽  
Sebastian M. Jud ◽  
...  

Two-thirds of all breast cancer patients with metastases have a hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype. Endocrine therapy is the treatment of choice in these patients since in addition to its effectiveness it can also maintain the patients' quality of life over a longer term. However, 44-62% of postmenopausal patients with metastatic breast carcinoma have primary tamoxifen resistance. After 3-5 years, 30-40% of the patients receiving tamoxifen treatment develop secondary resistance. Understanding the way in which resistance develops is therefore essential for developing treatment approaches that can prevent or reverse endocrine resistance. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role here. As a result of the numerous interactions involved, complex issues arise that need to be taken into account in the development and use of therapeutic agents. In addition, this signaling pathway is the one that most frequently undergoes mutations in breast cancer. The prognostic and predictive significance of individual mutations has not yet been fully explained, but it might provide a basis for patient selection in clinical studies. Initial research results on the use of PI3K inhibitors suggest that this may be a highly promising therapeutic approach, with an acceptable side effect profile.


2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 37-37
Author(s):  
Cike Peng ◽  
Rongxi Yang ◽  
Dharanija Madhavan ◽  
Markus Wallwiener ◽  
Anja Rudolph ◽  
...  

37 Background: Metastasis is the main course of death in breast cancer (BC) patients. Reliable prognostic markers are very much appreciated to evaluate possible outcome of patients. Circulating tumor cells (CTC) is a circulating prognostic tumor marker of metastatic breast cancer patients. Despite the big technical challenges in CTC detection, the reliability of CTC enumeration for the prognosis of BC is still on debate. Some studies have proved that the plasma level of X, a major component in extracellular matrix, was increased in patients with metastatic breast cancer. However, the association between the plasma X level and the prognosis of metastatic breast cancer is still unknown. Methods: Plasma X was measured by ELISA in 60 healthy controls, 48 primary breast cancer (PBC) patients, and 212 metastatic breast cancer (MBC) patients. Progression free survival (PFS) and overall survival (OS) were analyzed. An independent cohort with 210 primary and 69 patients with metastatic breast cancer were further investigated to validate our findings. Results: A 2-fold elevation was presented in MBC patients when compared with PBC patients and controls, regardless of their CTC status. A multivariate Cox regression demonstrated that lower X level at base line was associated with longer PFS (HR: 2.50, 95% CI: 1.72–3.63, p = 1.607 × 10-6), as well as longer OS (HR: 3.74, 95% CI: 1.65 – 8.51, p = 0.002). After 1stcycle of chemotherapy, plasma X level was still prognostic and was dramatically decreased in patients who had responded to the treatment (54%, IQR: 36%–64%). In the independent validation round, a 2-fold increase of plasma X was observed again in MBC patients, compared with PBC patients. The prognostic value was also validated for PFS (HR: 2.12, 95% CI: 1.43– 3.84, p = 0.001) and OS (HR: 2.91, 95% CI: 1.73–7.65, p = 0.002) in MBC patients. Conclusions: Plasma X could be used as a diagnostic and prognostic marker for metastatic breast cancer. Its reduction after 1st cycle of chemotherapy could be an indicator of treatment efficacy. This finding may further prevent unnecessary systemic therapy by facilitating personalized medicine in the treatment of metastatic breast cancer.


Author(s):  
Rismawati Tambunan ◽  
Fahriatni ◽  
Hasanuddin

Abstract Objective: Selective estrogen receptor modulators (SERMs) such as tamoxifen play a role in increasing the risk of developing uterine Fibroid.Methods:  Case reportCase: Mrs. 47 years old, Para 6, presented with chief complaints of vaginal bleeding since a year ago. The patient was diagnosed with breast carcinoma 4 years ago and has had a right mastectomy followed by 6 cycles of chemotherapy which is  then continued with tamoxifen treatment for 4 years, USG examination revealed uterine myoma to which we performed bilateral salphingoophorectomy hysterectomy, with anatomic pathology results of a uterine Fibroid and chronic endometritis.Conclusion: Selective estrogen receptor modulators (SERMs) such as tamoxifen exhibit antagonistic reactions in breast tissue which makes it appropriate to be used in the treatment of breast cancer. However, they can also be potentially agonistic on estrogen receptors in the uterus, which can cause the growth of uterine Fibroid. Nevertheless, the benefits of adjuvant tamoxifen for breast cancer outweighs its potential for developing uterine Fibroid and endometrial carcinoma, because metastatic breast cancer will always be fatal, whereas uterine myoma and endometrial cancer caused by the effects of tamoxifen can be prevented by regular evaluation and total hysterectomy.Keywords: breast cancer,tamoxifen, uterine fibroid,   Abstrak Tujuan: Selektif estrogen reseptor modulator (SERMs) seperti tamoksifen berperan dalam meningkatkan risiko mengembangkan mioma uteri. Metode: Laporan KasusKasus: Ny 47 Thn Para 6, datang dengan keluhan perdarahan dari jalan lahir yang dirasakan ibu selama 1 tahun ini, pasien telah menderita kanker payudara 4 tahun yang lalu dan telah dilakukan mastektomi mammae dextra dilanjutkan kemoterapi 6 siklus kemudian dilanjutkan dengan pengobatan tamoksifen selama 4 tahun ini, dari pemeriksaan USG didapatkan adanya mioma uteri kemudian dilanjutkan dengan tindakan histerektomi salphingooforektomi bilateral, dengan hasil patologi anatomi suatu mioma uteri dan endometritis kronis.Kesimpulan: Selektif estrogen reseptor modulator (SERMs) seperti tamoksifen merupakan reaksi antagonis reseptor estrogen pada jaringan payudara yang digunakan dalam pengobatan kanker payudara, tetapi dapat berpotensi agonis pada reseptor estrogen pada uterus sehingga dapat menyebabkan pertumbuhan mioma uteri. Tetapi penggunaan tamoksifen  ajuvan untuk kanker payudara lebih bermanfaat dibandingkan dengan potensinya untuk mengembangkan mioma uteri dan karsinoma endometrium, karena  kanker payudara metastatik akan selalu berakibat fatal, sedangkan mioma uteri dan kanker endometrium yang ditimbulkan oleh efek tamoksifen dapat dicegah dengan evaluasi teratur dan dilakukan tindakan total histerektom.Kata kunci: kanker payudara, mioma uteri, tamoksifen


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