Infertility in young BC patients, which often results from early menopause induced by chemotherapeutic agents, is a major source of distress in this population. Effects to preserve fertility can lead to increased quality of life for those who desire to have children after a BC diagnosis. However, concern exists whether fertility preservation (FP) methods can increase the risk of death, especially for methods that involve controlled ovarian stimulation (COS) resulting in supraphysiological estradiol levels.
Investigators in Sweden conducted the largest prospective cohort study to date involving 1,275 women from January 1, 1994, through June 30, 2017, to determine the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation (425 women) compared with a matched control group of women with BC who did not undergo FP (850 women).
Women aged 18 to 44 years with BC were included in the study. Controls were matched 2-to-1 for every study patient. Data were gathered from three BC registries in Sweden (Swedish National Quality Register, Stockholm-Gotland region, and West region). Patients were excluded from the study if they had BC in situ, distant metastases, T4 cancers, synchronic bilateral BC, had not undergone BC surgery, or if the indication for FP was not due to BC (in 14 women it was due to the presence of BRCA mutations).
FP exposures were divided into two groups: those who underwent cryopreservation of oocytes and/or embryos using hormonal stimulation (i.e., hormonal FP), or those who underwent cryopreservation of ovarian tissue without hormonal stimulation (i.e., nonhormonal FP). Hormonal FP was further stratified by coadministration of letrozole or standard stimulation protocols. Those who underwent a combination of hormonal FP and nonhormonal FP were classified as hormonal FP.
The primary outcome was disease-specific mortality (i.e., death due to BC). A secondary outcome was any event of death due to BC or relapse (local, regional, or systemic recurrence). While data on BC mortality were available for the whole cohort, data on relapse were only available for 723 women; data on relapse were not available from the Swedish National Quality Register.
Of the 1,275 women (who ranged in age from 21 to 42 years at the time of BC diagnosis), 425 received FP (58 nonhormonal FP [median age 32 years] and 367 received hormonal FP, including five who used a combination of nonhormonal and hormonal FP methods [mean age 33 years] and median age 34 years for the total group). Differences existed in parity, age, place of birth, educational level, biological characteristics, and treatment modalities, but there was no pattern of more aggressive disease observed in any particular group. Among the cohort of 723 women in which the risk of relapse was investigated, 198 underwent hormonal FP, 43 nonhormonal FP, and 482 served as controls.
Disease-specific mortality occurred in 17 women who underwent FP, seven women who underwent nonhormonal FP, and 80 controls. Follow-up ranged from approximately 4 years in those who underwent hormonal FP and their matched controls to 6.7 years for those who underwent nonhormonal FP and their matched controls. After accounting for confounders, the adjusted hazard ratios (aHRs) for the hormonal FP group and the nonhormonal group compared with the control group were not significantly different (aHR = 0.59; 95% CI, 0.32-1.09 and aHR = 0.51; 95% CI, 0.2-1.29, respectively).
Analysis of disease-specific mortality or relapse in the cohort of 723 women found that there was no statistically significant difference between the groups (hormonal FP aHR = 0.81, 95% CI, 0.49-1.37 and nonhormonal FP aHR= 0.75; 95% CI, 0.35-1.62, respectively).
There were no statistically significant differences in 5-year disease-specific survival between the hormonal FP, nonhormonal FP, and control group (96%, 93%, and 90%, respectively) or in the 10-year disease specific survival (88%, 90%, and 81%, respectively). A similar trend was seen for the 5-year relapse risk (89%, 83%, and 82%, respectively) and 10-year relapse risk (82%, 80%, and 73%, respectively).
The concomitant administration of letrozole in the hormonal FP group did not affect disease-specific mortality or disease-specific mortality and relapse.
Although the authors call for even longer follow-up, the findings of this study are reassuring about the safety of FP for both pharmacists and their young BC patients who are interested in preserving their fertility prior to undergoing BC treatment.
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