Burning Questions in the Oncofertility Counseling of Young Breast Cancer Patients

Arecco, Luca; Perachino, Marta; Damassi, Alessandra; Latocca, Maria Maddalena; Soldato, Davide; Vallome, Giacomo; Parisi, Francesca; Razeti, Maria Grazia; Solinas, Cinzia; Tagliamento, Marco; Spinaci, Stefano; Massarotti, Claudia; Lambertini, Matteo

doi:10.1177/1178223420954179

Cited by 21 publications

(18 citation statements)

References 226 publications

(205 reference statements)

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“…Over the last years, cancer death rate has been continuously dropping thanks to improvement in screening techniques and therapies ensuring early diagnosis and increased survival ( 1 ). Life-saving treatments such as chemotherapy or radiotherapy have several potential long-term adverse effects including gonadotoxicity ( 2 – 8 ). The subsequent risk of treatment-related infertility and the loss of ovarian endocrine function represent important causes of distress for patients who are diagnosed during their reproductive years ( 9 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Controlled Ovarian Stimulation With or Without Letrozole Co-administration for Fertility Preservation: A Systematic Review and Meta-Analysis

et al. 2020

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Background: The co-administration of letrozole during controlled ovarian stimulation (COS) with gonadotropins is used to limit the potentially harmful effects of a supra-physiological rise in estrogen levels on hormone-sensitive cancers. However, the efficacy and safety of adding letrozole to COS remain debated. Methods: This is a systematic review and meta-analysis of published studies that compared the efficacy and safety of COS with co-administration of letrozole vs. COS without letrozole in all patient populations. A secondary analysis was done including only the studies in breast cancer patients. The primary efficacy endpoint was the number of retrieved mature Metaphase II (MII) oocytes. Secondary efficacy and safety endpoints were total number of oocytes, maturation rate, fertilization rate, number of cryopreserved embryos, peak estradiol levels, progesterone levels, and total gonadotropin dose. Data for each endpoint were reported and analyzed thorough mean ratio (MR) with 95% confidence interval (CI). Results: A total of 11 records were selected including 2,121 patients (990 patients underwent COS with letrozole and 1,131 COS without letrozole). The addition of letrozole to COS did not have any negative effect on the number of mature oocytes collected (MR = 1.00, 95% CI = 0.87-1.16; P = 0.967) and the other efficacy endpoints. COS with letrozole was associated with significantly decreased peak estradiol levels (MR = 0.28, 95% CI = 0.24-0.32; P < 0.001). Similar results were observed in the secondary analysis including only breast cancer patients. Bonardi et al. Letrozole for Controlled Ovarian Stimulation Conclusions: These findings are reassuring on the efficacy and safety of COS with gonadotropins and letrozole and are particularly important for fertility preservation in women with hormone-sensitive cancers.

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Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Controlled Ovarian Stimulation With or Without Letrozole Co-administration for Fertility Preservation: A Systematic Review and Meta-Analysis

et al. 2020

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“…Moreover, oncological characteristics of the population were not reported, leading to important potential biases in the survival analysis (24). Therefore, defining the safety of performing COS for oocyte and/or embryo cryopreservation in breast cancer patients remains a clinical research priority (25). As shown in a recent survey involving breast cancer specialists, more than one third of them are concerned about the potential detrimental prognostic effect of COS in patients with breast cancer (10).…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor DNA to Interrogate the Safety of Letrozole-Associated Controlled Ovarian Stimulation for Fertility Preservation in Breast Cancer Patients

et al. 2021

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BackgroundCurrent fertility preservation strategies for young breast cancer patients planning a future motherhood include the association of controlled ovarian stimulation with the aromatase inhibitor letrozole (let-COS) to harvest mature oocytes while maintaining low estradiol levels. Despite this is a widely adopted protocol, the safety of let-COS on breast cancer outcomes has been poorly investigated and its use remains off-label. We assessed the safety of let-COS in breast cancer patients using circulating tumor DNA (ctDNA) as a surrogate biomarker of disease recurrence.MethodsBROVALE is an interventional non-randomized prospective study designed to evaluate the efficacy and safety of let-COS for fertility preservation in early breast cancer patients before starting (neo)adjuvant chemotherapy. Letrozole was administered throughout the COS cycle, until ovulation triggering. Safety was a secondary endpoint. Data on oncological outcomes were collected during the follow-up as well as plasma and whole blood for evaluation of ctDNA levels at the time of enrollment (i.e. before starting let-COS) and oocyte retrieval (i.e. 48 hours after the last administration of letrozole). Targeted gene sequencing on the primary tumor samples was performed to identify specific mutations used for ctDNA analysis by digital PCR. DNA extracted from whole blood samples was used to discriminate between somatic and germline mutations.ResultsFrom April 2014 to May 2017, 29 young early breast cancer patients enrolled in the BROVALE study who had available tissue samples participated to the ctDNA substudy. Among them, 15 had at least one validated somatic mutation. ctDNA was undetectable neither before nor after let-COS in 9 of them. Six patients had detectable ctDNA in the plasma samples collected before Let-COS. No change in ctDNA level after let-COS was observed in 3 patients and the level decreased (fold-change ≤ 0.5) in two women. One patient experienced an increased (fold-change ≥ 2) in ctDNA level but without disease relapse 34 months after diagnosis.ConclusionsNo increase in ctDNA level was observed in 93% (14/15) of the patients receiving let-COS supporting its use as a safe strategy for young women with early breast cancer interested in fertility preservation before chemotherapy.

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“…Chemotherapy and/or ovarian suppression can cause early (permanent or temporary) menopausal symptoms and reduce fertility. Many women are concerned about these issues, and it is important to provide them with proper counseling and treatment [ 28 ]. As regards menopausal symptoms, a large number of patients find these difficult to cope with, with a significant negative impact on their quality of life.…”

Section: The Neoadjuvant Oncologic Treatment Teammentioning

confidence: 99%

Neoadjuvant Chemotherapy in Breast Cancer: An Advanced Personalized Multidisciplinary Prehabilitation Model (APMP-M) to Optimize Outcomes

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Terribile

Magno

et al. 2021

JPM

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Neoadjuvant chemotherapy is increasingly being employed in the management of breast cancer patients. Efforts and resources have been devoted over the years to the search for an optimal strategy that can improve outcomes in the neoadjuvant setting. Today, a multidisciplinary approach with the application of evidence-based medicine is considered the gold standard for the improvement of oncological results and patient satisfaction. However, several clinical complications and psychological issues due to various factors can arise during neoadjuvant therapy and undermine outcomes. To ensure that health care needs are adequately addressed, clinicians must consider that women with breast cancer have a high risk of developing “unmet needs” during treatment, and often require a clinical intervention or additional care resources to limit possible complications and psychological issues that can occur during neoadjuvant treatment. This work describes a multidisciplinary model developed at “Fondazione Policlinico Universitario Agostino Gemelli” (FPG) in Rome in an effort to optimize treatment, ease the application of evidence-based medicine, and improve patient quality of life in the neoadjuvant setting. In developing our model, our main goal was to adequately meet patient needs while preventing high levels of distress.

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Burning Questions in the Oncofertility Counseling of Young Breast Cancer Patients

Cited by 21 publications

References 226 publications

Efficacy and Safety of Controlled Ovarian Stimulation With or Without Letrozole Co-administration for Fertility Preservation: A Systematic Review and Meta-Analysis

Efficacy and Safety of Controlled Ovarian Stimulation With or Without Letrozole Co-administration for Fertility Preservation: A Systematic Review and Meta-Analysis

Circulating Tumor DNA to Interrogate the Safety of Letrozole-Associated Controlled Ovarian Stimulation for Fertility Preservation in Breast Cancer Patients

Neoadjuvant Chemotherapy in Breast Cancer: An Advanced Personalized Multidisciplinary Prehabilitation Model (APMP-M) to Optimize Outcomes

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