The PREgnancy and FERtility (PREFER) Study Investigating the Need for Ovarian Function and/or Fertility Preservation Strategies in Premenopausal Women With Early Breast Cancer (original) (raw)

Dilemmas and Difficulties in Dealing with Receptor-positive Breast Cancer Patients Seeking Fertility Care: A Case Report!

Journal of South Asian Federation of Obstetrics and Gynaecology, 2024

Aim: Addressing the fertility preservation needs of breast cancer patients with receptor-positive presents considerable dilemmas and difficulties. Case description: Presenting a case of a 35-year-old unmarried female with receptor-positive breast malignancy who was referred for fertility preservation. Counseling regarding remote risk with controlled ovarian stimulation using antagonist protocol was done. Antiestrogen therapy with letrozole was added to minimize the risk with supraphysiologic estrogen levels. Five mature metaphase II (MII) oocytes were retrieved and cryopreserved for future use. Conclusion: Oocyte cryopreservation in unmarried cancer patients is an acceptable option. The addition of antiestrogen-like letrozole is advisable in estrogen receptor-positive cases. Fertility concerns of young patients should be addressed with a multidisciplinary approach.

Long-Term Outcomes With Pharmacological Ovarian Suppression During Chemotherapy in Premenopausal Early Breast Cancer Patients

Journal of the National Cancer Institute, 2021

BackgroundAlthough use of gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is an established strategy to protect ovarian function in premenopausal breast cancer patients, no long-term safety data are available, raising some concerns in women with hormone receptor–positive disease. There are controversial data on its fertility preservation potential.MethodsThe Prevention of Menopause Induced by Chemotherapy: a Study in Early Breast Cancer Patients—Gruppo Italiano Mammella 6 (PROMISE-GIM6) trial is a multicenter, randomized, open-label, phase III superiority trial conducted at 16 Italian centers from October 2003 to January 2008. Eligible patients were randomly assigned to (neo)adjuvant chemotherapy alone (control arm) or combined with the GnRHa triptorelin (GnRHa arm). The primary planned endpoint was incidence of chemotherapy-induced premature ovarian insufficiency. Post hoc endpoints were disease-free survival (DFS), overall survival (OS), and post-treatment pregnancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.ResultsOf 281 randomly assigned patients, 80.4% had hormone receptor–positive breast cancer. Median follow-up was 12.4 years (interquartile range = 11.3-13.2 years). No differences in 12-year DFS (65.7% [95% CI = 57.0% to 73.1%] in the GnRHa arm vs 69.2% [95% CI = 60.3% to 76.5%] in the control arm; HR = 1.16, 95% CI = 0.76 to 1.77) or in 12-year OS (81.2% [95% CI = 73.6% to 86.8%] in the GnRHa arm vs 81.3% [95% CI = 73.1% to 87.2%] in the control arm; HR = 1.17, 95% CI = 0.67 to 2.03) were observed. In patients with hormone receptor–positive disease, the hazard ratio was 1.02 (95% CI = 0.63 to 1.63) for DFS and 1.12 (95% CI = 0.59 to 2.11) for OS. In the GnRHa and control arms, 9 and 4 patients had a posttreatment pregnancy, respectively (HR = 2.14, 95% CI = 0.66 to 6.92).ConclusionsFinal analysis of the PROMISE-GIM6 trial provides reassuring results on the safety of GnRHa use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer, including those with hormone receptor–positive disease.

Comparing the Gonadotoxicity of Multiple Breast Cancer Regimens: Important Understanding for Managing Breast Cancer in Pre-Menopausal Women

Breast Cancer: Targets and Therapy, 2021

Over the last several decades, improvements in breast cancer treatment have contributed to increased cure rates for women diagnosed with this malignancy. Consequently, great importance should be paid to the long-term side effects of systemic therapies. For young women (defined as per guideline ≤40 years at diagnosis) who undergo chemotherapy, one of the most impactful side effects on their quality of life is premature ovarian insufficiency (POI) leading to fertility-related problems and the side effects of early menopause. Regimens, type, and doses of chemotherapy, as well as the age of patients and their ovarian reserve at the time of treatment are major risk factors for treatment-induced POI. For these reasons, childbearing desire and preservation of ovarian function and/or fertility should be discussed with all premenopausal patients before planning the treatments. This manuscript summarizes the available fertility preservation techniques in breast cancer patients, the risk of treatment-induced POI with different anticancer treatments, and the possible procedures to prevent it. A special focus is paid to the role of oncofertility counseling, as a central part of the visit in this setting, during which the patient should receive all the information about the potential consequences of the disease and of the proposed treatment on her future life.

An update on the screening, diagnosis & management of breast cancer: A review with considerations for future fertility

An update on the screening, diagnosis & management of breast cancer: A review with considerations for future fertility, 2021

The diagnosis along with management of Breast cancer(BC) are going through a prototype switch from the one size fitting all towards the period of individualized medicine. With the advances in diagnosis that is inclusive of sophisticated methods like molecular imaging in addition to genomic expression profile aid in enhancement of tumor characteristics to get unraveled. With these diagnostics, in combination with the newer surgical strategies in addition to radiation therapy cause a strategy that is inclusive of multiple disciplines cooperating with each other for reduction of recurrence to the utmost minimum. Here we conducted a review utilizing search engine pub-med, google scholar; web of science; embrace; Cochrane review library utilizing the MeSH terms like surgery; presence or absence of estrogen receptor(ER);progesterone receptor(PR); human epidermal growth factor receptor (HER2),; chemotherapy; triple negative breast cancer(TNBC); endocrine therapy; metastases; radio therapy; imaging modalities; causes of TNBC; drug resistance; prognosis; markers for TNBC; effective tamoxifen; negative neo adjuvant chemotherapy; gene markers; role of microRNAs, from 1980's till august 2021.We found a total of 442800 articles out of which we selected 86 articles for this chapter on update on breast cancer management. No meta-analysis was done. Further we have tried to explore a lot of modes by which TNBC treatment success can get escalated inclusive of the newer utilization of H2S pathway in cancer as well as mode by which it might work. Further with the escalated 5 yr survival along with advances in ovarian tissue cryopreservation oocyte cryopreservation prior to chemotherapy as well as radiotherapy one can consider ovarian tissue transplantation in such cases. With BCS an attempt at cosmetic surgery aids in women leading a more normal life. Thus we have tried to comprehensively detail all these features.

Adjuvant therapy with GnRH agonists/tamoxifen in breast cancer could be a good council for patients with hormone receptor-positive tumors and wish to preserve fertility

JBRA Assisted Reproduction

Infertility represents one of the main long-term consequences of combination chemotherapy used for the treatment of breast cancer. Approximately 60%-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ tumors with respect to recurrence-free survival and overall survival, Presentation of the hypothesis: It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. testing the hypothesis: Assessment of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen. The recurrence-free survival and overall survival should be analysed. Implications of the hypothesis: The major implication will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases.

Impact on disease-free survival of the duration of ovarian function suppression, as postoperative adjuvant therapy, in premenopausal women with hormone receptor-positive breast cancer: a retrospective single-institution study

Breast Cancer

Introduction Although tamoxifen (TAM) plus ovarian function suppression (OFS) is considered as a standard adjuvant treatment for premenopausal women with hormone receptor-positive breast cancer, the optimal duration of OFS has not yet been established. This retrospective study was designed to assess the duration of OFS and the impact of the duration of OFS on the DFS in these patients. Methods We retrospectively reviewed the data of premenopausal patients with breast cancer who received TAM + OFS (goserelin or leuprorelin) as adjuvant therapy between February 2004 and June 2015. The primary analysis was a comparison of the disease-free survival (DFS) between patients who received OFS for 3 years or less (OFS ≤ 3 years group) and those who received OFS for longer than 3 years (OFS > 3 years group). Results We analyzed the data of 215 premenopausal patients diagnosed as having hormone receptor-positive breast cancer. A propensity score-matched model showed the absence of any signif...

Who are the women who enrolled in the POSITIVE trial: A global study to support young hormone receptor positive breast cancer survivors desiring pregnancy

The Breast

Background: Premenopausal women with early hormone-receptor positive (HRþ) breast cancer receive 5e10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and fertility may wane. The POSITIVE study investigates the impact of temporary ET interruption to allow pregnancy. Methods: POSITIVE enrolled women with stage I-III HR þ early breast cancer, 42 years, who had received 18e30 months of adjuvant ET and wished to interrupt ET for pregnancy. Treatment interruption for up to 2 years was permitted to allow pregnancy, delivery and breastfeeding, followed by ET resumption to complete the planned duration. Findings: From 12/2014 to 12/2019, 518 women were enrolled at 116 institutions/20 countries/4 continents. At enrolment, the median age was 37 years and 74.9 % were nulliparous. Fertility preservation was used by 51.5 % of women. 93.2 % of patients had stage I/II disease, 66.0 % were node-negative, 54.7 % had breast conserving surgery, 61.9 % had received neo/adjuvant chemotherapy. Tamoxifen alone was the most prescribed ET (41.8 %), followed by tamoxifen þ ovarian function suppression (OFS) (35.4 %). A greater proportion of North American women were <35 years at enrolment (42.7 %), had mastectomy (59.0 %) and received tamoxifen alone (59.8 %). More Asian women were nulliparous (81.0 %), had nodenegative disease (76.2%) and received tamoxifen þ OFS (56.0 %). More European women had received chemotherapy (69.3 %). Interpretation: The characteristics of participants in the POSITIVE study provide insights to which patients and doctors considered it acceptable to interrupt ET to pursue pregnancy. Similarities and variations from a regional, sociodemographic, disease and treatment standpoint suggest specific sociocultural attitudes across the world.

Fertility preservation in women with breast cancer

2010

Fertility preservation is an important issue for young women diagnosed with breast cancer. The most well-established options for fertility preservation in cancer patients, embryo and oocyte cryopreservation, have not been traditionally offered to breast cancer patients as estradiol rise during standard stimulation protocols may not be safe for those patients. Potentially safer stimulation protocols using tamoxifen and aromatase inhibitors induce lower levels of estradiol while similar results in terms of number of oocyte and embryo obtained to standard protocols. Cryopreservation of immature oocytes and ovarian cortical tissue, both still experimental methods, are also fertility preservation options for breast cancer patients.