Ovarian Suppression: Early Menopause and Late Effects.

OPINION STATEMENT: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life.

Endometriosis presenting as relapsing haemorrhagic ascites in a South Asian woman: A case report.

Endometriosis presenting as ascites is a rare entity, and is more so in women of Asian ethnicity. Less than a hundred cases have been reported worldwide. Majority of patients present with abdominal dist ension and pa in, drai ning massive blood stained serosanguineous fluid. This hinders future fertility prospects of these women. O va rian suppression has been employed as a successful treatment, followed by definitive surgical treatment, such as bilateral salpingo -ooph orectomy, to end the possibility of recurrences, which are otherwise always possible. We present the case of a woman of reproductive age, seeking fertility treatment, who had a more subtle presentation of moderate, but relapsing ascites of un known origin in the past two years. Diagnostic laparoscopy and histopathology of the pe ritoneal deposits suggested endometriosis. Her ovarian func tion was s uppressed, and sh e is curre nt ly underway of a ssisted re produ ction for achieving a pregnancy.

Reproductive suppression of giraffe (Giraffa camelopardalis) under managed care using a GnRH immunological product.

Giraffe present unique contraception challenges as males persistently pursue females during estrus. Year-round pursuit during frequent recurring estrus can pose significant risk under slippery conditions. Complete ovarian suppression is a useful tool in giraffe because it eliminates estrous behavior, interest from the male, and controls reproduction. Effective reproduction control in giraffes has been achieved with porcine zona pellucida, oral melengestrol acetate, and depot medroxy-progesterone acetate. However, these methods allow some degree of folliculogenesis and estrous behavior. Improvest® is a gonadotropin releasing hormone (GnRH) immunological product that elicits antibodies against GnRH and abrogates the effects of endogenous GnRH. This study evaluated the efficacy of Improvest® for gonadal suppression in seven females and one male giraffe by monitoring steroid hormones. Seven female giraffe were treated intramuscularly with an initial dose, a booster at 4 weeks and maintenance boosters at 3-month intervals (600 µg/dose) for 12 months. Six females were on supplemental contraception during the induction phase because separation from males was not possible. In the male (treated with 400 µg), testosterone concentrations decreased after the second injection. However, even with low serum testosterone concentrations, mounting (of nontreated females) behavior was still observed occasionally. Ovarian activity was suppressed in all treated females and interest by the males stopped; supplemental contraceptives (during the induction phase) did not impede the effect of Improvest®. After 15.3 months (seven doses), Improvest® was discontinued in three females which no longer needed contraception. In these females, ovarian activity was noted approximately 90 days after the last dose.

Adherence to endocrine therapy including ovarian suppression: A large observational cohort study of US women with early breast cancer.

BACKGROUND: Recent clinical trials support adding ovarian suppression (OS) to oral endocrine therapy (ET) for premenopausal women with early breast cancer. The adoption of OS among real-world populations and the impact of OS on ET adherence have not been evaluated. METHODS: This study examined a retrospective, observational cohort of women under the age of 50 years with incident early breast cancer from 2001 to 2016. The IBM MarketScan Commercial insurance claims database was used to identify new users of ET with or without OS and to track discontinuation of or adherence to ET. In all, 21,948 women filled at least 1 prescription for ET within 12 months of their diagnosis after a washout period of 12 months with no prior claims. Patients who received an aromatase inhibitor without a synchronous OS drug were excluded. RESULTS: Use of OS increased over time and reached 11.3% in 2016. In an unadjusted analysis, 40.2% of ET+OS users discontinued ET early, whereas 48.8% of tamoxifen-alone users did. In adjusted analyses, ET+OS users had a similar likelihood of discontinuing ET in comparison with tamoxifen-alone users (hazard ratio, 0.92; 95% confidence interval, 0.83-1.03). Approximately 30% of women had low adherence over the first year of use. The likelihood of high adherence was similar, regardless of OS exposure. CONCLUSIONS: The use of OS among young, commercially insured patients with breast cancer increased over time in agreement with recent clinical trial results but remained relatively low. Nonadherence to ET was common, but the use of OS was not associated with lower adherence to ET in this observational, nonrandomized cohort. These findings may reassure oncologists that use of OS does not endanger ET adherence, although prospective studies are needed for confirmation.

Measuring Ovarian Escape in Premenopausal Estrogen Receptor-Positive Breast Cancer Patients on Ovarian Suppression Therapy.

PURPOSE: This study evaluated the proportion of premenopausal women who experience persistent ovarian escape (OE) while receiving ovarian suppression (OS) therapy for estrogen receptor-positive (ER+) breast cancer treatment. The study also examined clinical factors that may predispose to higher risk of persistent OE. MATERIALS AND METHODS: This was a retrospective, "real-world" study to evaluate premenopausal women receiving adjuvant endocrine OS therapy. The primary objective was to measure the percentage of persistent OE within the first 3 months of OS injections (using either leuprolide or goserelin). The secondary objective was to associate baseline clinical data (age, body mass index [BMI], and previous chemotherapy) with the probability of OE. RESULTS: Of the 46 patients included in this analysis, 11 (23.9%) women did not achieve OS within 3 months. Three women (6.5%) remained in OE at 12 months. Older age (odds ratio, 0.86; confidence interval, 0.76-0.98, p = .024) was associated with lower chance of developing OE. BMI, previous chemotherapy, and drug used (tamoxifen versus aromatase inhibitor) did not correlate with the likelihood of OE in this patient cohort. CONCLUSION: Among the premenopausal women who did not attain complete ovarian suppression, young age was a significant risk factor for likelihood of OE. Although the clinical relevance of this finding is not yet known, it should prompt further studies to determine whether inadequate OS is associated with higher recurrence risk for patients with ER+ breast cancer. IMPLICATIONS FOR PRACTICE: Because up to a quarter of premenopausal women do not attain adequate ovarian suppression within the first 3 months of gonadotropin-releasing hormone (GnRH) agonist therapy, bloodwork should be checked to ascertain hormone levels prior to starting aromatase inhibitor therapy, and at regular intervals, for these women.

Patient preferences and adherence to adjuvant GnRH analogs among premenopausal women with hormone receptor positive breast cancer.

PURPOSE: Adjuvant ovarian function suppression (OFS) in premenopausal hormone receptor (HR) positive breast cancer (BC) improves survival. Adherence to adjuvant gonadotropin-releasing hormone analogs (GnRHa) remains a challenge and is associated with toxicities and inconvenient parenteral administration. The goal of this study was to describe real-world adherence patterns and patient preferences surrounding adjuvant GnRHa. METHODS: We analyzed the medical records of premenopausal women with non-metastatic HR positive BC from January 2000 to December 2017; participants received adjuvant monthly goserelin or leuprolide at The Ohio State University. Data collected included demographics, clinicopathologic characteristics, and OFS adherence/side effects. We defined non-adherence as discontinuation of GnRHa within 3 years for a reason other than switching to an alternate OFS, delay > 7 days from a dose, or a missed dose. Chi-square tests assessed associations between clinical characteristics and outcomes. RESULTS: A total of 325 patients met eligibility. Of these, 119 (37%) patients were non-adherent to GnRHa; 137 (42%) underwent elective bilateral salpingo-oophorectomy after initial GnRHa. Those opting for surgery reported significantly more hot flashes (74% vs 48%, p < 0.001), arthralgias (46% vs 30%, p = 0.003), and vaginal dryness (37% vs 21%, p = 0.001) compared with patients remaining on GnRHa. CONCLUSION: Non-adherence to adjuvant GnRHa occurred in over a third of patients and almost half the patients initiating GnRHa underwent subsequent surgical ablation. These high frequencies highlight real-world patterns of OFS. Additionally, treatment toxicities may impact personal preference of OFS modality. Personalized practices to target predictors of adjuvant GnRHa non-adherence are critical to optimize symptoms, adherence, and survivorship.

Molecular Mechanism and Prevention Strategy of Chemotherapy- and Radiotherapy-Induced Ovarian Damage.

Fertility preservation is an emerging discipline, which is of substantial clinical value in the care of young patients with cancer. Chemotherapy and radiation may induce ovarian damage in prepubertal girls and young women. Although many studies have explored the mechanisms implicated in ovarian toxicity during cancer treatment, its molecular pathophysiology is not fully understood. Chemotherapy may accelerate follicular apoptosis and follicle reservoir utilization and damage the ovarian stroma via multiple molecular reactions. Oxidative stress and the radiosensitivity of oocytes are the main causes of gonadal damage after radiation treatment. Fertility preservation options can be differentiated by patient age, desire for conception, treatment regimen, socioeconomic status, and treatment duration. This review will help highlight the importance of multidisciplinary oncofertility strategies for providing high-quality care to young female cancer patients.

Changes in bone mineral density during 5 years of adjuvant treatment in premenopausal breast cancer patients.

PURPOSE: Adjuvant treatment for breast cancer in postmenopausal women is a risk factor for bone loss. However, the association between bone mineral density (BMD) changes in premenopausal breast cancer patients and various adjuvant treatment regimens is not well characterized. In this study, we evaluated the changes in BMD according to adjuvant treatment in premenopausal women with breast cancer. METHODS: Between 2006 and 2010, BMD data of 910 premenopausal women with breast cancer before operation and 1, 2, 3.5, and 5 years post-operation were retrospectively analyzed. The patients were divided according to the type of treatment: observation (O), tamoxifen (T), chemotherapy (C), C followed by T (C → T), and gonadotropin-releasing hormone (GnRH) agonist with T (G + T). RESULTS: After 5 years of follow-up, BMD changes were similar between the T and O groups (all p > 0.05). Within 1 year of treatment, the C group showed the most significant BMD loss. The C → T and G + T groups showed more significant BMD loss in the lumbar spine and femur than the O and T groups (both p < 0.001, both). After 1 year of treatment, BMD loss in the lumbar spine was significantly greater in the C → T and G + T groups than in the T group; this tendency was maintained for 5 years of treatment (all p < 0.005). CONCLUSION: Premenopausal women who received adjuvant treatment which induced menopause showed significant bone loss which lasted for 5 years. Although no significant difference was observed between the O and T groups, tamoxifen treatment during chemotherapy or GnRH agonist treatment might prevent bone loss.

Advances in the Treatment and Prevention of Chemotherapy-Induced Ovarian Toxicity.

Due to improvements in chemotherapeutic agents, cancer treatment efficacy and cancer patient survival rates have greatly improved, but unfortunately gonadal damage remains a major complication. Gonadotoxic chemotherapy, including alkylating agents during reproductive age, can lead to iatrogenic premature ovarian insufficiency (POI), and loss of fertility. In recent years, the demand for fertility preservation has increased dramatically among female cancer patients. Currently, embryo and oocyte cryopreservation are the only established options for fertility preservation in women. However, there is growing evidence for other experimental techniques including ovarian tissue cryopreservation, oocyte in vitro maturation, artificial ovaries, stem cell technologies, and ovarian suppression. To prevent fertility loss in women with cancer, individualized fertility preservation options including established and experimental techniques that take into consideration the patient's age, marital status, chemotherapy regimen, and the possibility of treatment delay should be provided. In addition, effective multidisciplinary oncofertility strategies that involve a highly skilled and experienced oncofertility team consisting of medical oncologists, gynecologists, reproductive biologists, surgical oncologists, patient care coordinators, and research scientists are necessary to provide cancer patients with high-quality care.

Treating HR+/HER2- breast cancer in premenopausal Asian women: Asian Breast Cancer Cooperative Group 2019 Consensus and position on ovarian suppression.

PURPOSE: Breast cancer in young Asian women has distinctive clinicopathological characteristics; hence, we question the universal generalizability of treatment recommendations based on data from predominantly non-Asian postmenopausal women. METHODS: The Asian Breast Cancer Cooperative Group (ABCCG) reviewed current ESO-ESMO and St. Gallen recommendations for treating hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer in premenopausal women. Points disputed by ≥ 3/12 members were discussed, and statements on contentious issues formulated for anonymous voting; consensus required a ≥ 75% majority. RESULTS: The ABCCG contends that: (1) Trials in premenopausal women are not only necessary, but also worthwhile if performed separately from others that also enroll postmenopausal participants. (2) Not all premenopausal women with HR+ early breast cancer need adjuvant ovarian function suppression (OFS). (3) Certain clinical factors might influence decision-making about prescribing OFS. (4) For early HR+/HER2- breast cancer in premenopausal patients with OFS, tamoxifen is preferred for intermediate-risk cases; for high risk, near-consensus supported aromatase inhibitor, despite no clear overall survival benefit versus tamoxifen. (5) Oncotype DX Breast Recurrence Score® has different treatment implications in patients aged ≤ 50 versus > 50 years. (6) High-risk patients (if premenopausal after chemotherapy) should receive adjuvant chemotherapy and OFS plus aromatase inhibitor. (7) For patients with advanced disease receiving OFS on a backbone of tamoxifen, gonadotrophin-releasing hormone agonists may be given 12-weekly. (8) For premenopausal women who decline OFS or oophorectomy, tamoxifen alone is still an option but is considered less effective; other monotherapies are also less effective than OFS plus such treatments. CONCLUSION: Premenopausal Asian women with breast cancer have unique disease characteristics and may benefit from treatment that differs somewhat from international guidelines. Given the great diversity of patients and clinical settings worldwide, the ABCCG advocates evidence-based yet flexible and individualized use of all potential options to improve breast cancer outcomes.

Tailoring breast cancer therapies to reduce mortality and improve quality of life: San Antonio Breast Cancer Symposium 2017 (part 1).

The 40th annual San Antonio Breast Cancer Symposium was convened in San Antonio, TX, USA on 5-9 December 2017. More than 7500 clinicians and scientists from around the world participated in the symposium which featured a range of presentations and keynote talks pertaining to breast cancer screening, prevention, loco-regional and systemic therapies. This two-part report highlights a selection of important studies presented at this premier breast cancer event with part 1 focusing on dose-intense radiotherapy, perioperative endocrine therapy, duration of bisphosphonates, immunotherapy, ovarian function suppression and acupuncture. The second part of this report will discuss a range of topics related to de-escalation of loco-regional therapies, the significance of complete pathological response, older patients and CDK 4/6 inhibitors, circulating tumor cells and plasma DNA as a tumor marker.

Tailoring breast cancer therapies to reduce mortality and improve quality of life: San Antonio Breast Cancer Symposium 2017 (part 2).

The 40th annual San Antonio Breast Cancer Symposium was convened in San Antonio, TX, USA on 5-9 December 2017. More than 7500 clinicians and scientists from around the world participated in the symposium which featured a range of presentations and keynote talks pertaining to breast cancer screening, prevention, loco-regional and systemic therapies. This two-part report highlights a selection of important studies presented at this premier breast cancer event with part 1 focusing on dose-intense radiotherapy, perioperative endocrine therapy, duration of bisphosphonates, immunotherapy, ovarian function suppression and acupuncture. The second part of this report will discuss a range of topics related to de-escalation of loco-regional therapies, the significance of complete pathological response, older patients and CDK 4/6 inhibitors, circulating tumor cells and plasma DNA as a tumor marker.

Antral follicle count recovery in women with menses after treatment with and without gonadotropin-releasing hormone agonist use during chemotherapy for breast cancer.

PURPOSE: After chemotherapy for breast cancer, most women will recover some ovarian function, but the timing and extent of this recovery are poorly understood. We studied post-chemotherapy ovarian recovery in women with and without a history of ovarian suppression during chemotherapy. METHODS: Reproductive age breast cancer patients who were seen prior to chemotherapy for fertility preservation consult were consented for follow-up ovarian function assessment (every 3-6 months after chemotherapy) with antral follicle count (AFC) in this prospective cohort study. We restricted our analysis to those with menses present after chemotherapy. Box plots were used to demonstrate the change in follow-up AFC versus time elapsed after chemotherapy. A mixed effects regression model was used to assess differences in AFC. RESULTS: Eighty-eight patients with a history of newly diagnosed breast cancer were included. Forty-five patients (51%) had ovarian suppression with GnRH agonist (GnRHa) during chemotherapy. AFC recovery appeared to plateau at 1 year after completing chemotherapy at a median of 40% of pre-chemotherapy AFC. After adjustment for age, initial AFC, cyclophosphamide exposure, combined hormonal contraceptive (CHC) use, and tamoxifen use, AFC recovered faster and to a greater degree for those women who underwent GnRHa therapy for ovarian protection during chemotherapy (P = 0.032). CONCLUSIONS: Women with menses after chemotherapy for breast cancer appear to recover their full potential AFC 1 year after their last chemotherapy dose. Treatment with GnRHa during chemotherapy is associated with a higher degree of AFC recovery. The findings of this study can aid in counseling patients prior to chemotherapy about expectations for ovarian recovery and planning post-treatment fertility preservation care to maximize reproductive potential when pre-treatment fertility preservation care is not possible or has limited oocyte yield.

Tight interplay in early pregnancy between follistatin and anti-mullerian hormone in women with polycystic ovarian syndrome (PCOS).

PURPOSE: Follistatin levels increase during the course of pregnancy and may play a role in ovarian arrest, reflected by the simultaneous decrease of anti-mullerian-hormone (AMH) levels. The aim of the study was to investigate AMH and follistatin levels during the hormonal window at the beginning of pregnancy. Since both parameters are described as deregulated in polycystic ovarian syndrome (PCOS), subgroup analysis of PCOS patients may additionally elucidate their interplay and effects on ovarian activity. METHODS: Serum samples were retrospectively analyzed using the AMH Gen II ELISA and the Human Follistatin Quantikine ELISA Kit. Samples were collected longitudinally from 57 patients (32 with PCOS and 25 controls) before conception and during the first trimester. In 18 patients, measurements from the early and the late first trimester were available. Potential associations of AMH and follistatin levels with PCOS-related parameters were compared between the subgroups as well as longitudinally before and in the first trimester of pregnancy. For statistical analysis, the Spearman's correlation, Wilcoxon test, t test, Friedman test and multiple linear regression analysis was performed. RESULTS: In contrast to AMH, follistatin levels differed not between controls and PCOS patients before and in pregnancy. In both subgroups, AMH levels significantly decreased and follistatin levels significantly increased in longitudinally performed measurements before conceiving and in the first trimester of pregnancy. CONCLUSION: Follistatin levels are not suited as a biomarker for PCOS, but could be involved in suppressing ovarian activity, as reflected by AMH levels at the beginning of pregnancy.

Adjuvant ovarian suppression for resected breast cancer: 2017 critical assessment.

Currently available data supporting adjuvant ovarian function suppression for resected breast cancer in premenopausal women in addition to standard chemotherapy and tamoxifen are not persuasive, even though an ASCO guideline supports them. Available information from the key trial, called "SOFT," has only 5-year follow-up in a 15-year disease. It employs breast cancer events as an endpoint, rather than distant metastases, or better still, death from any cause. The small advantages reported to date may disappear when aromatase inhibitors are given after the occurrence of menopause in the control population. Caution should be exercised in recommending ovarian suppression in all but the highest-risk situations.

Ovarian suppression in combination endocrine adjuvant therapy in premenopausal women with early breast cancer.

PURPOSE: The benefits of adding ovarian suppression to either tamoxifen or aromatase inhibitors as adjuvant breast cancer therapy in premenopausal women are controversial. Therefore, we performed a systematic literature review and meta-analysis of relevant randomized trials. METHODS: We identified and combined four qualifying trials reporting disease-free survival (DFS) and overall survival (OS) using meta-analysis. RESULTS: Combining ABCSG-12, SOFT, and TEXT studies, there were 65 fewer DFS events (HR 0.89, 95% CI 0.57-1.39) but 30 more deaths for ovarian suppression plus aromatase inhibitor compared to ovarian suppression plus tamoxifen (HR 1.31, 95% CI 0.93-1.84, P = 0.12, τ = 0.03, heterogeneity, P = 0.18). DFS and OS were more concordant for combined SOFT and E-3193 findings; for ovarian suppression plus tamoxifen compared to tamoxifen alone, there were 24 fewer DFS events (HR 0.83, 95% CI 0.67-1.07, P = 0.09, τ 2 = 0) and 14 fewer deaths (HR 0.76, 95% CI 0.53-1.07). The SOFT Estrogen Substudy demonstrated inconsistent estrogen suppression with combined ovarian suppression and aromatase inhibitor. CONCLUSION: Given the discordance between DFS and OS and inconsistent estrogen suppression with ovarian suppression plus aromatase inhibitor, adding aromatase inhibitor to ovarian suppression as adjuvant therapy in premenopausal women is premature.

Impact of CYP19A1 and ESR1 variants on early-onset side effects during combined endocrine therapy in the TEXT trial.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) and cytochrome P450 19A1 (CYP19A1) genes have been associated with breast cancer risk, endocrine therapy response and side effects, mainly in postmenopausal women with early breast cancer. This analysis aimed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes, sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial (TEXT). METHODS: Blood was collected from consenting premenopausal women with hormone-responsive early breast cancer, randomly assigned to 5-years of tamoxifen plus ovarian suppression (OFS) or exemestane plus OFS. DNA was extracted with QIAamp kits and genotyped for two CYP19A1 (rs4646 and rs10046) and three ESR1 (rs2077647, rs2234693 and rs9340799) SNPs by a real-time pyrosequencing technique. Adverse events (AEs) were recorded at baseline and 3-monthly during the first year. Associations of the genotype variants with grade ≥2 early-onset targeted AEs of hot flashes/sweating or musculoskeletal events were assessed using logistic regression models. RESULTS: There were 2660 premenopausal patients with breast cancer in the intention-to-treat population of TEXT, and 1967 (74 %) are included in this translational study. The CYP19A1 rs10046 variant T/T, represented in 23 % of women, was associated with a reduced incidence of grade ≥2 hot flashes/sweating (univariate odds ratio (OR) = 0.78; 95 % CI 0.63-0.97; P = 0.03), more strongly in patients assigned exemestane + OFS (TT vs CT/CC: OR = 0.65, 95 % CI = 0.48-0.89) than assigned tamoxifen + OFS (OR = 0.94, 95 % CI = 0.69-1.27, interaction P = 0.03). No association with any of the CYP19A1/ESR1 genotypes and musculoskeletal AEs was found. CONCLUSION: The CYP19A1 rs10046 variant T/T favors lower incidence of hot flashes/sweating under exemestane + OFS treatment, suggesting endocrine-mediated effects. Based on findings from others, this SNP may potentially enhance treatment adherence and treatment efficacy. We plan to evaluate the clinical impact of this polymorphism during time, pending sufficient median follow up. TRIAL REGISTRATION: ClinicalTrials.gov NCT00066703, registered August 6, 2003.

Goserelin toxicities and preferences for ovarian suppression method in pre-menopausal women with breast cancer.

BACKGROUND: Goserelin, a form of medical ovarian suppression, is an effective treatment for pre-menopausal women with breast cancer (PMBC). Meta-analysis data showed that similar efficacy is achieved with medical ovarian suppression and non-pharmacological ovarian suppression (NPOS) - oophorectomy or ovarian irradiation. The acceptance rate of NPOS remains low. AIMS: This study explored the reported toxicities of PMBC women and their preferred ovarian suppression method whilst on goserelin. METHODS: A postal survey consisting of 22 study-specific questions was sent to PMBC women who received goserelin at the Flinders Medical Centre. RESULTS: Nineteen women were identified from the database; 12 versus 7 women received goserelin in the adjuvant versus metastatic setting respectively. Thirteen (68.4%) responded to the survey. Women in the adjuvant cohort were more likely to report toxicities. The most common were hot flushes (100% vs 50% P = 0.033), myalgia/arthralgia (71.4% vs 16.7%, P = 0.048) and decreased libido (57/1% vs 16.7%, P = 0.135). NPOS was recalled to be offered to five (38.5%) women, with acceptance by one BRCA2 carrier. NPOS was declined initially due to fear of procedure, surgical/anaesthetic risk, invasiveness and planned future pregnancies. If given the option, upfront oophorectomy was indicated in seven (53.8%) women due to inconveniences with monthly goserelin. CONCLUSION: Half of PMBC women indicated a preference to NPOS, but only a minority recollected NPOS being discussed. Inconvenience with monthly goserelin is the main driver toward a preference of favouring NPOS. Clarification from larger trials that research patients' decision process and preferences regarding ovarian suppression is needed to validate our findings.

Laparoscopic Fertility-preserving Treatment of a Pure Nongestational Choriocarcinoma of the Ovary: Case Report and Review of Current Literature.

This case report demonstrates the feasibility of laparoscopic and fertility-preserving approach in nongestational choriocarcinoma of the ovary (NGCO). Pure NGCO is a rare malignant condition. In the last decade, only 14 cases have been reported in the literature. The use of laparoscopy and fertility-preserving procedures in nonepithelial ovarian malignancies is extremely controversial. A 23-year-old woman underwent emergency laparoscopy due to acute abdominal pain associated with an 8-cm large adnexal mass. The initial procedure consisted only of a left oophoroplasty, and histology revealed a tumor of high malignant potential compatible with a primary NGCO. Approximately 3 weeks after initial surgery, she was submitted to a laparoscopic staging surgery, including left adnexectomy, omentectomy, peritoneal biopsies, and retroperitoneal lymphadenectomy. Final pathology confirmed an International Federation of Gynecology and Obstetrics stage IIB NGCO. Before initiation of adjuvant chemotherapy based on 3 courses of bleomycin, etoposide, and cisplatin, the patient received goserelin for ovarian suppression. Nine months after therapy, the patient presented no signs of recurrence and reassumed normal menstruation cycles with normal levels of gonadotropins and tumor markers. The current report brings new insights into the possibility of using use minimally invasive surgery and a combination of fertility-preserving methods for the treatment of NGCO.

Adjuvant endocrine therapy for early breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline.

BACKGROUND: Cancer Care Ontario's Program in Evidence-Based Care (pebc) recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question "What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?" The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and her2 (human epidermal growth factor receptor 2)-targeted therapy. METHODS: For the systematic review, the literature in the medline and embase databases was searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. RESULTS: Several hundred documents that met the inclusion criteria were retrieved. Meta-analyses from the Early Breast Cancer Trialists' Collaborative Group encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. SUMMARY: The results of the systematic review constitute a comprehensive compilation of high-level evidence, which was the basis for the 2014 pebc guideline on systemic therapy for early breast cancer. The review of the evidence for systemic endocrine therapy (adjuvant tamoxifen, aromatase inhibitors, and ovarian ablation and suppression) is presented here; the evidence for chemotherapy and her2-targeted treatment-and the final clinical practice recommendations-are presented separately in this supplement.