Surgical Oophorectomy Research Articles

Leiomioma Metastásico Benigno Pulmonar

Benign metastatic leiomyomatosis (BML) is a neoplastic smooth muscle disease where the lung is the most affected organ. So, we will detail the literature by presenting the following case of a patient who underwent surgical treatment at the pulmonary level resection of the lung lesion with subsequent pathologic confirmation by biopsy. The clinical presentation of benign metastatic leiomyomatosis can range from asymptomatic onset to rapid progression that leads to respiratory failure and death. The patient presented with pulmonary symptoms such as cough, dyspnea, or chest tightness, with a diagnostic image of a simple and contrasted thoracic CT scan showing pleural effusion. A surgical procedure was performed by thoracoscopy with evidence of a tumor-like lesion with a cystic component. Pleurectomy with decortication was performed, and it was decided to perform a non-anatomic segmental pulmonary lobectomy. The pathological anatomy revealed benign leiomyomas without atypia and mitotic activity. The patient has not yet taken a standard treatment for benign metastatic leiomyomatosis due to the hormone-sensitive characteristics of the BML and is currently in multidisciplinary follow-up. Treatments are based on hormonal manipulation along with surgical or medical oophorectomy.

Monitoring of estradiol levels in premenopausal women receiving adjuvant abemaciclib and ovarian function suppression.

Approximately 15% of women who receive ovarian function suppression (OFS) as adjuvant treatment for high-risk, localized hormone receptor-positive (HR+) breast cancer may have inadequate estradiol suppression which can require therapeutic modification when used in combination with an aromatase inhibitor (AI). We previously reported that abemaciclib may interfere with the estradiol Abbott Alinity chemiluminescent microparticle immunoassay (CMIA) commonly used to monitor estradiol levels and suggested liquid chromatography-mass spectrometry (LC-MS/MS) is preferred in this setting. The aim of this study was to determine discrepancies in estradiol levels using CMIA compared to LC-MS/MS and subsequent treatment changes in a larger patient population. We conducted a retrospective review of premenopausal women with early-stage HR+ breast cancer at our institution who received adjuvant OFS and abemaciclib with at least 1 CMIA estradiol level drawn during abemaciclib therapy from October 2021 to April 2023. Of the 22 women who met criteria for review, 20 (90.9%) had CMIA estradiol levels in the premenopausal range, of whom 9 also had estradiol measured by LC-MS/MS. All 9 women receiving OFS and abemaciclib with estradiol measurements by both methods had premenopausal range CMIA estradiol levels and postmenopausal range LC-MS/MS estradiol levels. Of the 20 patients with premenopausal estradiol levels by CMIA estradiol, treatment changes included increased OFS dosage or preparation (n = 7), change from AI to tamoxifen (n = 3), and surgical oophorectomy (n = 7). Our findings suggest the likely interference of abemaciclib with the Abbott Alinity immunoassay which may lead to unnecessary treatment changes. It is recommended that the LC-MS/MS assay be used when monitoring estradiol levels in patients receiving abemaciclib concurrently with OFS.

Breast Carcinoma with Isolated Orbital Metastasis –A Rare Clinical Entity

Breast cancer with isolated orbital metastasis is a rare clinical entity.We hereby present a rare case report of 35 year old premenopausal lady with known case of carcinoma breast right side (operated for right modified radical mastectomy in year 2017 with final histopathology of pT2N2M0, hormone receptor-positive and Her2-negative disease). She completed adjuvant 8 cycles of standard dose chemotherapy with 4 cycles of Cyclophosphamide, Adriamycin followed by 4 cycles of Paclitaxel followed by local Radiation therapy. She was initiated Tab. Tamoxifen 20 mg once daily and was continued same for 4 years when in July 2021, she complained of sudden decreased visual acuity and diplopia of right eye lasting from last 1 month. Ophthalmological examination confirmed the findings with decreased visual acuity of 6/36 of right eye while visual acuity of left eye was normal. CT scan of orbits revealed 28 × 18mm heterogeneous enhancing soft tissue mass in right orbital compartment,extrabulbar, occupying postero-superior quadrant inseparable from lateral rectus muscle with optic nerve effacement. PET-CT scan was performed which revealed no metastasis elsewhere in the body. She was offered surgical oophorectomy followed by switch to another hormonal therapy of aromatase inhibitors. She showed complete response to treatment and is now disease from last 2 years.

Ovarian Insufficiency: Clinical Spectrum and Management Challenges.

The term "ovarian insufficiency" describes the decline of ovarian function resulting in fertility loss and the marked decrease of ovarian steroid hormone production. From a clinical standpoint, ovarian insufficiency presents in three different settings. The first is natural menopause at midlife occurring at the average age of 51 years. The second arises after surgical oophorectomy owing to disease or elective cancer prophylaxis. Finally, primary or premature ovarian insufficiency is characterized by menopause occurring before age 40, often of undetermined etiology, but at times linked with genetic mutations, autoimmune syndromes, metabolic conditions, iatrogenic etiologies, and toxic exposures. Each clinical situation presents unique concerns and management challenges. The majority of women with intact ovaries who live to age 51 experience natural menopause, with early menopause <45 years. In the United States, surgical menopause with bilateral oophorectomy occurs in ∼600,000 women per year. The timing and specific clinical indication for oophorectomy alters management. Primary ovarian insufficiency occurs in 1% of women, although recent estimates suggest the prevalence may be increasing. Symptoms of ovarian insufficiency include hot flashes or vasomotor symptoms, mood disorders, sleep disruption, and vaginal/urinary symptoms. Health concerns include bone, cardiovascular, and cognitive health. Management of symptoms and preventive strategies varies depending upon the age, clinical situation, and specific health concerns of each individual. Treatment options for symptom relief include cognitive behavior therapy and hypnosis, nonhormonal prescription therapies, and hormone therapy. Tailoring the therapeutic approach over time in response to age, emerging medical issues, and patient desires constitutes individualized care.

Ovarian Suppression: Early Menopause, Late Effects.

Pre-menopausal women diagnosed with hormone receptor (HR) breast cancer are candidates for prolonged hypoestrogenism to improve cancer outcomes. However, the disease benefit eclipses the toxicities associated with ovarian function suppression (OFS), which are often under-reported. Increased risk of mortality from cardiovascular disease, bone disorders, and metabolic disorders is well reported in women with no history of cancer, after surgical oophorectomy or premature ovarian failure. Vasomotor symptoms, urogenital atrophy, weight gain, sexual dysfunction, cognitive decline, and sleep disturbances contribute to the increased non-compliance associated with OFS, especially in younger women. Balancing the toxicities of prolonged OFS with its benefits should be critically analyzed by providers when making recommendations for their patients. Supportive care to manage multi-system toxicities and to counteract the long-term impact on all-cause mortality should be emphasized by every cancer program. Future studies with OFS should incorporate patient outcomes and strategies for symptom management in addition to focusing on improving disease outcomes.

Suboptimal use of ovarian function suppression in very young women with early breast cancer: a real-world data study.

The incidence of breast cancer in young women (BCYW) has increased in recent decades. Malignant disease in this subset is characterized by its aggressiveness and poor prognosis. Ovarian function suppression (OFS) in these patients improves survival especially in hormone receptor-positive (HR +) cases. The Regan Composite Risk (RCR) is a prognostic tool to identify high-risk HR + BC candidates for OFS. Our study sought to characterize a Chilean cohort of early HR + BCYW assessing the use of OFS and its related prognosis and the utility of RCR in our patients. This was a retrospective population cohort study that included ≤ 35-year-old early HR + /human epidermal growth factor receptor 2 -negative (HER2-) BC patients treated between 2001 and 2021. Analysis included clinical-pathological characteristics, treatment strategies, and survival. Also, we evaluated the association between RCR and survival. A total of 143 patients were included into our study, representing 2.9% of all early BC cases in our registry. Median age was 31years old (range: 19-35). Most patients (93%) received endocrine therapy (ET). Of these, 18% received OFS. No survival differences were observed among treatment strategies. Median RCR score for patients treated with CT plus ET was significantly higher vs. ET alone (2.95 vs. 1.91; p = 0.0001). Conversely, patients treated with tamoxifen alone had significantly lower RCR scores vs. OFS (2.72 vs. 3.14; p = 0.04). Higher RCR scores were associated with poorer overall survival. Less than 20% of very young women with early HR + /HER2-BC in our cohort received OFS, in most cases, this involved surgical oophorectomy. RCR score was higher in patients that underwent CT and OFS and was associated with survival, regardless of treatment. We confirm the RCR score as a valuable prognostic tool to identify high-risk BC patients who could benefit from OFS.

Non-psychoactive Cannabidiol Prevents Osteoporosis in an Animal Model and Increases Cell Viability, Proliferation, and Osteogenic Gene Expression in Human Skeletal Stem and Progenitor Cells.

Cannabidiol (CBD), the non-psychoactive component of the Cannabis sativa plant, is marketed as a potential therapeutic agent and has been studied for its roles in reducing inflammation and managing neuropathic pain. Some studies have reported that CB1 and CB2 receptor activation can attenuate and reverse bone loss in experimental animal models. Despite this, little is known about the impact of CBD on fracture healing. We investigated the effects of CBD in vitro using human osteoprogenitor cells and in vivo via murine femur fracture and osteoporosis models. In vitro mesenchymal stem cells were treated with increasing concentrations of crystalized pharmaceutical grade CBD or vehicle solution. Cell viability and proliferation were significantly increased in cells treated with CBD compared to vehicle control. Osteocalcin expression was also significantly higher in the CBD-treated human stem cells compared to vehicle control. In vivo the effect of CBD on bone mineral density and fracture healing in mice was examined using a two-phase experimental approach. Fluoxetine was used for pharmacologic induction of osteoporosis and surgical oophorectomy (OVX) was used for hormonal induction of osteoporosis. X-ray and microCT analysis showed that CBD prevented both fluoxetine- and OVX-induced osteoporosis. We found that while OVX resulted in delayed bone healing in control mice, CBD-pretreated mice exhibited normal bone healing. Collectively these in vitro and in vivo findings suggest that CBD exerts cell-specific effects which can be exploited to enhance bone metabolism. These findings also indicate that CBD usage in an osteoporotic population may positively impact bone morphology, warranting further research.

Abstract P4-07-05: Real world data of adjuvant endocrine therapy for breast cancer in very young women. A Chilean 20-year experience

Abstract BACKGROUND: Breast cancer (BC) is the most common cancer diagnosed in premenopausal women with an increasing incidence for age 35 or less. Although proportionally less frequent, hormone receptor (HR)–positive BC still remains the main subtype for this group, but given tumor characteristics and suboptimal adjuvant endocrine therapy (ET), present inferior long-term outcomes when compared to HR-positive BC in older women. Both Tamoxifen and Exemestane Trial (TEXT) and Suppression of Ovarian Function Trial (SOFT) have helped to optimize ET strategies for premenopausal women, identifying which patients benefit from ovarian function suppression (OFS). In Chile, we have scarce data on very young BC patients and limited access to proper OFS treatment specially in our public health system. Thus we aim to characterize a cohort of very young women regarding treatment strategies and survival, plus as an exploratory analysis evaluate Regan Score in our cohort. METHODS We conducted a retrospective population-cohort study involving women under 36 years of age, with early HR-positive/human epidermal growth factor receptor 2 (HER2)–negative BC, treated both at a community hospital and at an academic private hospital between 2001 and 2021. We did a descriptive analysis including stage distribution and treatment strategies (chemotherapy (CT), ET of choice and OFS use). We evaluated prognosis for the entire population. Survival analysis was carried out using the Kaplan-Meier method. RESULTS A total of 143 patients were included. Median age at diagnosis was 33 (19 - 36); 15.4% percent of patients were diagnosed in stage I, 51.4% stage II and 30.1% stage III. Eighty six percent received CT, 35.0% neoadjuvant. Ninety three percent received endocrine adjuvant treatment: 81.2% TAM alone, 6.8% TAM/OFS and 10.5% IA/OFS. Regarding OFS strategies only 38.5% received gonadotropin-releasing hormone (GnRH) agonists while the rest were oophorectomized. Regan median composite score was 2.77 (2.61 - 2.93) for the entire cohort. Rising to 2.95 (2.79 - 3.11) for patients treated with CT plus ET compared to 1.91 (1.55 - 2.27) for those treated with ET exclusively (p=0.0001). Patients that received TAM alone had a median Regan Score of 2.72 (0.77-4) compared to 3.14 (2.07-4.0) for patients that had OFS added (p=0.04). With a median follow-up of 59 months, 5-year Disease Free Survival (DFS), Distant DFS and Overall Survival (OS) for the entire cohort were 63.5%, 66.9% and 88.7%, respectively. CONCLUSION. To our knowledge this is one of the largest cohorts considering very young women BC in Latinamerica. We confirm their elevated overall risk with markedly higher Regan scores compared to SOFT and TEXT populations for both CT and ET exclusively treated patients. Due to access difficulties very few patients received OFS and when used, surgical oophorectomy was the main strategy of choice, with all the potential long term consequences it conveys. Thus OFS use was restricted to very high risk women, meaning that a large group of only TAM users were undertreated according to nowadays standards. This could explain the elevated recurrence risk observed in our population when compared to other under 35 years of age cohorts. Table 1. Cohort characteristics Table 2. Regan risk score Citation Format: Ana Heredia, Benjamin Walbaum, Francisco Acevedo, Cesar Sánchez. Real world data of adjuvant endocrine therapy for breast cancer in very young women. A Chilean 20-year experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-05.

Abstract P1-02-03: Real World Treatment Patterns of Adjuvant Endocrine Therapy and Ovarian Suppression in Premenopausal HR+/HER2+ Breast Cancer

Abstract Background: Approximately 10% of breast cancers (BC) are hormone receptor positive (HR+) and HER2 positive (HER2+). Despite treatment advances in the modern era of HER2 targeted therapies for early-stage disease, there remains a risk for late relapses. However, the role of adjuvant endocrine therapy (ET) to reduce recurrence in this BC subtype is unclear. Oncologists employ clinical judgment given lack of consensus, resulting in differences in treatment patterns. The ideal endocrine agent including the role of adding ovarian suppression (OS) in premenopausal women is unknown. These patients are largely underrepresented in clinical trials such as the phase III SOFT and TEXT studies. Additionally, these trials were initiated prior to the widespread use of trastuzumab with chemotherapy, which is now standard of care for HER2+ disease. We aimed to describe real world patterns surrounding choice of adjuvant ET and clinicopathologic features which predicted treatment with OS in premenopausal women with HR+/HER2+ BC. Methods: We performed a multi-institutional retrospective analysis of premenopausal women with non-metastatic HR+/HER2+ BC in the American Society of Clinical Oncology CancerlinQ® Discovery database from January 2010 to May 2020. Electronic health record data was obtained from 74 participating academic and community oncology sites. We collected clinical data on women less than 50 years who received chemotherapy, anti-HER2 therapy (trastuzumab with or without pertuzumab), and ET. Adjuvant OS was defined as receipt of at least 6 months of goserelin or leuprolide or surgical bilateral oophorectomy. Demographics, clinical characteristics, and treatment history was collected. Patients were categorized into 1 of 4 groups based on type of adjuvant ET prescribed at treatment initiation: aromatase inhibitor (AI) + OS, OS, tamoxifen + OS, or tamoxifen. Multivariable logistic regression was conducted to assess the association between clinicopathologic features and OS use. Results: Out of 360,540 patients with invasive breast cancer in the database, 937 met inclusion criteria. Mean age was 41.7 (SD 5.9) years; 83% had stage 1 or 2 BC and 78% had node positive disease. The majority (n=818, 87%) were prescribed tamoxifen whereas only 4 (0.4%), 50 (5.3%), and 65 (6.9%) received OS, tamoxifen + OS, and AI + OS, respectively. Table 1 includes demographic and clinical characteristics of the cohort. No clinicopathologic features predicted OS use apart from age; patients ≥35 years were less likely to receive OS compared with those &amp;lt; 35 (p&amp;lt; 0.001) (table 2). Conclusion: To our knowledge, this is the first real world study evaluating OS treatment in HR+/HER2+ BC. The use of OS was uncommon; this suggests a perception of its limited benefit when added to HER2-targeted therapy. Most patients received tamoxifen as the ET of choice. Age was the only factor to predict OS treatment; high risk features including node positivity and higher stage was not associated with its use. This highlights the wide variability in real world practice surrounding the clinical indications for OS. Further investigation is warranted to characterize the utility of ET including addition of OS to prevent recurrence in premenopausal HR+/HER2+ BC. This will better inform a personalized approach to tailor therapy for optimal outcomes in this distinct BC subtype. Table 1. Demographic and clinical characteristics of study participants by endocrine therapy treatment group. Table 2. Multivariable logistic regression model of clinicopathologic characteristics to predict use of ovarian suppression. Citation Format: Jasmine S. Sukumar, Sagar Sardesai, Andy Ni, Nicole Williams, Bhuvaneswari Ramaswamy, Robert Wesolowski, Mathew A. Cherian, Daniel Stover, Margaret Gatti-Mays, Ashley C. Pariser, Preeti K. Sudheendra, Mridula A. George, maryam lustberg. Real World Treatment Patterns of Adjuvant Endocrine Therapy and Ovarian Suppression in Premenopausal HR+/HER2+ Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-02-03.

PRIMARY OVARIAN LEIOMYOMA- CASE REPORT OF A COMMON TUMOUR IN AN UNCOMMON LOCATION

Primary leiomyoma of the ovary is a rare tumour, accounting for about 0.5–1% of all the benign ovarian tumours. Approximately 70 cases have been reported in the literature [1,2]. As these tumours are usually very small in size, they may be missed during the routine evaluation of the surgical oophorectomy specimens [3,4,5]. Here, we report a case of primary ovarian leiomyoma which was diagnosed incidentally on histopathological examination.

Circulating miRNome of Trachemysscripta after elective gonadectomy under general anesthesia

Post-surgical management is an important issue in veterinary medicine, requiring biomarkers with high sensitivity and specificity for timely and effective treatment. Emerging evidence suggests that miRNAs are promising stress- and pain-related markers. The aims were to profile the circulating miRNA signature in plasma of turtles (Trachemysscripta) and point out potential candidate biomarkers to assess the status of the animal. The plasma of female turtles underwent surgical gonadectomy were collected 24 h pre-surgery, and 2.5 h and 36 h post-surgery. The expression of miRNAs was profiled by Next Generation Sequencing and the dysregulated miRNAs were validated using RT-qPCR. The diagnostic value of miRNAs was calculated by ROC curves. The results showed that 14 miRNAs were differentially expressed over time. RT-qPCR validation highlighted that 2-miR-499-3p and miR-203-5p-out of 8 miRNAs tested were effectively modulated. The Area Under the Curve (AUC) of miR-203-5p was fair (AUC 0.7934) in discriminating pre- and 36 h post-surgery samples and poor for other time points; the AUC of miR-499-3p was excellent (AUC 0.944) in discriminating pre-surgery and 2.5 h post-surgery samples, and fair in discriminating pre-surgery and 36 h post-surgery (AUC 0.7292) and 2.5 h and 36 h post-surgery (AUC 0.7569) samples. In conclusion, we demonstrated for the first time that miRNAs profile changes in plasma of turtles underwent surgical oophorectomy and identified miR-203-5p and miR-499-3p as potential candidate biomarkers to assess animals' status. Further studies are necessary to confirm their diagnostic value and to investigate functional and mechanistic networks to improve our understanding of the biological processes.

Trends in use of ovarian suppression (OS) for premenopausal patients with early-stage hormone positive breast cancer and Intermediate Risk (IR) Oncotype Recurrence Scores (RS) from 2006-2020: A retrospective database analysis.

e12522 Background: Oncotype RS is a 21-gene assay used to predict the risk of recurrence and benefit from chemotherapy in early-stage, hormone positive (HR+), node-negative breast cancer (BC). The TAILORx trial showed that many patients with RS&lt;25 can avoid chemotherapy and the small absolute benefit may be due to chemotherapy-induced menopause in premenopausal patients. The SOFT-TEXT trials found that premenopausal women have higher rates of freedom from recurrence and 8-year survival when receiving OS with endocrine therapy (ET). These studies suggest that premenopausal women with IR RS (16-25) benefit from aggressive ET with OS but trends in OS use have not been adequately studied. We predict that OS use has increased in premenopausal patients over time. Methods: We identified 87 premenopausal patients with early-stage, HR+ BC with IR Oncotype RS (16-25) who were treated with ET between 2006-2020 at our large NYC academic cancer center. The Cochran-Armitage test was used for trends in the proportions of patients receiving OS and chemotherapy over time. The log-rank test was used to compare distributions of recurrence rates between RS groups. Results: Median age was 46 years and median RS was 19. Overall, 23 (26%) patients received chemotherapy and 30 (34%) received OS (via leuprolide, goserelin or surgical oophorectomy) with ET. 55 (63%) received tamoxifen alone, 10 (11%) tamoxifen + OS, and 20 (23%) aromatase inhibitor (AI) + OS. Between 2006-2010, 2 (17%) patients received OS and 2 (17%) received chemotherapy compared to 9 (24%) and 12 (32%) between 2011-2015, and 19 (51%) and 9 (24%) between 2016-2020, respectively (Table). There was a significant increasing proportion of patients receiving OS; p=0.0064, but no significant trend in chemotherapy receipt; p=0.8910. There were 8 (9%) patients that recurred, with a borderline significant difference in secondary invasive breast event rates in patients receiving tamoxifen alone (8, 15%) compared to those on tamoxifen + OS or AI + OS (0, 0%), (p=0.0520). There were no significant differences in recurrence rates based on chemotherapy receipt (p=0.1868) or RS group 16-20 vs 21-25 (p= 0.1836). Conclusions: There has been a significant increase in the use of OS with ET in premenopausal women with IR RS in our study population. This study shows how the results of the SOFT-TEXT trial have been adapted into current practice. Future studies are needed to evaluate real-world recurrence rates with the use of increased OS and whether chemotherapy rates have decreased over time.[Table: see text]

Adjuvant Surgical Oophorectomy Efficacy According to Hormonally-Determined Menstrual Cycle Phase

Purpose: While there is now considered to be no significant outcome impact of the timing of breast surgery in the menstrual cycle of premenopausal women with breast cancer, the data with respect to adjuvant surgical oophorectomy in women with breast cancer have received limited exposition and attention. In a trial investigating the timing of surgical oophorectomy in women with metastatic disease, we observed a trend for poorer overall survival in women in women in prolonged follicular phases of the menstrual cycle, with low progesterone levels. Methods: The data from a previously reported adjuvant randomized clinical trial addressing the timing of surgical oophorectomy in the menstrual cycle have been examined in detail, presenting here new data from pre-planned secondary analyses. Multivariable Cox models were used.

By the Metrics Surgical Oophorectomy Plus Tamoxifen is the First Adjuvant Treatment Option for Premenopausal Women with Hormone Receptor Positive Breast Cancer

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Conservative treatment in non-tubal ectopic pregnancy and predictors of treatment failure

ObjectivesTo find possible predictive factors to predict the failure of conservative treatment of non-tubal ectopic pregnancy. For that purpose, we assessed the rate of failure, complications and need for additional interventions of the different primary treatment regimens in non-tubal ectopic pregnancies that occurred in our center. Study designRetrospective single-center study conducted at Hospital Clínic of Barcelona (Spain). Conservative treatment regimens included medical (systemic single or multiple dose methotrexate; ultrasound-guided intrasaccular injection of methotrexate or chloride potassium; surgical (oophorectomy in case of ovarian ectopic pregnancy, surgical curettage). The main outcome measures were success of primary treatment and the need for additional interventions. The secondary outcomes were success rate of conservative treatment, incidence of complications, days to discharge from the hospital, days until negative β-hCG, days until complete resolution of the process. Possible predictor factors for primary treatment failure were assessed. ResultsA total of 39 cases were included. Primary treatment was successful in 74 % (29/39). The rate of failure of primary treatment was higher in the group with presence of embryo heartbeat than in the group without, 46 % vs. 15 % respectively (p < 0.0001). Among the cases that required additional treatments, none of them required hysterectomy. Presence of embryo heartbeat significantly increased the likelihood of failure of the primary treatment (OR 4.71, 95 % CI 1.03–21.65, p < 0.05). Every doubling of the β-hCG levels increased the risk of treatment failure by 54 % (OR 1.54, 95 % CI 1.03–2.39, p < 0.05). ConclusionsConservative treatment is a safe option for treatment of non-tubal ectopic pregnancy. The presence of embryo heartbeat and β-hCG levels at diagnosis may be used as predictive factors of failure of conservative treatment.

Surgical oophorectomy or GnRH plus tamoxifen adjuvant therapy for breast cancer in low-risk premenopausal women: comparative benefits and risks

Background: While the combination of ovarian suppression or ablation treatment and tamoxifen or an aromatase inhibitor has been demonstrated to provide better outcomes as adjuvant therapies in premenopausal women with hormone receptor positive breast cancer, than treatment with tamoxifen alone, the details of applying these results in clinical practice, and the risks and benefits of the different ovarian treatments, particularly in women at lower risk for disease recurrence and death, have received limited attention. Methods: Details of clinical trials investigating combination hormonal adjuvant therapies, particularly with tamoxifen, were reviewed focusing on issues pertinent to assessment of risks and benefits in clinical practice. Results: Equivalent survival outcomes from surgical oophorectomy (SO) or GnRH agonist treatment plus tamoxifen, for which there are the most data at present, make the major decision issues for individual patients in choosing between these treatments: interest in future pregnancy, availability of data on secondary biological effects, capacity to adhere to a GnRH injection program for 5years, and ability to optimize dental hygiene (for taking bisphosphonate additional treatment). Other considerations applicable in individual patients include comparative secondary treatment effects, financial costs, and psychological impacts. Conclusion: If a patient with low-risk for recurrence breast cancer has interest in a future pregnancy, GnRH treatment is clearly appropriate. Otherwise, all major and minor risks of GnRH treatment are greater than those for SO treatment, when combined hormonal treatment with tamoxifen is taken.

Adjuvant Surgical Oophorectomy Plus Tamoxifen: New Efficacy and Secondary Effects Data

Recent publication of the 8-year update of the SOFT and TEXT trials indirectly calls attention to the leading role that surgical oophorectomy plus tamoxifen (SO+T) should now play in global breast cancer care. The here-reviewed breadth of its therapeutic effects, and its practicality, distinguish this treatment from GnRH plus tamoxifen treatment. Ovarian function suppression, whether by surgery or by GnRH treatment, in combination with tamoxifen, has been repeatedly-and now conclusively with the TEXT and SOFT results-- demonstrated to be more effective as adjuvant therapy than tamoxifen alone. The magnitude of this benefit should be greater absolutely in more commonly higher-risk cases seen in low- and middle-income countries. SO+T has additional benefits on rates of cardiovascular disease and lung and ovarian cancers, which significantly outweigh minor increases in endometrial cancers and thromboembolism. The bone loss toxicity profile of SO+T is unique and salutary: no loss of hip bone mineral density in the first two years and modest loss only in the first year in the lumbar spine. In contrast, multiple clinical issues compromise the efficacy in clinical practice, safety and practicality of GnRH + tamoxifen treatment, and long-term effects on cardiovascular events and rates of other cancers are unknown. In achieving potential population benefits, surgical oophorectomy plus tamoxifen is an optimal therapy---the surgery can be obtained by the majority of global patients with very low complication rates, tamoxifen is inexpensive, and the drop out from any hormonal treatment is reduced. Key words: Adjuvant therapy;Surgical oophorectomy;Tamoxifen; Secondary effects;

SUN-481 A Coexisting Primary Papillary Thyroid Carcinoma in a Case of Malignant Struma Ovarii with Follicular Thyroid Carcinoma: 2 Types of Thyroid Cancer in the Same Patient

Introduction: Struma ovarii is a rare monodermal variant of ovarian teratoma diagnosed when thyroid tissue is more than 50% of the overall tissue. It represents only 1% of all ovarian tumors. The vast majority of struma ovarii are benign (95%); however, malignant tumors have been reported in a small percentage of cases. The most common type is papillary carcinoma(PTC), followed by typical follicular carcinoma found in the pathology after surgical oophorectomy. We report a case of malignant struma ovarii with follicular carcinoma in the setting of additional micro PTC found after total thyroidectomy. Case report: A 48-year-old female presented with right-sided pelvic pain and a mobile pelvic mass. Pelvic MRI showed noted a large complex solid mass with cystic components in the right adnexa. It measured 7.7 x 8.4 x 6.7 cm. Subsequently, the patient underwent a robotic hysterectomy, bilateral salpingo-oophorectomy (TAHBSO), bilateral pelvic and para-aortic lymph node sampling, omentectomy and resection of nodules. Final pathology noted an ovary with struma ovarii with well-differentiated follicular carcinoma, peritoneal nodules containing thyroid tissue and benign lymph nodes. Subsequently, iodine 123 SPECT CT showed physiologic uptake in the thyroid with increased uptake in the pelvis, right perirectal region indicating residual thyroid tissue. The patient underwent total thyroidectomy with radioactive ablation with I131 (154.7 mCi). Pathology detected incidental 0.5mm micro PTC and it was classified as staged pT1aN. 6 months postoperatively, thyroglobulin (Tg) and Tg antibodies were undetectable with no abnormalities found on repeat whole-body scans. The patient has been following up with no new issues for the past 5 years indicating a good prognosis with low risk of recurrence. Discussion and Conclusion: In the literature, Struma ovarii containing thyroid-type carcinoma and papillary or follicular thyroid carcinoma metastasizing to the ovary has been documented. The standard treatment of a patient with malignant struma ovarii is TAHBSO and complete surgical staging, including peritoneal washings for cytology, pelvic and para-aortic lymph node sampling, and omentectomy. In cases with the residual malignant disease after surgery, total thyroidectomy and radioactive ablation are recommended. Our case is a unique case given the presence of 2 different thyroid carcinoma in the same patient. In addition, our patient had multiple risk factors for recurrence including large lesions>4 cm, extra ovarian extension, and the coexisting synchronous primary thyroid cancer, however, she had a good prognosis with no recurrence during the 5 years follow up period.

Abstract P5-06-11: Serum thymidine kinase-1 activity (TKa) as a prognostic marker in premenopausal women with hormone receptor positive (HR+) operable breast cancer (BC)

Abstract Introduction: Thymidine kinase is an established marker of cancer cell proliferation and its activity can be measured in blood. We and others have recently shown that baseline and dynamic evaluation of circulating thymidine kinase activity (TKa) during treatment gives prognostic and predictive information in patients with HR+, HER2-negative metastatic BC treated with endocrine therapy alone, as well as in the setting of CDK4/6 inhibition. However, there is limited data regarding the role of TKa as a prognostic biomarker in operable BC. Here we present a retrospective analysis of TKa in serum samples collected in a cohort of premenopausal women with operable BC enrolled in a phase III adjuvant multicenter clinical trial (NCT00201851). Materials and methods: Serum samples were available for 644 (87%) of participants prospectively enrolled in a randomized trial between 2003 and 2009 in South East Asia. All women were premenopausal, had stage II-IIIB HR+ operable BC and uniformly received bilateral surgical oophorectomy concurrent with mastectomy followed by tamoxifen alone for five years. Patients did not receive chemotherapy or targeted therapy pre- or post-operatively. Participants were randomized in the study according to the timing of surgery with respect to the phase of the menstrual cycle. Serum samples were collected preoperatively on the day of surgery. Serum TKa was measured using the ELISA-based DiviTum™ assay (Biovica, Sweden). TKa analysis was performed at a central laboratory, blind to clinical data. Baseline TKa values were correlated with clinico-pathological characteristics and clinical outcome. Clinical outcome was estimated using the Kaplan-Meier method. Results: The majority of patients had both estrogen and progesterone receptor positive tumors (94% and 92% respectively), 65% were HER2 negative (18% positive; 17% unknown). Most had pT2 or pT3 disease (60% and 27% respectively), and more than half were node-positive (pN0 42%, pN1 27%, pN2 19%, pN3 11%, pNx 1%). The overall median TKa value was 65.4 Du/L. At five years, patients with a baseline TKa value below the median had a disease-free survival (DFS) rate of 75% versus 61% in those with a baseline over the median (HR 1.82, 95% CI 1.37-2.4, p&amp;lt;0.001). Similar results were observed when women with HER2+ disease were excluded from analysis (HR 1.71, 95% CI 1.21-2.42, p=0.0025). Further prognostic precision was achieved when TKa values were divided by quartiles, with a 5 year DFS rate of 81%, 69%, 63% and 58% observed in the 1st, 2nd, 3rd and 4th quartiles respectively. After adjusting for major prognostic factors and randomization arm, TKa remained an independent marker. Conclusions: This study shows pre-operative TKa measured in serum is a strong prognostic marker in a large cohort of women with HR+ operable BC uniformly treated within a clinical trial. The notable rate of recurrence seen within this cohort of patients derived from non-high income countries may be mainly attributed to the relative degree of disease burden at diagnosis. TKa may be seen as a potential circulating marker of proliferation akin to tumor Ki67, which may provide useful prognostic information to guide adjuvant therapies. Citation Format: Luca Malorni, Ilenia Migliaccio, Chiara Biagioni, Lorenzo Rossi, Irene De Santo, Richard L Love, Amelia McCartney, Mattias Bergqvist, Martina Bonechi, Francesca De Luca, Francesca Galardi, Matteo Benelli, Dario Romagnoli, Emanuela Risi, Laura Biganzoli, Adriano Laudico, Nguyen Van Dinh, Angelo Di Leo. Serum thymidine kinase-1 activity (TKa) as a prognostic marker in premenopausal women with hormone receptor positive (HR+) operable breast cancer (BC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-11.

Controversies Regarding Ovarian Suppression and Infertility in Early Stage Breast Cancer.

A common side effect of chemotherapy in breast cancer is early menopause in premenopausal patients, which is mainly a result of an indirect form of ovarian ablation, and is associated with substantial impairment of quality of life. Suppressing the production of ovarian estrogen has been shown to reduce the recurrence of hormone receptor-positive early breast cancer in premenopausal women, but whether it has an added advantage over tamoxifen is being discussed. Types of permanent ablation of the ovarian function include surgical oophorectomy and radiation-induced ovarian failure. Both are associated with similar response rates in hormone receptor-positive metastatic breast cancer. Medical castration with luteinizing hormone-releasing hormone analogs (LHRHa) has the benefit of being a reversible approach. Another advantage that premenopausal patients who wish to reduce the risk of developing premature ovarian insufficiency induced by chemotherapy may be offered LHRHa irrespective of whether they desire pregnancy and their age at diagnosis. This also helps reduce the risk of menopausal signs and symptoms as well as the loss of bone density in the long-term, which are primary concerns for women. This is of utmost importance to premenopausal women who do not want to conceive after treatment or are not candidates for fertility preservation strategies because of age. It should be emphasized that for women who are interested in fertility preservation, gamete cryopreservation remains the first option, and LHRHa is not an alternative. During chemotherapy, however, temporary ovarian suppression with LHRHa may be given to women who either have no access to a fertility clinic or who have declined chemotherapy or have contraindications.