Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Letrozole

Triptorelin Pamoate

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

2.5 mg letrozole every day for six months

2.5 mg letrozole daily along with a GnRH analogue for ovarian suppression, which was administered as an intramuscular injection of 3.75 mg triptorelin every 28 days for 6 months.

Letrozole 2.5Mg Tablet

GnRH analogue

The study aimed to compare the duration to complete or partial response (CR/PR) and the overall response rates (ORR) after six months of neoadjuvant endocrine therapy between pre-menopausal group and post-menopausal group with highly endocrine responsive operable mammary carcinoma.

Estrogen receptor (ER) positive constitutes about 75% of all breast cancer(BC). Neoadjuvant endocrine therapy(NET) plays an important part in primary therapy of the hormone receptor (HR) -positive and HER2 -negative breast cancer. Recent studies revealed that the third-generation aromatase inhibitors (AIs) have superior ORR than tamoxifen in the HR-positive BC post-menopausal patients. The Z1031 trial showed that Letrozole obtained better ORR than the other two AIs anastrozole and exemestane after 16-18 weeks NET, although without any statistically significance.

In spite of these findings, the optimal duration of NET has not been fully elaborated, Although prolonged treatment might further reduce the tumor size. Further clinical benefits were achieved when the period of treatment of neoadjuvant letrozole prolonged more than three to four months. The 2015 St. Gallen International Consensus Conference recommended continuing neoadjuvant therapy in highly hormone-sensitive breast cancer for a minimum of 4-8 months. However, most studies aim to identify the excellent efficacy of the AIs compared with other drugs but not the duration of NET therapy. Antonio et al. suggest that the time to maximum clinical efficacy may be the optimal period of treatment for the patients; And the median time to maximum efficacy was 4.2 months (95% CI, 4.0-4.5). The present study evaluated the time to CR/PR and the ORR after 6 months of NET.

Previous clinical studies investigating NET mainly focused on post-menopausal women, data on pre-menopausal women is still relatively lacking due to the widely perception that more benefit may be achieved from neoadjuvant chemotherapy (NCT) among younger patients. The result of Z1031 trial showed superiority of neoadjuvant of AIs and promoted wider application of AIs as NET in the HR-positive post-menopausal women, and the clinical response rate (CRR) of letrozole was 74.8% after 16-18 weeks of treatment. The combination of AIs and GnRH analogue may be alternative for selected pre-menopausal patients. The STAGE trial showed the overall response rates of anastrozole plus goserelin in pre-menopausal patients was 70.4% after 6 months of NET. However, studies comparing the ORR and optimal duration of NET between pre-menopausal and post-menopausal patients were rare.

The purpose of the our research was to compare the duration to CR/PR and the ORR after 6 months of NET between pre-menopausal and post-menopausal women with highly endocrine responsive operable BC.

Neoadjuvant Endocrine Therapy in Breast Cancer

Letrozole as Neoadjuvant Treatment in Postmenopausal and Premenopausal Patients With Highly Endocrine Responsive Operable Breast Cancer

Guangdong Provincial People's Hospital

Leiomyoma

Myofibroma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Connective Tissue Diseases

Leuprolide

Imidacloprid

Ulipristal acetate

Antineoplastic Agents, Hormonal

Contraceptive Agents

Contraceptive Agents, Hormonal

Contraceptive Agents, Female

women will be treated with an oral dose of ulipristal acetate 5 mg/day for 3 months

Women will be treated with an intramuscular (IM) injection of leuprolide acetate 11.25 mg in the luteal phase

5 mg/day will be administered starting from day 1 of the cycle and up to three months later

ulipristal acetate

One dose of 11.25 GnRH analogue depot will be administered in the luteal phase of the menstrual cycle (days 21-24)

Leuprolide acetate

Fulvio Zullo, MD,PhD

Roberta Venturella, MD

Fulvio Zullo

Roberta Venturella

Cellular leiomyomas (CLs) are described as leiomyomas that are significantly more cellular than the surrounding myometrium, often with crowding and overlapping of nuclei. they often are soft and appear more tan or yellow and less circumscribed than the usual leiomyomas. Pre-operatively CLs can be recognized at ultrasound evaluation because they appear as hypoechoic uterine lesions. patients with hypoechoic myoma have a significantly longer surgery time after treatment with a gonadotropin-releasing hormone (GnRH) analog probably related to degenerative changes induced by this treatment. Hypoechoic CLs should be more responsive to ulipristal acetate treatment than common leiomyomas. The antiproliferative ulipristal effect, moreover, induces a condition of apoptotic necrosis that, compared to GnRH-a myxoid necrosis, probably allows an easier surgical enucleation of the tumor.

Rationale why study should be conducted: Leiomyomas are the most common benign neoplasm in women; it has been estimated that these tumors occur in at least 25% of all women, which is probably an underestimation, because this figure is based on a select population. They are histologically composed by smooth muscle cells with bland, uniform, cigar-shaped nuclei that are arranged in interlacing bundles, showing little or no mitotic activity. Cellular leiomyomas (CLs) are described as leiomyomas that are significantly more cellular than the surrounding myometrium, often with crowding and overlapping of nuclei.

The presenting symptoms do not differ from those of patients with typical leiomyomas. On gross examination, CLs are more often soft and appear more tan or yellow and less circumscribed than the usual leiomyomas.

Pre-operatively, anyway, CLs can be recognized at ultrasound evaluation because they appear as hypoechoic uterine lesions. It has been demonstrated that patients with hypoechoic myoma have a significantly longer surgery time after treatment with a GnRH analog than for the rest of the pretreated fibroids or the untreated patients with hypoechoic myomas. Considering the predominant relevance of the traction maneuvers in laparoscopic myomectomy, the difficulty in adequately grasping the tumor is the key element in the longer operative time. The greater softening of the fibroid tissue is probably related to degenerative changes induced by the GnRH-analog pretreatment, particularly in those fibroids without an adequate fibrous "skeleton" and thus with the appearance as hypoechoic at the admission ultrasonography. From a pathologic point of view, these fibroids, when pretreated, showed a predominance of areas of coagulative necrosis and mixoid degeneration, causing longer operative time and showing unequivocally the negative effect of preoperative GnRH analog treatment for these kinds of uterine fibroids.

At the same time, hypoechoic CLs should be more responsive to ulipristal acetate treatment than common leiomyomas, given its antiproliferative activity in cultured leiomyoma cells.

The antiproliferative ulipristal effect, moreover, induces a condition of apoptotic necrosis that, compared to GnRH-a myxoid necrosis, probably allows an easier surgical enucleation of the tumor.

Ulipristal Acetate for the Preoperative Management of Hypoechoic Cellular Leiomyomas

Advantages of Ulipristal Acetate for the Preoperative Treatment of Hypoechoic Cellular Leiomyomas

To evaluate the difference in terms of operative times in patients with hypoechoic CLs submitted to laparoscopic myomectomy and preoperatively treated by ulipristal acetate or GnRh-a .

To compare surgical feasibility (VAS) in patients treated with Ulipristal Acetate and GnRH-a.

To compare blood loss (delta HB) in patients treated with Ulipristal Acetate and GnRH-a.

This is a composite outcome aimed to compare pathological myoma characteristics (cellularity, necrosis, fibrosis) in patients treated with Ulipristal Acetate and GnRH-a.

University Magna Graecia

Full professor

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Nervous System Diseases

Pain

Pelvic Pain

Endometriosis

Adenomyosis

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neurologic Manifestations

Uterine Diseases

Patients with uterine myoma, endometriosis, fibromatous uterus, chronic pelvic pain in list for surgery are usually pharmacologically treated by administration of GnRHa, 11.25 mg at 21° day of the menstrual cycle and repeated after 3 months to reduce pain symptoms, menstrual blood loss, uterine or fibroids vascularization and size, during the months spent on surgery waiting list.

Patients enrolled will be subjected to valuation of ovarian reserve: specifically, serum levels of AMH and antral follicle count (AFC) between 1 and 4 days of the menstrual cycle will be measured at study entry and at 1, 3 and 6 months after the administration of the first vial of GnRH-a

Patients with uterine myoma, endometriosis, fibromatous uterus, chronic pelvic pain in list for laparoscopic surgery or laparotomy are usually pharmacologically treated by administration of GnRHa, 11.25 mg at 21° day of the menstrual cycle and repeated after 3 months. This treatment is part of our preoperative routine in order to reduce pain symptoms, menstrual blood loss, uterine or fibroids vascularization and size, during the months spent on surgery waiting list.

Patients who will satisfy inclusion and exclusion criteria will be enrolled in this study protocol and will be subjected to valuation of ovarian reserve: specifically, serum levels of AMH and antral follicle count (AFC) between first and fourth days of the menstrual cycle will be measured.

To evaluate the variation of AMH levels in women undergoing treatment with GnRHa, and to assess whether this variation correlates with changes in the antral and pre-antral follicle ultrasonographic count (AFC).

The anti Mullerian hormone (AMH) is a glycoprotein produced by granulosa cells of antral and preantral ovarian follicles.

Several studies have shown that the AMH levels provide a reliable indication of the size of the growing follicles pool (1). AMH is now commonly used as a biomarker for improving the ovarian reserve in women of reproductive age because it is related with outcomes of assisted reproduction cycles, chances of pregnancy and distance from menopause (2-4).

For several years GnRH agonists have been used for the purpose of preserving fertility in the course of chemotherapy in young women with cancer (5). Their effectiveness, however, isn't 100% and there is the need to monitor the ovarian reserve in the course of treatment in these young women. With the administration of GnRHa, the FSH levels (the most used hormone for improve the ovarian reserve, although it is less reliable and less manageable because of its intra-cyclic variations) cannot be used to measure the residual ovarian function due to the physiological reduction of gonadotropins induced by the treatment. AMH levels, conversely, are relatively stable both during the menstrual cycle (6) and during administration of the contraceptive pill (7,8), suggesting the gonadotrophin independence of this molecule. AMH could therefore be a useful biomarker of ovarian reserve in the course of GnRHa treatment.

The use of GnRHa for fertility preservation during chemotherapy is controversial because of inconclusive outcome data on fertility (9) and because the mechanism by which GnRHa may act to preserve fertility is unknown. The major function of GnRHa is to suppress the production of pituitary gonadotrophins, acting indirectly on the ovarian follicles, not exposing growing follicles to the toxicity of chemotherapy and thus protecting the future ovarian function.

Determine the effect of GnRHa on AMH serum level is an essential step to determine both the effectiveness of the treatment in terms of preservation of fertility and the reliability of this marker for ovarian reserve in cancer patients treated with GnRHa. Up to now, the published studies have shown extremely contrasting data. Considered that GnRHa is largely used in non-oncological patients for preoperative pharmacological preparation in various benign gynecological conditions, it is possible to exploit the high number of patients with these characteristics for the non-invasive assessment of analogue effect on the AMH levels.

AMH Levels Change During Treatment With GnRh Agonist

AMH Levels Change During Treatment With GnRh Agonist: A Prospective Observational Study.

Full Professor Obstetric Gynecology

Shusen Wang

Kuikui Jiang

Shusen Wang, doctor

Breast cancer is one of the most common malignant tumor in women. About 60% of breast cancer patients are still in premenopausal status at the time of diagnosis in China. It is a multicenter prospective observational study. We will collect basic information, medical history, chemotherapy-related adverse reactions, and the results of hormone, blood lipid, and bone density test before, during and after adjuvant or neoadjuvant chemotherapy. The aim of the study is to evaluate the effect of chemotherapy on ovarian function and fertility and the protective effect of GnRHa. In addition, the collected information of the subjects are analyzed to provide suggestions for the relevant prevention strategy.

Breast cancer is one of the most common malignant tumor in women, and it occurs at a younger median age in Chinese women than in western white women. About 60% of breast cancer patients are still in premenopausal status at the time of diagnosis in China. Chemotherapy is one of the important treatments for breast cancer, but it brings a series of adverse effects. It is a multicenter prospective observational study. The premenopausal breast cancer women patients who are planning adjuvant or neoadjuvant chemotherapy are enrolled in the study after signing the informed consent form and passing the screening. We collect their basic information, medical history, chemotherapy-related adverse reactions, and the results of hormone, blood lipid, and bone density test before, during and after chemotherapy. The aim of the study is to evaluate the effect of adjuvant or neoadjuvant chemotherapy on ovarian function and fertility and the protective effect of GnRHa by investigating the menopausal symptoms, pregnancy, menstruation condition, hormone levels, blood lipid, bone density, and the usage of GnRHa in the premenopausal women with breast cancer. In addition, the collected information of the subjects are analyzed to provide suggestions for the relevant prevention strategy.

A Prospective Observational Study About Adjuvant or Neoadjuvant Chemotherapy Related Adverse Effects in Premenopausal Breast Cancer Patients

A Prospective Observational Study About Adjuvant or Neoadjuvant Chemotherapy Related Adverse Effects in Premenopausal Women With Breast Cancer

The number of patients reporting pregnancy and attempting pregnancy

Amenorrhea for 6 months and postmenopausal FSH levels at 24 months (amenorrhea and postmenopausal hormone levels

Sun Yat-sen University

Professor

Womens will be treated with 5 mg/day of oral ulipristal acetate for 3 months

women will be treated with 1 IM injection of leuprolide acetate 11,25 mg in in the luteal phase

The uterine leiomyoma is the most common female benign disease. Submucosal fibroid are about 10%, they distort the endometrial cavity causing heavy and/or irregular bleeding (AUB) and infertility. Hysteroscopic removal of submucosal myomas improves this conditions. GnRH analogues are commonly used before hysteroscopic myomectomy to make surgery easier and safer, but they are expensive, have potential side effects and lack a robust evidence base to support this practice. Ulipristal acetate treatment was able and faster to control in 90% of cases uterine bleeding associated with fibroids than GnRH agonists. UPA significantly improved quality of life and pain reduction.

The uterine leiomyoma is the most common benign tumor of the female genital tract. The myomas are usually clinically apparent in 25% of patients. Submucosal fibroid are about 10% of all uterine myoma; they distort the endometrial cavity causing heavy and/or irregular bleeding (AUB) and infertility. According to the degree of myometrial penetration, the European Society for Gynaecological Endoscopy (ESGE) classified submucosal myomas in Type 0 (totally intracavitary fibroids), Type I (\<50% myometral penetration), or Type II (\>50% myometral penetration).

Hysteroscopic removal of submucosal myomas improves menorrhagia and AUB. GnRH analogues are commonly used before hysteroscopic myomectomy to make surgery easier and safer, but they are expensive, have potential side effects and lack a robust evidence base to support this practice. A recent meta-analysis of data demonstrated that symptomatic relief in patients undergoing surgery was similar either following pre-operative GnRH-a administration or without GnRH-a administration, mainly due to the persistence of abnormal bleeding due to the protrusion of the myoma into the uterine cavity.

In recent studies, Ulipristal acetate treatment was able to control uterine bleeding associated with fibroids in more than 90% of cases. Moreover, it controlled bleeding faster than GnRH agonists, with median times to amenorrhea of 5-7 days in patients receiving UPA compared to 21 days in patients receiving a GnRH agonist. It was demonstrated that UPA significantly improved also quality of life. Pain, as measured by the visual analogue scale, showed a degree of relief similar to that achieved for postoperative pain with narcotic and non-narcotic analgesics. This pain reduction is related to the high amenorrhea rate during treatment (severe bleeding being responsible for uterine contractions and prostaglandin secretion). No sub-analysis have been conducted on submucosal fibroids but, according to our experience, this subgroup of myomas may be the one who most benefits from the administration of UPA.

Ulipristal Acetate Versus GnRH Analogue Treatment Before Hysteroscopic Resection of Uterine Leiomyoma

To compare the proportion of controlled uterine bleeding in patients with submucous myoma preoperatively treated by ulipristal acetate or by GnRh-a

Surgeon experience about the hysteroscopy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Endocrine Therapy in Breast Cancer	NCT03397537	Highly Endocrin...	Letrozole 2.5Mg... GnRH analogue	18 Years -	Guangdong Provincial People's Hospital
Ulipristal Acetate for the Preoperative Management of Hypoechoic Cellular Leiomyomas	NCT02361905	Fibroid	ulipristal acet... Leuprolide acet...	18 Years - 55 Years	University Magna Graecia
AMH Levels Change During Treatment With GnRh Agonist	NCT02086279	Uterine Fibroid... Endometriosis Endometriosis o... Pelvic Pain	GnRH analogue	18 Years - 45 Years	University Magna Graecia
AMH Levels Change During Treatment With GnRh Agonist	NCT02086279	Uterine Fibroid... Endometriosis Endometriosis o... Pelvic Pain	GnRH analogue	18 Years - 45 Years	University Magna Graecia
A Prospective Observational Study About Adjuvant or Neoadjuvant Chemotherapy Related Adverse Effects in Premenopausal Breast Cancer Patients	NCT03543059	Breast Cancer	GnRH analogue	18 Years -	Sun Yat-sen University
Neoadjuvant Endocrine Therapy in Breast Cancer	NCT03397537	Highly Endocrin...	Letrozole 2.5Mg... GnRH analogue	18 Years -	Guangdong Provincial People's Hospital
Ulipristal Acetate Versus GnRH Analogue Treatment Before Hysteroscopic Resection of Uterine Leiomyoma	NCT02361879	Fibroid	ulipristal acet... Leuprolide acet...	18 Years - 55 Years	University Magna Graecia

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