Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Carcinoma

Recurrence

Hyperplasia

Carcinoma, Intraductal, Noninfiltrating

Neoplasm Recurrence, Local

Disease Attributes

Breast Diseases

Skin Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Carcinoma in Situ

Breast Carcinoma In Situ

Neoplastic Processes

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Anticoagulants

Other Dietary Supplements

Tamoxifen

Citric Acid

Sodium Citrate

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Citrate

tamoxifen at daily dose of 5 mg for a total treatment time of 3 years

placebo at daily dose of 5 mg for a total treatment time of 3 years

placebo

Andrea DeCensi, MD

The aim of the study is to evaluate whether tamoxifen at a low dose of 5mg/d reduces in the long term the incidence of invasive breast cancer and ductal carcinoma in situ, DCIS (DIN 1c, 2, 3) of the breast, in woman operated for lobular intraepithelial neoplasia (LIN1, 2 and 3) or ER-positive ductal intraepithelial neoplasia (DIN 1b, DIN2, DIN3, 1a excluded) of the breast.

To improve the risk-benefit ratio, the use of lower doses of the drug has been proposed.

Biomarker trials revealed that 5 mg/d was noninferior to 20 mg/d in inhibiting proliferation of breast cancer and normal endometrial tissue.

By contrast, the risk of endometrial cancer si dose-dependent, and the dose reduction can lead a substantial decrease. Morover a dose of 5 mg/day is associated with an overall decrease of the estrogenic activity of tamoxifen on insulin like growth factor (IGF-I), sex hormone-binding globulin (SHBG) and antithrombin-III, with a decrease of venous thromboembolic events. Moreover, tamoxifen exhibits a high tissue distribution, so that a dose of 5 mg/day attains at the breast tissue level a concentration 10 times higher than that needed to inhibit cell growth in vitro.

A prospective cohort study also showed that 10 mg on alternate days halves recurrence of DCIS in postmenopausal women.

It has been shown that the treatment of dysplasia or pre-cancer drives the reduction of the invasive neoplasms onset. This is a chemoprevention trial designed to validatate the low-dose Tamoxifen in women with diseases at high evolutionary risk. The demonstration of efficacy and safety of such a treatment for the prevention of the invasive breast cancer would lead improvements in term of survival and quality of life for the patients at increased risk.

Italian, multicenter, phase III trial: controlled, parallel group comparision, randomized (1:1) duble blind, tamoxifen 5 mg/d versus placebo administered for 3 years. A total of 500 women 75 years of age or younger with newly diagnosed non-invasive breast cancer have been included in the study. The long-term study implies a minimum 10 year follow up after treatment completion.

Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up

Randomized Placebo-controlled Phase III Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up

Authors are open to share data based on a request for collaboration that includes a data analysis plan.

Please send an e-mail to both: andrea.decensi@galliera.it; mpuntoni@ao.pr.it

Number of neoplastic events, i.e., invasive breast cancer or ductal carcinoma in situ of the breast from the start of treatment up to at least 16 years from treatment initiation.

Number of other non-invasive breast disorders (LCIS, atypical ductal or lobular hyperplasia), endometrial cancer, ovarian cancer, thromboembolic events; bone fractures, cardiovascular and thromboembolic events, clinically manifested cataracts and melanoma; change of mammographic density from the start of treatment up to at least 16 years from treatment initiation.

Blood concentrations of metabolites including circulating IGF-I,IGFBP-3, SHBG, hormones (testosterone, estradiol, SHBG, CRP), tamoxifen metabolites (4OH tamoxifen and endoxifen).

Esploratory analisis of some SNPS of the cytochrome P450 genes involved in tamoxifen metabolism such as CYP2D6.

Associazione Italiana per la Ricerca sul Cancro

European Institute of Oncology

Andrea DeCensi

Medical Oncology Director

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Hypoglycemic Agents

Reproductive Control Agents

Metformin

Progesterone

Medroxyprogesterone Acetate

Medroxyprogesterone

Patients with BMI≥25kg/m2 in the experimental group are treated with medroxyprogesterone acetate (MPA) 0.25g/d plus metformin and are followed-up of baseline data, hormone levels,

Patients with BMI≥25kg/m2 in the none intervention group are treated with MPA 0.25g/d alone and are followed-up of baseline data, hormone levels, and endometrial pathology every 3 months until 12 months.

Jianliu Wang, Professor

Rong Zhou, Professor

The purpose of this study is to investigate the effect of Fertility-sparing Therapy of Early Endometrial Cancer.

This is a prospective, multi center, open, randomized, controlled clinical trial. All endometrial cancer (EC) or atypical hyperplasia (AH) patients who met the fertility-sparing indications in the hospitals involved in this study were recruited. Then the investigators conducted assessment, treatment and follow up according to the standard procedure. General information, therapeutic regimen, side effects, oncological and pregnant results were collected for risk factors analysis.

Effect of Fertility-sparing Therapy of Early Endometrial Cancer

Pathology shows atypical hyperplasia or carcinoma again after complete response.

Histologically shows absence of pathological hyperplasia or carcinoma.

Pregnancy test shows pregnancy after complete response.

Peking University First Hospital

Peking University Third Hospital

Tianjin Medical University General Hospital

Maternal and Child Health Hospital of Hubei Province

First Affiliated Hospital, Sun Yat-Sen University

Qilu Hospital of Shandong University

Peking University People's Hospital

Weight Loss

Body Weight

Body Weight Changes

Anti-Obesity Agents

Progestins

Levonorgestrel

Tirzepatide

Incretins

Tirzepatide injection, starting dose is 2.5mg injected subcutaneously once weekly. After 4 weeks, dose should be increased to 5mg once weekly. The dose then can be increased in 2.5mg increments after no less than 4 weeks on current dose to maximum dose of 15mg once weekly.

Mounjaro

Levonorgestrel-releasing Intrauterine System (52mg) to deliver up to 20 mcg levonorgestrel per day

Mirena

Vanessa Ballin

Rachel Soyoun Kim, MD

Sarah E Ferguson, MD

The incidence of endometrial cancer is increasing at an alarming rate. This trend parallels the rising rate of obesity, the most significant risk factor for endometrial cancer. Young women with obesity and endometrial cancer or atypical hyperplasia who want to maintain their fertility are treated with progestin therapy, such as progestin intra-uterine device (pIUD), which is associated with a mediocre response rate and high recurrence rate, and does not address the underlying cause, obesity. Therefore, the investigators want to assess whether the addition of a weight-loss drug to pIUD will improve their oncologic, reproductive and metabolic outcomes.

The research aims to answer the question: "Does the addition of Glucagon-like Peptide-1 (GLP-1) agonist to standard progestin treatment lead to a higher complete response rate compared to historical response rates using progestin alone in young patients with endometrial cancer/atypical hyperplasia who wish to preserve their fertility?".

This is a multicentre single arm, historically controlled, open-label phase 2 study to assess the safety and efficacy of the combination of semaglutide (GLP-1) and pIUD.

This is a prospective, randomized, open label, multicentre, phase II, non-comparative study to determine the efficacy and safety of a GLP-1R/GIPR coagonist in combination with standard pIUD in patients with EC/AH who wish to preserve their fertility.

Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium

Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium (WE-FiERCE)

Proportion of patients (%) who achieve pathological complete response at 48 weeks after initiation of pIUD and tirzepatide.

University Health Network, Toronto

This group will receive a progestin intrauterine device and be offered to undergo bariatric surgery.

This group will receive a progestin intrauterine device alone.

Patients who are randomized to the intervention group will receive a progestin intrauterine device and be referred for bariatric service to undergo bariatric surgery within 3 months of their study consent.

Bariatric Surgery

Tara Zad

A growing population of young women with obesity are developing atypical hyperplasia (pre-cancer) and endometrial cancer. Progestin is the standard treatment for women who wish to preserve fertility, but this approach does not address the underlying cause of endometrial cancer/atypical hyperplasia (obesity); thus response rates are low and recurrence rates are high. Significant weight loss by bariatric surgery, in combination with progestin therapy may result in greater and more durable response rates.

The incidence of endometrial cancer is increasing at an alarming rate (2.6% per year). This trend parallels the rising rate of obesity, the most significant increasing risk factor for endometrial cancer. Young women with obesity and endometrial cancer or atypical hyperplasia who want to maintain their fertility and thus avoid hysterectomy are treated with progestin therapy, such as progestin intra-uterine device (pIUD). However, the pIUD achieves cancer regression in only 50-70% of women, and over 50% of initial responders will develop recurrence within two years. The effectiveness of the pIUD may be improved if the driver of endometrial cancer (obesity) was simultaneously addressed. Multiple epidemiologic studies have demonstrated that bariatric surgery reduces the risk of developing endometrial cancer. Our research aims to answer the question: "Is bariatric surgery in addition to the pIUD a feasible and acceptable option for young women with endometrial cancer/atypical hyperplasia who wish to maintain their childbearing potential compared to standard treatment of pIUD alone?

This is a pilot randomized controlled trial to assess the feasibility of a full-scale randomized controlled trial. Eligible women will be identified and consented over a 21-month period, and participants will be randomized to bariatric surgery plus standard pIUD (intervention group) or to standard pIUD alone (non-intervention group) in a 1:1 fashion.

Intervention Group: Bariatric Surgery and Progestin Intrauterine Device (pIUD) Non-Intervention Group: Progestin Intrauterine Device (pIUD) alone

Participants who consent will be randomized in a 1:1 allocation.

Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium

To determine the proportion of eligible women who agree to participate in the study (recruitment rate). The primary outcome will be met and a full scale randomized controlled trial to assess efficacy will be conducted if ≥ 40% recruitment rate is achieved. Patients' reasons for participation or non-participation will be recorded.

Proportion of patients who complete bariatric surgery within 3 months of randomization. A rate of \>85% will be considered feasible.

Loss to follow-up rate, defined as proportion of patients who do not complete 15-month assessment. A loss to follow-up rate of \<20% will be considered feasible.

Completion rate of patient reported outcomes that will be used in the full-scale randomized controlled trial. Completion of \>80% of patient reported outcomes at baseline will indicate that use of these questionnaires is feasible.

Overall complete response rate (CRR) after treatment with progestin intrauterine device (pIUD). This study is not powered to detect an improvement in CRR in the intervention vs. non-intervention group. However, the proportion of women who obtain a complete response in the pIUD alone group at 15 months will be used as the baseline CRR for this population and will be used to derive a sample size for a full-scale randomized controlled trial. We believe that this will be more accurate than using published data retrospective studies that are not specific to women with obesity. We will also collect the following data: (a) time to complete response, (b) overall recurrence rate, and (c) time to recurrence.

Carcinoma, Lobular

Participants will self-administer FHIR-enhanced RealRisks with access to risk communication games, family history pedigree and modules on chemoprevention and genetics testing, if relevant to them based on their risk and family history. The investigators are interested in gaining short-term feedback on patient activation and other patient reported outcomes, which will be assessed before and within 2 weeks after using RealRisks.

RealRisks is a web-based patient-centered decision aid (DA) designed to improve: 1) accuracy of breast cancer risk perceptions; 2) chemoprevention knowledge, and 3) informed choice. The DA includes audio and modules about breast cancer risk (including interactive games on risk communication) and chemoprevention. Through RealRisks, the investigators will collect information on breast cancer risk factors to calculate a patient's BCSC breast cancer risk score and also factors that influenced decision-making about chemoprevention through the preference elicitation game. RealRisks generates an action plan for patients summarizing their personalized breast cancer risk profile and preference elicitation for chemoprevention. Of note, the tool is designed for patients with varying levels of health literacy and numeracy and is available in English and Spanish.

RealRisks

Rita Kukafka, DrPH, MA

Katherine Crew, MD, MS

Electronic health records (EHRs) are an increasingly common source for populating risk models, but whether used to populate validated risk assessment models or to de-facto build risk prediction models, EHR data presents several challenges. The purpose of this study is to assess how the integration of patient generated health data (PGHD) and EHR data can generate more accurate risk prediction models, advance personalized cancer prevention, improve digital access to health data in an equitable manner, and advance policy goals for Patient Generated Health Data (PGHD) and EHR interoperability.

While breast cancer (BC) mortality has declined, this decline has begun to plateau, particularly among racial/ethnic minorities. Women identified as high-risk for BC may benefit from chemoprevention, testing for BC susceptibility genes, screening, and other personalized risk reducing strategies; however, barriers exist including the time required to conduct risk assessment of each woman in a population. Electronic health records (EHRs), a common source for populating risk assessment models present challenges, including missing data, and data type more accurate when provided by patients compared to EHRs. The investigators previously extracted EHR data on age, race/ethnicity, family history of BC, benign breast disease, and breast density to calculate BC risk according to the Breast Cancer Surveillance Consortium (BCSC) model among 9,514 women. Comparing self-reported and EHR data, more women with a first-degree family history of BC (14.6% vs. 4.4%) and benign breast biopsies (21.3% vs. 11.3%) were identified with patient reported data, but EHR data identified more women with atypia or lobular carcinoma in situ (1.1% vs. 2.3%). The EHR had missing data on race/ethnicity for 26.8% of women and on first-degree family history of BC for 87.2%. Opportunely, Fast Healthcare Interoperability Resources (FHIR), application programming interfaces (APIs), and new legislation offer an elegant solution for automated BC risk assessment that integrates both patient-generated health data and EHR data to harness the strengths of each approach. In prior work, the investigators developed the RealRisks decision aid using an iterative design process to equitably maximize acceptability, and usability. RealRisks promotes understanding of BC risk and collects patient-entered data to calculate BC risk according to the Gail model, BCSC, and BRCAPRO. When FHIR became available, the investigators updated RealRisks to automatically populate information for BC risk calculation from the EHR, and designed a prototype interface that shows this data to patients with a request to review and modify data before running the risk assessments. The investigators recently conducted a feasibility study to demonstrate that EHR data from FHIR could be incorporated into automated BC risk calculation. To increase the likelihood of developing disseminatable and equitable strategies that integrate EHR and PGHD data for risk assessment and personalized BC risk-reduction, the focus is to refine and test our approach among diverse multiethnic women. The aims are: 1) conduct user evaluations to refine FHIR-enhanced RealRisks; 2) assess the effect of the FHIR-enhanced RealRisks on patient activation, risk perception, and usability in a pilot study of multiethnic high-risk women; and 3) identify multilevel barriers to implementing FHIR-enhanced RealRisks into clinical care. Given the mortality associated with BC, focused efforts are needed to provide accurate risk assessment and shared decision-making about risk-reducing strategies, especially in minority women who are more likely to be diagnosed with advanced stage BC. If successful, the approach tested in this application may provide a roadmap for broadly improving digital access to health data and reducing BC mortality in an equitable manner.

The investigators will conduct a pre-/post- feasibility study of 55 high-risk diverse multiethnic women with follow-up to assess accuracy of breast cancer risk perception (perceived lifetime risk minus actual risk according to the Gail model) and patient activation.

RealRisks is a patient-facing, web-based decision support tool that was developed using multiple design sessions, participatory workshops, and usability studies to arrive at guiding principles that focus on 1) personalized breast cancer risk calculation, 2) interactive games to communicate breast cancer risk, and 3) patient preferences elicitation to elicit values supporting breast cancer options. The FHIR enhanced-RealRisks functionality that this research focuses on will allow RealRisks to utilize a patient's electronic health record data to support accurate risk assessment.

FHIR-Enhanced RealRisks to Improve Accuracy of Breast Cancer Risk Assessments

Integrating EHR and Patient-generated Health Data for Breast Cancer Risk Assessment and Decision Support in a Diverse Multiethnic Population

Measured via the Perceived Health Web Site Usability Questionnaire (PHWSUQ), three separate sections to evaluate patient satisfaction (e.g., "It is easy to find specific information"), ease of use (e.g., "It was easy to understand how to get to EHR data"), and usefulness (e.g., "Using the FHIR-enhanced RealRisks will help me improve my understanding about my BC risk; what I can do to reduce my risk"). The PHWSUQ consists of 12 items on a 7-point Likert scale ranging from Very Unsatisfied (1) to Very Satisfied (7). Scores range from 12-84, with a higher scores indicating greater overall usability of the tool.

Validated 13-item Patient Activation Measure, which measures patient knowledge, skill, and confidence in self-management of health. Scores range from 0 to 100; higher scores indicate greater activation.

Difference between perceived numeric risk estimate and actual lifetime breast cancer risk score, according to the Gail or BCSC risk models, categorized as accurate if the difference between subjective and objective risk estimates are 10% in either direction, underestimate if \>10% below objective risk, and overestimate if \>10% above objective risk.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up	NCT01357772	Carcinoma, Intr... Recurrence, Loc... Breast Neoplasm... Atypical Hyperp...	Tamoxifen placebo	18 Years - 75 Years	Ente Ospedaliero Ospedali Galliera
Effect of Fertility-sparing Therapy of Early Endometrial Cancer	NCT03538704	Endometrial Can... Fertility	Metformin	18 Years - 40 Years	Peking University People's Hospital
Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up	NCT01357772	Carcinoma, Intr... Recurrence, Loc... Breast Neoplasm... Atypical Hyperp...	Tamoxifen placebo	18 Years - 75 Years	Ente Ospedaliero Ospedali Galliera
Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium	NCT06073184	Endometrial Can... Atypical Hyperp...	Mounjaro Mirena	18 Years - 41 Years	University Health Network, Toronto
Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium	NCT04008563	Endometrial Can... Atypical Hyperp... Bariatric Surge...	Bariatric Surge...	18 Years - 41 Years	University Health Network, Toronto
Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium	NCT04008563	Endometrial Can... Atypical Hyperp... Bariatric Surge...	Bariatric Surge...	18 Years - 41 Years	University Health Network, Toronto
FHIR-Enhanced RealRisks to Improve Accuracy of Breast Cancer Risk Assessments	NCT05810025	Breast Cancer	RealRisks	35 Years - 74 Years	Columbia University
Effect of Fertility-sparing Therapy of Early Endometrial Cancer	NCT03538704	Endometrial Can... Fertility	Metformin	18 Years - 40 Years	Peking University People's Hospital

Spots Global Cancer Trial Database for atypical hyperplasia