Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Ductal

Carcinoma in Situ

Carcinoma, Lobular

Carcinoma, Intraductal, Noninfiltrating

Breast Carcinoma In Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Hormones

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Tamoxifen 10 mg (1 tablet) every other day for 6 months.

Tamoxifen 10 mg (1 tablet) every other day for 6 months + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)

Step counter device + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)

One tablet of Tamoxifen 10 mg every other day for 6 months

Tamoxifen 10 mg Tablet

"5:2 diet": 5 days a week at regular energy intake and 2 days/week at 75% energy deficit (diet will be restricted at 500-800 kcal corresponding to a 75% reduction compared to normal size)

Intermittent caloric restriction

Participants will receive personal advice on healthy lifestyle and a step counter

Step counter Device

Bernardo Bonanni, MD

Aliana Guerrieri-Gonzaga, MSc

Andrea DeCensi, MD

Matilde Pensabene, MD

Stefania Zovato, MD

Circulating levels of Sex Hormone Binding Globulin (SHBG) are significantly associated with a decreased risk of breast cancer.

The main aim of this clinical trial is to verify whether Low Dose Tamoxifen (LDT) increases circulating levels of SHBG more than lifestyle intervention (LI) with or without intermittent caloric restriction (ICR) after 6 months in women at increased risk of breast cancer (i.e., healthy participants carriers of a germline pathogenic/likely pathogenetic variant in at least one of the following genes: BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51C or RAD51D, or with \> 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models or with a recently resected intraepithelial neoplasia of the breast (IEN).

The secondary aims are:

* to verify whether ICR significantly modulates primary and secondary endpoints such as Homeostasis Model Assessment (HOMA) index, immune and inflammatory markers, lipid profile, Adiponectin/Leptin (A/L) ratio, quality of life (QoL), Body mass index (BMI), fat body composition, safety and toxicity;
* to verify whether LDT significantly modulates secondary endpoints, such as HOMA-index, immune and inflammatory markers, lipid profile, A/L ratio, QoL, BMI, fat body composition, safety and toxicity;
* to investigate differences in microbiome composition by arms and the effect of changes in microbiome on QoL taking into account circulating biomarkers, cytokines, immune modulators, and inflammatory proteins in serum;
* to investigate MD (Mammographic Breast Density) changes by LDT vs. LI, with or without ICR. This aim will be performed in a subgroup of participants (not all the participants will undergo mammography due to younger age).

Italian, multicenter, phase II, biomarker trial. A total of 200 women aged 18-70 years will be randomly assigned (1:1:1:1) to one of the four intervention arms Arm 1: Low dose Tamoxifen (LDT) i.e. 10 mg every other day; Arm 2: Low dose Tamoxifen (LDT) + Intermittent Caloric Restriction (ICR); Arm 3: Lifestyle intervention (LI) using a step counter; Arm 4: Lifestyle intervention (LI) using a step counter + Intermittent Caloric Restriction (ICR).

Participants will be stratified by center and by disease status (high risk vs. previous IEN) and intervention will last six months for all arms.

Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion

Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion: a Randomized Phase II Biomarker Trial in Subjects at Increased Risk

Sex hormone binding globulin level after 6 months of intervention

Ente Ospedaliero Ospedali Galliera

Istituto Oncologico Veneto IRCCS

Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

European Institute of Oncology

Rare Diseases

Radiation Induced Cancer

Anticoagulants

Other Dietary Supplements

Citric Acid

Sodium Citrate

Citrate

Patients receive tamoxifen citrate PO QD for 24 months in the absence of disease progression or unacceptable toxicity.

Patients receive placebo PO QD for 24 months in the absence of disease progression or unacceptable toxicity.

Tamoxifen Citrate

Placebo

Digital mammography

immunohistochemistry staining method

pharmacological study

laboratory biomarker analysis

protein expression analysis

pharmacogenomic studies

questionnaire administration

Fine needle aspiration

Quality of Life Assessment

Smita Bhatia, MD

Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells

This phase IIb trial studies how well low-dose tamoxifen citrate works in reducing breast cancer risk in radiation-induced cancer survivors.

PRIMARY OBJECTIVES:

I. To determine the impact of a two-year course of low-dose tamoxifen (tamoxifen citrate) administered at 5 mg per day on surrogate endpoint biomarkers of breast cancer (BC) risk, including: mammographic breast density (MBD), an established radiographic biomarker of BC risk; cytomorphology and proliferative index, tissue biomarkers closely linked to BC risk; and sex steroid hormones and insulin growth factors, circulating biomarkers of BC risk.

II. To establish safety and tolerability of this low-dose tamoxifen regimen, assessing both objective measures (lipid profiles, clotting factors and bone metabolism markers) and patient-reported outcomes.

III. To examine the modifying effect of demographic, clinical, and molecular characteristics on the risk: benefit ratio from this two-year low dose tamoxifen intervention.

IV. To explore the relationship between this low-dose tamoxifen regimen and clinical measures of efficacy (new breast cancer and ductal carcinoma in situ \[DCIS\] diagnoses) and toxicity (thromboembolic events, reports of hot flashes and gynecological symptoms, liver function abnormalities, and other cancer diagnoses).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive tamoxifen citrate orally (PO) once daily for 24 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO once daily for 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 10 years.

Low-Dose Tamoxifen Citrate in Reducing Breast Cancer Risk in Radiation-Induced Cancer Survivors

Low-Dose Tamoxifen for Radiation-Induced Breast Cancer Risk Reduction: A Phase IIB Randomized Placebo-Controlled Trial

Mammographic density was quantified as percentage of fibroglandular tissue. Using an intention-to-treat analysis, mammographic breast density (MBD) was compared between patients in the low dose tamoxifen intervention and placebo group by applying the linear mixed effects model for normally distributed data.

IGF1 will be treated as a continuous measure. The linear mixed effects model for between group comparisons of measures from 3 time points will be applied. The unstructured mean model and linear in time model will be employed.

Will be tabulated by treatment arm. Differences by treatment arm will be evaluated using Fisher exact tests.

Total cholesterol, low and high density lipoprotein, triglycerides, and anti-thrombin III enzymatic assay measurements will be treated as continuous variables. Transformed to normality as appropriate, the linear mixed effects model will be applied, using the unstructured mean model and linear in time model to assess the effects of low-dose tamoxifen on these measurements over time.

The number of pills taken out of the total prescribed in a 3-month period will be modeled as a random effects binomial regression model. The binomial rates from 8 time points (month 3-24) will be modeled as unstructured mean model with 7 indicator variables as well as polynomial models over time. The random-intercept and the random intercept and slope models will be considered. The significance of the time indicators or parameters by treatment interaction will be evaluated for treatment difference in compliance.

The outcomes will be scored as a 5-point Likert-type scale (0-4) in response to questions on how much the patients are bothered by certain symptoms. The questionnaire will be administered every 6 months. The responses will be treated as normally distributed, as ordinal or dichotomized variable, and the linear mixed effects of general linear mixed model (GLMM) methods will be applied to compare changes between treatment groups. Piecewise models will also be fitted with join point at 6 months, considering linear and curvilinear trajectories between 6 and 24 month time points.

IGF3 will be treated as a continuous measure. The linear mixed effects model for between group comparisons of measures from 3 time points will be applied. The unstructured mean model and linear in time model will be employed.

Serum bone-specific alkaline phosphatase measurements will be treated as continuous variables. Transformed to normality as appropriate, the linear mixed effects model will be applied, using the unstructured mean model and linear in time model to assess the effects of low-dose tamoxifen on these measurements over time.

Urine n-telopeptide measurements will be treated as continuous variables. Transformed to normality as appropriate, the linear mixed effects model will be applied, using the unstructured mean model and linear in time model to assess the effects of low-dose tamoxifen on these measurements over time.

National Cancer Institute (NCI)

St. Jude Children's Research Hospital

University Health Network, Toronto

University of Michigan

Dana-Farber Cancer Institute

Mayo Clinic

University of Washington

City of Hope National Medical Center

M.D. Anderson Cancer Center

University of Chicago

University of Minnesota

University of Colorado, Denver

Wake Forest University

University of Alabama at Birmingham

Principal Investigator

Patients receive tamoxifen citrate PO QD for 24 months in the absence of disease progression or unacceptable toxicity.

Tamoxifen Citrate: 5 mg PO Daily

Digital mammography: Correlative studies

immunohistochemistry staining method: Correlative Studies

pharmacological study: Correlative Studies

laboratory biomarker analysis: Correlative Studies

protein expression analysis: correlative studies

pharmacogenomic studies: correlative studies

questionnaire administration: Ancillary studies

Fine needle aspiration

Quality of Life Assessment: Ancillary Studies

Arm I (Tamoxifen Citrate)

Patients receive placebo PO QD for 24 months in the absence of disease progression or unacceptable toxicity.

Placebo: 1 tablet daily

Digital mammography: Correlative studies

immunohistochemistry staining method: Correlative Studies

pharmacological study: Correlative Studies

laboratory biomarker analysis: Correlative Studies

protein expression analysis: correlative studies

pharmacogenomic studies: correlative studies

questionnaire administration: Ancillary studies

Fine needle aspiration

Quality of Life Assessment: Ancillary Studies

Arm II (Placebo)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Region of Enrollment

Slower than expected accrual, and financial constraints of supporting the study drug costs necessitated study closure before attainment of planned study enrollment.

Dr. Smita Bhatia

Mammographic Breast Density

Insulin Growth Factor Levels (IGF1)

Number of Grade 2-4 Toxicities

Total Cholesterol

Low-density lipoprotein

High-density lipoprotein

Triglycerides

Anti-thrombin III

Biomarker Levels

Percentage of Pills Taken Out of the Total Prescribed

Interrupted sleep

General aches or pains

Hot flashes

Joint pain or stiffness

Feeling unusually tired

Heartburn and/or acid stomach

Headaches

Muscle cramps or soreness

Symptoms with \>10% prevalence are reported; patients were dichotomized into 2 groups: those that rated the symptom as moderately or extremely bothersome vs. slightly or quite a bit bothersome

Number of Participants With Different Patient Reported Symptoms, Measured by Questionnaire

Insulin Growth Factor Levels (IGF3 )

Biomarker Levels - Alkaline Phosphatase

Biomarker Levels - Urine N-telopeptide

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion	NCT06033092	BRCA Mutation PALB2 Gene Muta... Ductal Carcinom... Lobular Carcino... ATM Gene Mutati... CHEK2 Gene Muta... CDH1 Gene Mutat... RAD51C Gene Mut... RAD51D Gene Mut...	Tamoxifen 10 mg... Intermittent ca... Step counter De...	18 Years - 70 Years	European Institute of Oncology
Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion	NCT06033092	BRCA Mutation PALB2 Gene Muta... Ductal Carcinom... Lobular Carcino... ATM Gene Mutati... CHEK2 Gene Muta... CDH1 Gene Mutat... RAD51C Gene Mut... RAD51D Gene Mut...	Tamoxifen 10 mg... Intermittent ca... Step counter De...	18 Years - 70 Years	European Institute of Oncology
Low-Dose Tamoxifen Citrate in Reducing Breast Cancer Risk in Radiation-Induced Cancer Survivors	NCT01196936	Breast Cancer	Tamoxifen Citra... Placebo Digital mammogr... immunohistochem... pharmacological... laboratory biom... protein express... pharmacogenomic... questionnaire a... Fine needle asp... Quality of Life...	25 Years -	University of Alabama at Birmingham
Low-Dose Tamoxifen Citrate in Reducing Breast Cancer Risk in Radiation-Induced Cancer Survivors	NCT01196936	Breast Cancer	Tamoxifen Citra... Placebo Digital mammogr... immunohistochem... pharmacological... laboratory biom... protein express... pharmacogenomic... questionnaire a... Fine needle asp... Quality of Life...	25 Years -	University of Alabama at Birmingham

Spots Global Cancer Trial Database for low dose tamoxifen