Endocrine Disruptors and Life STILe in Breast Cancer Development (STILVARCA)

Endocrine Disruptors and Life STILe in Patients Carrying BRCA Pathogenic VAriants With Breast and/or Ovarian CAncer and Women Without Neoplasm: the STILVARCA Study

The aim of the study is to evaluate the role of lifestyle and environmental factors ( environmental contaminants such as Cd) on the penetrance of BRCA1/2 genes in BRCAm patients with Breast cancer and/or Ovarian cancer and in BRCAm healthy women without cancer diagnosis

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Ovarian Cancer; BRCA1 Mutation; BRCA2 Mutation; Life Style; Cadmium Exposure

Detailed Description

Breast cancer (BC) is the most frequent neoplasm in women; the lifetime probability of developing invasive breast cancer is estimated to be 12.8%. Ovarian cancer (OC) represents the second most common type of gynecologic neoplasm, with an incidence of about 1.5%. A sedentary lifestyle and being overweight seem to play a role in the development of these diseases; an increase in body mass index (BMI) of 5 units is correlated with a 12% increased risk of developing BC and 7-10% increased risk of developing OC. Exposure to environmental toxic factors, such as Cadmium (Cd), has also been found to play a role in the development of BC and OC. Indeed, it has been shown that Cd is involved in the pathogenesis of these neoplasms as it would act as an endocrine disruptor: through binding to the estrogen receptor it would determine its activation thereby promoting cell proliferation. Cd is released into the soil, water and air from natural sources but, most importantly, as a result of industrial processing the processing of nonferrous metals, the production of batteries and paints, the production and application of phosphate-based artificial fertilizers, the use of coal and petroleum, incineration and waste disposal. The general population may be exposed to Cd through: contaminated food and drinking water; cigarette smoking (active and passive), as tobacco leaves accumulate Cd from the soil; and inhalation of dust and fumes, especially for people living near industries that process or emit Cd. At the same time, it is well known that genetic factors are also related to the pathogenesis of BC and OC. In about 20% of patients with triple-negative BC and 20-25% of women with high-grade serous OC, a pathogenetic variant of these genes can be found. In subjects carrying constitutional pathogenetic variants (VPs) in the BRCA1/2 (BRCA1/2m) genes, the absence of repair of damage to the DNA double helix causes its accumulation favoring the development of neoplasms. This results in individuals carrying these variants having a cumulative risk of developing BC of 72% in the case of BRCA1 and 62% in the case of BRCA2. With regard to OC, the risk associated with the presence of VP in the case of BRCA1 is 44% and 17% in the case of BRCA2. These observations are consistent with the hypothesis that genetic risk related to cancer development is modified by environmental or other molecular factors. Several studies have evaluated factors such as lifestyle, overweight, weight gain, and physical inactivity as potential risk elements of BC or OC in BRCA1/2m mutation carriers. The aim of this study is to evaluate the possible interference of environmental factors in the development of BC or OC in women VP carriers of BRCA 1 and BRCA 2

• Study Type: Observational
• Enrollment (Actual): 275

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00164
    • Alessandra Fabi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient with pathogenic mutation of BRCA1 or BRCA2 gene with/without development of BC and/or OC

Description

Inclusion Criteria:

• Age>18 years
• Histologic diagnosis of early-stage BC (stage I, II, III operated; luminal, HER2+, triple-negative tumors) or OC (high-grade epithelial any stage and histotype); presence of germline variant of BRCA1 or BRCA2, class 4 or 5
• Patients carrying germline variant of BRCA1 or BRCA2, class 4 or 5, in the absence of BC and/or OC, who have not undergone prophylactic mastectomy and/or bilateral ovariectomy surgery.
• Patients with malignancy must have undergone surgery and be currently disease-free or in complete or partial remission in the case of OC.
• Adjuvant/neoadjuvant systemic therapy as well as maintenance therapy (PARP-inhibitors for example) is permitted.
• Signature of informed consent.
• ECOG: 0.1.
• Compliance with questionnaire completion

Exclusion Criteria:

• Prophylactic breast or ovarian surgery
• Germinal variant of BRCA1 or BRCA2, class 1,2, 3.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients with BRCA pathological variants with breast or ovarian cancers; Patient with pathogenetic mutation of BRCA 1 or 2 gene who have developed breast or ovarian neoplasm
Patients with BRCA pathological variants without diagnosis of cancer; Patient with pathogenetic mutation of BRCA 1 or 2 gene without diagnosis of malignancy and without prophylactic surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to mediterranean diet	Identification of adherence to the Mediterranean diet assessed through the PREDIMED questionnaire, a validated 14-item Questionnaire of Mediterranean diet adherence. The score can range from 0 to 14. A score less than 5 indicates poor adherence to the Mediterranean diet; a score between 6 and 9 means average adherence and greater than 10 good adherence.	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of fisical activity	Assessment of physical activity (assessed through the IPAQ questionnaire). Questionnaire measures the type and amount of physical activity performed by the subject during the week and it is divided into intense, moderate and light. Each activity is assigned a score. A total score below 700 Met indicates inactivity of the subject, between 701 and 2519 sufficient activity, above 2520 adequate activity	10 years
Assessment of smoke habits	An assessment of the subject's smoking habit. It evaluate the number of cigarettes smoked daily and years from beginning. The score is expressed by "pack-years" index.	10 years

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Alessandra Fabi, Medicina di precisione in senologia, policliclinico A. Gemelli - IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Estimated): June 15, 2024
• Study Completion (Estimated): July 15, 2024

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: February 25, 2023
• First Posted (Actual): February 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: 4472

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No