Endocrine Disruptors and Life STILe in Breast Cancer Development

Trial Title: Endocrine Disruptors and Life STILe in Breast Cancer Development

NCT ID: NCT05748353

Condition: Breast Cancer
BRCA1 Mutation
BRCA2 Mutation
Ovarian Cancer
Life Style
Cadmium Exposure

Conditions: Official terms:
Breast Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial

Study type: Observational

Overall status: Active, not recruiting

Study design:

Time perspective: Retrospective

Summary: 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

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

Criteria for eligibility:

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

Sampling method: Non-Probability Sample
Criteria:
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.

Gender: Female

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Locations:

Facility:
Name: Alessandra Fabi

Address:
City: Roma
Zip: 00164
Country: Italy

Start date: January 1, 2012

Completion date: July 15, 2024

Lead sponsor:
Agency: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Agency class: Other

Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05748353