Integrative Profiling of Primary Breast Cancer on the Basis of Divergent Exercise Exposure
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 42
- 试验地点
- 7
- 主要终点
- differences in DNA somatic mutational profile
研究概览
简要总结
This study is designed to find out how engaging in regular exercise (or not) alters the biology of breast tumors as well as the normal tissue (if available) surrounding the tumor. The investigators hope that findings from this initial study will guide the design of future studies to examine how changes in exercise alter breast tumor biology.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Cohort 1: Breast Cancer Patients
- •Ages 21-80 years
- •Histologically confirmed ER receptor positive (>1% staining), HER2 negative (FISH ratio <1.8), untreated operable breast cancer
- •Stage I to II disease
- •Scheduled for surgical resection by any type of mastectomy or lumpectomy at MSK
- •Tumor size ≥1cm by preoperative imaging or physical examination
- •Categorization into self-reported exercise history exposure classifications as follows: (1) exercising: ≥120 minutes of vigorous-intensity exercise/wk for the past 12 months, and (2) sedentary (non-exercising): ≤ 30 minutes of moderate-intensity exercise/week for the past months using the Harvard Health Professionals survey.(34)
- •Ability to read and understand English
- •Willing and able to comply with requirements of the protocol
- •Cohort 2: High-Risk Patients
- •Women at high-risk of breast cancer, as defined by one of the following:
- •Cytologically confirmed atypical hyperplasia
- •confirmed LCIS
- •Being a carrier for BRCA1 and/or BRCA2
- •Predicted lifetime risk of breast cancer >20% based on family history
- •Predicted 10-year risk of breast cancer of ≥2.31%
- •Predicted 5-year risk of breast cancer ≥1.67%
- •Aged 21-80 years old
- •If a female of child-bearing potential, must not be pregnant or planning to become pregnant during the study.
- •Women <50 years old of child-bearing potential must have a negative pregnancy test (urine HCG or serum) within 14 days of enrollment.
排除标准
- •Received any form of neoadjuvant treatment
- •Presence of any other concurrent, actively treated malignancy
- •Presence of metastatic disease
- •If performing a CPET, any of the following contraindications:
- •Acute myocardial infarction within 3-5 days of any planned study procedures;
- •Unstable angina
- •Uncontrolled arrhythmia causing symptoms or hemodynamic compromise
- •Recurrent syncope
- •Active endocarditis
- •Acute myocarditis or pericarditis
- •Symptomatic severe aortic stenosis
- •Uncontrolled heart failure
- •Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures
- •Thrombosis of lower extremities
- •Suspected dissecting aneurysm
- •Uncontrolled asthma
- •Pulmonary edema
- •Respiratory failure
- •Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis).
- •Mental impairment leading to inability to cooperate
- •If performing a CPET, room air desaturation at rest ≤ 85%
- •Any other condition or intercurrent illness that, in the opinion of the investigator, makes the participant a poor candidate for the study.
- •Use of any selective estrogen receptor modulator or aromatase inhibitor within 6 months of consent, including, but not limited to: tamoxifen, raloxifene, arzoxifene, acolbifene, anastrozole, exemestane, and letrozole.
- •Enrollment on an interventional investigational study
- •Bilateral breast implants
- •History of any of the following:
- •Invasive breast cancer
- •Any current invasive cancer diagnosis
- •Metastatic malignancy of any kind
- •If performing a CPET, any of the following contraindications:
- •Acute myocardial infarction within 3-5 days of any planned study procedures;
- •Unstable angina
- •Uncontrolled arrhythmia causing symptoms or hemodynamic compromise
- •Recurrent syncope
- •Active endocarditis
- •Acute myocarditis or pericarditis
- •Symptomatic severe aortic stenosis
- •Uncontrolled heart failure
- •Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures
- •Thrombosis of lower extremities
- •Suspected dissecting aneurysm
- •Uncontrolled asthma
- •Pulmonary edema
- •Respiratory failure
- •Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis).
- •Mental impairment leading to inability to cooperate
- •If performing a CPET, room air desaturation at rest ≤ 85%
- •Any other condition or intercurrent illness that, in the opinion of the investigator, makes the participant a poor candidate for the core biopsy or the study.
研究组 & 干预措施
Regular exercisers and non-exercising groups who have been diagnosed with breast cancer
There is no treatment on this study, it is a onetime assessment. exercisers: ≥120 minutes of vigorous-intensity aerobic exercise;There is no treatment on this study, it is a onetime assessment. non-exercisers: ≤ 30 minutes of moderate-intensity exercise per week.
干预措施: Harvard Health Professionals survey (Behavioral)
Regular exercisers and non-exercising groups who have been diagnosed with breast cancer
There is no treatment on this study, it is a onetime assessment. exercisers: ≥120 minutes of vigorous-intensity aerobic exercise;There is no treatment on this study, it is a onetime assessment. non-exercisers: ≤ 30 minutes of moderate-intensity exercise per week.
干预措施: Blood draw (Other)
Regular exercisers and non-exercising groups who have been diagnosed with breast cancer
There is no treatment on this study, it is a onetime assessment. exercisers: ≥120 minutes of vigorous-intensity aerobic exercise;There is no treatment on this study, it is a onetime assessment. non-exercisers: ≤ 30 minutes of moderate-intensity exercise per week.
干预措施: CPET Procedures (Other)
Regular exercisers and non-exercising groups who have been diagnosed with breast cancer
There is no treatment on this study, it is a onetime assessment. exercisers: ≥120 minutes of vigorous-intensity aerobic exercise;There is no treatment on this study, it is a onetime assessment. non-exercisers: ≤ 30 minutes of moderate-intensity exercise per week.
干预措施: stool sample (Other)
Regular exercisers and non-exercising groups who have been diagnosed with breast cancer
There is no treatment on this study, it is a onetime assessment. exercisers: ≥120 minutes of vigorous-intensity aerobic exercise;There is no treatment on this study, it is a onetime assessment. non-exercisers: ≤ 30 minutes of moderate-intensity exercise per week.
干预措施: Research Tissue sampling (Procedure)
Regular exercisers who are at high risk of developing breast cancer
≥120 minutes of vigorous-intensity aerobic exercise;
干预措施: Harvard Health Professionals survey (Behavioral)
Regular exercisers who are at high risk of developing breast cancer
≥120 minutes of vigorous-intensity aerobic exercise;
干预措施: Research Tissue sampling (Procedure)
结局指标
主要结局
differences in DNA somatic mutational profile
时间窗: 2 years
Eight-μm-thick representative sections of the fresh-frozen sample will be microdissected with a needle under a stereomicroscope (Olympus SZ61), to ensure \>70% of tumor cell content as previously described.(36) Matched germline DNA will be microdissected from adjacent normal breast tissue (if available) for each case; to avoid the possibility of morphologically appearing non-neoplastic cells harboring somatic mutations; we will prioritize the microdissection of stromal cells and avoid normal breast ducts and lobules.
differences in RNA sequencing
时间窗: 2 years
The initial analysis will focus on immune signatures (i.e., immune activation, as well as preexisting immune and related signatures) characterization using RNA-seq
次要结局
未报告次要终点