The Effects of HER2 Receptor Signaling on Human Brown Fat Activity

Summary

The objective of this observational study is to investigate the significance of the HER2 receptor for brown fat activity in humans. Our preliminary data clearly demonstrates that the ErbB signaling pathway, which includes the HER2 receptor, strongly promotes development and function of cultured human BAT cells. The HER2 receptor is a part of the ErbB signaling pathway, and antibodies against thee HER2 receptor are a part of the standard treatment for HER2-positive breast cancer. Therefore, the hypothesis is that the activity of brown fat will be reduced in patients treated with HER2 blocking antibody compared to patients who are not treated with HER2 blocking antibody. The present study simply takes advantage of the treatment protocol to explore the contribution of the HER2 receptor in the development of brown adipose tissue in humans. Participants will complete two testing days, one before and one after their treatment period of approx. one year. On the testing days, identification of brown fat activity will be performed using cooling and infrared thermography. In addition, resting metabolic rate and a glucose tolerance test will be performed. Since presence of active brown adipose tissue in humans is inversely related to obesity, total and visceral fat mass, plasma glucose levels, presence of cardiovascular disease and diabetes status, it is of great importance to investigate the molecular mechanisms for development of brown fat tissue and may lead to discovery of novel strategies to counteract obesity and obesity related disorders.

Eligibility

General inclusion criteria:

* Female
* Age \> 18 years
* Histologically confirmed breast cancer
* No prior neoadjuvant treatment
* Estrogen receptor positive (\>1%)
* Presence of cold activated brown fat as evidenced by a change in Δtemp. of \>1°C (post cooling - precooling temperature).

HER2 positive group: HER2-positive (HER2+) and Estrogen receptor-positive (ER+) breast cancer patients (N = 15):

* HER2 positive breast cancer as defined by ASCO/CAP criteria
* Scheduled to receive adjuvant chemotherapy, a total of 17 series of trastuzumab and endocrine treatment

Control group: HER2-negative breast cancer patients (HER2-) and Estrogen receptor-positive (ER+) breast cancer patients (N = 15):

* HER2 negative breast cancer as defined by ASCO/CAP criteria
* Scheduled to receive adjuvant chemotherapy and endocrine treatment

Exclusion Criteria:

* Any other cancer (excluding carcinoma in situ and radically operated localised squamous skin cancer) with clinical activity within the last 2 years
* Metastatic breast cancer
* Metabolic diseases such as diabetes (exceptions can be made if the disease is well treated, assessed by the clinically responsible medical doctor (see section 18))
* Regular use of prednisolone - use in relation to chemotherapy only is ok
* Pregnancy
* Untreated or dysregulated hypertension defined as outpatient clinic systolic BP \> 155 and diastolic BP \> 95
* Clinically significant ventricular or atrial arrhythmia
* Untreated coronary artery disease or angina pectoris
* Symptomatic heart failure (NYHA ≥ 2)
* Known cold urticaria

Conditions2

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