A Prospective Validation Study of a Rapid Point-of-Care Breath Test for Breast Cancer

Introduction

Clinical perspective on breath testing for breast cancer:

Breast cancer is the most commonly diagnosed cancer in women, in whom it is second only to
lung cancer as a cause of cancer death. The National Cancer Institute estimated that more
than 232,000 US women would be diagnosed with breast cancer in 2013 and nearly 40,000 would
die of the disease.

Screening mammography and its limitations: In order to reduce the number of breast cancer
deaths, many countries have established screening mammography programs to detect and treat
early-stage disease. However, the impact of screening mammography on mortality has been
questioned. Also, screening mammography is limited by its very low yield: a 2005
retrospective analysis reported that 510 US radiologists performed 2,289,132 screening
mammograms and found 9,030 cancers i.e. only one cancer was found for every 253 mammograms.
99.6% of all screening mammograms were negative for cancer: they provided reassurance, but at
a human cost of millions of women exposed to potentially hazardous radiation and discomfort,
and a financial cost of several million dollars. Also, screening mammography may be
associated with an increased risk of radiation-induced breast cancer, as well as with
overdiagnosis and overtreatment. Many women decide not to take the test even when it is
readily available, and screening mammography may be underutilized because of fear of pain and
radiation exposure, ethnicity, poverty, and level of education.

Breath tests - a new diagnostic tool: Abnormal volatile organic compounds (VOCs) in breath
have been identified in breast cancer. Breath VOC biomarkers have been reported in other
disorders including bronchial asthma, lung cancer, active pulmonary tuberculosis, radiation
exposure, and heart transplant rejection. The Food & Drug Administration (FDA) approved the
nitric oxide breath test in bronchial asthma, the urea breath test for H. pylori, and
Menssana Research's Heartsbreath test for heart transplant rejection under the Humanitarian
Device Exemption regulations.

Inclusion Criteria:

1. Female aged 18 years or over

2. Referred for mammography for a breast-related concern (e.g. breast mass, nipple
discharge etc.)

3. Understands the study, and is willing to give written informed consent to participate

4. Approves collection of relevant additional data for clinical research record if and
when it becomes available, including results of mammogram and any other imaging
studies, biopsy results, TNM staging, and other relevant biomarker data e.g. status of
BRCA1, BRCA2, HER2 and receptors (ER+ or ER-) and progesterone (PgR+ or PgR-)

Exclusion Criteria:

1. Known serious or potentially life-threatening disease (e.g. severe cardiac or
infectious disease)

2. Previous history of treated breast cancer, or cancer of any other site, with the
exception of basal cell carcinoma of skin.