Early Detection of Taxane-Induced Neuropathy in Women With Breast Cancer

Purpose: The study has four aims;

- The primary aim of the study is to determine whether women who are receiving either
weekly Taxol (80-100 mg/m2) or bi-weekly Taxol (i.e.,dose-dense; 175 mg/m2) show
deficits in axon-reflex mediated vasodilation (AMV) over the course of six weeks of
Taxol therapy similar to those that have been reported in patients with diabetic and
genetically-inherited neuropathies.

- The second aim of the study is to determine whether women who are receiving either
weekly or dose-dense Taxol develop changes in AMV before developing signs & symptoms of
chemotherapy-induced peripheral neuropathy (CIPN) in a way that supports using changes
in AMV as an early detection method for small-fiber CIPN.

- A third (exploratory) aim of the study is to determine whether any changes in AMV
detected during the study are significantly correlated with self-reported CIPN in a way
that would support using changes in AMV as a confirmatory marker for CIPN.

- A final (exploratory) aim of the study is to describe the size of axon reflexes and axon
flares in women receiving weekly Taxol before they start their pre-Taxol anthracycline &
cyclophosphamide (AC) therapy.

Inclusion Criteria for Women with Breast Cancer:

- Age 18-85

- Able to read, write, and understand English

- Diagnosed with histologically-confirmed, first-time, non-metastatic breast cancer
(stage I-IIIB)

- No prior exposure to neurotoxic chemotherapy or radiation at the time of enrollment,

- Will be receiving weekly paclitaxel (Taxol® or generic paclitaxel, 80- 100mg/m2) or
bi-weekly Taxol (i.e., dose-dense; 175 mg/m2) as a part of their cancer treatment
regimen OR

- Will be receiving an anthracycline and cyclophosphamide (AC) followed by weekly
paclitaxel (Taxol® or generic paclitaxel, 80-100mg/m2) or bi-weekly Taxol (i.e.,
dose-dense; 175 mg/m2) as a part of their cancer treatment regimen;

Inclusion Criteria for Healthy Controls:

- Aged 18-85

- Can read, write, and understand English

Exclusion Criteria:

- A history of cardiovascular disease, hypertension, or peripheral arterial/vascular
disease;

- Current use of (1) medications/supplements to control blood pressure (e.g.
beta-blockers, nitrates, calcium channel blockers, Phosphodiesterase-5 (PGE5)
inhibitors) or (2) the use of statins for cholesterol;

- Suspected or diagnosed diabetes (with the exception of gestational diabetes);

- Pre-existing neuropathy, neuropathic pain, or nerve injury;

- Pain or significant arthritis in the toes of either foot;

- Current skin disease or fungal infection of the feet;

- Significant damage or deformity to the feet that would alter blood flow or make it
impossible to measure/interpret findings;

- Diagnosed or suspected vasospastic disease such as Raynaud's syndrome;

- Current use of tobacco/tobacco-containing products;

- Diagnosis of restless leg syndrome or other movement disorders that would prevent
accurate data from being able to be collected.

In-Study Restrictions:

- No caffeine- or alcohol-containing products for 12 hours prior to their study visit;

- No food for at least one hour prior to blood flow monitoring;

- No non-steroidal anti-inflammatory drugs (NSAIDS) for 24 hours prior to study visits
unless directed by a physician to do so.

(Note: These restrictions are designed to improve the rigor and quality of the data, but
non-compliance will not be grounds for study exclusion; adherence to these restrictions
will be monitored during self-report).