Defined as women who:

• Are 18 to 85 years old at the time of enrollment;
• Have histologically-confirmed, first-time, non-metastatic breast cancer (Stage I-IIIB);
• Have no history of neurotoxic chemotherapy or radiation treatment at the time of enrollment;
• Will be receiving weekly paclitaxel (Taxol® or generic paclitaxel), 80-100mg/m2, or bi-weekly (i.e., dose-dense) Taxol, 175 mg/m2, as a part of their treatment regimen OR
• Will be receiving an anthracycline and cyclophosphamide (AC) therapy followed by weekly or bi-weekly (i.e., dose-dense; 175 mg/m2) paclitaxel (Taxol® or generic paclitaxel, 80-100mg/m2);
• Are willing to participate in up to four study sessions.

Defined as women who:

• Are 18 to 85 years old at the time of study enrollment;
• Can read, write, and understand English,
• Are willing to participate in three planned study sessions.

*Axon reflexes will be evoked in the palmar surface of the right great toe using local skin heating with a 0.33 cm2 heat probe using the following protocol:

• Baseline: Heating the skin of the toe for a minimum of 5 minutes at 33*C.
• Heat Ramp: Increasing the heat in the heat probe to 42*C at approx. 0.1*C/10 sec.
• Skin Heating: Heating the skin of the toe for 30 minutes 42*C.
• Heat Ramp: Increasing the heat in the heat probe to 44*C at 0.1*C/10 sec..
• Skin Heating: Heating the skin for an additional 5 minutes at 44*C.

The size of the axon reflex during this skin heating protocol will be imaged using Laser Doppler Flowmetry (LDF). In the case that participants develop CIPN on their left side only, the left toe will be substituted.

• Hypothesis: (Cross-Sectional): There WILL NOT be a significant difference in the mean size of axon reflexes (expressed as a %CVCmax) in the great toe between healthy women and women with breast cancer before they start Taxol (i.e., Day 1).
• Definitions/Notes: The mean size of axon reflexes will be determined by averaging the peak laser doppler values (in tissue perfusion units (TPUs)) that occur during a stable 30-90 second period after increasing the probe temperature to 42*C. The maximum circulatory vascular conductance (%CVCmax) for each participant will be determined by dividing the raw TPU values by the participant's mean arterial blood pressure (MAP) during the axon reflex. The size of axon reflexes for each group will be then calculated by averaging the %CVCmax values corresponding to each individual's axon reflex for each group at that time point. Differences between groups in the size of axon reflexes at Day 1 will be compared using two-tailed t-tests, α=0.05.

• Hypothesis (Cross-Sectional): There WILL be a significant difference in the mean size of axon reflexes generated on the palmar surface of the right great toe between healthy controls and women with breast cancer during their initial six weeks of Taxol therapy (i.e., day 14 and 42, respectively).
• Notes: The mean size of axon reflexes during Taxol therapy will be determined by averaging the size of axon reflexes for participants in each group at day 14 and 42, respectively. Differences between groups in the size of axon reflexes at day 14 and 42 will be compared using two-tailed t-tests, α=0.05.

• Hypothesis (Longitudinal): There WILL be a significant difference in the mean size of axon reflexes generated on the palmar surface of the great toe of women with breast cancer from (a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42.
• Note: Differences in mean size of axon reflexes over the course of Taxol therapy will be calculated using repeated-measures analysis of covariance (RM-ANCOVA).

• Hypothesis (Cross-Sectional): There WILL NOT be a significant difference in the mean size of heat-evoked axon flares generated on the palmar surface of the great toe between healthy women and women with breast cancer before starting Taxol therapy (day 1).
• Note: A "heat-evoked axon flare" is defined as the area of increased cutaneous blood flow surrounding heat probe that is at least three standard deviations (3SD) above blood flow measured during prior to local skin heating. The size of each axon flare will be expressed in centimeters squared (cm2). The mean size of axon flares for each group will be calculated by averaging the size of axon flares for healthy women at baseline and the size of axon flares for women with breast cancer at day 1 (before starting Taxol). Differences in the mean size of axon flares between both groups at day 1 will be compared using two-tailed t-tests, α=0.05.

• Hypothesis: There WILL BE a statistically significant, inverse correlation between (a) the size of axon reflexes generated on the great toe and (b) the mean total m-TNS scores for women with breast cancer receiving Taxol at Days 1, 14, and 42 (respectively).
• Note: The 'size of axon reflexes' will be defined using the criteria above. The 'average m-TNS score' will be calculated by averaging the total Modified-Total Neuropathy Score (m-TNS) score (1-20) for each woman with breast cancer, at each time point. Pearson R will be used to determine the magnitude, direction, and statistical significance of bivariate correlations between (a) axon reflex size and (b) average mTNS scores for women with breast cancer receiving Taxol at each study time point.