Background: Adjuvant chemotherapy treats micro-metastatic disease and decreases the risk of breast cancer recurrence. However, it may be associated with distressing side effects, including alopecia. Women with breast cancer rate chemotherapy-induced alopecia as one of the most severe, troublesome, and distressing side effects of chemotherapy. In many countries, scalp cooling has been introduced to prevent or reduce chemotherapy-induced alopecia. The theory is that scalp cooling causes cutaneous vasoconstriction, which reduces blood flow to the hair follicles during peak plasma concentrations of the chemotherapeutic agents and therefore reduces cellular uptake of these agents. It also results in reduced biochemical activity, which makes hair follicles less susceptible to the damage of the chemotherapy agents. Historically, success rates have been variable, but based on non-randomized studies, scalp cooling appears to be effective in preventing chemotherapy-induced alopecia especially in more recent studies. Methods: We are conducting a multi-center randomized non-blinded controlled prospective trial to evaluate the safety and efficacy of the Orbis Paxman Hair Loss Prevention System in reducing the incidence of chemotherapy-induced alopecia. Women with stage I-II breast cancer who will receive neoadjuvant or adjuvant anthracycline- or taxane-based chemotherapy, for at least four cycles are eligible. Participants are randomized in a 2:1 ratio to scalp-cooling or no cooling. Scalp-cooling is done using the Orbis Paxman Hair Loss Prevention System prior to, during and after each chemotherapy administration. The primary efficacy endpoints are hair preservation, defined as CTCAE v4 alopecia < 2, and device safety. Two hundred and thirty five (235) patients will be enrolled which will provide 85% power to detect a 20% difference in hair preservation, 15% in control group and 35% in scalp-cooling group . Secondary endpoints include: wig/scarf use and quality of life assessed by the EORTC QLQ-30, HADS and BIS. Study participants will be followed for 5 years post-study for time to first recurrence, overall survival, site of first recurrence, and incidence of isolated scalp metastasis. Clinical trial information: NCT01986140