• Investigate the ability of alpha lipoic acid to counter act anthracycline associated cardiotoxicity and cumulative taxens-related PN in patients with breast cancer.

Fifty breast cancer patients with stage from stage I to stage III will be involved in this study. Staging is done according to the American joint committee on cancer: TNM staging of breast cancer.

• All participants will be recruited from Tanta Oncology Center. The study will be approved by Research Ethics Committee of Damanhour University. All participants will give their consent.
• All 64 patients will be scheduled to receive 4 cycles of AC: cycled every 21 days followed by weekly cycle of taxol for 12 weeks.

Patients will be classified as follow:

• Group one: 32 patients will receive four cycles of AC followed by weekly taxol for 12 weeks plus placebo.
• Group two: 32 patients will receive the same regimen as group 1 in addition to oral 600 mg alpha lipoic acid (ALA) once daily.

All patients will be submitted to:

1. Full patient history and clinical examination.
2. Venous blood will be collected before the first cycle of chemotherapy and after the last cycle of chemotherapy.

1- Cardio-toxcity assessment: i. Echo-cardiogram. ii. Troponin I. iii. The Brain Natriuretic Peptide (BNP). 2- Neurotoxicity assessment: i. National Cancer Institute common Terminology criteria for Adverse Effect grading: NCI-CTCAE version 4.0.

ii. Neurotoxicity questionnaire from the validated Functional Assessment of cancer therapy/gynecologic oncology group taxane specific neurotoxicity questionnaire: FACT-Taxane.

iii. Neurotensin 3- Oxidative stress and inflammatory markers: i. Malondialdehyde (MDA). ii. TNF-alpha

Inclusion Criteria:

1. All patients age ≥ 18 and < 70 years old with confirmed stage from stage I to stage III.
2. No evidence of metastases at initial assessment.
3. Patients has to have a good performance status (ECOG 0-2) according to Eastern Cooperative Oncology Group (ECOG) score.
4. Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin level ≥ 10g/dL).
5. Patients with adequate liver function (serum creatinine < 1.5 mg/dL) and adequate renal function (serum creatinine < 1.5 mg/dL, creatinine clearance (CrCl) > 45 ml/min).
6. Either pre operative or post operative chemotherapy are allowed.

Exclusion Criteria:

1. Evidence of metastases at initial assessment.
2. Pregnancy or breast-feeding patients.
3. Prior exposure to neurotoxic chemotherapy was not allowed (no carboplatin, vincristine, vinblastine, paclitaxel, or docetaxol ) for 6 months prior study treatment.
4. Clinical evidence of serious cardiac illness (myocardial dysfunctional, angina pectoris requiring anti-angina medication, poorly controlled hypertension, and uncontrolled arrhythmias).
5. Patients with a reduced cardiac output with a left ventricular ejection fraction (LVEF) ejection fraction < 50%.
6. Patients who had evidence of pre-existing peripheral neuropathy resulting from another reason (diabetes).
7. Patients with a history of allergy to alpha-lipoic acid.
8. Concomitant use of multivitamins (vitamin E), opioids, anticonvulsants, tricyclic antidepressants, other neuropathic pain medication modifying agents (e.g., gabapentin, lamotrigine, carbamazepine, phenytoin, or tricyclic antidepressants) are not allowed