NEOMET is an exploratory randomized prospective, multicenter study whose primary aim is to explore if metabolomic signatures can be modified by a lifestyle intervention including dietary supplements and physical exercise intervention, in eBC patients candidate to NAT. Eligible patients will be randomised to one of 4 groups: A. NAT, according to molecular subtype; B. NAT plus nutritional supplementation; C. NAT plus supervised physical exercise; D. NAT plus supervised physical exercise plus nutritional supplementation. Nutritional supplementazion will consist of two main long-chain polyunsaturated fatty acids omega-3 (n-3 Lc-PUFA), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) plus a source of palmitoleic acid (hexadecenoic acid).

The primary objectives are: 1. To explore the impact of a lifestyle intervention including dietary supplements and physical exercise on the modulation of metabolomic signatures in eBC patients candidate to NAT; 2. To assess the Omega-3 Index at baseline and before surgery in all patient cohorts. Secondary objectives are: Impact of the combined lifestyle intervention on patient metabolic profile and body composition, by bioelectrical Impedance analysis; assessment of the immunophenotype of lymphocyte subpopulations and their correlation with metabolomic profile and response to therapy; characterization of immune-related and metabolic-related gene-expression signatures in tumor tissue and their correlation with metabolomic profile and response to therapy; evaluation of the pharmacokinetic interactions between nutritional supplementation and chemotherapy; evaluation of pCR in the different treatment arms; changes in health-related QoL (EORTC QLQ-C30, QLQ-BR45, and EQ-5D-5L), and safety and toxicity profiles according to the NCI-CTCAE v.5.0.

Due to explorative intent of the study no formal sample size calculation is provided. A total of 160 consecutive patients will be enrolled into the four arms of the study, with an allocation ratio equal to 1:1:1:1 (40 pts/arm). It can be estimated that the accrual will be completed in 20 months. Data collection, molecular assessments and data analysis with final scientific output are expected to extend the study duration to a total of 26 months.

The following analyses will be performed: - Conversion rate from a poor to a good metabolomic prognostic signature from baseline to end of NAT. - Change in Omega-3 Index and body composition variation.

- The association between Immunophenotype of lymphocyte subpopulations and tissue-based metabolic and immune-related gene-expression signatures will be described according to the type of metabolomic profile at baseline (poor versus good) and with response to therapy (pCR versus RD).

Inclusion Criteria:

• - Women (regardless of menopausal status) ≥ 18 years of age
• Pathologic confirmation of breast cancer by tumor biopsy
• Immunohistochemical assessment (as per local standards) of ER and PgR status, HER2 status;
• Stage I-III breast cancer without evidence of distant metastases
• Being candidate to standard neoadjuvant therapy
• Having available tumor tissue from breast and/or lymph node at baseline
• Ability to fill a nutritional daily diary
• Medical clearance for non-agonistic physical activity
• Written informed consent to study-specific procedures

Exclusion Criteria:

• - locally advanced or inflammatory or stage IV BC;
• tumor size < 1 cm with negative nodes (pT1a, N0);
• chronic diseases or orthopedic issues that might interfere with ability to undertake a dietary and physical activity program;
• personal history of eating disorders.
• women engaged in agonistic/vigorous sport activities, not able to be compliant to exercise schedules