DEFINITIVE: Diagnostic HER2DX-guided Treatment for Patients wIth Early-stage HER2-positive Breast Cancer

Change from baseline in all other functional and symptom scales (items 1 to 28) from the EORTC QLQ-C30 questionnaire version 3.0 to assesses cancer-related symptoms, impacts, and treatment-related symptoms. The items are rated on a 4-point rating scale ranging from 0 ("not at all") to 4 ("very much").

Change from baseline in the score of the EuroQol-5D. The 5-level version EQ-5D-5L is a 6-item generic patient-reported preference-based instrument designed to assess health status of patients. The EQ-5D-5L consists of 2 sections: * the EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels of severity: the dimensions of mobility, self-care, and usual activity are rated ranging from 1 (no problem completing task) to 5 (unable to complete task) while the dimensions of pain/discomfort and anxiety/depression are rated ranging 1 (no symptom) to 5 (extreme symptom). * the EuroQoL visual analogue scale (EQ-VAS) is for patients to self-rate their (global) health state utilizing a vertically oriented visual analogue scale where 100 represents the "best possible health state" and 0 represents the "worst possible health state".

pCR rates between groups at randomization and according to the predefined HER2DX pCR score as a continuous variable and as group categories. pCR will be defined as the complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination at the time of definitive surgery, irrespective of in situ carcinoma in the breast.

RCB between groups at randomization and according to HER2DX pCR score as a continuous variable and as group categories. Residual cancer burden (RCB) is defined as classes 0, 1, 2 and 3, according to the MD Anderson Cancer Center recommendations by local evaluation.

Invasive disease-free survival (iDFS) between groups at randomization and according to HER2DX pCR score in continuous variable and risk group. iDFS is defined as the time from surgery until the date of the first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumor, recurrence of ipsilateral locoregional invasive disease, a distant disease recurrence, contralateral invasive breast cancer, second primary or death from any cause.

Distant metastasis free survival (DMFS) between groups at randomization and according to HER2DX pCR score in continuous variable and risk group. DMFS is defined as the time from surgery to date of first event of distant metastatic recurrence or death (any cause). Contralateral breast cancer and secondary cancers will not be considered. Patients who do not have a DMFS event will be censored at the last recurrence assessment. Patients alive with no evidence of metastasis at the time of their last visit are censored at the time of the last examination.

Recurrence-free interval (RFI) between groups at randomization and according to HER2DX pCR score in continuous variable and risk group. RFI is defined as from surgery until the date of the first occurrence of one of the following events: recurrence of ipsilateral breast tumor (in situ or invasive), recurrence of ipsilateral locoregional invasive disease, a distant disease recurrence, contralateral invasive breast cancer or death from breast cancer.

Event free survival (EFS) between groups at randomization and according to HER2DX pCR score in continuous variable and risk group. EFS is defined as the time from randomization to the first documented disease recurrence, unequivocal tumor progression determined by the treating investigator, or death from any cause, whichever occurs first.

Incidence, duration, and severity of adverse events (AEs) assessed by the NCI Common Terminology for Classification of AEs (CTCAE) version 5, including dose reductions, delays, and treatment discontinuations.

Patient-reported Experience Measurement (PREM) data will be elicited from the patients in this study to fully understand the experience of patient. Team accessibility, Communication, Information from care providers, Care continuum coordination, respect and courtesy, secondary effects management, shared-decision making, language barriers and overall care perception, will be evaluated using the Drug Therapy Team survey and the Supplementary Items survey from the CAHPS cancer care survey (AHQR). The Drug Therapy Team Survey is a 56 items questionnaire designed to measure accessibility to the care team, quality of information provided, quality of the visit, management of the impact of the disease on daily life, quality of the administration staff support, and a global scale from 0 to 10 to rate the quality of the team. The supplementary items survey is a 16 items questionnaire and measure three dimensions of experience: access, information and shared-decision making.

Health economic evaluation to analyse the cost-effectiveness in patients with and without HER2DX test information, not only direct cost for hospitals/public health system, but also indirect cost from a societal perspective. The EuroQol-5D-5L questionnaire will be used to calculate a health status utility score for use in health economic analyses.

To evaluate whether the potential treatment de-escalation following tailored treatment by HER2DX could have impact in the work productivity using the Work Productivity and Activity Impairment Questionnaire (WPAI- GH).The WPAI-GH is a 6-item instrument that gauges absenteeism (missed work time due to the health issue), presenteeism (decreased productivity while working due to the health problem), overall work hindrance, and limitations in daily activities.