The EXActDNA-003 study will prospectively enroll participants who are planning to undergo chemotherapy for high-risk, early breast cancer, who are willing to provide tissue and blood specimens for circulating tumor DNA (ctDNA) analysis.

Participants will be followed for up to 5.5 years.

Inclusion Criteria:

1. The participant or a legally authorized representative must provide study-specific informed consent prior to study entry.

2. The participant must be ≥ 18 years of age.

3. ECOG performance status 0 or 1.

4. Histologically confirmed invasive carcinoma of the breast.

5. Planned neoadjuvant therapy which includes cytotoxic chemotherapy.

6. Tumor size ≥ 2.1 cm in greatest diameter.

7. Unifocal or multifocal cancer documented to be the same histologic clinical subtype.

8. Clinically node positive or if node negative, any one of the following:

   1. TNBC or HER2+ subtype
   2. HR+/HER2-negative with at least one of the following:

   i. High tumor grade (G3) ii. Ki67 index of 20% or higher iii. High genomic risk (Oncotype DX® (ODX) Breast Recurrence Score of > 25, MammaPrint® High, etc.)

9. Willing and able to comply with the study requirements, which includes the collection of a total of 34 cc (2.5 Tablespoons) of blood for each research blood draw.

10. Available residual tissue from diagnostic biopsy from the breast or an involved ipsilateral lymph node for submission to create a bespoke ctDNA assay.

Exclusion Criteria:

1. Definitive clinical or radiologic evidence of metastatic disease.
2. Initiated neoadjuvant therapy for current breast cancer diagnosis.
3. Synchronous diagnosis of another invasive cancer, other than this breast cancer, except for non-melanoma skin cancers.
4. Completed all therapy (including endocrine therapy) <5 years ago for any previous invasive solid organ malignancy (with exception of non-melanoma skin cancers) including prior breast cancer. Individuals with a prior history of noninvasive (in situ) carcinomas may participate if they have received definitive treatment.
5. Completed all therapy for any previous hematologic malignancy < 5 years ago.
6. Multicentric or contralateral invasive breast cancers.
7. Known pregnancy at time of enrollment.
8. Prior solid organ transplant.
9. Prior allogeneic hematopoietic stem cell transplant.

Patients over the age of 18 who will undergo neoadjuvant treatment for high-risk, early breast cancer

Individual participant data that underlie the results reported in publications of the study will be shared after deidentification. This may include test, tables, figured, and appendices. The study protocol, statistical analysis plan (when applicable), informed consent form (when applicable). May not be reproduced nor disseminated outside of Exact Sciences without permission and the clinical study report (when applicable) will also be shared

Data will be available from 2 years and ending 4 years after publication

Proposals for access to data should be directed to clinicaltrials@exactsciences.com. To gain access, data requestors will need to provide a methodologically sound proposal and sign a data access agreement. Researchers are required to obtain necessary Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) approvals or waivers as applicable to conduct research.