Abstract Introduction In patients with early breast cancer, there is a trend towards conservative axillary surgery but there are concerns that patients with high volume axillary metastases may receive sub-optimal axillary treatment leaving them vulnerable to local recurrence. Determining the metastatic status of sentinel lymph nodes (SLN) in the pre-operative/ diagnostic period would allow focussed surgical planning and facilitate decisions regarding adjuvant therapy early in the patient pathway. Methods 654 patients with primary invasive breast cancer and a normal grey-scale axillary ultrasound were included in the analysis. Pre-operatively, patients received periareolar intra-dermal injection of microbubble contrast agent, breast lymphatics were visualised by ultrasound and followed to identify axillary SLN. Contrast-pulse sequencing and grey-scale ultrasound modalities were used to image SLN. Sentinel lymph nodes were then subjected to core biopsy. Patients subsequently underwent tumour excision and axillary node clearance (ANC) or surgical sentinel node biopsy (SNB) using blue-dye and isotope +/- completion ANC. Results Sentinel lymph nodes were clearly visualised in 605 patients and successfully (B2-B5) core biopsied in 555. The test identified 53% of all SLN metastases with 100% specificity. The negative predictive value was 88%. The prevalence of axillary lymph node metastases was 23%. Given a benign (B2) SLN biopsy result, the post-test probability that a patient had SLN metastases on subsequent surgical excision was 12%. Following ANC, 55% of patients with a malignant (B4/5) biopsy result were found to have high volume axillary disease (2 macro metastases or more) whereas 21% of patients with an initial benign (B2) biopsy result and metastatic cells found at SNB had high volume axillary disease identified after completion ANC (P value less than 0.001). In total, only 2% of patients with a benign (B2) SLN core biopsy result had high volume axillary metastases and half of these had either multifocal cancer or invasive lobular carcinoma. Conclusions SLN can be readily identified and biopsied in the breast clinic using intradermal microbubbles and CEUS. In patients with primary invasive breast cancer and a normal grey scale axillary ultrasound, a benign (B2) SLN core biopsy result may be highly predictive of either no metastases or low volume metastatic disease in the ipsilateral axilla. This group of patients is therefore likely to benefit from axillary conservation and in certain cases, it may be appropriate to completely omit a surgical SNB. Citation Format: Karina Cox, Jennifer Weeks, Ritchie Chalmers, Pippa Mills, David Fish, Ali Sever. In patients with breast cancer, pre-operative sentinel node biopsy using intradermal microbubbles and contrast enhanced ultrasound predicts volume of axillary metastases [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-06.