Circulating Proteins Associated with Response and Resistance to Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.

Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens should be avoided. Serum biomarker levels are being studied more and more for their ability to predict therapy response and aid in the development of personalized treatment regimens. This study aims to identify effective protein networks and biomarkers to predict response to NAC in HER2-positive BC patients through an exhaustive large-scale LC-MS/MS-based qualitative and quantitative proteomic profiling of serum samples from responders and non-responders. Serum samples from HER2-positive BC patients were collected before NAC and were processed by three methods (with and without nanoparticles). The qualitative analysis revealed differences in the proteomic profiles between responders and non-responders, mainly in proteins implicated in the complement and coagulation cascades and apolipoproteins. Qualitative analysis confirmed that three proteins (AFM, SERPINA1, APOD) were correlated with NAC resistance. In this study, we show that serum biomarker profiles can predict treatment response and outcome in the neoadjuvant setting. If these findings are further developed, they will be of significant clinical utility in the design of treatment regimens for individual BC patients.

Predicting axillary response to neoadjuvant chemotherapy: the role of diffusion weighted imaging.

OBJECTIVE: The aim of this study is to investigate whether the primary tumour response to neoadjuvant chemotherapy (NAC), based on the increase in the ADC-values (apparent diffusion coefficient) within the breast lesion, could help to predict axillary complete response. METHODS: We retrospectively included 74 patients who were treated with NAC followed by surgery at Lucus Augusti Hospital between January 2015 and September 2020. Simple logistic regression was used to evaluate the factors associated with axillary pathological complete response, including the changes in breast tumour ADC-values due to the treatment. RESULTS: Axillary complete response was correlated with negative oestrogen receptor status, Her2 positivity and response of primary tumour. It was achieved in 31% of the patients. In addition, the increase in the tumour ADC-values with NAC was higher for responders. Among the tumours that demonstrated an increase in ADC-value >0.92 ×10-3 mm2/s, 42.8% (15/35) showed axillary complete response. Eight (20.5%) breast cancers with an increase in ADC below the cut-off value were found to have no metastatic nodes after treatment (p = 0.038). CONCLUSION: Our results suggest that the performance of models predicting axillary response to NAC can be improved by adding the tumour response determined also using diffusion-weighted imaging. ADVANCES IN KNOWLEDGE: For the fist time, we investigate the relation between tumour response to NAC, assessed using diffusion-weighted imaging, and axillary pathologic complete response.

Can dedicated breast PET help to reduce overdiagnosis and overtreatment by differentiating between indolent and potentially aggressive ductal carcinoma in situ?

OBJECTIVES: To analyze the utility of metabolic imaging, and specifically of dedicated breast positron emission tomography (dbPET) to differentiate between indolent and potentially aggressive ductal carcinoma in situ (DCIS). METHODS: After institutional review board approval, we retrospectively reviewed the cases of pure DCIS who underwent dbPET before biopsy and surgery in Lucus Augusti Universitary Hospital (Lugo, Spain) and in Fudan Cancer Institute (Shanghai, China) between January 2016 and May 2018. Grade 1 and "non-comedo" grade 2 DCIS were considered low-risk disease, while intermediate-grade with necrosis or grade 3 cases were included in the high-risk group. DbPET sensitivity and specificity to differentiate between indolent and potentially aggressive DCIS were determined along with their respective 95% confidence intervals. RESULTS: We enrolled 139 surgery-confirmed pure DCIS cases. Fifty were high-risk neoplasms and 89 low-risk DCIS. Only seven low-risk lesions were positive at dbPET and five of potentially aggressive neoplasms did not show FDG uptake, all included into the field of view (FOV). Sensitivity and specificity of dbPET to differentiate between indolent and potentially aggressive DCIS were 90% (95% CI, 77-96%) and 92% (95% CI, 84-97%), respectively. CONCLUSION: Metabolic imaging could help to identify the subgroup of indolent lesions from those potentially aggressive ones that may be managed by active surveillance. KEY POINTS: • Low- and high-grade DCIS likely arise from two distinct evolutionary paths and when low-grade lesions progress to invasive cancer, the tumor is frequently low grade and well differentiated. • Ongoing clinical trials evaluate whether patients with low-risk DCIS could be safely managed by an active surveillance approach, with avoidance of unnecessary treatments and without impact on ipsilateral invasive breast cancer free survival time. • Dedicated breast PET may differentiate harmless from potentially hazardous DCIS, supporting active surveillance for the management of those women with low-grade DCIS, decreasing the rate of the upgrade to invasive carcinoma at surgical excision.

Percutaneous removal of benign phyllodes tumor of the breast: An alternative to surgery.

We aimed to evaluate the efficacy of vacuum assisted percutaneous excision in the treatment of benign phyllodes tumors of the breast. From 2007 to 2016, a total of 160 benign fibroepithelial nodules were percutaneously removed in our department. Ultrasonographic follow-up was performed 12 months after the procedure to assess recurrence. Out of the 160 nodules excised, 11 lesions corresponded to benign phyllodes tumors. The median patient age was 39.7 years. The average size of the lesion was 16.9 mm. Ultrasound-guided biopsy was performed before the percutaneous removal in eight of them. Six were histopathologically diagnosed as fibroadenomas, one as phyllodes tumor and in one case histological findings were inconclusive. The mean surveillance period was 27.7 months. During the follow-up period, local recurrence was detected in one patient (9%). We conclude that percutaneous excision of benign phyllodes tumors is not associated with greater risk of recurrence than surgery.