Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer.

Mammography is extensively used for breast cancer screening but has high false-positive rates. Here, prospectively collected blood samples were used to identify circulating microRNA (miRNA) biomarkers to discriminate between malignant and benign breast lesions among women with abnormal mammograms. The Discovery cohort comprised 72 patients with breast cancer and 197 patients with benign breast lesions, while the Validation cohort had 73 and 196 cancer and benign cases, respectively. Absolute expression levels of 324 miRNAs were determined using RT-qPCR. miRNA biomarker panels were identified by: (1) determining differential expression between malignant and benign breast lesions, (2) focusing on top differentially expressed miRNAs, and (3) building panels from an unbiased search among all expressed miRNAs. Two-fold cross-validation incorporating a feature selection algorithm and logistic regression was performed. A six-miRNA biomarker panel identified by the third strategy, had an area under the curve (AUC) of 0.785 and 0.774 in the Discovery and Validation cohorts, respectively, and an AUC of 0.881 when differentiating between cases versus those with benign lesions or healthy individuals with normal mammograms. Biomarker panel scores increased with tumor size, stage and number of lymph nodes involved. Our work demonstrates that circulating miRNA signatures can potentially be used with mammography to differentiate between patients with malignant and benign breast lesions.

Understanding the Psychosocial Needs of Women who Present with Advanced Breast Cancer.

INTRODUCTION: Advanced breast cancer (ABC) remains common in Singapore. In 2019, 22.1% of breast cancer patients presented with ABC in our institution. Despite increasing affluence and the advent of national mammographic screening, the incidence of ABC has not changed significantly. This suggests inherent differences in women who present late. We aim to explore the socio-economic background, knowledge and attitudes of women who present with ABC. METHODS: Between December 2013 and July 2015, 100 patients who presented consecutively with ABC in a tertiary institution in Singapore were recruited to participate in an interviewer-led questionnaire exploring psychosocial and economic issues. RESULTS: Among the 100 patients, 63 and 37 presented with stages 3 and 4 breast cancer respectively. Median age was 57 (27-86), 52% had at least secondary education, 53% had no formal employment and 71% were married; 88% were aware of breast cancer symptoms, 82% were aware that mammography can help detect cancer, 82% believed that current treatment modality for breast cancer is effective, 96% had never undergone a mammography and 52.9% felt mammograms were unnecessary. A total of 64% presented symptomatic from the breast tumour, with a median duration of 3 months. Many of the patients were aware of breast cancer symptoms and the utility of mammography. However, a group of patients did not comply with screening. This may be due to poor understanding about breast screening and detection in its asymptomatic phase. CONCLUSION: Further public education to improve understanding of breast cancer and screening mammography may help to improve rates for earlier detection of breast cancer.

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms.

Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training (n = 125) and test (n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms.

Predictors of invasive breast cancer in ductal carcinoma in situ initially diagnosed by core biopsy.

BACKGROUND: Some patients who are initially diagnosed with ductal carcinoma in situ (DCIS) by core biopsy eventually have their disease upstaged to invasive carcinoma on final excision, thus warranting some form of axillary staging. This study aimed to identify the predictors of invasive breast cancer in DCIS diagnosed by core biopsy, which could then help clinicians decide which cases of biopsy-diagnosed DCIS should undergo concurrent sentinel lymph node biopsy during excision. METHODS: The records of 95 consecutive patients diagnosed with pure DCIS from 100 core biopsies from January 2005 to August 2007 were retrospectively reviewed. The clinical, radiological and pathological characteristics of these 100 cases were correlated with the presence of invasion or microinvasion on excision. RESULTS: Factors that are associated with invasive or microinvasive foci on excisional histology are: size of target lesion on radiography ≥ 20 mm [odds ratio: 6.738 (1.050-43.236), p = 0.044] and ≤ 10 cores obtained [odds ratio: 22.343 (2.351-212.385), p = 0.007]. CONCLUSION: Underestimation of invasive breast cancer in core biopsy-diagnosed DCIS is related to the size of the lesion on radiography, as well as the number of cores obtained during biopsy.

Use of the extended V-Y latissimus dorsi myocutaneous flap for chest wall reconstruction in locally advanced breast cancer.

The extended V-Y latissimus dorsi myocutaneous flap described by Micali and Carramaschi provides an innovative method of closing large anterior chest defects after resection of breast cancer. The technique provides robust chest wall coverage that is able to withstand immediate postoperative radiotherapy. The aim of this article is to confirm the usefulness of the flap's design and describe modifications to the technique. The modifications to technique include: a curvilinear design that recruited more skin for closure in patients with wounds extending laterally or superiorly, routine transposition of latissimus dorsi insertion inferio-medially onto the chest wall to maximize pedicle reach, and the use of small split skin grafts or delayed primary closure if there was tension in closing. Twelve patients who underwent resection of locally advanced breast cancer had immediate chest wall reconstruction with the extended V-Y latissimus dorsi musculocutaneous flap. The V to Y design of the flap's cutaneous island allowed primary closure of chest wound and donor defect. There were no instances of chest wound dehiscence. The chest wounds healed, allowing patients to undergo adjuvant radiotherapy in a mean time interval of 6 weeks after surgery.