Proteins and carbohydrates in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy

Abstract

BackgroundHerein we present the results of two related investigations. The first study determined if concentrations in breast nipple discharge (ND) of two proteins (urinary plasminogen activator, uPA and its inhibitor, PAI-1) predicted the presence of breast atypia and cancer in pre- and/or postmenopausal women requiring surgery because of a suspicious breast lesion. The second study assessed if these proteins increased the predictive ability of a carbohydrate (Thomsen Friedenreich, TF) which we previously demonstrated predicted the presence of disease in postmenopausal women requiring surgery.MethodsIn the first study we prospectively enrolled 79 participants from whom we collected ND, measured uPA and PAI-1 and correlated expression with pathologic findings. In the second study we analyzed 35 (uPA and PAI-1 in 24, uPA in an additional 11) ND samples collected from different participants requiring breast surgery, all of whom also had TF results.ResultsuPA expression was higher in pre- and PAI-1 in postmenopausal women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .018 and .025, respectively), or benign pathology (p = .017 and .033, respectively); and 2) abnormal (atypia or cancer) versus benign pathology (p = .018 and .052, respectively). High uPA and PAI-1 concentrations and age were independent predictors of disease in premenopausal women, with an area under the curve (AUC) of 83-87% when comparing diseased vs. benign pathology. uPA, TF, and age correctly classified 35 pre- and postmenopausal women as having disease or not 84-91% of the time, whereas combining uPA+PAI-1+TF correctly classified 24 women 97-100% of the time.ConclusionsuPA and PAI-1 concentrations in ND were higher in women with atypia and cancer compared to women with benign disease. Combining uPA, PAI-1 and TF in the assessment of women requiring diagnostic breast surgery maximized disease prediction. The assessment of these markers may prove useful in early breast cancer detection.

Array-Based Sensing Using Nanoparticles: An Alternative Approach for Cancer Diagnostics

“…Noninvasive biofluids are easily-accessibe biological samples, which usually do not involve instrument insertion into the patient’s body. Besides breath, urine, saliva and sweat, other minimally invasive procedures such as nipple aspiration along with ductal lavage can provide many cells collected from the milk ducts [32]. …”

Far Beyond the Usual Biomarkers in Breast Cancer: A Review

“…However, the combination of both TF and uPA biomarkers in nipple aspirate fluid predicted breast cancer in both pre- and postmenopausal women with 84-92% accuracy 21. When used in combination with uPA, PAI-1 and TF have higher predictive capacities to detect breast cancer and achieved accuracy values of 97-100% 21 in nipple aspirate fluid. Therefore, large clinical trials are needed to validate the combination of these biomarkers for the early diagnosis of breast cancer.…”

Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome

“…In the frame of searching cancer biomarkers in breast microenvironment [26,27], a recent study published in BMC Cancer [65] reports an interesting and innovative combinatory analysis of three well-known predictive biomarkers (uPA, PAI-1, and TF) in NAF collected noninvasively (or spontaneously secreted) from healthy women, patients with breast atypia and cancer (in pre- and post-menopause), requiring surgery because of a suspicious breast lesions.…”

“…Although these biomolecules appeared individually not perfectly accurate in predicting the presence of BC during different menopausal status, Sauter’s research team demonstrated the innovative biomarker combination in NAF [65]: 1) uPA concentration alone was more predictive of disease in premenopausal women (AUC values 0.83-0.87); 2) the range of AUC values for uPA+PAI-1 expression in all women was 0.72-0.75; 3) TF antigen alone was better at predicting BC in postmenopausal women showing range of AUC values 0.81-0.83. While TF antigen + uPA expression predicted breast diseases in both pre- and post-menopausal women with 84-92% of accuracy, interestingly and surprisingly when TF uPA + PAI-1 were combined, the predictive ability approached 97-100% allowing the near absolute prediction of both atypia or cancer disease in women requiring surgery because of a suspicious breast lesions (Figure  1).…”