Successful oxytocin-assisted nipple aspiration in women at increased risk for breast cancer

Suijkerbuijk, Karijn P M; Wall, Elsken van der; Meijrink, H; Pan, Xun; Rinkes, Inne H.M. Borel; Ausems, Margreet G. E. M.; Diest, Paul J. van

doi:10.1007/s10689-010-9344-7

Cited by 24 publications

(41 citation statements)

References 10 publications

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“…In order to provide a suitable screen approach for breast cancer specific biomarkers, increased success in expression and collection will be required. Improved expression rates can be achieved with the aid of oxytocin nasal spray [18,40] as well as application of manual or mechanical pumps that are normally used for milk expression by mothers with preterm infants [41].…”

Section: Discussionmentioning

confidence: 99%

Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Shaheed

Tait

Kyriacou

et al. 2017

Proteomics Clinical Apps

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PurposeNipple secretions are protein‐rich and a potential source of breast cancer biomarkers for breast cancer screening. Previous studies of specific proteins have shown limited correlation with clinicopathological features. Our aim, in this pilot study, was to investigate the intra‐ and interpatient protein composition of nipple secretions and the implications for their use as liquid biopsies.Experimental designMatched pairs of nipple discharge/nipple aspirate fluid (NAF, n = 15) were characterized for physicochemical properties and SDS‐PAGE. Four pairs were selected for semiquantitative proteomic profiling and trypsin‐digested peptides analyzed using 2D‐LC Orbitrap Fusion MS. The resulting data were subject to bioinformatics analysis and statistical evaluation for functional significance.ResultsA total of 1990 unique proteins were identified many of which are established cancer‐associated markers. Matched pairs shared the greatest similarity (average Pearson correlation coefficient of 0.94), but significant variations between individuals were observed.Conclusions and clinical relevanceThis was the most complete proteomic study of nipple discharge/nipple aspirate fluid to date providing a valuable source for biomarker discovery. The high level of milk proteins in healthy volunteer samples compared to the cancer patients was associated with galactorrhoea. Using matched pairs increased confidence in patient‐specific protein levels but changes relating to cancer stage require investigation of a larger cohort.

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Section: Discussionmentioning

confidence: 99%

Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Shaheed

Tait

Kyriacou

et al. 2017

Proteomics Clinical Apps

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“…After this feasibility study, we started the prospective collection of nipple fluid in women at increased risk of breast cancer, our target population for introducing a potential new screening method. Preliminary results showed that NFA was also possible in this group of women [ 21 ]. In the present follow-up study, we show for the first time in a large group of high-risk women that repetitive NFA is a feasible and safe method.…”

Section: Discussionmentioning

confidence: 99%

“…Although low nipple volumes may hamper a multidisciplinary biomarker approach, we believe much of its limitations can be overcome due to the continuous development of increasingly sensitive techniques, and all-in-one DNA/RNA/protein isolation methods. Besides, we have already demonstrated that methylation analysis in nipple fluid samples from high risk women is feasible [ 21 ]. At this moment we are analysing the nipple fluid samples to investigate if the process of breast carcinogenesis can be predicted by the occurrence of methylation aberrations.…”

Section: Discussionmentioning

confidence: 99%

“…The technique of NFA has been previously described [ 17 , 21 ]. In short, anaesthetic cream (Emla) was applied onto the nipple, after which the breasts were warmed with hot pads.…”

Section: Methodsmentioning

confidence: 99%

“…Besides being less invasive, NFA causes less discomfort and is easier to perform compared to invasive techniques [ 19 ]. We have previously shown that, with this technique, nipple fluid can be obtained successfully and without discomfort in healthy women and women at increased risk of breast cancer [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Repeated Nipple Fluid Aspiration: Compliance and Feasibility Results from a Prospective Multicenter Study

et al. 2015

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BackgroundDespite intensive surveillance, a high rate of interval malignancies is still seen in women at increased breast cancer risk. Therefore, novel screening modalities aiming at early detection remain needed. The intraductal approach offers the possibility to directly sample fluid containing cells, DNA and proteins from the mammary ductal system where, in the majority of cases, breast cancer originates. Fluid from the breast can non-invasively be obtained by oxytocin-assisted vacuum aspiration, called nipple fluid aspiration (NFA). The goal of this feasibility study was to evaluate the potential of repeated NFA, which is a critical and essential step to evaluate its possible value as a breast cancer screening method.MethodsIn this multicenter, prospective study, we annually collected nipple fluid for up to 5 consecutive years from women at increased breast cancer risk, and performed a questionnaire-based survey regarding discomfort of the aspiration. Endpoints of the current interim analyses were the feasibility and results of 994 NFA procedures in 451 women with total follow-up of 560 person years of observation.ResultsIn this large group of women at increased risk of breast cancer, repetitive NFA appeared to be feasible and safe. In 66.4% of aspirated breasts, nipple fluid was successfully obtained. Independent predictive factors for successful NFA were premenopausal status, spontaneous nipple discharge, smaller breast size, bilateral oophorectomy and previous use of hormone replacement therapy or anti-hormonal treatment. The procedure was well tolerated with low discomfort. Drop-out rate was 20%, which was mainly due to repeated unsuccessful aspiration attempts. Only 1.6% of women prematurely declined further participation because of side effects.ConclusionsRepeated NFA in women at increased breast cancer risk is feasible and safe. Therefore, NFA is a promising method to non-invasively obtain a valuable source of potential breast cancer specific biomarkers.

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Diagnostic values of GHSR DNA methylation pattern in breast cancer

Botla

Gholami

Malekpour

et al. 2012

Breast Cancer Res Treat

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DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (n = 52, p < 2.1 × 10(-4)) and its performance was assessed through bisulphite pyrosequencing in an independent validation set (n = 65, p < 1.9 × 10(-7)). The signature is associated with SFRP2 and GHSR genes, and exhibited significant hypermethylation in cancers. Normal-appearing breast tissues from cancer patients were also methylated at these loci but to a markedly lower extent. This occurrence of methylated DNA in normal breast tissue of cancer patients is indicative of an epigenetic field defect. Concerning diagnosis, receiver operating characteristic curves and the corresponding area under the curve (AUC) analysis demonstrated a very high sensitivity and specificity of 89.3 and 100 %, respectively, for the GHSR methylation pattern (AUC >0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion.

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Successful oxytocin-assisted nipple aspiration in women at increased risk for breast cancer

Cited by 24 publications

References 10 publications

Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Repeated Nipple Fluid Aspiration: Compliance and Feasibility Results from a Prospective Multicenter Study

Diagnostic values of GHSR DNA methylation pattern in breast cancer

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