Is There a Future for Ductal Lavage?

Abstract

Non-lesion-directed minimally invasive breast tissue sampling is currently used in the research setting both for risk stratification and for acquisition of material for response biomarkers in phase II chemoprevention trials. Prospective data linking morphology to eventual development of cancer are currently available only for nipple aspirate fluid harvest (NAF) and random periareolar fine needle aspiration (RPFNA). The finding of atypia with either of these two techniques increases relative risk to a level at least as great as that which would be expected with atypical hyperplasia in a diagnostic biopsy (1, 2). Both techniques improve risk predictions based on the widely used Gail model. NAF has been shown to improve discriminatory accuracy for average risk (3), and RPFNA improves discriminatory accuracy for high-risk (4) cohorts. The main drawback for NAF is that f15% to 50% of women do not produce it and, even if produced, NAF generally contains few epithelial cells (1, 5). Although RPFNA produces an evaluable cytomorphology specimen in more than 90% of high-risk women (2), if severe atypia is encountered, the location of the abnormality is uncertain. It was hoped that ductal lavage would overcome the drawbacks of both the NAF and RPFNA procedures. Ductal lavage might provide more cells and evaluable cytomorphology more frequently than NAF. The ability to identify and recannulate specific ducts would theoretically give ductal lavage an advantage over RPFNA by reducing sampling variance in prevention trials as well as providing a means of identifying the site of very abnormal cells if and when they are encountered.At first, the future seemed bright for ductal lavage. Dooley et al. (5) in a multicenter study reported that 60% of high-risk women presenting for breast tissue -based risk assessment were able to produce NAF, successfully underwent duct cannulation, and had evaluable epithelial cells in their ductal lavage specimen. Further, the median number of cells from evaluable specimens was increased from 120 with NAF to 4,000 to 13,500 with ductal lavage (5). Other investigators reported similar results (6, 7). Investigators highly skilled in this technique have reported that even non -NAF-producing ducts could be cannulated, and epithelial cells harvested (8 -10); however, a lavage is more likely to yield adequate cells if women undergoing this procedure produce NAF and are premenopausal (11,12). Based on these preliminary studies, an industry-sponsored trial was initiated in which women undergo ductal lavage at intervals and are then followed for the development of breast cancer.A study by Khan et al. (9) markedly diminished hope that ductal lavage might be used as a reliable early detection tool because the sensitivity of lavage in breasts known to have cancer was only 13% to 42%, depending on whether mild or severe atypia was used as the indicator lesion. This seeming paradox may be explained by the fact that not all cancers are associated with fluid production, nor do they all originate in ducts that empt...

Ductal Lavage in Women from BRCA1/2 Families: Is There a Future for Ductal Lavage in Women at Increased Genetic Risk of Breast Cancer?

“…Neither NAF production nor 5-year Gail risk >1.7% (15) predicted atypia in ductal lavage specimens from high-risk women (7, 16). Whether women with atypia detected by ductal lavage will show an increased prospective risk of breast cancer is unknown, and there is increasing evidence that reproducibility of cytologic diagnoses in benign duct epithelial specimens and in specimens with atypia found on ductal lavage is fair to poor (9, 11, 17). …”

Tolerability of breast ductal lavage in women from families at high genetic risk of breast cancer

“…It was hypothesized that women with cellular atypia in DL samples would also be at increased breast cancer risk. However, obtaining adequate numbers of cells from DL samples for both cytological review and biomarker development has been a challenge [ 6 ]. Reliably obtaining NAF from all or most women studied, and acquiring samples with cell counts adequate for cytologic evaluation (> 10 evaluable cells) from DL specimens has been problematic [ 1 , 7 - 19 ].…”

“…Reliably obtaining NAF from all or most women studied, and acquiring samples with cell counts adequate for cytologic evaluation (> 10 evaluable cells) from DL specimens has been problematic [ 1 , 7 - 19 ]. Neither NAF production nor 5-year Gail risk > 1.7% [ 6 , 20 , 21 ] predicted atypia in DL specimens from high-risk women [ 9 , 21 ]. It is possible to detect atypia in both NAF-yielding and non-NAF-yielding ducts from women at high-risk of breast cancer [ 6 , 7 , 9 , 12 ]; however, it is not known whether the atypia detected by DL will demonstrate an increased prospective risk of breast cancer in women at high genetic risk of breast cancer, and there is increasing evidence that reproducibility of cytologic diagnoses in benign duct epithelial specimens and in specimens with atypia found on DL is only fair-to-poor [ 6 , 11 , 13 , 17 ].…”

Η κλινική σημασία της διερεύνησης των γαλακτοφόρων πόρων του μαστού με την τεχνική First Cyt® σε γυναίκες χαμηλού κινδύνου για ανάπτυξη καρκίνου του μαστού

“…Συνήθως η ενδοεπιθηλιακή νεοπλασία των λοβίων είναι τυχαίο εύρημα χωρίς κλινική συμπτωματολογία. Η υποδιαίρεση σε ALH και LCIS είναι σημαντική διότι ο κίνδυνος εξέλιξης σε διηθητικό καρκίνο είναι διαφορετικός (RR 3-5,3 για το ALH, RR 5,7-11 για το LCIS).Βάσει νέων δεδομένων, οι παρόμοιες γενετικές αλλοιώσεις σε LIN και λοβιακό καρκίνωμα (βλάβη χρωμοσωμικού υλικού σε 16q και 17p ) δείχνουν ότι τα LIN αποτελούν ένα πρόδρομο στάδιο πρόδρομο καρκινώματος75 .Ο κίνδυνος ανάπτυξης καρκίνου μαστού σε άτομα με καλοήθη νοσήματα είναι υπαρκτός, με τα νοσήματα αυτά να είναι ποικίλων ιστολογικών υποτύπων όπως αναφέρθηκε παραπάνω.O όρος benign proliferative breast disease (BPBD) αφορά πολλούς ιστολογικούς τύπους καλοήθων νοσημάτων των οποίων η επιδημιολογία έχει μελετηθεί πολύ ,όπως και η ποικιλία των ιστολογικών της τύπων.Είναι γνωστό ότι ο κίνδυνος ανάπτυξης των ΒΡΒD αυξάνεται όταν ο μαζικός αδένας διαθέτει >25% αυξημένη πυκνότητα[76][77][78][79][80][81][82][83] . Η πιθανή διάγνωση των BPBD (τα οποία είναι κυρίως με τη μορφή ψηλαφητού ή μη μορφώματος ή και μικροαποτιτανώσεων του μαστού ) τίθεται σχεδόν αποκλειστικά με τις απεικονιστικές μεθόδους .Η ταξινόμηση των ευρημάτων ακολουθεί την κατηγοριοποίηση κατά BIRADS (Breast Imaging Reporting and Data System) ,βάσει της οποίας αποφασίζεται η περαιτέρω προσέγγιση.…”