Available online http://breast-cancer-research.com/content/7/6/R1017
Vol 7 No 6Research article
Patterns of reduced nipple aspirate fluid production and ductal
lavage cellularity in women at high risk for breast cancer
Susan A Higgins1, Ellen T Matloff2, David L Rimm3, James Dziura4, Bruce G Haffty5 and
Bonnie L King6
1Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA
2Yale Cancer Center Genetics Counseling Shared Resource, Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
3Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
4General Clinical Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA
5Department of Radiation Oncology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
6Department of Biological Sciences, Quinnipiac University, Hamden, CT, USA
Corresponding author: Bonnie L King, email@example.com
Received: 9 Aug 2005 Accepted: 23 Sep 2005 Published: 24 Oct 2005
Breast Cancer Research 2005, 7:R1017-R1022 (DOI 10.1186/bcr1335)
This article is online at: http://breast-cancer-research.com/content/7/6/R1017
© 2005 Higgins et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/
2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Introduction Nipple aspiration is a noninvasive technique for
obtaining breast fluids from the duct openings of the nipple for
the evaluation of abnormalities associated with breast cancer.
Nipple aspirate fluid (NAF) can be elicited from 48 to 94% of
healthy women, and its production has been linked to an
increased relative risk for breast cancer development. NAF
production has been used in studies to guide the selection of
ducts for ductal lavage, a procedure in which ducts are
cannulated and flushed with saline to collect cells. In a previous
multicenter trial to evaluate intraductal approaches in women at
high-risk for breast cancer, NAF production was observed in
84% of the subjects. However, we observed a significantly
lower proportion of fluid-yielding subjects in a similar series of
high-risk women. The purpose of the present study was to
identify variables associated with this reduction.
Method Nipple aspiration was performed on 33 high-risk
women (defined as having a 5-year Gail model index of more
than 1.7, a personal or family history of breast cancer, and/or a
BRCA1 or BRCA2 germline mutation) to identify ductal orifices
for lavage procedures. Lavage was performed on all fluid-
yielding ducts and on nine non-fluid-yielding ducts.
Results Fluid-yielding ducts were identified in 12 of 33 (36%)
of the subjects in the present series, compared with 16 of 19
(84%) of the subjects undergoing identical procedures at our
facility during a multicenter trial (P = 0.001). Reduced NAF
yields were associated with postmenopausal status (P = 0.02),
BRCA germline mutations (P = 0.004), and risk reduction
therapies, including bilateral salpingo-oophorectomy (BSO)
and/or selective estrogen receptor modulators (SERMs; P =
0.009). All nine (100%) of the ductal lavage specimens
collected from non-fluidyielding ducts were acellular, in
comparison with 3 of 13 specimens from fluid-yielding ducts (P
Conclusion Analysis of high-risk women in the present series
revealed patterns of reduced NAF production and ductal lavage
cellularity compared with a previous multicenter trial. The
present series included more BRCA-positive women, many of
whom had undergone BSO and/or were using SERMs. Our
data suggest that endocrine mechanisms associated with these
risk-reducing therapies may be related to patterns of diminished
breast fluid production.
Nipple aspiration is a noninvasive suction technique used to
obtain breast fluid from the duct openings at the nipple. The
procedure elicits droplet formation from one or more ducts in
48 to 94% of healthy, nonlactating women, and these fluids
often contain exfoliated ductal epithelial cells [1-10]. The nip-
ple aspiration technique has been studied for several decades
as a potential screening tool to detect cytologic abnormalities
associated with proliferative breast lesions [1,5,7,11-13].
Long-term follow-up of women undergoing nipple aspiration
BRCA = breast cancer predisposition gene; BSO = bilateral salpingo-oophorectomy; ICMD = insufficient cells to make a diagnosis; NAF = nipple
aspirate fluid; SERM = selective estrogen receptor modulator.
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