Background: We previously showed that women with abnormal cytology in breas
t fluid obtained by nipple aspiration had an increased relative risk (RR) o
f breast cancer compared with women from whom fluid was not obtained and wi
th women whose fluid had normal cytology. This study extends the followup i
n the original study group (n = 4046) and presents the first follow-up for
a second group of women (n = 3627). Methods: We collected nipple aspirate f
luid from women in the San Francisco Bay Area during the period from 1972 t
hrough 1991, classified the women according to the most severe epithelial c
ytology observed in fluid specimens, and determined breast cancer incidence
through March 1999. We estimated RRs for breast cancer using Cox regressio
ns, adjusting for age and year of study entry. All statistical tests were t
wo-sided. Results: For women in the first and second study groups, the medi
an years of follow-up were 21 years and 9 years, respectively, and breast c
ancer incidences were 7.8% (285 cases in the 3633 women for whom breast can
cer status could be determined) and 3.5% (115 of 3271), respectively. Compa
red with women from whom no fluid was obtained, whose incidences of breast
cancer were 4.7% (39 of 825) and 3.3% (65 of 1950) for those in group 1 and
group 2, respectively, incidences and adjusted RRs were 8.1% (34 of 422),
with RR = 1.4 (95% confidence interval [CI] = 0.9 to 2.3), and 0% (0 of 31)
, respectively, for those with unsatisfactory aspirate specimens and 8.2% (
148 of 1816), with RR = 1.6 (95% CI = 1.1 to 2.3), and 3.1% (25 of 811), wi
th RR = 1.2 (95% CI = 0.8 to 2.0), respectively, for those with normal cyto
logy in aspirates. Compared with women from whom no fluid was obtained, inc
idences and adjusted RRs for women in group 1 with epithelial hyperplasia a
nd atypical hyperplasia in aspirates were 10.8% (52 of 483), with RR = 2.4
(95% CI = 1.6 to 3.7), and 13.8% (12 of 87), with RR = 2.8 (95% CI = 1.5 to
5.5), respectively, while those for women in group 2 were 5.5% (25 of 457)
and 0% (0 of 22), respectively, with a combined RR = 2.0 (95% CI = 1.3 to
3.3). Conclusion: The results obtained with the newly followed women indepe
ndently confirmed previous findings that women with abnormal cytology in ni
pple aspirates of breast fluid have an increased risk of breast cancer.