Cancer - 1 July 1983 - Ownby - Peripheral Lymphocyte and Eosinophil Counts As Indicators of Prognosis in Primary Breast
Cancer - 1 July 1983 - Ownby - Peripheral Lymphocyte and Eosinophil Counts As Indicators of Prognosis in Primary Breast
Cancer - 1 July 1983 - Ownby - Peripheral Lymphocyte and Eosinophil Counts As Indicators of Prognosis in Primary Breast
See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Peripheral Lymphocyte and Eosinophil Counts as
Indicators of Prognosis in Primary Breast Cancer
HELEN E. OWNBY, PHD, LARRY D. ROI, PHD, RUTH R. ISENBERG, BA, MICHAEL J. BRENNAN, MD, AND
THE BREAST CANCER PROGNOSTIC STUDY ASSOCIATES
As a part of a major study on the pathophysiologic indices for recurrence of human breast cancer,
preoperative eosinophil and lymphocyte counts were determined on 419 and 581 primary breast cancer
patients, respectively. Patients with lymphocyte counts less than or equal to 1500/mm3 and/or eosin-
ophil counts of less than 55/mm3 had significantly higher risk of recurrent disease than those patients
who had normal or high levels of eosinophils and/or lymphocytes. These findings may indicate that
the immunologic activities of eosinophils and lymphocytes enhance the patients’ ability to respond
against disease.
Cancer 52:126-130, 1983.
126
10970142, 1983, 1, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19830701)52:1<126::AID-CNCR2820520123>3.0.CO;2-Y by Cochrane Mexico, Wiley Online Library on [24/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
No. I EOSINOPHIL
A N D LYMPHOCYTE
LEVELSIN BREASTCA Ownby et al. 127
Results
'"1
0
p = 0178
14 28 42 56 70
2
three, and four years is 3 1.2 k 5.1, 3 1.2 f 5.1, and 35.3
k 6.3, respectively. In contrast, 302 patients having lym-
phocyte counts greater than 1500 cells/mm3 and eosin-
ophil counts greater than 54 cells/mm3 had estimated
respective two, three, and four-year recurrence rates of
19.1 k 2.6, 25.8 f 3.1, and 29.3 f 3.6% for the three
time periods. As shown in Figure 4,the curves for the
two groups are significantly different (P< .01).After age
adjustment of the lymphocyte counts, 143 patients hav-
ing either low lymphocyte (<2000 cells/mm3) and low
eosinophil ( 4 5 cells/mm3) counts or a combination of
low eosinophil, high lymphocyte or high eosinophil, low
01
4 lymphocyte counts, the estimated recurrence rates for
this group at two, three, and four years are 29.6 f 4.3,
0 14 28 42 56 70
32.3 -t 4.5, and 37.1 -t 5.3, respectively. In contrast, 265
Time (Months)
patients with high lymphocyte and eosinophil counts
FIG.3. Time to recurrence for patients with age-adjusted peripheral had estimated respective two, three, and four-year re-
lymphocyte counts less than 2 0 0 0 cells/mm' (- - -) and equal to or currence rates of 18.1 f 2.8, 24.5 f 3.3, and 26.9
greater than 2000 cells/mm' (-).
f 3.6% for the three time periods. As shown in Figure
5 , the curves for the two groups are significantly different
cells/mm3. The two-year estimated recurrence rate is (P< 0.002).
28.5 f 3.9%, for patients with less than 2000 cells/mm3 The above analysis indicates that these associations
and 18.9 t 2.3% for those patients with greater than or between cell counts are highly significant predictors of
equal to 2000 cells/mm3. In Figure 3 the percent of recurrence. Further analysis of our data was camed out
patients disease-free as a function of time is plotted for to see whether lymphocyte and eosinophil counts are
both groups. The time to recurrence is significantly dif- independent predictors of recurrence or, alternatively,
ferent between the two groups (P< 0.005). whether their significance may be explained by associ-
One hundred and six of the patients examined above ation with other predictors. The percentage of counts
have either low eosinophil and low lymphocyte counts, in the low group for both eosinophils and lymphocytes
or a combination of low eosinophil, high lymphocyte is associated with the clinical stage (TNM)" of the dis-
or high eosinophil, low lymphocyte counts. The esti- ease (Tables 2 and 3), in that a higher percentage of
mated percent recurrence rates for this group at two, patients in Stage 4 have low eosinophil counts and/or
100 100
90 90
(u a,
2
Lf 60
:
Lt
80
e,
m v,
m
0
c High ;
-
n
e,
C
70
L - --- -- -- -
(n = 302) -
m
C
70
0 Low
2 60 (n = 106) $
a
6C
5c "= 002
50 p = 0252
0 0
0 14 28 42 56 70 0 14 28 42 56 70
FIG.4. Time to recurrence for patients with unadjusted lymphocyte FIG.5. Time to recurrence for patients with age-adjusted lympho-
and eosinophil counts, low for both or low for either lymphocyte or cyte and eosinophil counts, low for both or low for either lymphocyte
eosinophil counts (- - -)and high for both lymphocyte and eosinophil or eosinophil counts (- - -) and high for both lymphocyte and eosin-
counts (-). ophil counts (-).
10970142, 1983, 1, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19830701)52:1<126::AID-CNCR2820520123>3.0.CO;2-Y by Cochrane Mexico, Wiley Online Library on [24/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
No. 1 EOSINOPHIL
AND LYMPHOCYTE
LEVELSIN BREASTCA * Ownby ef a/. 129
low lymphocyte counts. Examination of the number of TABLE3. Relationship of Lymphocyte Count
lymphocytes and eosinophils however by stage did not to Clinical Stage (TNM)
show any groups with significantly different counts (< 1650/mm’)
(Kruskal-Wallis, Student’s t, or median test) for all pa- Stage No. patients Ilow lymph
tients or for those in age groups 20-39, 40-59, 60-79, 1 213 23.9
or older than 80 years (Table 4 and 5). Neither lym- 2 252 18.3
phocyte nor eosinophil counts were related to the age 3 39 20.5
of the patient by Spearman’s rho rank correlation coef- 4 -71 33.8
ficient (P> 0.05). Also, the cell counts are not associated 575*
individually by other prognostic indicators such as nodal ( x z ) P < 0.05 for differences among all four stages
status (P< 0.2), maximum tumor diameter (P< O.l), P < 0.02 for stages 1-111 versus IV
Bloom and Richardson tumor grade (P < 0.3), or es-
trogen receptor content of the tumor (P< 0.3). * Six patients with lymphocyte counts were not staged.
After taking into account nodal status, maximum tu-
mor diameter, tumor grade and estrogen receptor, nei- TABLE4. Pretreatment Peripheral Lymphocyte
Counts by Stage and Age
ther the eosinophil count (P< 0.2) nor the lymphocyte
count (P> 0.3) were significantly associated with time Age (YB)
to recurrence by likelihood ratio chi-square in the Cox
Stage 20-39 40-59 60-79 80+ All ages
regression analysis.
I 27/2214* 10412282 9212 176 I 112085
Discussion (1041) (966) (772) (873)
I1 1612231 14512197 1 1312I80 1312009
To our knowledge, this is the first time that a low (740) (847) (791) (870)
Ill 0 312166 251201 5 1312207 312654
eosinophil count has been implicated as an indicator of ( 1404) (896) (684) (969)
poor prognosis in breast cancer. The role of the eosin- IV 312217 3012095 4411859 213045
ophil has remained one of mystery since its discovery (778) (939) (697) (822)
by Ehrlich over a century ago.” The current hypothesis * No. patientstmean count (SD).
for the role of these cells include two very diverse modes
of operation; one which considers the role of eosinophils parallel the magnitude of eosinophilic response in tissues
as protective against parasitic and antimicrobial infec- to a variety of material^.'^"^ Therefore, it is impossible
tions and another which considers the eosinophil as a to predict the patient’s eosinophilic response to her tu-
modulator of anaphylaxis. ‘**I3 mor by her peripheral blood cell counts. Over 50 cases
Jong and KlebanoP4 have shown that intact stimu- of hypereosinophilia among patients with various can-
lated guinea pig eosinophils are cytotoxic to mouse as- cers including two with breast cancer have been re-
cites lymphoma cells (LSTRA) by the mechanism of the In most cases, metastases were already pres-
eosinophil peroxidase-peroxide-halide system. The as- ent, and the high eosinophil counts were considered to
sociation of low peripheral eosinophil count with early be indicators of poor prognosis.
development and metastatic breast cancers may have The lymphocyte count has been implicated as an in-
such a basis. However, other studies have established dicator of prognosis for breast cancer patients by nu-
that the circulating eosinophil level does not necessarily merous investigators. Riesco” found a positive corre-
(<55/mm3) Age
Stage No. patients Ilow EOS
Stage 20-39 40-59 60-79 80+ All ages
1 152 7.2
2 183 7.7 I 21/155* 791160 581166 1641163
3 30 3.3 ( I 40) (134) (118) (128)
II 81129 1041231 881162 2 101196
4 -50 20
( 1 16) (69 1) ( 1 33) (495)
415. III 41143 211126 51157 331138
( x 2 ) P < 0.02 for differences among all four stages (120) (70) (73) (75)
IV 312 17 2011 10 311164 561149
( x 2 ) P < 0.003 for Stages 1-111 versus 1V ( 1 19) (90) (1 70) (144)
* Four patients with eosinophil counts were not staged. * No. patientstmean count (SD).
10970142, 1983, 1, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19830701)52:1<126::AID-CNCR2820520123>3.0.CO;2-Y by Cochrane Mexico, Wiley Online Library on [24/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
130 CANCERJuly 1 1983 Vol. 52
lation between breast cancer “curability” and the total of eosinophils and lymphocytes in breast cancer patients
number of peripheral lymphocytes. In a study of 305 who subsequently develop metastatic disease.
breast cancer patients Papatestas and Kark4 showed that
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