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Usefulness of the Minimum Resistance Index in the Benign–Malignant Discrimination of Breast Tumors
Fig. 38.3 Hypovascular breast carcinoma with a RI of 0.75.
0.4
38
max
0.3
, and RI
mean
, RI
0.2
min
0.1
0.0
–0.1
–0.2
–0.3
03
12 45678 910
for each of the three resistance indices: RI
Difference between tumor-area RI and average RI for 8 quadrants
Number of vascular segments in tumor area
RI
RI
RI
Fig. 38.5 Differences between the resistance indices in the tumor
area and the mean indices for the eight healthy quadrants (positive
difference above thezero axis, negative difference belowthe zero axis)
for the parameters RI
min
(left), RI
(center) and RI
mean
(right), plotted
max
against the number of vascular segments sampled in the tumor area.
max
mean
min
Fig. 38.4 Hypervascular breast carcinoma with a RI of 0.69. Comparing the two postmenopausal women (who were not receiving HRT) in
Figs. 38.3 and 38.4, we note that increasing blood flow is associated
with a proportional decrease in RI.
measured in that area. An average of 1.5 vessels were sampled
in each of the eight healthy quadrants. The mean value of the
RI
of the eight quadrants was 0.65 ⫾ 0.08 SD.
min
When we compare the tumor region with the lowest RI
of all 8–16 sampled vessels (RI
= 0.54 ⫾ 0.1 SD), we find a
min
min
highly significant but opposite difference. This means that—
analogous to our analysis in the tumor area—the calculation of
the lowest RI
and the highest RI
min
in healthy breast tissue
max
again depends on the number of vessels that are sampled.
This also means that the RI
is significantly lower than in
min
the tumor area when 8–16 vessels (12 on average) can be
sampled in the healthy breast tissue. This weakens the basic
hypothesis that tumors constitute a low-resistance system,
and it implies that the RI
in the tumor area would also reach
min
a value of 0.54 if an average of 12 tumor vessels could b e
sampled there. This analysis is outlined in Table 38.
cludes a similar analysis for RI
mean
and RI
max
No Benign–Malignant Discrimination with RI
and RI
max
2, which in-
.
min
We postulate that a similar number of vessels result in similar
values for RI
. This is further supported by the following
min
analysis: of the 114 patients evaluated, one or two vessels were
362
Table 38.2 Mean-value comparison of the parameters RI
min
,RI
mean
, and RI
in the tumor area and in healthy breast tissue, calculated using the
max
two methods described
Parameters Mean value
Tumor area all resistance indices (8 quadrants)
for 8 quadrants
Mean number of vessels 1.5 3.3 12
RI
(n = 114) 0.65 (⫾ 0.08) 0.62 (⫾ 0.11) 0.54 (⫾ 0.1)
min
p = 0.0001 p ⬍ 0.0001
RI
(n = 114) 0.68 (⫾ 0.07) 0.69 (⫾ 0.09) 0.68 (⫾ 0.07)
mean
p =0.13
(n = 114) 0.70 (⫾ 0.07) 0.75 (⫾ 0.1) 0.80 (⫾ 0.07)
RI
max
p ⬍ 0.0001 p ⬍ 0.0001
Standard deviation in parentheses
Summary
sampled from the tumor area in 51 cases. The average RI
min
in
these cases, which included both benign and malignant lesions, was 0.65 (⫾ 0.11 SD). An average of 1.6 vessels were
sampled. The mean RI
for the eight quadrants in these cases
min
was 0.66 (⫾ 0.08 SD). On average, 1.5 vessels were sampled per
healthy quadrant. With an almost equal number of sampled
vessels, no statistically significant differences were found between the calculated values of RI
RI
appears to depend chiefly on the number of vessels ex-
min
(p = 0.67). Consequently,
min
amined and not on the type of tissue examined (tumor or
healthy tissue). Meanwhile, calculation of the RI
min
from all
8–16 sampled vessels yielded a significantly lower value of
0.55 (⫾ 0.01 SD).
Table 38.3 Mean values of RI
in healthy breast tissue (calculated by different methods) compared with mean values in tumor areas having one
min
Since it could be supposed that tumors with a small num-
ber of vessels (one or two) may have a higher RI
with more than two vessels, the first two resistance indices
measured in all 114 of the tumors were analyzed in an
analogous way. The results were essentially equal. This proves
conclusively that RI
sampled (Table 38.
is dependent on the number of vessels
min
3).
This dependence on the number of measurements also
holds for the parameter RI
RI
are not suitable blood flow parameters for a representa-
max
max
tive characterization of the vascular resistance in breast
tumors. Accordingly, these parameters should not be used for
the benign–malignant discrimination of breast lesions.
or two vessels and with the first two vessels sampled in all 114 tumors
1 or 2 vessels in the
tumor area (n =51)
Mean value for
8 quadrants
Tumor area with
1 or 2 vessels
Mean number of vessels 1.5 1.6 12
RI
min
0.66 (⫾ 0.8) 0.65 (⫾ 0.11) 0.55 (⫾ 0.01)
p = 0.67 p ⬍ 0.00001
All tumors
(n =114)
Mean value for
8 quadrants
First 2 RIs
measured in tumor area
than tumors
min
. It is clear, then, that RI
All RI
(8 quadrants)
All RI
(8 quadrants)
min
and
Gynecological Ultrasound
Mean number of vessels 1.5 2.0 12
RI
min
0.65 (⫾ 0.01) 0.64 (⫾ 0.01) 0.54 (⫾ 0.01)
p = 0.63 p⬍ 0.00001
Standard deviation in parentheses
Summary
The results of this study prove the existence of a purely mathematical minimization and maximization effect that substantially influences the calculation of RI
hood of determining the very lowest RI
highest RI
) is critically determined by the number of vessels
max
min
and RI
min
. The likeli-
max
(and the very
that are sampled. These results call into question the validity of
RI
min
(and RI
) in the assessment of true vascularresistance. If
max
any resistance index is to be used in characterizing breast
tumors, our analysis indicates that only the RI
mean
should be
considered.
References
1 Burns PN, Halliwell M, Wells PNT, Webb AJ: Ultrasonic doppler studies
of the breast. Ultrasound in Med. Biol. 8 (1982) 127–143
2 Folkman J: How is blood vessel growth regulated in normal and neo-
plastic tissue? Cancer Res. 46 (1986) 467–473
3 Less JR, Skalak TC, Sevick EM, Jain RK: Microvascular architecture in a
mammary carcinoma: a branching patterns and vessel dimensions.
Cancer Res. 51 (1991) 265–273
4 Madjar H, Prömpeler H, Wolfahrt R, Bauknecht T, Pfleiderer A: Farb-
dopplerflußdaten von Mammatumoren. Ultraschall Med. 15 (1994)
69–76
5 Minasian H, Bamber JC: A preliminary assessment of an ultrasonic
doppler method for the study of blood flow in human breast cancer.
Ultrasound Med. Biol. 8 (1982) 357–364
6 Villena-Heinsen C, Mink D, Ertan AK, Holländer M, Schmidt W: Bewer-
tung der Aussagekraft der Farb- und Spektral-Doppler-Sonographie
bei Mammatumoren. In Schmidt W (ed.): Jahrbuch der Gynäkologie
und Geburtshilfe (1995/1996). Biermann, Zülpich 1996, 121–136
7 Villena-Heinsen C, König J, von Tongelen B et al.: Validity of the mini-
mal Resistance Index for discrimination between benign and malignant Breast Tumours. Eur. J. Ultrasound 7 (1998) 189–193
363
Effect of Menopausal Status and Hormone Replacement on
39
Therapy Resistance Indices and Blood Flow Velocities in Breast
Tumors
C. Villena-Heinsen, I. Tossounidis, and W. Schmidt
Menopausal Status and Benign–Malignant Tumor Discrimination
Patients in Doppler studies. In the relatively few Doppler ultra-
sound studies that have been published on breast tumors, the
focus has been on testing the ability of the various techniques
(CW Doppler, duplex scanning, color Doppler) to discriminate
between benign and malignant lesions. For the most part,
these studies have disregarded the potential effects of
menopausal status and hormone replacement therapy on
blood flow parameters. One group of authors
menopausal status but did not make a systematic comparison
of premenopausal and postmenopausal women. Another
39
group that made a side-to-side comparison between the tumor
and contralateral breast found that the average resistance indices and S/D ratio in premenopausal women were lower than
in postmenopausal women
turn out to be statistically significant, no further importance
was attached to menopausal status. Subsequent studies on the
discriminating potential of Doppler ultrasound did not take
into account menopausal status or hormone replacement therapy.
2
. Because these differences did not
1
mentioned
Divergent results. Generally, then, Patient groups of different
ages and menopausal status have been compared with regard
to benign–malignant tumor discrimination. This helps to explain why such divergent results have been reported. As our
own study results indicate
tend to be in an older, predominantly postmenopausal age
group, whereas patients with benign tumors are mostly
younger, premenopausal women. Additionally, a significant effect of hormone replacement is observed in postmenopausal
women.
Because neither menopausal status nor hormone replacement was taken into account in previously published studies,
we must question the validity of comparing different patient
groups with benign and malignant tumors, as well as the validity of the results.
In this chapter we analyze the effects of menopausal status
and hormone replacement on the various flow resistance indices and blood flow velocities that are measured in healthy
breast tissue and in breasts with benign and malignant tumors.
3
, patients with malignant tumors
364
Authors’ Studies
Patients and Methods
Study design. A total of 114 women were examined. B-mode
ultrasound with the assessment of tumor size was followed by
the color Doppler imaging of as many tumor vessels as possible
and Doppler spectral sampling. Next, all of the healthy breast
tissue was examined. For this purpose each breast was divided
into four quadrants. After the vessels were defined by colorflow imaging, Doppler velocity spectra were recorded from a
maximum of two vessels in each quadrant.
Parameters and velocities. The 114 patients were subdivided
into three groups: premenopausal (PRE), postmenopausal
(POST), and postmenopausal with hormone replacement therapy (POST HRT). The following parameters were calculated for
the tumor area and for each of the eight quadrants in the
healthy breast tissue: RI
and the following velocities:
➤
Maximum peak systolic velocity (peaksys V
➤
Mean peak systolic velocity (peaksys V
➤
Minimum peak systolic velocity (peaksys V
➤
Mean average velocity over a whole cycle (average V
➤
Mean end-diastolic velocity (enddias V
min
,RI
mean
,RI
max
,PI
, mean S/D ratio,
mean
)
max
)
mean
)
min
)
mean
mean
)
The velocity measurements were not corrected for insonation
angle. This step was omitted to save time, as most of the vessels
were very small and would have been difficult to define in
longitudinal section.
For each parameter, a mean value was taken from the corresponding eight values for the quadrants to represent the
healthy breast tissue. The Mann–Whitney U test was used for
statistical analysis.
Patient ages. The average age of the patient population as a
whole was 55 years (21–87). Histological evaluation showed
that 63 of the patients had a carcinoma and 51had a benign lesion. The average age of the carcinoma patients was 60 years
(33–87). The average age of the benign cases was 49 years (21–
84). The age difference between these two groups was statistically significant (p = 0.0001).
Menopausal status and hormone replacement therapy. Thirty-
five of the patients were premenopausal, 24 were postmenopausal on hormone replacement therapy (HR T), and 55
were postmenopausal without HRT. Both groups also differed
significantly in their menopausal status (p = 0.0001). In the
group with benign tumors, 49% of the women were pre-
Authors’ Studies
Table 39.1 Comparison of the benign and malignant tumor groups according to menopausal status (PRE = premenopausal; POST HRT = post-
menopausal on hormone replacement therapy; POST = postmenopausal without hormone replacement therapy)
Menopausal status Number Benign lesions (%) Menopausal status Number Malignant tumors (%)
PRE 25 49.0 PRE 10 15.9
POST HRT 11 21.6 POST HRT 13 20.6
POST 15 29.4 POST 40 63.5
Total 51 100.0 Total 63 100.0
menopausal (n = 25), 21.6% were postmenopausal with HRT
(n = 11), and 29.4% were postmenopausal without HRT (n = 15).
The group with malignant tumors was structured as follows:
15.9% premenopausal (n = 10), 20.6 % postmenopausal with
HRT (n = 13), and 63.5 % postmenopausal (n = 40). Table 39.
shows a breakdown of the benign and malignant groups according to menopausal status.
Results
Effect of Menopausal Status on Resistance Indices
in Healthy Breast Parenchyma
Patient groups. Healthy breast parenchyma was represented
by the mean valuesof the minimum, mean, and maximum RI of
the eight quadrants. Since we were dealing with healthytissue,
the effect of menopausal status was investigated regardless of
whether the particular case was benign or malignant. As Table
39.
2 shows, the patients were divided into three groups: pre-
menopausal, postmenopausal with HRT, and postmenopausal.
The minimum, mean, and maximum RI were calculated for
each patient group along with the standard deviation and
range of values. The three flow-resistance parameters differed
from one another but showed a congruent relationship.
Table 39.2 Mean values, standard deviations, and ranges for the pa-
,RI
rameters RI
patient groups: premenopausal (PRE), postmenopausal on hormone
replacement therapy (POST HRT), and postmenopausal without hormone replacement therapy (POST)
1
Menopausal
status
PRE (n = 34) 0.61 ⫾ 0.07
POST HRT (n = 24) 0.64 ⫾ 0.07
POST (n = 54) 0.68 ⫾ 0.07
Table 39.3 Statistical comparison based on the mean values listed in
Table 39.2 (PRE = premenopausal; POST HRT = postmenopausal on
hormone replacement therapy; POST = postmenopausal without hormone replacement therapy)
Menopausal
status
PRE vs. POST HRT p =0.12 p = 0.26 p = 0.30
PRE vs. POST p ⬍ 0.0001 p = 0.0004 p = 0.0001
POST HRT vs. POST p = 0.01 p = 0.07 p = 0.004
min
mean
, and RI
RI
min
0.50 – 0.78
0.50 – 0.75
0.55 – 0.85
RI
min
in the healthy breast tissue of the
max
RI
mean
0.64 ⫾ 0.06
0.53 – 0.78
0.66 ⫾ 0.06
0.54– 0.75
0.71 ⫾ 0.06
0.59 – 0.85
RI
mean
RI
max
0.66 ⫾ 0.06
0.53 – 0.78
0.68 ⫾ 0.06
0.54– 0.77
0.73 ⫾ 0.06
0.59 – 0.85
RI
max
Gynecological Ultrasound
RI
. As an example, we will review our analysis of RI
min
min
—the
most widely used parameter for determining flow resistance.
The mean values of RI
were 0.61 in the premenopausal
min
patients, 0.64 in the postmenopausal patients on HRT, and 0.68
in the postmenopausal patients. Both postmenopausal groups
showed a higher RI
than the premenopausal group, but the
min
highest mean value within the postmenopausal group was
found in the women who were not receiving HRT.
Pooled groups. Table 39.
3 shows the statistically significant
differences between the three groups with regard to the three
flow-resistance parameters that were analyzed. It can be seen
that both the premenopausal patients and the postmenopausal patients on HRT differed significantly from the
postmenopausal patients without HRT. Moreover, there were
no significant differences between the premenopausal
patients and the postmenopausal patients on HRT. These results demonstrate that premenopausal patients and postmenopausal patients on HRT have very similar resistance indices. We therefore pooled both groups and compared them as
a unit with the group of postmenopausal patients without HRT
in further analyses.
Effect of Menopausal Status on Resistance Indices
in the Tumor Area
Tumor-specific effect. The same type of analysis was done for
the tumor area as for the healthy breast tissue. The results are
shown in Tables 39.
previous findings, except that the statistical comparison between the postmenopausal patients with and without HRT
shows only minor differences compared with the results in
healthy breast tissue. All the resistance indices in the postmenopausal patients are higher than in the postmenopausal
patients on HRT. They show different degrees of statistical significance, however: RI
slightly higher and RI
pared with healthy breast parenchyma could be related to a
tumor-specific effect in postmenopausal women (with or
without HRT).
Regardless of whether the tumors were benign or malignant, these results prove the statistically significant effects of
menopausal status and hormone replacement on blood flow
resistance.
4 and 39.5. They basically confirm all of the
is substantially higher while RI
max
is not significant. This difference com-
min
mean
is
365
Effect of Menopausal Status and Hormone Replacement on Resistance Indices and Blood Flow Velocities in Breast Tumors
Table 39.4 Mean values, standard deviations, and ranges for the
blood flow parameters RI
min
mean
, and RI
measured in the tumor
max
,RI
area of the patient groups: premenopausal (PRE), postmenopausal on
hormone replacement therapy (POST HRT), and postmenopausal
without hormone replacement therapy (POST)
Menopausal
RI
min
RI
mean
RI
max
status
PRE (n = 34) 0.58 ⫾ 0.10
0.37– 0.78
POST HRT (n = 25) 0.62 ⫾ 0.13
0.37– 0.89
POST (n = 55) 0.65 ⫾ 0.10
0.42 – 0.81
0.65 ⫾ 0.09
0.52 – 0.86
0.68 ⫾ 0.10
0.43 – 0.89
0.72 ⫾ 0.07
0.50 – 0.85
0.71 ⫾ 0.10
0.45 – 0.95
0.72 ⫾ 0.10
0.55 – 0.90
0.79 ⫾ 0.08
0.50 – 0.96
Table 39.5 Mean-value comparison of the groups in Table 39.4
(PRE = premenopausal; POST HRT = postmenopausal on hormone replacement therapy; POST= postmenopausal without hormone replacement therapy)
Menopausal
RI
min
RI
mean
RI
max
status
39
PRE vs. POST HRT p = 0.28 p = 0.26 p = 0.79
PRE vs. POST p = 0.0055 p = 0.0004 p= 0.0002
POST HRT vs. POST p = 0.25 p = 0.07 p = 0.004
Table 39.6 Comparison of the patient groups: premenopausal (PRE +
POST HRT) and postmenopausal (POST) based on the mean values of
the blood flow parameters, calculated for healthy breast parenchyma
(peaksys V
age mean velocity during one cycle, enddias V
tolic velocity)
Parameters
measured in
healthy breast
parenchyma
= maximum peak systolic velocity, average V
max
mean
PRE +
POST HRT
POST
(n =54)
(n = 58)
mean
= mean end-dias-
p-Value
= aver-
Blood Flow Parameters in the Healthy Tissue of
Premenopausal and Postmenopausal Patients
As Table 39.6 indicates, the group of postmenopausal patients
shows significantly higher mean values for all resistance in-
dices compared with the hormonally active patients (premenopausal and postmenopausal on HRT). The characteristic
resistance indices in the healthy breast tissue of the different
groups are shown in Figs. 39.
1– 39.3. A similar analysis of the
different blood flow velocities shows almost equal values in
both groups.
Premenopausal and Postmenopausal Patients
The above results are also confirmed in the tumor area. As we
see in Table 39.
7, postmenopausal patients have significantly
higher resistance indices than premenopausal patients (Figs.
39.
4, 39.5). In the velocity measurements, which were per-
formed without angle correction, hormone-related differences
are definitely present but are neutralized by the broad overlaps
in the ranges of values.
Discussion
Allowance for menopausal status. Our analysis demonstrates
the statistically significant effect of menopausal status on
blood flow parameters. Any attempt to improve benign–malignant tumor discrimination by an analysis of blood flow parameters should take into account menopausal status and hor-
Table 39.7 Same comparison as in Table 39.6, calculated for the
tumor area
Parameters
measured in
tumor area
PRE +
POST HRT
(n = 59)
POST
(n = 55)
p-Wert
366
RI
min
RI
mean
RI
max
PI
mean
S/D
mean
peaksys V
peaksys V
peaksys V
average V
enddias V
max
mean
min
mean
mean
0.62 ⫾ 0.07
0.50 – 0.78
0.65 ⫾ 0.06
0.53 – 0.78
0.67 ⫾ 0.06
0.53 – 0.78
1.16 ⫾ 0.24
0.75 – 1.76
3.11 ⫾ 0.68
2.14– 5.40
0.12 ⫾ 0.05
0.05 – 0.28
0.10 ⫾ 0.04
0.05 – 0.24
0.09 ⫾ 0.04
0.04 – 0.19
0.06 ⫾ 0.03
0.02 – 0.15
0.04 ⫾ 0.02
0.01– 0.10
0.68 ⫾ 0.07
0.55 – 0.85
0.71 ⫾ 0.06
0.59 – 0.85
0.73 ⫾ 0.06
0.59 – 0.85
1.42 ⫾ 0.30
0.92 – 2.05
3.83 ⫾ 0.96
2.59 – 6.69
0.12 ⫾ 0.04
0.06 – 0.28
0.11 ⫾ 0.03
0.06 – 0.23
0.09 ⫾ 0.03
0.06 – 0.18
0.06 ⫾ 0.02
0.03 – 0.14
0.03 ⫾ 0.01
0.01– 0.09
⬍ 0.0001
⬍ 0.0001
⬍ 0.0001
⬍ 0.0001
⬍ 0.0001
0.54
0.23
0.20
0.49
0.053
RI
min
RI
mean
RI
max
PI
mean
S/D
mean
peaksys V
peaksys V
peaksys V
average V
enddias V
max
mean
min
mean
mean
0.60 ⫾ 0.11
0.37– 0.89
0.66 ⫾ 0.10
0.43 – 0.89
0.72 ⫾ 0.10
0.45 – 0.95
1.22 ⫾ 0.43
0.54– 3.08
3.42 ⫾ 1.53
1.8– 10.94
0.17 ⫾ 0.13
0.03 – 0.65
0.12 ⫾ 0.07
0.03 – 0.34
0.08 ⫾ 0.04
0.03 – 0.19
0.07 ⫾ 0.04
0.01– 0.21
0.04 ⫾ 0.03
0.01– 0.15
0.65 ⫾ 0.10
0.42 – 0.81
0.72 ⫾ 0.07
0.50 – 0.85
0.79 ⫾ 0.08
0.50 – 0.96
1.47 ⫾ 0.34
0.69 – 2.27
4.18 ⫾ 1.65
2.00 – 11.33
0.18 ⫾ 0.12
0.04 – 0.54
0.13 ⫾ 0.08
0.04 – 0.35
0.09 ⫾ 0.06
0.04 – 0.28
0.07 ⫾ 0.04
0.02 – 0.17
0.04 ⫾ 0.04
0.01– 0.33
0.012
0.0007
⬍ 0.0001
⬍ 0.0001
0.0002
0.31
0.51
0.51
0.74
0.49
Authors’ Studies
Fig. 39.1 Very high RI
values (0.83–0.86) are found
in the healthy breast tissue
of a postmenopausal patient
not receiving HRT.
Fig. 39.2 Low RI values
(0.50–0.64) in a premenopausal patient.
Gynecological Ultrasound
367
Effect of Menopausal Status and Hormone Replacement on Resistance Indices and Blood Flow Velocities in Breast Tumors
Fig. 39.3 Low RI values
(0.50–0.63) in a postmenopausal patient on HRT.
These values occupy the
same range as in premenopausal women.
39
Fig. 39.4 Low RI in a premenopausal patient with a
breast carcinoma. The RI
values range from 0.50 to
0.63.
368
Authors’ Studies
Fig. 39.5 High RI values
(0.80–0.82) are measured in
the tumor area of a postmenopausal patient with
breast cancer who was not
on HRT.
mone replacement therapy. As Table 39.1 indicates, there were
twice as many postmenopausal women in the malignant
tumor group as in the group with benign lesions. This fact
alone could produce a statistically significant increase in impedance to flow, calling into question the discriminating
potential of a blood flow parameter. The discovery that the
composition of the groups being compared critically affects
the blood flow parameters, could presumably account for
many of the divergent and sometimes contradictory results
that have been reported.
Significance of hormone replacement therapy. Marked differences in mean values are found between premenopausal
patients, postmenopausal patients on HRT, and postmenopausal patients without HRT, both in healthy breast
tissue and in breast tumors. It is clear that premenopausal
patients do not differ significantly from postmenopausal
patients on HRT, but both of these groups differ significantly
from postmenopausal patients not receiving HRT. The differences are minor only in the tumor area. The reasons for this
may relate to the number of patients or to a possible tumorspecific effect, which would be relevant in postmenopausal
women. When the premenopausal patients and post-
Gynecological Ultrasound
menopausal patients on HRT are placed in one group and compared with the postmenopausal patients not receiving HRT, the
latter group is found to have significantly higher mean values
for all resistance indices, as one would expect.
Angle correction in velocity measurements. This clear, systematic dependence is not seen in parameters that are based on the
absolute measurement of blood flow velocities. These results
show that absolute flow velocities can be used for intergroup
comparisons only if they have been corrected for the insonation angle. As noted earlier, this was not done in the present
study because of time constraints. Absolute velocity measurements that are not angle-corrected show a large scatter of
values. The areas of overlap between different groups—in this
case premenopausal and postmenopausal women—are very
broad and neutralize the menopause-related difference. These
results plainly show that absolute flow velocities without
angle correction are not suitable for the comparison of two
groups.
Exactly the same principles are found in the tumor area as
in healthy breast parenchyma, underscoring the validity of the
findings.
369
Effect of Menopausal Status and Hormone Replacement on Resistance Indices and Blood Flow Velocities in Breast Tumors
Summary
In summary, the effect of menopausal status can be objectively
documented with Doppler parameters both in healthy breast
tissue and in breast tumors. Postmenopausal women must be
viewed differently depending on whether or not they are receiving HRT. Postmenopausal patients on HRT and premenopausal patients comprise a physiological unit. As a basic
principle, only angle-independent parameters should be analyzed when two groups are compared. Menopausal status and
HRT have a statistically significant effect on Doppler parameters. Menopausal status should be taken into account in studies
dealing with the benign–malignant discrimination of breast
tumors.
39
References
1 Minasian H, Bamber JC: A preliminary assessment of an ultrasonic
doppler method for the study of blood flow in human breast cancer.
Ultrasound Med. Biol. 8 (1982) 357–364
2 Sohn Ch, Stolz W, Grischke EM, Wallwiener D, Bastert G, von Fournier
D: Die dopplersonographische Untersuchung von Mammatumoren
mithilfe der Farbdopplersonographie, der Duplex-Sonographie und
des CW-Dopplers. Zentralbl. Gynäkol. 114 (1992) 249–253
3 Villena-Heinsen C, Ertan AK, Tossounidis I, Holländer M, König J,
Schmidt W: Diagnostische Aussagekraft der Farbdoppler-Sonographie
bei Mammatumoren. Geburtshilfe. Frauenheilkd. 55 (1995) 541–547
370
Benign–Malignant Tumor Discrimination and Prognostic
40
Evaluation of Breast Tumors with Color Doppler Sonography
C. Villena-Heinsen, A. K. Ertan, D. Mink, and W. Schmidt
Applications of Color Doppler Sonography in Breast Cancer
Technological evolution of color Doppler sonography. In most
studies published on color Doppler sonography in patients
with breast tumors, the goal has been to use this modality to
help discriminate between benign and malignant lesions. Very
few publications have dealt with the use of color Doppler in
making a prognosis or evaluating response to treatment. Palpation, mammography, and sonography have become the pillars of breast diagnosis. There is still a need, however, to improve sensitivity and specificity through the use of new
methods. Today, color Doppler sonography has reached a relatively high level of sophistication that offers decisive advantages. It can easily be incorporated into established preoperative diagnostic protocols. Tumors can be characterized and
measured with conventional B-mode imaging, and color
Doppler can be added both, to provide a qualitative color display of blood flow and to allow spectra to be sampled from
selected vessels. This provides an opportunity for objective
flowmetry based on the measurement of blood flow velocities
and the calculation of resistance indices.
Blood flow parameters. In the past, resistance indices have
been the most commonly used parameters for the benign–
malignant discrimination of tumors. But as the preceding
chapters have made clear, two important aspects must be considered when resistance indices are used: first, the blood flow
parameter used for comparison should be a mean value and
not an extreme value (e.g., the maximum or minimum flow resistance) within a tumor; and second, it is important to consider the menopausal status and the use or nonuse of hormone
replacement therapy by the patients. The potential of color
Doppler sonography in the benign–malignant differentiation
and prognostic assessment of breast tumors should be evaluated exclusively by an analysis that takes these criteria into
account.
Specificity of benign–malignant discrimination. The color
Doppler systems available today are not sensitive enough to
detect lesions by an abnormal flow pattern that are not detectable by conventional imaging. The goal of color Doppler
imaging, rather, is to improve the specificity of benign–malignant discrimination.
Prognostic evaluation. There is also a need for new parameters
in prognostic evaluation, for despite the availability of various
prognostic indicators, the future course of a disease after primary treatment remains uncertain in many cases. The relative
uncertainty of prognostic assessment is illustrated by the fact
that approximately 30% of patients with a prognostically
favorable, node-negative breast cancer will experience a progression of disease within 10 years after primary treatment
Blood flow can provide information on the metabolism and
proliferative behavior of tumors. Weidner et al.
a positive correlation between the density of neovascularity in
breast carcinomas and the risk of distant metastases.
Todate there have been only isolated reports on the evalua-
tion of tumor prognosis with Doppler ultrasound
8
et al.
found that heavily vascularized tumors had a strong propensity for recurrence, metastasis, and early mortality. Tumor
blood flow also correlated with lymph-node and negative hormone-receptor status, but it did not correlate with tumor size
or histopathological grade. So far only Cosgrove et al.
Delorme et al.
breast tumors with color Doppler ultrasound. Cosgrove et al.
created a special semiquantitative scoring system to assess
tumor vascularity and found no correlation between color
Doppler scores and conventional prognostic indicators (lymph
node status, survival). Delorme et al.
lation between the maximum systolic flow velocity in the
tumor-feeding vessels and the tumor volume.
17
documented
1, 8, 13
. Madjar
3
4
have reported on the vascularity assessment of
4
found only a weak corre-
5, 11
and
Gynecological Ultrasound
.
3
371