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Robert L. Elliott, M.D., Ph.D.,*
Pamela B. Rice,* L.R.T.R.M, Joe A. Suits, R.N., O.C.N,*
Alan J. Ostrowe, M.D.^, Jonathan F. Head, Ph.D.*
From *The Elliott-Elliott-Head Breast Cancer
Research and Treatment Center ^and Pain Management Services,
Baton Rouge, LA
A nonpalpable breast lesion
was detected in a 71-year-old woman who had returned for
her annual mammogram. Stereotactic core needle biopsy
revealed an infiltrating ductal carcinoma. The patient
agreed to stereotactic localization and radiofrequency
ablation of the lesion followed after 4 weeks by open
surgical biopsy. The breast lesion was localized and the
radiofrequency ablation performed under local anesthesia
in the outpatient/office setting. The lesion was ablated
for a total of 20 minutes at a sustained mean temperature
of 75 degree C. After a 30-second cooldown the peripheral
temperature of the four peripheral thermocouples ranged
from 58 degree C to 70 degree C. A surgical clip was placed
at the site of the ablated lesion. The postprocedure course
was uneventful and the patient proceeded to open biopsy
4 weeks later. The open biopsy specimen, a left segmental
mastectomy, underwent specimen radiography, which confirmed
the surgical clip in the center of the lesion. There was
extensive central necrosis and hemorrhage surrounded by
fat necrosis. There was no definite viable residual rumor
and the margins were clear. This is the first case in
a clinical protocol designed to determine the efficacy
of stereotactic localization and radiofrequency ablation
of nonpalpable breast lesions. Additional ablations will
be required to define the procedure but the results from
this initial patient suggest that this is a promising
minimally invasive curative approach for nonpalpable breast
lesions. Minimally invasive
diagnostic techniques are well accepted for breast masses
and mammographically detected nonpalpable lesions. Core
biopsy under local anesthesia of palpable masses and
image-guided stereo-tactic or ultrasound biopsy of nonpalpable
masses or calcifications seen on mammograms are now
routine diagnostic procedures. Increased use of mammography
has resulted in more cancers being detected earlier
at a much smaller size; thus less invasive therapeutic
surgical procedures are being done. Lumpectomy with
or without postoperative radiation is now common practice,
and with the evolution of sentinel node biopsy even
less violation of the axilla for staging may be done
in the future. Recently Jeffrey et al. have reported
on ultrasound-guided radiofrequency ablation of locally
advanced breast cancer under general anesthesia, and
Dowlatshahi et al. have reported on stereotactically
guided laser therapy of occult breast tumors. In the
present communication we report a case of stereotactic
localization and radiofrequency ablation of a nonpalpable
invasive ducal carcinoma under local anesthesia. The
mass was detected by screening mammography and its pathology
was confirmed by stereotactic core needle biopsy. This
is the first reported case of radiofrequency ablation
of a nonpalpable breast cancer by stereotactic technique.
This case is the first in a prospective study under
the protocol presented in this communication.
Case Report
The patient is a 71-year-old woman
who has been coming to the Elliott Mastology Center
Breast clinic for breast screening since January 20,
1976. On October 31, 2000 she came for her routine annual
mammogram, and there had been an interval change showing
a small spiculated and irregular density (1.6 cm) inferiorly
in the left breast (Fig. 1). That same day a stereotactic
core needle breast biopsy was performed at our office
(Fig. 2). Histologic examination revealed invasive ductal
carcinoma (Fig. 3). Immunohistocytochemistry was done
on the core specimens for estrogen receptors, progesterone
receptors, and HER2/neu protein, and they were reported
as positive, negative, and negative respectively. The
patient’s physical examination was unremarkable,
there was no local regional lymphadenopathy, and routine
staging revealed no evidence of systemic disease. After
numerous consultations about her options for therapy
the patient elected and signed an Informed Consent Form
to have radiofrequency ablation of her lesion before
excision of her tumor (protocol MRI 200002; see Table
1). On November 15, 2000 the patient was placed on a
Lorad stereotactic table (LORAD, Danbury, CT), and under
local anesthesia and intravenous sedation she had a
12-guage 16-cm-long RITA StarBurst WL radiofrequency
ablation probe (RITA Medical Systems, Mountain View,
CA) was inserted through the Bard cannula and the nine
arrays were deployed to 3cm through the tumor. After
the position of the electrode was confirmed by X-ray
(Fig. 5) the tumor was ablated with a RITA model 1500
generator at an average temperature of 75 degree C for
approximately 20 minuets with the maximum power set
at 25 W (Table 2). After a 30-second cooldown the peripheral
temperature of the four peripheral thermocouples ranged
from 58 degree C to 70 degree C. The patient experienced
no pain of discomfort. She was observed in the office
for one hour after the procedure and was discharged
with a small dressing, surgical bra, and ice pack. When
she was examined on week later there was a slight swelling
of that area. The patient’s mediolateral mammographic
view of the breast showed the tumor to be much smaller
with very little reaction mammographically (Fig. 6).
A week later she was examined and her left breast had
a little more induration and tenderness in the lower
quadrant, which was the area of radiofrequency ablation.
There were no skin changes. On December 13, 2000 the
patient came to our clinic and had needle localization
of the surgical area that had previously undergone radiofrequency
ablation and placement of a surgical clip (Fig. 7).
She then had a segmental mastectomy for this lesion
as an outpatient at the hospital. The specimen was inked
by the pathologist and specimen radiography performed
(Fig. 8).
Then the specimen was sectioned and photographs were
taken of the gross specimen sections (Fig. 9). Multiple
sections were taken for histology and no viable tumor
was identified (Fig. 10). The margins were clear. The
patient’s postoperative course was uneventful.
She was placed on anti-estrogen therapy. Annual follow
up is planned.
Discussion
The ablation of nonpalpable breast
cancer lesions without surgical removal is an idea that
has previously been unobtainable. Two techniques had
to be developed and united for this procedure to be
successful. One technology that has been developed over
the last decade is stereotactic localization of a breast
lesion followed by exact (i.e., within 1 mm) placement
of a biopsy needle. The second required method is the
ability to ablate a tumor by using either cooling or
heating, or laser. Jeffrey et al. have reported on five
women with advanced invasive breast cancer whose tumors
were treated with radiofrequency energy, and this resulted
in cancer cell death. Dowlatshahi et al. have reported
on laser ablation of stereotactic localized mammographically
detected breast cancers. The conditions for laser ablation
are still being evaluated as the present procedure only
achieves complete necrosis of tumors in 66% of patients.
In the present case report we have
combined what we think are the best aspects of the two
recently reported studies: stereotactic localization
of the breast lesion and radiofrequency ablation. The
stereotactic method allows a very quick and accurate
localization of the nonpalpable breast lesion under
local anesthesia in an outpatient/officer setting, which
was not done in the previously reported radiofrequency
ablation technique. The radiofrequency method as presently
developed seems superior to the laser ablation method
because radiofrequency ablation destroyed all of the
cancer cells in the ablated area in 80 per cent (four
of five patients) of tumors as measured by NADH (nicotinamide
adenine dinucleotide, reduced from)-diaphorase cell
viability staining. Furthermore this occurred in tumors
of greater size/volume than the tumors in the laser
study.
The better tumor cell destruction
rate that occurred with radiofrequency ablation as compared
with the laser probe probably results from more even
heating by the nine elongated heat sources of the extended
radiofrequency probe compared with the focal heat source
of the laser probe. The radiofrequency probe would result
in more even heating of the tumor and especially radiation
and convection of heat to the margins and beyond the
margins of the tumor. Thermal damage to the cells of
tissue begins around 41 degree C and when the tissue
reaches 46 degree C the mechanism of cell and tissue
death changes from apoptosis to necrosis. It is well
accepted that 54 degree C is acutely lethal to cells;
in the two previous studies a maximum temperature of
70 degree C was achieved in the previous radiofrequency
ablation procedure and a temperature of 60 degree C
was sustained in the laser procedure. In the present
study using stereotactic radiofrequency ablation the
temperature within and surrounding the lesion was sustained
at between 58 degree C and 70 degree C.
There are further advantages to
the present procedure. The procedure reduces the morbidity
associated with open biopsy as it only resulted in two
needle scars and minor induration after 4 weeks. Also
there were no major side effects with little pain during
or after the procedure and no drainage. This procedure
is also suitable for small nonpalpable tumors that cannot
be visualized by ultrasound, which was a shortcoming
of the Jeffery et al. procedure. Additionally this is
a very cost-effective procedure in that it is done without
general anesthesia in an outpatient/office setting.
The future of stereotactic localization
followed by radiofrequency ablation of nonpalpable breast
cancers is very promising. Further studies need to be
done to work out the many details of the procedure and
to determine the maximum size of the lesion that can
be completely ablated by radiofrequency. The minimum
temperature and for what maximum period of time-which
we believe to be 60 degree C for 20 minutes-must be
confirmed or adjusted higher if viable residual tumor
is later demonstrated. Also we believe there is a limit
to the maximum temperature that the patient will tolerate
under local anesthesia, and sedation must also be determined.
However, we believe that when these details are worked
out stereotactic radiofrequency ablation will be a viable
curative procedure for minimal breast cancer.
| TABLE
1. Protocol for a Prospective Study of Radiofrequency
Ablation of Nonpalpable Breast Cancer |
| 1. Informed
consent will be obtained from each patient before
enrolling her in the study. |
| 2. There
is minimal risk to the patient as she will receive
standard of care for her breast cancer with insertion
of radiofrequency ablation between her biopsy and
definitive surgical procedure. |
| 3. The study
will enroll patients until 25 patients with mammographically
detected nonpalpable masses (suspicious densities
but not microcalcification) are diagnosed as invasive
breast cancers by histopathological examination
of their biopsy tissue obtained by sterotactic core
needle biopsy of their nonpalpable lesions. Estrogen
receptors, progesterone receptors, and Her-2/neu
will be determined on paraffin sections of the initial
biopsy of each patient before radiofrequency ablation
of the lesion. |
| 4. Sentinel
node biopsy will be done to determine the breast
cancer patient’s nodal status. If the sentinel
node is negative for breast cancer then the patient
can proceed with radiofrequency ablation of her
nonpalpable breast lesion. |
| 5. The sentinel
node-negative beast cancer patient will be brought
back for stereotactic localization of the density
followed by insertion of the radiofrequency ablation
probe. |
| 6. The radiofrequency
ablation procedure, as defined by the radiofrequency
probe manufacturer in conjunction with staff of
the mastology Research Institute, will be done to
achieve a 1-cm margin if possible. Individualized
radiofrequency ablation procedures will be applied
to each patient. |
| 7. A clip
will be placed in the ablated area for future localization.
|
| 8. Four weeks
later the patient will proceed to open biopsy to
check the margins of the ablated area by histopathological
examination in order to determine the efficacy of
the procedure. At this time definitive surgery will
be performed without consideration of the results
of the radiofrequency ablation. |
| 9. Standard
histopathology will be performed to determine margins
and to determine the effectiveness of the radiofrequency
ablation. |
| TABLE
2. Temperature, Resistance, and Energy in Area of
Radiofrequency Ablation with Increasing Time |
Time (Minutes) |
Temperature (degree C) |
Resistance (ohms) |
Energy (W) |
| 3 |
70 |
197 |
19 |
| 4 |
75 |
195 |
19 |
| 5 |
75 |
193 |
19 |
| 8 |
75 |
190 |
19 |
| 9 |
75 |
188 |
19 |
| 11 |
74 |
188 |
19 |
| 14 |
75 |
187 |
19 |
| 16 |
75 |
186 |
19 |
| 18 |
75 |
185 |
19 |
| 20 |
75 |
183 |
17 |
| 22 |
75 |
182 |
17 |
| 24 |
74 |
181 |
17 |
Acknowledgement
This work was supported by funds
from The Breast Foundation (Baton Rouge, LA).
References
1. Parker SH, Lovin JD, Jobe
WE, et al. Nonpalpable breast lesion:
Stereotactic automated large-core biopsies. Radiology
1991; 180:403-7
2. Dowlatshahi K, yaremko ML, Kluskens LF, Jokick PM.
Nonpalpable breast lesions: Findings of stereotaxic
needle-core biopsy and fine-needle aspiration cytology.
Radiology 1991;181:745-50.
3. Elliott RL, Haynes AE, Bolin JA, Boagni EM, Head
JF. Sterotactic needle localization and biopsy of occult
lesions: First year experience. Am Surg 1992;58:126-31.
4. Head JF, Haynes AE, Elliott MC, Elliott RL. Stereotactic
localization and core needle biopsy of nonpalpable breast
lesions: two-year follow-up of a prospective study.
Am Surg 1996;62:1018-23.
5. Jeffery SS, Birdwell RL, Ikeda Dm, et al. Radiofrequency
ablation of breast cancer: First report of an emerging
technology.
Arch Surg 1999;134:1064-8.
6. Dowlatshahi K, Fan M, Gould VE, et al. Stereotactically
guided laser therapy of occult breast tumors: Work-in-progress
report. Arch Surg 2000;135:13456-52.
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