Download Intent of Therapy in Metastatic Breast Cancer with Isolated Ipsilateral

Original Article
Intent of Therapy in Metastatic Breast Cancer with
Isolated Ipsilateral Supraclavicular Lymph Node
Spread — A Therapeutic Dilemma
SVS Deo*, J Purkayastha**, NK Shukla***, V Raina#, Sonal Asthana**, DK Das**,
GK Rath+
Abstract
Aims of the Study : Isolated ipsilateral supraclavicular lymph nodal (IISCLN) metastasis was considered
part of locally advanced breast cancer (LABC) previously but the recent staging system categorised this
group to metastatic disease (stage IV). There is no clear consensus on intent of therapy in patients with
IISCLN. A retrospective comparative analysis of IISCLN and LABC patients treated with a curative
multimodality approach was performed to evolve guidelines on treatment approach in patients with IISCLN
spread.
Methodology : A total number of 670 patients with breast cancer treated in the Department of Surgical
Oncology, IRCH, AIIMS, during the period between January, 1993 to December, 2000 were studied
retrospectively. Out of these 16 (2.4%) patients with cytology proven isolated metastasis to ipsilateral
SCLN without any other distant disease and 299 LABC patients were analysed. All patients received neoadjuvant anthracycline based chemotherapy, surgery, postoperative radiotherapy (50Gy) including
supraclavicular fossa. The relapse patterns and survival in both the groups were compared.
Results : At a median follow up of 36 months (range 9-72 months) the total recurrence in the IISCLN
group was 31% and in the LABC group was 26%, the systemic recurrence was equal at 25% in each group
while the locoregional recurrence was 12% and 7% in the IISCLN and LABC groups respectively. The
overall survival (OS) was 81% and 91% whereas the disease-free survival (DFS) was 12% and 7% in the
IISCLN and LABC groups, respectively.
Conclusion : Intent of therapy in metastatic breast cancer is palliative. However, patients with IISCLN
metastasis have a relatively less aggressive biologic behaviour as compared to patients with spread to
other distant sites. Results of the current study shows that the relapse patterns and survival of IISCLN
group and LABC are comparable. Hence, despite being staged as metastatic disease, patients with IISCLN
spread should be treated with combined modality approach for prolonged survival.
INTRODUCTION
A
ssessment of the lymph nodal status is of utmost
importance in the work up of a patient with breast cancer
and is considered the most valuable prognostic factor. The
regional lymph nodes in the axilla are always critically
*Assistant Professor; **Senior Resident; ***Additional Professor and
Head, Department of Surgical Oncology; #Additional Professor,
Department of Medical Oncology; +Professor and head, Department
of Radiation Oncology, Institute Rotary Cancer Hospital (IRCH), All
India Institute of Medical Sciences (AIIMS), New Delhi - 110 029, India.
Received : 13.11.2001; Revised : 14.2.2002; Accepted : 28.7.2002
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evaluated in assigning the clinical stage and taking therapeutic
decisions. The supraclavicular lymph nodes (SCLN) are in
direct extension of the lymphatic drainage of the apex of the
axilla.1 Therefore, their involvement in patients of breast
cancer has importance in determining prognosis and in
imparting treatment.1
Isolated metastasis to ipsilateral SCLN without any other
distant spread was previously staged as N3 (stage IIIB)
subcategory. 2 However in 1988, in the American Joint
Committee on Cancer (AJCC) revised staging system, this
group of patients were moved to stage IV category3,4 and given
‘M1’ status since it was believed that their prognosis is poor
as their biological behaviour is like that of patients with other
JAPI • VOL. 51 • MARCH 2003
distant metastasis.
Conventionally metastatic breast cancer is considered
incurable and the goals of management are to palliate
symptoms, improve quality of life and prolong life. At present,
all non-metastatic breast cancer patients (stage I-III) are
treated with curative intent whereas those with stage IV
disease receives therapy with a palliative intent. However, a
significant number of patients with breast cancer presents
with SCLN metastatic disease and in view of the changes in
the staging system, physicians are often not clear regarding
the intent of therapy in patients with isolated ipsilateral SCLN
(IISCLN) metastatic disease without any other distant spread.
Patients with supraclavicular nodal spread are surgically
incurable, however with combination of chemotherapy and
radiotherapy to supraclavicular fossa the disease can be
controlled in a significant number of patients. In our
institution, as a policy, patients with IISCLN metastasis were
treated like those with locally advanced breast cancer (LABC)
with an intent to cure by combined-modality approach using
chemotherapy, surgery and radiotherapy. We present our
experience of the management of this subset of patients treated
with curative intent in terms of local control, disease-free
survival (DFS) and overall survival (OS).
MATERIAL AND METHODS
A retrospective analysis of breast cancer database of the
Surgical Oncology unit of Institute Rotary Cancer Hospital
(IRCH), All India Institute of Medical Science (AIIMS), New
Delhi was performed. Between January, 1993 to December,
2000 a total of 670 patients were operated including 16
patients (2.4%) with FNAC proven IISCLN metastasis
without evidence of any other distant spread. The records of
all these patients were analysed for treatment details,
recurrence pattern, DFS and OS. A subgroup analysis of
LABC (stage III) that included 299 (45%) patients was also
performed separately and compared with IISCLN group of
patients. Historical data of metastatic breast cancer patients
survival was used for comparison.
Treatment protocol : The patients were initially evaluated
in the Breast Cancer Clinic with clinical history and physical
examination. They were investigated, to exclude any other
distant metastasis, with a complete haemogram, liver function
test, chest X-ray, nuclear bone scan and ultrasonography of
the liver. Thereafter, all patients with LABC (stage III) and
stage IV with IISCLN spread were treated with a combined
multimodality approach with six cycles of anthracycline based
chemotherapy, surgery, locoregional radiotherapy (LRRT)
with or without hormonal therapy. Neo-adjuvant
chemotherapy was given initially and the clinical response
was assessed after each cycle with physical examination of
the primary tumour and the axilla. The response of SCLN
was also determined. The patients who responded were given
the full course of neo-adjuvant chemotherapy followed by
surgery whereas those who did not respond were taken up
for surgery after 2 or 3 cycles. The surgical procedure
consisted of modified radical mastectomy or radical
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mastectomy. Thereafter, all the patients received adjuvant
postoperative radiotherapy (LRRT) 50 GY in 25 fractions
over five weeks, to the chest wall, axilla and supraclavicular
fossa. Hormonal therapy with tamoxifen 20 mg daily was
given to all patients who were estrogen receptor positive.
After the completion of treatment, regular follow-up was
undertaken at three months interval in the first two years,
once every six months in the next three years and yearly
thereafter. At each visit assessment was done with a clinical
history, physical examination, liver function test and chest
X-ray. Any abnormality in these were further evaluated with
ultrasonography, bone scan or computed tomography as
indicated. Mammography of the contralateral breast was done
yearly. A record of local, regional and systemic metastasis
was maintained.
RESULTS
The incidence of IISCLN disease in this study was 2.4%
(16 patients) who had a mean age of 46.5 (range 30-60) years.
The primary tumour was mostly large with a mean size of
7.75 (range 3-12) cm and had an advanced T stage with 12
(75%) patients having T4 b while four (25%) had T3 lesions.
The axillary nodal status was advanced (N2) in eight (50%)
patients while N1 and N0 status was seen in six (38%) and
two (12%) patients respectively. All the patients had FNAC
proven metastasis to ipsilateral SCLN without any other
distant spread.
All the patients completed full course (6 cycles) of
chemotherapy. The most commonly used regimen was
cyclophosphamide, epirubicin and fluorouracil (CEF) in eight
patients (50%) and rest consisted a combination of epirubicin
and other agents. Complete clinical response of
supraclavicular nodes to neo-adjuvant chemotherapy was
observed in all the patients. The overall response of primary
tumour to chemotherapy was 75% in IISCLN group and 76%
in LABC group. Pathological complete response was 13% in
IISCLN group and 11% in LABC group.
The surgical procedures included modified radical
mastectomy (MRM) in 14 patients (88%) and radical
mastectomy (RM) in two (12%). RM was required for large
tumours with pectoralis major muscle infiltration. All patients
completed planned locoregional radiotherapy after surgery.
The estrogen receptor positivity rate in the IISCLN group
was 44% (seven patients) while the progesteron receptor
positivity rate was 31% (five patients) and they were put on
tamoxifen for five years. At a median follow-up of 36 (range
9-72) months the recurrence patterns observed in the IISCLN
and LABC groups are shown in Table 1. Comparative diseasefree survival and overall survival between the two groups
are shown in Fig. 1.
DISCUSSION
Rapid advances have been made in the management of
breast cancer in recent years. Despite this, the presence of
distant metastatic disease is thought to have ominous
implications and is considered incurable. The presence of
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Fig. 1 : Comparison of survival between IISCLN metastasis and LABC groups. IISCLN - Isolated ipsilateral supraclavicular lymph node;
LABC - Locally advanced breast cancer; OS - Overall survival; DFS - Disease-free survival.
Table 1 : Comparison of recurrences patterns between
IISCLN metastasis and LABC groups
Total No.
Recurrence
Total
Systemic
Loco-regional
IISCLN
LABC
16
299
5 (31%)
4 (25%)
2 (12%)
77 (26%)
75 (25%)
21 (7%)
IISCLN - Isolated ipsilateral supraclavicular lymph node;
LABC - Locally advanced breast cancer
IISCLN metastasis constitutes a subgroup of patients who
are included in the stage IV category of the AJCC
classification system2,3 as it was believed that their prognosis
is dismal and similar to that of patients having metastasis to
other distant sites. However, until 1988 they were included
in the N3 (stage IIIB) subcategory1 before being ascertained
the M1 status. Currently, there is no clear consensus on the
treatment policy to be adopted in patients with IISCLN
metastatic disease.
It has been seen that the median survival of patients with
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metastatic breast cancer is 2 to 3 years and even with therapy
the median prolongation of survival is a matter of months.5
Zlotecki et al observed that the median survival in metastatic
breast cancer ranges from 4 to 15 months in most series with
a two year survival rate of only 15 to 20%.6 Hence the outlook
of these patients is very grim and once distant metastatic
disease is detected death is considered imminent. On the other
hand, the outcome in LABC is comparatively better especially
when multimodality approach is adopted using anthracycline
based chemotherapy, surgery and radiotherapy. Amongst the
larger series, Hortobagyi et al7 could attain 5-year OS and
DFS of 56% and 33% while in the Milan trial the 5-year OS
and DFS were 49.4% and 25% respectively8 using combined
modality treatment including anthracycline based
chemotherapy.
The presence of IISCLN metastasis is being considered a
grave sign, an indicator of distant metastatic disease with a
poor survival. Halstead9 reported survival of more than five
years in only 5% patients with histologically proven
involvement of supraclavicular lymph nodes during prechemotherapy era. Kiricuta et al10 observed a 2- and 5-year
JAPI • VOL. 51 • MARCH 2003
survival of 52% and 34% respectively in this group of patients
which was similar to that seen in LABC patients in postchemotherapy era. Supraclavicular disease is surgically
incurable but with a combination of chemotherapy and
radiotherapy the disease can be controlled in a significant
number of patient. At the University of Texas MD Anderson
Cancer Centre, this subgroup of patients have been
categorised as “Regional stage IV LABC”11 and are being
treated with combined modality approach like that in other
LABCs.7,11,12 Hortobagyi et al reported a five year diseasefree survival of 29% and overall survival of 42% with this
approach in patients with IISCLN metastasis.9 Subsequently
Brito et al11 have analysed the outcome of combined modality
approach in subset of patients with IISCLN involvement and
reported an overall survival of 41% and disease-free survival
of 34% at five years. This survival was not significantly
different from that of patients with stage IIIB disease while it
was superior to that of patients having metastasis to other of
patients having metastasis to other distant sites.
In our institution, the patients with IISCLN metastasis
without any other distant disease are being treated with
combined multidisciplinary approach with an intent to cure.
The relapse rates and survival IISCLN group patients were
comparable to that of LABC patients. The outcome in patients
with IISCLN metastasis appears better than what have been
described in literature in patients with spread to other distant
sites. Based on the recent literature and results of the current
study we recommend a multimodality treatment approach
with curative intent in patients with IISCLN spread. We also
feel that the staging of this group patients in the metastatic or
stage IV category may be inappropriate and there is a need to
revise the TNM staging system.
CONCLUSION
Breast cancer patients can present with IISCLN metastatic
disease in about 2.4% cases. This subgroup of patients have
a less aggressive biological behaviour compared to that of
patients having metastasis to other distant sites. Advent of
multiagent chemotherapy and radiotherapy to supraclavicular
fossa has altered the outcome of disease significantly in these
patients. Hence, these patients should be included in the
JAPI • VOL. 51 • MARCH 2003
locally advanced group instead of metastatic group and treated
aggressively using multimodality approach for prolonged
survival.
REFERENCES
1. Jackson SM. Carcinoma of the breast: The significance of
supraclavicular lymph node metastasis. Clin Radiol 1966;17:10714.
2. American Joint Committee on Cancer: Manual for staging of
cancer (ed. 2). Philadelphia. Lippincott, 1983.
3. American Joint Committee on Cancer: Manual for staging of
cancer (ed. 3). Philadelphia.PA. Lippincott, 1988.
4. American Joint Committee on Cancer: Manual for staging of
cancer (ed. 5). Philadelphia. PA. Lippincott-Raven, 1997.
5. Winner EP, Morrow M, Osborne CK, et al. Malignant tumours
of the breast. In DeVita VT, Hellman S, Rosenberg SA Ed.,
Cancer: Principles and Practice of Oncology, 6th ed.
Philadelphia: Lippincott Williams and Wilkins, 2001;Sec.
2,Chap. 37:1651-1740.
6. Zlotecki RA, Mendentall NP. Palliative radiotherapy for
disseminated breast cancer. In Bland KI, Copeland III EM Ed.,
The Breast: Comprehensive Management of Benign and
Malignant Diseases, 2th ed. Philadelphia: WB Saunders Co.,
1998;Sec XXI,Chap 71:1304-23.
7. Hortobagyi GN, Blumenschein GR, Spanos W, et al.
Multimodal treatment of locoregionally advanced breast
cancer. Cancer 1983;51:763-8.
8. Valugussa P, Zambeti M, Bignani P. T3b-T4 breast cancer:
Factors affecting results in combined modality treatments.
Clin Exp Metastasis 1983;1:191-202.
9. Halstead WS. The results of radical operations for cancer of
the breast. Ann Surg 1907;46:1-5.
10. Kiricuta JC, Willner J, Kolbl O, et al. The prognostic significance
of the supraclavicular lymph node metastasis in breast cancer
patients. Int J Radiat Oncol Biol Phys 1993;28:387-93.
11. Brito RA, Valero V, Buzdar AU, et al. Long term results of
combined modality therapy for locally advanced breast cancer
with ipsilateral supraclavicular metastasis: The University of
Texas MD. Anderson Cancer Centre experience. J Clin Oncol
2001;19-3:628-33.
12. Hortobagyi GN, Ames FC, Budzar AU, et al. Management of
stage III primary breast cancer with primary chemotherapy,
surgery and radiation therapy. Cancer 1988;62:2507-16.
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