Download Resection of Solitary Metastases in Breast Cancer Patients: a Case

case presentation
Resection of Solitary Metastases in Breast Cancer Patients:
a Case Report
Ramona Matei, Gergely Holló
1) Institute of Oncology Prof. Dr. I. Chiricuta Cluj Napoca, Romania
Although metastatic breast cancer is widely believed to carry a grim prognosis, treatment developments over the past 25 years have greatly improved
survival outcomes in the patients. Bone is one of the earliest and most common sites of breast cancer metastasis and it is generally associated with better
outcomes than visceral involvement. Standard treatment for breast cancer bone metastasis is systemic hormonal therapy or chemotherapy. We report the
case of a 52-year old breast cancer patient with a history of serial resections for solitary bone and lung metastases, treated with curative intent.
Key words: breast cancer, solitary metastasis, curative treatment, surgery
Introduction
Breast cancer is the most frequent malignancy in the
female population and a significant cause of morbidity and
mortality. With earlier age and stage at presentation, the
survival rate is expected to increase. Early detection surgical
removal of the lesion, systemic therapy and radiotherapy are
effective in managing the disease. However, 30-80% of the
patients will develop metastatic disease following surgery
and/or chemotherapy, endocrine therapy or radiotherapy.
Although distant spread from breast cancer is commonly
found in bones, lungs, liver, central nervous system and
skin, other less common sites have been occasionally
reported (1).
Bone metastasis in breast cancer is a significant clinical
problem. They usually indicate incurable disease with a
guarded prognosis, but are also associated with skeletalrelated morbidities including bone pain, pathological
fractures, spinal cord compression, and hypercalcaemia.
In patients with bone metastases, the goal of management
is to prevent further skeletal-related events, manage
complications, reduce bone pain, and improve quality of
life.
Journal of Radiotheraphy & Medical Oncology
June 2013 Vol. 19 No 1: 35-38
Address for correspondence:
Ramona Matei
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Institute of Oncology
Prof. Dr. I. Chiricuta
Cluj Napoca, Romania
Email:[email protected]
Bone metastasis involves a vicious cycle of close
interaction between the tumor and the bone microenvironment.
Bisphosphonates are a proven therapy for the above
indications. Other strategies of clinical value may include
surgery, radiotherapy, radiopharmaceuticals, and, of course,
effective systemic therapy.
Lung metastasis, are generally associated with a
poorer prognosis and a shorter median survival than bone
metastasis. Patients with isolated lung metastases are
rare; usually, local or diffuse lymphangitis with single or
multiple lung metastases is found. Multiple lung metastasis
require systemic treatment, either hormonal therapy or
chemotherapy. Despite optimal treatment, lung metastasis
still remains an important cause of death for breast cancer
patients, accounting for more than one half of breast cancer
related deaths.
Metastatic breast cancer is by definition a systemic
disease, and the standard approach is to obtain disease
control with effective systemic therapies, while use of local
interventions such as radiotherapy and surgery is limited, and
has the goal to palliate symptoms. However, more recently,
in selected cases with single bone or lung metastasis the
surgical intervention proved valuable in achieving long
asymptomatic survival, especially in metastatic patients
receiving effective systemic therapy- usually endocrine
therapy.
Case presentation
We report the case of a 52-year old Caucasian woman,
without classic risk factors for breast cancer, who was referred
36
Matei & Holló
to The Oncology Institute „Prof. Dr. Ion Chiricuţă” in august
2006 for the management of a lump in the left breast.
Breast conserving surgery was first performed
(lumpectomy with axillary lymph node dissection). The
histopathological exam showed a 2.5 cm macroscopic
tumor which microscopically was compatible with a grade
Nottingham I invasive ductal carcinoma .The tumor was
55% ER positive, PR negative. HER-2/neu assessment
was not performed. 17 axillary lymph nodes were negative.
Pathological stage was pT2NoMoLoVoRo. . The workup did
not show any distant metastases
She finished her adjuvant chemotherapy (4 cycles of
epirubicin 100 mg/mp and cyclophosphamide) -in .December
2006. She was then included in a randomized, phase III trial
comparing the efficacy of Exemestane versus Anastrozole
in hormone receptor positive postmenopausal breast cancer;
adjuvant hormonal therapy with Anastrozole was started in
january.2007. She also received adjuvant radiotherapy with
a total dose of 6oGy/30fr/44days on tumor bed.
In March 2009, 26 months after adjuvant hormonal
therapy with Anastrozole was started, the patient presented
with left posterolateral thoracic pain and left mastodynia.
Clinical exam revealed rib pain produced by palpation of
IV and V posterior left ribs.
A chest X-ray was performed which showed the presence
of a suspicious osteolytic area located on the posterolateral
IV costal arch. Bone scintigraphy showed hypercaptation
of respective area, with no other bone lesions. Thorax CT
confirmed the presence of the unique osteolytic lesion, with
no visceral involvement.
In the differential diagnosis a solitary bone plasmacytoma
was excluded by hematological exam.
Consequently, we concluded that the patient had solitary
metastatic disease to the rib. Various therapeutic options
were discussed with the patient, including systemic hormonal
therapy together with bisphosphonates therapy, or the same
plus the addition of local radiotherapy to control pain; taking
into consideration that this was a solitary metastasis, we also
discussed the surgical resection of the lesion.
Fig. 2. Computer Frontal chest radiograph shows the
solitary osteolytic rib metastasis.
Fig. 3. 99mTc-HMDP bone scintigraphy with solitary
rib metastasis.
Fig. 1. Computer Tomography imaging of axial plan
demonstrating an osteolytical mass of the left rib.
In May 2009 the patient underwent surgery. Posterolateral
IV rib arch resection was performed. The histopathological
exam showed a 2/4 cm bone fragment with invasive ductal
carcinoma infiltration.
The final diagnosis was a completely resected breast
origin solitary bone metastases.
On May 2009 hormonal therapy with Tamoxifen was
started along with bisphosphonates (Zometa).
In January 2012, 31 months after hormonal therapy with
Tamoxifen was started, routine CT examination revealed
Resection of solitary metastases in breast cancer patients
the presence of an 8 mm solitary pulmonary nodule, located
in the left superior lobe. There were no other metastatic
lesions. She had no symptoms. Considering the patient’s
good clinical status ,the presence of one solitary metastasis
and taking into account the 31 months free of disease interval
following first solitary metastases resection, re-resection
was decided. She underwent surgery again on May 2012. A
left upper lobectomy was performed. The histopathological
exam showed a breast origin metastasis. The tumor was 90%
ER positive, PR negative and HER-2/neu was 2+.
On June 2012 hormonal therapy with Letrozole was
started.
The last control was in April 2013. Clinical exam,
thoracic radiography and abdominal echography were
performed and the results showed maintained clinically
complete response.
Discussion
The traditional belief of both patients and their
physicians has been that metastatic breast cancer offers only
the grimmest prognosis, with average survival times of 1-2
years. This belief has fostered treatment regimens based on
the notion that palliative treatment is the optimal choice for
most patients, with more aggressive therapeutic approaches
likely to result in useless patient distress.
A more aggressive treatment approach may be
appropriate for those patients in whom metastatic disease is
limited to a solitary lesion or to multiple lesions at a single
organ site. When those patients can be rendered clinically
disease free by local treatment (surgery or radiation), there
is the potential of achieving a complete remission from
chemotherapy, and patients can remain disease free for
prolonged periods of time (15-20 years or more). In a clinical
trial conducted at the M.D. Anderson Cancer Center by
Holmes and colleagues (2), patients with solitary metastases
were treated with surgical resection with or without radiation
therapy, followed by systemic chemotherapy, consisting
of fluorouracil, doxorubicin, and cyclophosphamide, and
hormonal therapy, consisting of Tamoxifen. Nearly 25% of
patients were alive without disease 15 years after treatment,
and only two additional events have occurred at a maximum
follow-up of 26 years (2,3).
Bone is one of the earliest and most common sites of
breast cancer metastasis. The usual first treatment choice for
bone metastasis not at risk for fracture is systemic therapy,
either hormonal therapy or chemotherapy. This is especially
true for isolated lesions, which account for approximately
20% of all bone metastasis (4). Isolated bone metastasis
have a somewhat indolent course and generally respond
well to hormonal therapy (5-7).For patients in whom the
metastasis are hormone-receptor negative, or whom become
refractory to hormonal treatment, chemotherapy has been
shown to be effective (8). In metastatic disease confined
to the skeletal system and treated with hormonal therapy
,with or without chemotherapy, median survival time of 48
37
months and a 5-year survival rate of 39% have been reported.
(5,9). More recently, osteoclast inhibitory therapy using
bisphosphonates has become widely used (10). Radiation
therapy, either locally or through the systemic administration
of radioisotopes, has also been used effectively in these
patients, providing pain relief and, in some cases, evidence
of bone healing (11,12).
The use of surgery for the treatment of bone metastases
has typically been reserved for lesions that are not responsive
to systemic therapy and that are associated with a serious
potential for decline in the quality of life in order to reduce
fractures, treat spinal cord or nerve compression, and
prophylaxes of imminent fractures.
The use of surgery as a curative treatment option for
bone metastasis has been actively considered in the case
of isolated metastases to the sternum. Two studies from the
1980s presented results from a limited number of patients
indicating that surgical resection of solitary sternum
metastasis, where there was no evidence of systemic spread,
may have lead to significantly better survival (13). Based
on the results of those studies we aimed to treat our patient
with curative intent by performing posterolateral IV rib
arch resection.
As for pulmonary solitary metastases, surgery tends to
become a standard treatment for this category of patients
regardless the primary tumor site. There have been some
retrospective studies which examined survival outcomes in
breast cancer patients with isolated metastases to the lung
treated with surgery, with or without postsurgical systemic
therapy (14-21). Median survival times ranged from 42
months to 79 months, with 5-year actuarial survival rates
ranging from 35-80% and 10 year actuarial survival rates
ranging from 8-60%. In two studies that presented outcomes
from patients who received medical treatment only for
pulmonary metastases (17,20), survival was significantly
lower for those patients. It has been shown that better
outcome after surgery was associated with good performance
status, long DFI after the treatment of the primary tumor
(16,18,21)and complete resection of the tumor (14,19,21).
Conclusions
Treatment recommendations for metastasis breast cancer
patients continue to evolve every day. We are perhaps today
in the position to treat solitary breast cancer metastasis with
curative intent, using surgery with or without radiotherapy
or chemotherapy. The data are suggestive and support the
need for well-designed clinical trials to determine the exact
role of surgical intervention in such patients with solitary
metastasis.
References
1. Schwarz RE, Klimstra DS, Turnbull ADM: Metastatic breast cancer
masquerading as gastrointestinal primary. Am J Gastroenterology,
93: 111-114, 1998.
38
2. Holmes FA, Buzdar AU, Kau SW et al. Combined-modality approach
fór patients with isolated recurrences of breast cancer (IV-NED): the
M.D. Anderson experience. Breast Disease 1993;7:7-20.
3. Rivera E, Holmes FA, Buzdar AU et al. Fluorouracil, doxorubicin,
and cyclophosphamide followed by tamoxifen as adjuvant treatment
for patients with stage IV breast cancer with no evidence of disease.
Breast J 2002;8:2-9.
4. Boxer Dl, Todd CE, Coleman R et al. Bone secondaries in breast
cancer: the solitary metastasis. J Nucl Med 1989;30:1318-1320.
5. Sherry MM, Greco FA, Johnson DH et al. Metastatic breast cancer
confined to the skeletal system. An indolent disease. Am J Med 1986;
81:381-386.
6. Leone BA, Romero A, Rabinovich MG et al. Stage IV breast
cancer: clinical course and survival of patients with osseous versus
extraosseous metastases at initial diasnosis. The GOCS (Grupo
Oncologico Cooperativo dél Sur) experience. Am J Clin Oncol
1988;11:618-622.
7. Coleman RE, Rubens RD. The clinical course of bone metastases
from breast cancer. Br J Cancer 1987;55:61-66.
8. Scheid V, Buzdar AU, Smith TL et al. Clinical course of breast
cancer patients with osseous metastasis treated with combination
chemotherapy. Cancer 1986;58:2589 2593.
9. Durr HR, Muller PE, Lenz T et al. Surgical treatment of bone
metastases in patients with breast cancer. Clin Orthop 2002;396:191196.
10. Coukell AJ, Markham A. Pamidronate: a review of its use in
the management of osteolytic boné metastases, tumourinduced
hypercalcaemia and Paget’s disease of boné. Drugs Aging
1998;12:149-168.
Matei & Holló
11. Cheng DS, Seitz CB, Eyre HJ. Non-operative management of
femoral, humeral, and acetabular metastases in patients with breast
carcinoma. Cancer 1980;45:1533-1537.
12. Robinson RG. Radionuclides for the alteration of bone pain in
advanced malignancy. Clin Oncol 1986;5:39-49.
13. Takanami I, Ohnishi H. Study of surgical resection of sternal
metastasis from carcinoma of the breast. Gan No Rinsho
1989;35:1735-1738. Japanese.
14. McDonald ML, Deschamps C, Ilstrup DM et al. Pulmonary resection
for metastatic breast cancer. Ann Thorac Surg 1994;58:1599-1602.
15. Ishida T, Kaneko S, Yokoyama H et al. Metastatic lung tumors and
extended indications for surgery. Int Surg 1992;77:173-177.
16. Lanza LA, Natarajan G, Roth JA et al. Long-term survival after
resection of pulmonary metastases from carcinoma of the breast.
Ann Thorac Surg 1992;54:244-248.
17. Staren ED, Salemo C, Rongione A et al. Pulmonary resection for
metastatic breast cancer. Arch Surg 1992;127:1282-1284.
18. Simpson R, Kennedy C, Carmalt H et al. Pulmonary resection for
metastatic breast cancer. Aust N Z J Surg 1997;67:717-719.
19. Livartowski A, Chapelier A, Beuzeboc P et al. (Surgical excision of
pulmonary metastasis of cancer of the breast: apropos of 40 patients).
Bull Cancer 1998;85:799-802. French.
20. Murabito M, Salat A, Mueller MR. (Complete resection of isolated
lung metastasis from breast carcinoma results in a strons increase
in survival). Minerva Chir 2000;55:121-127. Italian.
21. Friedel G, Pastorino U, Ginsberg RJ et al. Results of lung
metastasectomy from breast cancer: prognostic criteria on the basis
of 467 cases of the International Registry of Lung Metastases. Eur
J Cardiothorac Surg 2002;22:335-344.