INTRODUCTION
Pancreatic metastases from primary malignant tumors at other sites are rare, constituting about 2% of the neoplasms that affect the pancreas.1 In most cases, the involvement occurs through hematological and lymphatic dissemination, as in cases of kidney and lung carcinomas. It can also occur through contiguous invasion of neighboring organs such as the liver, stomach and spleen. Pancreatic metastasis from breast cancer is extremely rare and difficult to diagnose, because its clinical and radiological presentation is similar to that of a primary pancreatic tumor.2,3,4,5 The objective of the present study was to report on a case of pancreatic metastasis of breast cancer, along with the treatment that was proposed.
CASE REPORT
A 64-year-old female underwent neoadjuvant chemotherapy consisting of doxorubicin, cyclophosphamide and paclitaxel, with subsequent quadrantectomy and axillary lymph node dissection due to a right-side breast neoplasm. Histopathological examination revealed a ductal carcinoma classified as T2N2M0, consisting of a 4-cm tumor with spreading to six axillary lymph nodes but without distant spreading to bones, liver, brain or lungs). It was triple-negative, for estrogen, progesterone and human epidermal growth factor receptor 2 (HER2) receptors. Radiation therapy was subsequently implemented. The patient was then followed up with serial investigations (mammogram, bone scintigraphy scan and computed tomography scans of the cranium, thorax and abdomen) for locoregional and distant relapses every six months.
Twenty-four months after receiving the diagnosis, she evolved with a complaint of left-flank pain, inappetence and loss of seven kilograms in four months. She presented dyspeptic symptoms characterized by early satiety and pain in the upper abdomen after feeding. On physical examination, the abdomen was painful to deep palpation. There was no evidence of relevant laboratory abnormalities.
Abdominal computed tomography demonstrated a hypervascularized solid lesion of 6.6 cm x 6.0 cm x 7.0 cm in the tail of the pancreas. It had an irregular outline and partially defined borders, presented a central area of necrosis and was in contact with the anterior margin of the spleen and greater gastric curvature. It was not possible to determine any cleavage plane. A small amount of free liquid was present (Figure 1). Cancer antigen (CA)-19.9, carcinoembryonic antigen (CEA) and CA-125 levels were within the normal ranges. No other sites with suspected lesions were detected through positron-emission computed tomography.
Because the hypothesis of pancreatic neoplasia needed to be clarified and no endoscopic ultrasound-guided biopsy was available, prompt surgery was warranted given that there was no evidence of other sites of active disease. The patient underwent distal pancreatectomy with splenectomy and left adrenalectomy (Figure 2), with uneventful postoperative outcomes. She had good evolution in the postoperative period, with complete remission of symptoms.
The histopathological diagnosis consisted of metastasis from breast carcinoma. The results from the immunohistochemical analysis were positive for the cytokeratin-7 (CK7) marker and negative for the mucin 5AC (MUC-5AC), CEA, CA-19.9, estrogen receptor (ER), progesterone receptor (PR) and Breast-2 (BRST-2) markers. Although negativity for ER, PR and BRST-2 does not favor a breast origin, these markers do not preclude this origin. On the other hand, negativity for the MUC-5AC, CEA and CA-19.9 markers does not favor a pancreatobiliary origin and favors the breast as the primary site. A chemotherapy regimen consisting of paclitaxel was administered for 12 weeks following the patients recovery from the operation, and currently she is being followed up with serial screenings for locoregional and distant spreading of disease every six months. As of 18 months after the diagnosis was made, there is no evidence of active disease.
DISCUSSION
Breast cancer causes metastases especially to bones, liver and lungs. Pancreatic involvement in solitary metastases from a primary breast neoplasm is rare, occurring in less than 3% of the cases. A review of the literature was conducted through an online search for the Medical Subject Headings (MeSH) terms “breast neoplasms”, “pancreas” and “neoplasm metastasis” in MEDLINE (via PubMed) and LILACS (via BVS) (Table 1). We included original studies that reported single cases or case series of this disease or correlated conditions. All the papers were checked according to their titles and abstracts (screening). Full papers were obtained from journals available on the website of the Commission for Improvement of Higher Education Personnel (Comissão de Aperfeiçoamento de Pessoal de Nível Superior, CAPES) (Ministry of Education, Brazil). Unavailable articles were requested from their authors. Articles presenting potentially relevant studies were read and analyzed to assess the inclusion criteria. We excluded articles that consisted of in vitro or animal studies, articles in which the participants’ characteristics did not match those mentioned above, poster session abstracts, review articles and other types of publications. Other papers were used for contextualization and discussion.
Table 1. Database search results for pancreatic metastasis arising from primary breast cancer
Electronic databases | Search strategies | Results |
---|---|---|
MEDLINE (PubMed) | (Breast neoplasms) AND (Pancreas) AND (Neoplasm Metastasis) | 17 case reports 6 case series |
LILACS (BVS) | (((Breast neoplasms) OR (Neoplasias da mama) OR (Neoplasias de la mama)) AND ((Pancreas) OR (Pâncreas) OR (Páncreas)) AND ((Neoplasm Metastasis) OR (Metástase Neoplásica) OR (Metástasis de la Neoplasia))) | 1 case report |
After extensive online research, we identified 23 studies, 17 case reports and 6 case series, totaling 28 reported cases of pancreatic metastases from breast cancer. Table 2 2,3,6,7,8,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27 summarizes the main articles found and their reported outcomes. Figure 3 presents a flow diagram of the articles selected. In the majority of the cases described, spreading to the head of the pancreas was more common than to the tail, and the most common histological type was lobular carcinoma; the predominant metastatic pattern was solitary. The average interval between the diagnoses of primary breast neoplasm and pancreatic metastasis was 43.3 months.2 In our case, the patient presented metastasis to the region of the tail of the pancreas, with a histopathological diagnosis of ductal carcinoma, and the asymptomatic interval was 24 months.
Table 2. Reported cases of pancreatic metastases arising from primary breast cancer
Authors | Breast cancer subtype | Age (years) | Disease-free interval (months) | Presenting symptoms | Location of metastases at diagnosis | Profile of the metastatic disease at diagnosis | Clinical management | Overall survival (months) |
---|---|---|---|---|---|---|---|---|
Akashi et al.6 | Lobular | 47 | 41 | NR | Head of pancreas | Solitary | Pancreaticoduodenectomy | 28 |
Azzarelli et al.7 | Lobular | 49 | 43 | Jaundice | Head of pancreas | Solitary | Pancreaticoduodenectomy, radiation therapy | 72 |
Bednar et al.8 | Lobular Phyllodes |
75 57 |
96 48 |
Jaundice, pain Abdominal pain |
Head of pancreas Head of pancreas, lung |
Solitary Widespread disease |
Pancreaticoduodenectomy Chemotherapy |
48 15 |
Bonapasta et al.2 | Ductal | 51 | 24 | Jaundice, pain | Head of pancreas | Solitary | Pancreaticoduodenectomy | 36 |
Crippa et al.10 | Lobular Lobular Lobular |
46 70 57 |
60 36 84 |
Jaundice Jaundice, pain Jaundice, pain |
Head of pancreas Head of pancreas Head of pancreas |
Solitary Solitary Solitary |
Pancreaticoduodenectomy Pancreaticoduodenectomy Pancreaticoduodenectomy |
22 38 26 |
Dar et al.11 | Ductal | 76 | 108 | NR | Pancreas, liver | Widespread disease | Palliative bypass | 6 |
Engel et al.12 | Signet-ring cells | 59 | 46 | Pruritus, choluria | Head of pancreas | Solitary | Palliative bypass, Chemotherapy | 15 |
Estraviz et al.13 | Ductal | 56 | 36 | Jaundice | Head of pancreas | Solitary | Pancreaticoduodenectomy | 6 (still alive at the time of report) |
Haque et al.14 | Lobular | 85 | 168 | Jaundice, pain | Head of pancreas | Solitary | Palliative bypass | NR |
Kita m ura et al.15 | Ductal | 55 | 117 | Jaundice | Head of pancreas | Solitary | Percutaneous drainage | 1 |
Le Borgne et al.16 | Lobular | 48 | Synchronous | Jaundice | Head of pancreas | Solitary | Pancreaticoduodenectomy, chemotherapy | 12 |
Mehta et al.17 | Comedo type | 30 | 36 | Jaundice, pruritus | Head of pancreas | Solitary | Pancreaticoduodenectomy, chemotherapy, hormonal therapy | 27 |
Molino et al.3 | Lobular | 68 | Synchronous | Jaundice | Head of pancreas | Solitary | Pancreaticoduodenectomy, hormonal therapy | 12 (still alive at the time of report) |
Mountney etal.18 | Lobular | 57 | 16 | Jaundice | Head of pancreas | Solitary | Palliative bypass, hormonal therapy | 24 |
Moussa et al.19 | Ductal Lobular |
53 35 |
132 45 |
Acute pancreatitis Abdominal mass |
Head of pancreas Body of pancreas |
Solitary Solitary |
Radiation therapy, chemotherapy, hormonal therapy Total pancreatectomy, chemotherapy |
50 7 |
Nomizu et al.20 | Lobular | 46 | 80 | Jaundice | Head of pancreas | Solitary | Pancreaticoduodenectomy, chemotherapy, hormonal therapy | 18 |
Odzak et al.21 | Lobular | 48 | Synchronous | Jaundice, ascites | Head of pancreas | Widespread disease | Palliative care | NR |
Pan et al.22 | Lobular | 59 | 182 | Jaundice | Head of pancreas | Solitary | Chemotherapy, hormonal therapy | 21 |
Pappo et al.23 | Lobular | 52 | 24 | Jaundice | Pancreas, gallbladder | Widespread disease | Palliative bypass, hormonal therapy | 16 |
Pérez Ochoa et al.24 | Lobular Ductal |
60 55 |
1 108 |
Jaundice None |
Head of pancreas, bone Tail of pancreas |
Widespread disease Solitary |
Biliary stent, pancreaticoduodenectomy, chemotherapy Distal pancreatectomy, splenectomy, chemotherapy |
2 2 |
Razzetta et al.25 | Lobular | 51 | Synchronous | Jaundice, pain, diarrhea | Head of pancreas, bone | Widespread disease | Pancreaticoduodenectomy, neoadjuvant chemotherapy, mastectomy | 5 |
Tohnosu et al.26 | Scirrhous type | 54 | 52 | None | Tail of pancreas | Solitary | Distal pancreatectomy, chemotherapy, hormonal therapy | 5 |
Z’graggen et al.27 | Lobular | NR | 96 | Jaundice | Head of pancreas | Solitary | Biliary and gastric bypass, chemotherapy | 54 |
Current study | Ductal | 64 | 24 | Pain | Tail of pancreas | Solitary | Distal pancreatectomy, chemotherapy | 18 (still alive at the time of report) |
NR = not reported.
The clinical signs of this condition are unspecific, with abdominal pain and obstructive jaundice as the main findings.4 The absence of characteristic clinical signs and symptoms leads to investigation by means of imaging tests. Ultrasonography, computed tomography and magnetic resonance imaging are frequently used for making this diagnosis; however, the radiological features of primary pancreatic tumors and pancreatic metastases are difficult to differentiate. Use of serum markers such as CA-15.3 may help in making the diagnosis, although in some cases its serum elevation is not relevant.2,5,6,7,8,9,28 The most accurate diagnostic method is pancreatic biopsy. Some studies have suggested that fine-needle biopsies guided by endoscopic ultrasound or percutaneously should be used.3 The unavailability both of tests for this marker and of endoscopic ultrasound at our service precluded their use in the present case; however, this should not prevent the oncology and surgery teams from recommending operative treatment in cases without widespread disease.
The prognosis for patients with pancreatic metastatic disease is usually better than for patients with primary pancreatic tumors.2 Masetti et al. analyzed the prognostic factors relating to metastatic tumors in the pancreas and found two and five-year survival rates of 57.1% and 34.3% in cases of pancreatic metastasis due to breast cancer, respectively.28 Surgical resection in cases with disease limited to the pancreas is considered to be the main form of treatment, despite its morbidity.3