Long-term survival after pancreatic metastasis resection from breast cancer: a systematic literature review

Background Patients with advanced-stage breast cancer often demonstrate pancreatic metastases. However, pancreatic metastases resection from breast cancer has been rarely performed, with only 20 cases having been reported to date. Case presentation A 49-year-old woman presented to our hospital in September 2003 with complaints of uncontrollable oozing from her left breast tumor. Computed tomography revealed a left breast tumor approximately 9.3 cm in diameter as well as heterogeneously enhanced solid mass lesions with necrotic foci in the pancreatic tail and body, up to 6.2 cm, which were radiologically diagnosed as pancreatic metastases from breast cancer. An emergent left simple mastectomy was performed to control bleeding. After epirubicin and cyclophosphamide hydrate treatment failed to improve her condition, the pancreatic metastases responded to weekly paclitaxel treatment, but eventually regrew. The patient underwent distal pancreatectomy with splenectomy, left adrenalectomy, partial stomach resection, and paraaortic lymph nodes excision in December 2004 after no other metastasis was confirmed. Furthermore, she received radiation therapy for left parasternal lymph node metastasis 6 months later. The patient recovered well. Consequently, she has no evidence of disease > 15 years after pancreatectomy. Conclusions This is the first reported case of pancreatectomy for pancreatic metastases from breast cancer, which was simultaneously diagnosed. Patients with no metastasis other than resectable pancreatic metastases and breast cancer and who possess some sensitivity for chemotherapy may benefit from pancreatectomy.


Case presentation
A 49-year-old woman complaining of uncontrollable oozing from her left breast tumor presented to our hospital in September 2003. She had been aware of her left breast tumor for > 10 years and had self-managed her left breast erosion for > 3 years. Laboratory test results revealed anemia (hemoglobin 9.1 g/dL) and elevated levels of carcinoembryonic antigen (CEA; 65.2 ng/mL) and carcinoma antigen 15-3 (44.2 U/mL). However, the carbohydrate antigen 19-9 value was not elevated (12.1 U/mL).

Open Access
*Correspondence: tnoie@east.ntt.co.jp 1 Department of Surgery, NTT Medical Center Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo 141-8625, Japan Full list of author information is available at the end of the article Furthermore, the late arterial phase of dynamic contrastenhanced computed tomography (CT) revealed heterogeneously enhanced multiple solid mass lesions with necrotic foci in the pancreatic tail and body [19]-up to 6.2 cm in size-with peripancreatic and paraaortic lymph node swelling (Fig. 1). A left breast tumor projecting to the skin approximately 9.3 cm in diameter (Fig. 2) as well as left axillary lymph node swelling was simultaneously noted. The largest pancreatic mass, in this case, was a solid mass that was contrast-enhanced to the same extent as the surrounding pancreatic parenchyma although the common imaging finding of pancreatic ductal carcinoma is hypovascular. This mass was also not hypervascular enough to raise the suspicion of a pancreatic neuroendocrine tumor. In addition, other noncontiguous pancreatic masses were found, and the presence of breast cancer was suggested, which led to the suspicion of pancreatic metastases from breast cancer rather than the primary pancreatic tumor, radiologically. The next day, emergent left simple mastectomy and reconstruction of the left breast by inferior lateral rectus abdominis muscle flap [20] were performed to control bleeding. Macroscopically, the tumor was 7 cm in diameter and protruded from the skin. The cut surface of the tumor was solid and grayish-white with central necrosis, and the surgical margin was negative. Microscopically, the tumor was composed of large nests with central comedo necrosis. The tumor cells had large, round vesicular nuclei, prominent nucleoli, and pale eosinophilic granular cytoplasm. Mitotic figures were frequently observed (Fig. 3). Immunohistochemically, the tumor was negative for estrogen receptor (ER) and progesterone receptor (PR), and the HercepTest score was 0.
She began chemotherapy 2 weeks later with epirubicin and cyclophosphamide hydrate once every 3 weeks. Her CEA level increased (83.6 ng/mL) after four treatment cycles, and CT demonstrated a slight expansion of the pancreatic tumor. Weekly paclitaxel treatment started in December 2003. Her CEA level decreased gradually (to a minimum of 6.1 ng/mL in June 2004), and CT performed in July 2004 revealed shrunken pancreatic tumors that could not be recognized as masses with different densities. Thereafter, her CEA level increased again (up to 14.0 ng/mL in She underwent DP with splenectomy, left adrenalectomy, partial stomach resection, and paraaortic lymph nodes excision in December 2004. A gross examination of the resected specimen revealed a multinodular tumor at the pancreas tail, 3.5 × 3 × 2 cm in size. The tumor invaded the lymph nodes around the pancreas. The cut surface of the tumor was solid and grayishwhite with focal hemorrhaging. Microscopically, the tumor invaded the pancreas and surrounding tissue, forming solid nests with central necrosis. The tumor cells had large round vesicular nuclei with prominent nucleoli and pale eosinophilic granular cytoplasm. Mitotic figures were frequently found (Fig. 4). These histological features were similar to those of this patient's primary breast cancer (Fig. 3). Immunohistochemically, the tumor was negative for ER, PR, gross cystic disease fluid protein-15, and mammaglobin. Although immunohistochemical markers of breast cancer were negative, the patient was diagnosed with primary breast cancer metastases to the pancreas based on the histological similarity between these two tumors.
Ultrasonography and CT performed in May 2005 revealed left parasternal lymph node metastasis, which was subsequently treated by radiation therapy comprising 60 Gy/30 f. She took 5′-deoxy-5′-fluorouridine for 2 years after pancreatectomy. The patient was doing well with no evidence of disease as of January 2020.

Discussion and conclusions
Metastatic pancreatic tumor resection has been increasingly reported in proportion to decreased morbidity and mortality after pancreatectomy [21][22][23]. Careful patient selection can improve the survival of patients with metastatic pancreatic cancer after undergoing pancreatectomy [23].
Preoperative diagnosis of pancreatic metastasis was achieved in only two cases. One was diagnosed with pancreatic metastasis from breast cancer by radiologic examination [7], as in the present case, and another was diagnosed by fine-needle aspiration cytology under endoscopic ultrasonography [9]. In the remaining 18 patients, the preoperative diagnosis was pancreatic head cancer or another one other than pancreatic metastasis from breast cancer. The final diagnosis was achieved after a pathological examination. PD (including pylorus-preserving PD), DP, total pancreatectomy, and enucleation were performed in 14, 4 (including the present case), 1, and 1 case, respectively. However, the surgical method was not reported in one case. Lymph node metastases from pancreatic metastases were present in 5 of 10 cases. Six patients expired between 7 months and 3 years after undergoing pancreatectomy, and 13 cases, including four cases with recurrence, survived from 2 months to 6.7 years. Two patients survived without a recurrence for > 5 years after undergoing pancreatectomy [2,6]. The cumulative 5-year survival rate is as high as 52%, partly owing to many cases having been reported to be alive.
Metastatic breast cancer (MBC) is generally an incurable disease and its prognosis is unfavorable [25,26], especially in patients with triple-negative breast cancer (TNBC) [27,28], defined by negative expressions of ER and PR and the lack of amplification of the human epidermal growth factor-2 (HER2) gene. Systemic therapy is the standard care for patients with MBC [29,30]. However, selected patients with very limited or oligometastatic distant disease may benefit from the addition of metastases-directed local therapy on rare occasions [31,32]. Patients with liver metastases from breast cancer, which are more frequently encountered than pancreatic metastases, are indicated for hepatectomy only if they have favorable prognostic markers, such as positive ER, HER2 overexpression, or stable disease after neoadjuvant therapy [33][34][35]. The study on stereotactic body radiotherapy (SBRT) for patients with oligometastases mentioned that MBC patients who experienced stable or regressive disease after systemic therapy before SBRT survived significantly longer than MBC patients who experienced lesion progression [36]. However, pancreatic metastases were progressive following regression before pancreatectomy in this patient, and her cancer was TNBC. For pancreatic metastasis from breast cancer, the favorable prognostic features after pancreatectomy are uncertain because of the few numbers of cases. Thus, if a patient has no metastasis other than resectable pancreatic metastases and is sensitive to chemotherapy, she may benefit from pancreatectomy because no biomarker for patient identification with the true oligometastatic disease is clinically available37.
The patient in this study was the first to be simultaneously diagnosed with pancreatic metastases with breast cancer and undergo pancreatectomy. Moreover, the present case highlights the potential for long-term survival after resection of pancreatic oligometastases from breast cancer.