Recurrent Pure Mucinous Carcinoma of the Breast With Mediastinal Great Vessel Invasion: HER-2/Neu Confers Aggressiveness
By Adair, Jamie D Harvey, Kyle P; Mahmood, Ali; Caralis, James; Gordon, William; Yanish, Gregory
Mucinous carcinoma of the breast, also known as colloid carcinoma, is a less common variant of breast cancer constituting less than five per cent of breast cancers. We report the case of a 42-year-old premenopausal female who presented with a palpable chest wall recurrence 4 years after simple mastectomy, axillary node dissection, and TRAM flap reconstruction for pure mucinous carcinoma. The recurrent neoplasm was a pure mucinous carcinoma and was found to be invading the mediastinum into the great vessels. The tumor was estrogen receptor positive, progesterone receptor negative, and HER-2/neu positive, which is an unusual finding for mucinous carcinoma. The fact that this tumor demonstrated HER-2/neu positivity may explain the uncharacteristic aggressive nature of this normally indolent type of breast tumor. To our knowledge, this is the first reported case of any mucinous breast cancer invading the mediastinal great vessels and its subsequent en-bloc resection. Mucinous breast cancer has classically been known as a less aggressive type of tumor, which tends to have a better prognosis than other breast malignancies. These tumors occur in two forms, as either pure or mixed type, the latter being more common. The treatment of this type of breast cancer is similar to invasive ductal carcinoma. Current genetic techniques allow us to determine receptor status and predict how a tumor may behave. We are able to predict certain features and behaviors of breast cancer that we were unable to predict in the past. This has led to new and exciting treatment options for all types of breast cancer. In recent years, there has been a great deal of interest in HER-2/neu receptor status and the aggressive nature that tumors possessing mis receptor exhibit. In this case report, we present a recurrent pure mucinous tumor that demonstrated angiolymphatic invasion microscopically and grossly was found to be invading the mediastinal great vessels. The recurrent tumor was ER+/PR- and HER-2/neu positive.
The patient is a 42-year-old premenopausal female who was diagnosed with a pure mucinous carcinoma of the right breast in 2001. A core-needle biopsy at that time revealed a pure mucinous tumor. The patient underwent simple mastectomy, axillary node dissection, and immediate TRAM flap reconstruction. The primary tumor was 3.5 centimeters in size with two positive lymph nodes (out of 20). Sentinel lymph node biopsy was not performed because there were clinically positive nodes in the axilla. A metastatic work-up consisting of routine lab work and a CT scan of the thorax did not reveal any metastases. The tumor was ER+/PR- and exhibited HER-2/ neu overexpression. Postoperative therapy included FAC (5- Fluoracil, Adriamycin [Pharmacia Inc., Kalamazoo, MI], and Cytoxan [Bristol-Myers Squibb Company, Princeton, NJ]) followed by radiation and tamoxifen citrate. The patient had been asymptomatic for almost 4 years. She had follow-ups every 6 months for the first 3 years and was then scheduled for annual visits. Shortly before her first annual visit, she noticed an enlarging chest wall mass over a period of 3 months. A metastatic work-up was initiated. CT scan of the abdomen and pelvis were negative for metastases. CT scan of the thorax revealed a large anterior chest wall mass measuring 4 x 4 x 7 centimeters causing local destruction of the sternum and mediastinal invasion (Fig. 1). CT guided needle biopsy was then performed and several specimens sent to pathology. The specimen consisted of connective tissue heavily infiltrated by a malignant neoplasm that was consistent with a pure mucinous carcinoma (Fig. 2). A whole body bone scan after intravenous injection of technetium- 99 showed only focal uptake in the right manubrium, which corresponded to the palpable sternal mass.
The patient was experiencing significant pain and emotional distress over this rapidly enlarging cosmetically disfiguring chest wall mass. She was young, extremely motivated, and had no comorbid conditions. The case was presented at a multidisciplinary tumor conference for possible treatment options. Thoracic surgery was consulted for management of the chest wall tumor for possible excision. After a long discussion with the patient, and the limited treatment options, decision was made to proceed with surgery for excision of the chest wall mass with the understanding that this may be only palliative.
FIG. 1. Preoperative CT scan of the thorax revealing a large anterior chest wall mass invading the mediastinum, (t = tumor, a = aorta, S = sternum)
FIG. 2. Neoplastic hyperchromatic cells varying in size with some areas showing clusters and nests of neoplastic cells surrounded by pools of mucin. The tumor also demonstrates bony erosion. [H&E stain]
En-bloc chest wall resection was done through a transverse incision directly over the tumor anterior to the manubrium. Dissection of the mass circumferentially revealed a fingerlike projection on the inferior aspect of the tumor projecting deeper into the mediastinum. There appeared to be direct invasion at the junction of the superior vena cava (SVC) and innominate vein (Fig. 3). The vascular invasion was not seen on the preoperative CT scan. Ballottable palpation verified the intravascular nature of the tumor. The decision at that time was to gain vascular control with inflow occlusion technique and remove the tumor. The area of the vein at the junction of the SVC and innominate vein where the tumor was infiltrating was resected and the tumor removed. The SVC was then closed primarily. The patient recovered uneventfully from the surgery with no complications.
FIG. 3. Dissection of the tumor in the mediastinum ultimately revealed it to be invading the junction of SVC and innominate vein.
Postoperatively the case was again presented at a multidisciplinary breast tumor conference for possible treatment options. The characteristics of the tumor, which included hormone receptor status, type of mucinous carcinoma, and vascular invasion were all considered. The past treatment of her primary breast cancer was also considered. The patient was offered and consented to the chemotherapeutic regimen consisting of Herceptin(R) (Genentech Inc., South San Francisco, CA) and Taxotere(R) (Sanofi-Aventis, US, LLC, Bridgewater, NJ). Radiation was contraindicated because the patient had received prior radiation to the breast.
Mucinous carcinoma, also known as colloid carcinoma, is a less common variant of breast cancer constituting less than five per cent of all breast cancers. These tumors tend to be in multiple series, less aggressive in nature than other more common types of breast cancer, and are also more likely to occur in older patients with a mean age of sixty- seven. These tumors have substantially less nodal involvement, exhibit ER+/PR+, and are HER-2/neu negative compared with other common breast carcinomas.1^ One study reported that the survival of patients with mucinous carcinoma is not significantly different from that of the general population and that systemic adjuvant therapy and node dissection may be avoided in many patients with these types of carcinoma.5, 6 However, over 30 years ago, Silverberg et al.7 concluded there was insufficient evidence that treatment should be conservative. We agree with this statement and recommend taking into account the HER-2/neu status when deciding on treatment options.
There is sparse information in the literature regarding the more aggressive variant of mucinous carcinoma with very few case reports.8 To our knowledge, mere are no reported cases of mediastinal vascular invasion of either pure or mixed type mucinous carcinoma of the breast. Pure mucinous carcinomas tend to have a less aggressive growth pattern and have less lymph node metastases.9 These tumors’ recurrence rates tend to be late and few, with no increase in mortality compared with other breast cancer types.10
Our case illustrates a patient with a recurrent tumor hormonal receptor status of ER+/PR- with HER-2/neu overexpression. ER+/PR+ tumors are known to have a better prognosis than ER+/PR- tumors. ER+/ PR- tumors express higher levels of HER-2/neu. HER-2/neu is seen in 20 to 30 per cent of all breast cancers and is well known to be a negative prognostic factor. These tumors also have increased disease recurrence and metastases. Signaling through HER-2/neu receptors reduces progesterone receptor expression in experimental models, thus ER+/PR- receptors with HER-2/neu overexpression are more likely to have a higher recurrence.11-14 This seems to be consistent with our recurrent tumor as HER-2/neu was positive by fluorescence in situ hybridization (FISH) analysis. This emphasizes the importance of HER-2/neu status regarding all breast cancer including the mucinous type.
Diagnostic work-up of mucinous tumors may be approached by fine needle aspiration (FNA) or core biopsies. Core biopsy can achieve 100 per cent sensitivity and accuracy in the diagnosis of malignant lesions including mucinous carcinoma.15 Diagnosis is confirmed with histology revealing the mucoid component consisting of ribbons, small tubules, cribiform areas, and deposits of mucin surrounding isolated islands of cells with hyperchromatic nuclei. The Stanford School of Medicine Surgical Pathology Criteria defines pure mucinous carcinoma of the breast as a breast carcinoma of which at least one mird of the volume of the tumor is extracellular mucin throughout. Furthermore, if a tumor has focal areas that are not at least 33 per cent mucinous, then the designation is mixed mucinous/ductal carcinoma.16 The recurrent mucinous carcinoma in our case was found to be invading the junction of the superior vena cava and innominate vein. The veins were resected and the tumor completely removed. Vessel reconstruction after resection can be approached with several different variations and have been described primarily for lung cancer invading the great vessels. To our knowledge, resection of a great vessel has never been done for vascular invasion of a mucinous breast cancer. The tumor and vein were resected and a direct running suture repair was performed.
Postoperatively the patient recovered without complication. She was placed on Herceptin(R) with chemotherapy because it has been shown to benefit patients with HER-2/neu positive metastatic breast cancer.17 After en-bloc resection of the tumor and adjuvant chemotherapy, the patient has had follow-ups with periodic CT scans of the chest and abdomen and most recently with a PET scan. Nearly 2 years after surgery for recurrent disease, the patient remains asymptomatic and does not have any evidence of metastases on imaging.
Although the literature generally confers a mucinous type of breast cancer as being a less aggressive tumor of the breast, it may behave uncharacteristically, especially when HER-2/neu receptor positive. When the patient presented to us 4 years after her initial surgery with a disfiguring recurrent breast cancer involving the chest wall, it presented a challenge. Due to the nature of the local recurrence, the patient’s age, good health status, and motivation, en-bloc resection of the chest was performed. The patient received adjuvant therapy after recovering from surgery. We are pleased to report that after 2 years, the patient is alive and well with no evidence of recurrent disease.
1. Li C, Moe R, Daling J. Risk of mortality by histologic type of breast cancer among women aged 50 to 79 years. Arch Intern Med 2003;163:2149-53.
2. Northridge ME, Rhoads GG, Wartenberg D, et al. The importance of histologic type on breast cancer survival. J Clin Epidemiol 1997;50:283-90.
3. Norris HJ, Taylor HB. Prognosis of mucinous (gelatinous) carcinoma of the breast. Cancer 1965;18:879-85.
4. Rosen PP, Wang TY. Colloid carcinoma of the breast: Analysis of 64 patients with long term follow up. Am J Clin Pathol 1980;73:304.
5. Diab S, Clark G, Osborne K, et al. Tumor characteristics and clinical outcome of tubular and mucinous breast carcinomas. J Clin Oncol 1999; 17:1442.
6. Fentiman IS, Millis RR, Smith P, et al. Mucoid breast carcinomas: Histology and prognosis. Br J Cancer 1997;75:1061-5.
7. Silverberg SG, Kay S, Chitale AR, Levitt SH. Colloid carcinoma of the breast. Am J Clin Path. 1971;55:355-63.
8. Ishikawa T, Hamaguchi Y, Ichikawa Y, et al. Local advanced mucinous carcinoma of the breast with sudden growth acceleration: A case report. Jpn J Clin Oncol 2002;32:64-7.
9. Rasmussen BB, Rose C, Christensen IB. Prognostic factors in primary mucinous breast carcinoma. Am J Clin Path 1987;87: 155-60.
10. Toikkanen S, Kujari H. Pure and mixed mucinous carcinomas of the breast: A clinicopathologic analysis of 61 cases with long-term follow-up. Hum Pathol 1989;20:758-64.
11. Arpino G, Weiss H, Lee AV, et al. Estrogen receptorpositive, progesterone receptor-negative breast cancer: Association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst 2005;97:1238-9.
12. Menard S, Fortis S, Castiglioni F, et al. HER-2 as a prognostic factor in breast cancer. Oncology 2001;61(suppl 2):67- 72.
13. Ross JS, Fletcher JA. The HER-2/neu oncogene in breast cancer: Prognostic factor, predictive factor, and target for therapy. Stem Cells 1998;16:413-28.
14. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/ neu oncogene. Science 1987;235:177-82.
15. Lam WW, Chu WC, Tse GM, et al. Role of fine needle aspiration and tru cut biopsy in diagnosis of mucinous carcinoma of the breast- from a radiologist’s perspective. Clin Imaging 2006;30:6-10.
16. Stanford School of Medicine Surgical Pathology Criteria. Pure mucinous carcinoma of the breast. 2007 Stanford University School of Medicine; available at http://surgpathcriteria.stanford.edu/breast/ mucincabr/index.html.
17. Slamon DJ, Leyland-Jones B, Shak S, et al. Concurrent administration of anti-HER-2 monoclonal antibody and first line chemotherapy for HER-2 overexpressing metastatic breast cancer: A phase III, multinational, randomized control trial. N Engl J Med 2001;783:792.
IAMIE D. ADAIR, M.D., KYLE P. HARVEY, M.D., ALI MAHMOOD, M.D., IAMES CARALIS, D.O.,
WILLIAM GORDON, M.D., GREGORY YANISH, M.D.
From the St. Joseph Mercy Oakland Hospital, Pontiac, Michigan
Address correspondence and reprint requests to Kyle P. Harvey, M.D., St. Joseph Mercy Oakland Hospital, 44405 Woodward Avenue, Pontiac, MI 48341.
Copyright Southeastern Surgical Congress Feb 2008
(c) 2008 American Surgeon, The. Provided by ProQuest Information and Learning. All rights Reserved.