Toshiharu Kanai

Multimodality therapeutic outcomes In anaplastic thyroid carcinoma: Improved survival in subgroups of patients with localized primary tumors

The aim of the present study was to investigate the role of a multimodality treatment for anaplastic thyroid carcinoma (ATC).

ENDOSCOPIC-ASSISTED SKIN-SPARING MASTECTOMY COMBINED WITH SENTINEL NODE BIOPSY

Breast‐conserving surgery (BCS) has been carried out as desirable choice for patients with early‐stage breast cancer. However, many patients obliged to abandon BCS because of tumours accompanied by extended intraductal components or multiple tumours. The purpose of this study was to develop a novel endoscopic‐assisted technique for skin‐sparing mastectomy (SSM) combined with sentinel node biopsy (SNB), followed by immediate breast reconstruction with mammary prosthesis. Between April 2000 and November 2006, 33 patients diagnosed with primary breast cancer underwent endoscopic‐assisted SSM. Immediate reconstruction with the mammary prosthesis was carried out in 30 of 33 patients. On postoperative histopathological diagnosis, 21 tumours were diagnosed as ductal carcinoma in situ or lobular carcinoma in situ. Twelve tumours were diagnosed as invasive carcinoma. Eight of 12 invasive carcinomas were accompanied by a wide spreading intraductal component. Two patients were diagnosed as having multicentric carcinomas, which made the standard breast‐conserving treatment difficult. After a mean follow‐up period of 51.2 months (range 16–86 months), neither locoregional recurrence nor distant metastasis has been detected. Thus, combining SSM and SNB with immediate reconstruction with the mammary prosthesis may offer the selected patients with early‐stage breast cancer favourable aesthetic results without incurring additional oncological risks. The procedure could be an alternative treatment option for patients with widely spreading intraductal component or multiple tumours.

CSLEX (Sialyl Lewis X) is a Useful Tumor Marker for Monitoring of Breast Cancer Patients

BACKGROUND CSLEX is a type II carbohydrate antigen that interacts with the CSLEX-1 monoclonal antibody. CSLEX in combination with carbohydrate antigen 15-3 may be more useful than Carcinoembryonic Antigen with carbohydrate antigen 15-3 as tumor markers for monitoring of breast cancer. METHODS The serum levels of tumor markers, including CSLEX, were measured in 480 consecutive breast cancer patients with or without metastasis who visited the outpatient clinic of the Division of Breast and Endocrine Surgery, Shinshu University Hospital, between April 2007 and September 2007. RESULTS Serum levels of each of the tumor markers correlated significantly with the status of metastasis (P < 0.01). Combinations of Carcinoembryonic Antigen and carbohydrate antigen 15-3, Carcinoembryonic Antigen and Nation Cancer Center-Stomach-439, Carcinoembryonic Antigen and CSLEX, carbohydrate antigen 15-3 and Nation Cancer Center-Stomach-439, and carbohydrate antigen 15-3 and CSLEX levels also correlated significantly with the status of metastasis (P < 0.01). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were almost the same for CSLEX and Nation Cancer Center-Stomach-439, which are both type II carbohydrate antigens. The cutoff indexes of serum CSLEX and Nation Cancer Center-Stomach-439 for detection of breast cancer metastasis were 38.8 ± 52.7-fold and 22.1 ± 27.8-fold, respectively (P = 0.16). CONCLUSIONS These data suggest that the diagnostic values of CSLEX and Nation Cancer Center-Stomach-439 are similar in single or combined use. However, the cutoff index of serum CSLEX tended to be higher than that of Nation Cancer Center-Stomach-439, which may make CSLEX more useful for detection of breast cancer metastasis.

A Case of Brain Metastases from Breast Cancer that Responded to Anastrozole Monotherapy

To the Editor: Brain metastases are less common in breast cancer patients than bone or visceral metastases; however, brain metastasis is one of the most critical metastatic lesions in the treatment of breast cancer because of the progressive neurological disability caused by the lesions and the lack of effective treatment as seen in visceral or bone metastasis (1,2). Treatments for brain metastases of breast cancer include corticosteroids, whole-brain radiation therapy, surgical resection, and stereotactic radiosurgery (1). However, after such treatment, median survival has been only slightly extended by several months. Generally, chemotherapy is not considered a useful strategy in the management of brain metastases because the tight junctions of the blood–brain barrier preclude the entry of most chemotherapeutic agents into the central nervous system (CNS) (3). With regard to endocrine therapy, there have been a certain number of reports of breast cancer patients with brain metastasis responding well to tamoxifen therapy (4–7), however, there have been only a few reports regarding the effects of aromatase inhibitors in the treatment of brain metastasis (8). In this study, we report a very rare case of brain metastases from hormone-sensitive breast cancer that responded well to the aromatase inhibitor, anastrozole for a prolonged period. A 73-year-old woman visited her family physician due to a common cold in June 2004. Chest roentgenogram showed multiple nodular shadows in bilateral lung fields. Her clinical history included right radical mastectomy for left breast cancer in 1985 at the age of 54. Based on her clinical history, the multiple nodular shadows in the lung were suspected to be metastases of breast carcinoma. Furthermore, positron emission tomography and computed tomography also revealed multiple metastases in her bones, lymph nodes, and subcutaneous tissues. Core needle biopsy of one of the subcutaneous tumors revealed that the cancer was estrogen receptor-positive, progesterone receptor (PgR)-positive, and human epidermal growth factor receptor type 2 (Her2)-negative. As systemic therapy for the recurrent breast cancer, anastrozole was administered at a dose of 1 mg ⁄ day. To prevent progression of bone metastases, 45 mg of pamidronate disodium was also administered every four weeks. Although she was neurologically asymptomatic, screening magnetic resonance imaging (MRI) of the brain revealed more than 20 metastatic lesions in her brain (Fig. 1). Although a radiologist recommended the patient undergo whole-brain radiation therapy (WBRT) to treat the multiple brain metastases, she refused due to fear of adverse events caused by the therapy. Consequently, she continued oral anastrozole therapy alone as systemic therapy for the multiple-organ metastatic breast cancer lesions, and intended to undergo radiation therapy of the lesions in the brain if they progressed further or became symptomatic. Two months after administration of anastrozole, marked decreases in levels of tumor markers, such as CEA, CA15-3, and NCC-ST439, were observed. Three months after the initiation of anastrozole, MRI of the brain revealed reductions in the metastatic tumors in her brain. Subsequently, 6 months after the initiation of anastrozole, MRI of the brain revealed gross reductions in the metastatic tumors in the brain (Fig. 2). Eight months after initiation of anastrozole, all except one of the metastatic lesions in the brain remained stable in size and she still was neurologically asymptomatic. However, she accepted radiation therapy for the brain metastases at this point because of the slight increase in size of one metastatic lesion. She preferred SRS to WBRT. Subsequently, SRS was applied to 10 metastatic regions in her brain. Thereafter, her metastatic cancer in the brain gradually reduced in size. As the multiple bone metastases progressed gradually, anastrozole was changed to exemestane for second line endocrine therapy in July 2005, and then Address correspondence and reprint requests to: Ken-ichi Ito, MD, PhD, Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan, or e-mail: kenito@shinshu-u.ac.jp

Two cases of sarcoidosis discovered accidentally by positron emission tomography in patients with breast cancer.

To the Editor: Follow-up of women with breast cancer to detect recurrence and distant metastases is critical because earlier detection of recurrence can result in earlier and probably more efficient treatment. F-2-deoxy-2-florod-glucose (FDG) positron emission tomography (PET) provides information about the metabolic activity of tumors that can complement the anatomical information provided by other imaging modalities. Several studies have demonstrated that whole-body FDG-PET is superior to conventional imaging in detecting recurrent and metastatic disease from breast cancer (1–7). However, false positive results are sometimes encountered in FDG-PET due to interpretative pitfalls and the non-specificity of FDG. Here, we present two cases of advanced breast cancer that showed false positive results on FDG-PET due to sarcoidosis that developed during the period of follow-up of breast cancer.

Breast metastases of gastric signet-ring cell carcinoma: a report of two cases and review of the literature.

It is occasionally difficult to diagnose breast metastasis of gastric carcinoma because of its rarity. However, to appropriately treat patients with breast tumors without delay, it is important to distinguish metastatic cancer from primary breast cancer. We report two cases of breast metastasis of gastric carcinoma and review the literature. The first case was a 41-year-old female diagnosed with bilateral pelvic tumors who visited the outpatient clinic because of pain and enlargement of both breasts. Ultrasonography showed diffuse hypoechoic lesions, which were enhanced on gadolinium-enhanced magnetic resonance imaging in the bilateral mammary gland. Core needle biopsy of the right breast revealed signet-ring cells, which were also identified in the resected bilateral pelvic tumors. Subsequent upper gastrointestinal endoscopy revealed signet-ring cell carcinoma in the stomach, and the bilateral breast lesions were diagnosed as metastases of gastric carcinoma. The second case was a 34-year-old female diagnosed with cervical metastasis of signet-ring cell carcinoma who was referred to the breast cancer clinic because of a nodule in the left breast detected by computed tomography. Ultrasonography showed a hypoechoic nodule that was enhanced on gadolinium-enhanced magnetic resonance imaging. Because the pathologic findings for the left breast nodule were quite similar to those of gastric cancer and its cervical metastasis, the breast nodule was diagnosed as a metastasis of gastric carcinoma. When a breast tumor is suspected to have metastasized from a primary tumor in another organ, particularly if signet-ring cells are found, the possibility that gastric cancer is present should be considered.

Evaluation of a new method for the diagnosis of alterations of Lens culinaris agglutinin binding of thyroglobulin molecules in thyroid carcinoma

Abstract Background: The measurement of serum thyroglobulin (Tg) is widely used as a marker for recurrence of thyroid carcinoma following total thyroidectomy. However, this method cannot differentiate between benign and malignant disease. We focused on the sugar chain in the Tg molecule and investigated the usefulness of Lens culinaris agglutinin (LCA)-reactive Tg ratios in sera and wash fluids obtained during fine-needle aspiration (FNA) for the detection of thyroid carcinoma. Methods: The study was performed using 203 serum samples (115 from patients with benign thyroid disease and 88 from patients with thyroid carcinomas) and 176 wash fluid samples (143 benign, 21 malignant, and 12 inconclusive). LCA-reactive Tg ratios were determined using an enzyme-linked immunosorbent assay, and a comparison was made between malignant and benign lesions. Results: In serum, the ratio in patients with malignancy was 79.5±6.0 [mean±standard deviation (SD)], significantly lower than in patients with benign lesions (84.9±3.5). The ratios in wash fluid from malignant lesions (75.8±18.9) were also significantly lower than those from benign lesions (85.6±3.9). Conclusions: These results suggest that this method could distinguish between benign and malignant lesions and may be useful for screening serum and wash samples. Clin Chem Lab Med 2009;47:1285–90.

Lipid-rich carcinoma of the breast that is strongly positive for estrogen receptor: a case report and literature review.

Lipid-rich carcinoma (LRC) of the breast is a rare breast cancer variant that accounts for <1% of all breast malignancies. It has been reported that LRCs are negative for estrogen receptor. Here, we report a case of LRC of the breast that was strongly positive for estrogen receptor and treated with endocrine adjuvant therapy. A 52-year-old postmenopausal female noticed a lump in her right breast by self-examination and presented to our hospital. Physical examination revealed an elastic 30 mm ×20 mm hard mass in the upper medial part of her right breast. The findings obtained using ultrasonography, mammography, and contrast-enhanced magnetic resonance imaging suggested breast cancer. Core needle biopsy resulted in the diagnosis of invasive carcinoma. The patient underwent mastectomy and sentinel lymph node biopsy. Histopathologically, the tumor cells were abundant in foamy cytoplasm. Because the presence of marked cytoplasmic lipid droplets was confirmed by Sudan IV staining and electron microscopic examination of the tumor and the lipid droplets were negative for periodic acid–Schiff staining, the tumor was diagnosed as an LRC. Immunohistochemically, estrogen and progesterone receptors of the tumor were strongly positive, human epidermal growth factor receptor type 2 was negative, and the ratio of Ki-67-positive cells was ~30%. After surgery, the patient underwent combination chemotherapy with anthracycline, cyclophosphamide, and 5-fluorouracil, followed by docetaxel. Thereafter, the pateint was treated with letrozole and has remained well for 24 months with no signs of recurrence.

Human 3β-hydroxysteroid dehydrogenase type 1 in human breast cancer: clinical significance and prognostic associations.

Active sex steroids including estrogens and androgens are locally produced from circulating inactive steroids by various steroid‐metabolizing enzymes, and play pivotal roles in the progression of hormone‐dependent breast cancers. Human 3β‐hydroxysteroid dehydrogenase type 1 (3β‐HSD type 1) is a critical enzyme in the formation of all classes of active steroid hormones, and is also involved in the inactivation of potent androgen dihydrotestosterone (DHT). Therefore, this enzyme is suggested to modulate active sex steroid production or inactivation, with a role in hormone‐dependent breast cancer. The purpose of this study was to investigate the clinical significance of 3β‐HSD type 1 in human breast cancer. Using immunohistochemistry (IHC), we evaluated 3β‐HSD type 1 expression in 161 human breast cancers and analyzed correlations of 3β‐HSD type 1 expression with various clinicopathological factors. Of 161 breast cancer cases, 3β‐HSD type 1 expression in cancer cells was detected in 119 cases (73.9%), and was positively correlated with estrogen receptor (ER)‐positivity but not HER‐2 status. In ER‐positive cases (n = 130), 3β‐HSD type 1 expression was inversely correlated with invasive tumor size (P = 0.0009), presence of invasive region (P = 0.0107), and lymphatic involvement (P = 0.0004). 3β‐HSD type 1 expression was significantly associated with decreased risk of recurrence or improved prognosis by both univariate (P = 0.0003 and P = 0.009, respectively) and multivariate (P = 0.027 and P = 0.023, respectively) analyses. Our findings indicate that this enzyme is a prognostic factor in hormone‐dependent breast cancer.

Sebaceous carcinoma of the breast: a case report

BackgroundSebaceous carcinoma of the breast is a distinct variant of invasive ductal carcinoma. It is rare and only several cases have been reported.Case presentationAn 80-year-old woman noted bloody discharge from her left nipple and palpated a lump in her left breast. Ultrasonography revealed a 19-mm mass in the left breast. Fine-needle aspiration suggested invasive ductal carcinoma. Partial mastectomy and sentinel lymph node biopsy were performed. On histological examination, the tumor revealed solid growth of small, round uniform cells with clear cytoplasm, partially intermingled with vacuolated cells indicative of sebaceous differentiation. The tumor cells contained abundant Sudan Black B-positive lipid droplets in the cytoplasm, and they were immunohistochemically positive for adipophilin. They were negative for estrogen receptor, progesterone receptor, and androgen receptor; positive for cytokeratin 7 and Ber-EP4; and partially positive for epithelial membrane antigen. Based on these findings, the patient was diagnosed with sebaceous carcinoma of the breast.ConclusionsWe diagnosed a rare case of sebaceous carcinoma of the breast.