Primary non-Hodgkin's lymphoma of the breast treated nonsurgically: report of three cases.

Extranodal non-Hodgkin's lymphoma (NHL) is a rare breast disease. Here we report three cases of primary NHL of the breast. The first patient was a 29-year-old woman with a firm mass in her right breast with ipsilateral axillary lymphadenopathy. An excisional biopsy revealed NHLs. Clinical stage was IIAE. The tumor and enlarged lymph nodes had successfully been treated following the combination therapy. The second patient was a 70-year-old women with an elastic hard mass in her left breast. An excisional biopsy revealed NHLs and clinical stage was 1AE. The tumor disappeared following the combination therapy. The third patient was a 67-year-old women with a hard mass in her left breast. Core needle biopsy revealed NHLs and clinical stage was 1AE. The tumor disappeared following chemotherapy. All patients are alive with no evidence of recurrence 4-8 years after the initial treatment. Although a standard treatment has yet to be established, an initial treatment with combination therapy without surgical intervention including axillary dissection appears to be appropriate for this rare disease.

21-Gene expression profile assay on core needle biopsies predicts responses to neoadjuvant endocrine therapy in breast cancer patients.

This study examined postmenopausal estrogen receptor-positive breast cancer patients who received prospective neoadjuvant endocrine therapy (NAET) with tamoxifen or anastrozole to determine if the 21-gene recurrence score (RS) predicts NAET responses. RS scores were determined from pretreatment core biopsy specimens. Although half of the specimens yielded insufficient RNA, the remaining samples were highly representative. Patients with a low RS tended to respond better than those with an intermediate or high RS (n=43). Response rates by RS were similar between the tamoxifen and anastrozole groups. Patients with a low RS tended to have better relapse-free survival (RFS) than those with an intermediate or high RS (5y-RFS; 100% vs. 84% and 73%, respectively). These results suggest that RS predicts responses to NAET with tamoxifen or anastrozole. Because this pilot study examined a small sample size, these results should be validated in larger studies.

Association between frequent CpG island methylation and HER2 amplification in human breast cancers.

The presence of frequent methylation of CpG islands (CGIs), designated as the CpG island methylator phenotype in some cancers, is associated with distinct clinicopathological characteristics, including gene amplification, in individual tumor types. Amplification of HER2 in human breast cancers is an important prognostic and therapeutic target, but an association between HER2 amplification and frequent CGI methylation is unknown. To clarify the association, we here quantified methylation levels of promoter CGIs of 11 genes, which are unlikely to confer growth advantage to cells, in 63 human breast cancers. The number of methylated genes in a cancer did not obey a bimodal distribution, and the 63 cancers were classified into those with frequent methylation (n = 16), moderate methylation (n = 26) and no methylation (n = 21). The incidence of HER2 amplification was significantly higher in the cancers with frequent methylation (11 of 16) than in those with no methylation (2 of 21, P = 0.001). Also, the number of methylated genes correlated with the degree of HER2 amplification (r = 0.411, P = 0.002). Correlation analysis with clinicopathological characteristics and methylation of CDKN2A, BRCA1 and CDH1 revealed that frequent methylation had significant correlation with higher nuclear grades (P = 0.001). These showed that frequent methylation had a strong association with HER2 amplification in breast cancers and suggested that frequent methylation can be a determinant of various characteristics in a fraction of human breast cancers.

Primary small cell carcinoma of the breast.

Primary small cell carcinoma of the breast is a very rare disease, and only a few case reports have described small cell carcinoma of the breast that responds to chemotherapy. Here, we report a case of primary small cell carcinoma of the breast that was treated with surgery and chemotherapy for postoperative local recurrence in the chest wall and metastasis to the liver. The metastatic lesions showed a partial response (PR) to carboplatin and irinotecan, but did not respond to subsequent Taxotere and doxifluridine (5'-DFUR) treatment. We then treated the metastatic lesions with CBDCA and etoposide (VP-16), and were able to stop disease progression. Small cell carcinoma of the breast is as aggressive as its pulmonary counterpart. Therefore, the best therapy for primary small cell carcinoma of the breast may be surgery followed by adjuvant therapy similar to that recommended for small cell lung carcinoma.

Whole-breast volume perfusion images using 256-row multislice computed tomography: visualization of lesions with ductal spread.

BACKGROUND: The aim of this study was to apply perfusion techniques to breast tumors using a prototype 256-row multislice computed tomography (CT) scanner (which allows a wide range of 128 mm to be scanned and can provide whole-breast perfusion maps without any dead angles) to improve contrast and assess the possibility of precisely depicting the extent of breast cancer. PATIENTS AND METHODS: The study group included seven patients with breast cancer who were scheduled to undergo radical surgery and radiotherapy. Dynamic scanning was performed using a 256-row multislice CT scanner during normal respiration. Volume perfusion images of the entire breast were obtained using the maximum slope method. Perfusion map images and early-phase breast CT images at 54 s were compared by means of pathological examination. RESULTS: All breast cancers could be distinguished from normal mammary glands based on the perfusion value. The extent of cancer depicted in perfusion images showed excellent agreement with the pathology findings for invasive ductal carcinoma and ductal carcinoma in situ. In three patients, all ductal spread, parts of which were not visualized by early-phase CT, were depicted in volume perfusion images. Simulation analysis suggested that perfusion maps could be generated with fewer scanning points. CONCLUSION: The results of the present study suggest that volume perfusion imaging may be useful for depicting the extent of breast cancer, with excellent sensitivity. Further research is needed to determine the clinical relevance of these findings.

Brain metastases after achieving local pathological complete responses with neoadjuvant chemotherapy.

BACKGROUND: We encountered two patients with inflammatory breast carcinoma who developed symptomatic brain metastases after achieving local pathological complete responses (pCR) with neoadjuvant chemotherapy (NAC). CASE PRESENTATIONS: The first patient is a 39-year-old woman (Case 1), who underwent NAC with AC (doxorubicin + cyclophosphamide)followed by weekly paclitaxel. After achieving a clinical CR (cCR), we conducted a modified radical mastectomy. Pathological evaluation confirmed no residual malignant cells within the breast tissue or lymph nodes. However, she developed neurological symptoms from brain metastases one month postoperatively. The second patient is a 44-year-old woman (Case 2). Again, no residual malignant cells were detected within the breast tissue or lymph nodes following NAC, but the patient developed symptomatic brain metastases eight months postoperatively. When primary breast tumors are locally advanced, it may be worthwhile to rule out brain metastases even if pCR is obtained after NAC.

Favorable outcome in patients with breast cancer in the presence of pathological response after neoadjuvant endocrine therapy.

Neoadjuvant endocrine therapy (NAET) can expand the number of breast cancer patients who can be treated with breast-conserving surgery and can predict benefit from adjuvant endocrine therapy. Because no validated surrogate markers for long-term outcome have been established, we conducted prospective trials to evaluate pathological response and Ki-67 index following treatment with tamoxifen or anastrozole. The study population included postmenopausal women with operable breast tumors that were both estrogen and progesterone receptor-positive and larger than 3 cm. Response was classified as pathological response (minimal response or better) and non-response. Non-responding (25.5%, vs. response 85.9%, p=0.002), axillary node-positive (58.4% vs. node negative 100%, p=0.045), and high pretreatment Ki-67 index (41.4% vs. low Ki-67 87.1%, p=0.03) patients were significantly associated with poor 5-year relapse-free survival. Multivariate analysis of relapse-free survival indicated that pathological response was independent. Therefore, pathological response may be a favorable prognostic factor after NAET.

Preoperative evaluation of thyroid pathology in patients with primary hyperparathyroidism.

In parathyroidectomy, it has been recognized that a shift to a minimally invasive procedure may be accompanied by a possibility of missing thyroid pathology. However, only a few findings concerning preoperative thyroid evaluation have been reported. We investigated the prevalence of concomitant thyroid pathology by preoperative neck ultrasonography (US) in patients with primary hyperparathyroidism. There were 85 patients (66 women, 19 men; mean age 57 years) in the study group. The mean preoperative calcium level was 11.2mg/dL, and the mean intact parathyroid hormone level was 206 pg/mL. All patients underwent neck US following fine-needle aspiration biopsy (FNAB). Of the 85 patients, 21 (24.7%) had thyroid nodules. Among 21 patients with thyroid nodules, 9 (10.6%) had malignant thyroid tumors, while 12 (14.1%) patients had benign thyroid nodules including multinodular goiter. Of the 9 patients with malignant thyroid nodules, 4 had papillary carcinomas with lymph node metastases. The prevalence of thyroid disease associated with hyperparathyroidism is high, and evaluation of the thyroid pathology by US enables the shift from bilateral neck exploration to the minimally invasive parathyroid surgery.