Clinical application of the one-step nucleic acid amplification method to detect sentinel lymph node metastasis in breast cancer.

BACKGROUND: The one-step nucleic acid amplification (OSNA) method can assess the expression level of cytokeratin 19 mRNA in sentinel lymph nodes in breast cancer. We compared the time required for diagnosis and concordance of results between the OSNA method and conventional intraoperative pathological examination. We then examined the relationship between the frequency of non-sentinel lymph node metastasis and (1) the expression level of CK19 mRNA in the sentinel lymph nodes and (2) clinico-pathological features of the primary tumor. METHODS: In the comparison study, pairs of sentinel lymph node sections from 53 consecutive patients were examined: one section by hematoxylin-eosin staining and the other by OSNA assay. The latter involved reverse-transcription loop-mediated isothermal amplification of cytokeratin 19 mRNA, assessed quantitatively. In the second phase, 306 sentinel lymph nodes were removed from 248 consecutive patients, and whole sentinel lymph nodes were examined by OSNA assay alone. RESULTS: OSNA assay was a little more time-consuming than conventional pathological diagnosis (34-45 vs. 22-25 min, p < 0.0001). Concordance between the two methods was 93%. The frequency of non-sentinel lymph node metastasis (p < 0.0001) and the total number of lymph node metastases (p < 0.0001) increased with the amount of cytokeratin 19 mRNA on OSNA assay. We found no significant relationship between the amount of cytokeratin 19 mRNA in sentinel lymph nodes and breast cancer immunohistochemical subtype. CONCLUSIONS: The OSNA method is suitable to detect sentinel lymph node metastasis and to predict the possibility of non-sentinel metastasis. This semi-automated quantitative analysis system reduces the burden on pathologists.

Adverse events and bone health during anastrozole therapy in postmenopausal Japanese breast cancer patients.

BACKGROUND: Although anastrozole (ANA), an aromatase inhibitor (AI), has been widely used for breast cancer patients; adverse events during ANA therapy in Japanese patients have not been reported. METHODS: The study included 656 postmenopausal breast cancer patients receiving ANA as postoperative adjuvant therapy in our hospital. Adverse events during ANA therapy, such as musculoskeletal effects and cerebro- and cardiovascular accidents, were investigated over a 5-year period. The percentage changes in lumbar (L2-4) spine bone mineral density (BMD) were determined in 71 patients receiving ANA alone and 26 patients receiving bisphosphonate in combination with ANA for 7-24 months. RESULTS: The follow-up period ranged from 6 to 60 months (median 23 months). Joint pain, the most common adverse event, was observed in 3.6% (24/656) of the patients. Cerebral infarctions occurred in 0.3% (2/656) of the patients, and no cardiovascular accidents occurred. Bone fractures occurred in nine patients receiving ANA alone. The mean age and BMD of the nine patients were 67.6 years and 71.8% (compared to the young adult mean BMD), respectively. Accumulated and annual fracture rates were 1.3 and 0.8%, respectively. A decrease in BMD was observed in 62.0% (44/71) of the ANA group compared to 26.9% (7/26) of the combination bisphosphonate group (P < 0.01). CONCLUSION: Incidence of adverse events during AI therapy in this Japanese postmenopausal population appears to be lower than that of the ATAC trial. The incidence of bone fractures during AI therapy is lower in Japan, and the addition of bisphosphonates enhances bone health. We should perform a prospective trial in the future to investigate the precise risk of bone fractures in Japanese patients.

[Preoperative therapy using trastuzumab and weekly paclitaxel in a stage IIIB inoperable locally advanced HER2- positive breast cancer with complete pathologic response].

A 63-year-old woman had a 12 cm tumor on her right breast with broad skin redness, satellite lesions and 8 cm ipsilateral lymph nodes swelling(T4bN2aM0, Stage IIIB). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor(ER-, PgR-)and overexpression of HER2 (HercepTest 3+). She was treated with weekly paclitaxel(80 mg/m(2), 4 administrations with a week rest)and a com- bination with weekly trastuzumab(initially 4 mg/kg followed by 2 mg/kg every week, totally 11 administrations). After 3courses of administration, the breast tumor, skin redness and axillary swelling were completely disappeared(clinical complete response), then mastectomy with axillary dissection was performed. Histopathology of the breast and lymph nodes showed complete disappear of invasive cancer cells with only 2x1 mm residue of ductal component(pCR, grade 3, DC+). We conclude that the combination of weekly paclitaxel and trastuzumab is a promising neoadjuvant therapy regimen for HER2 positive, ER-negative breast cancer.

[Comparison of the pharmacokinetics and safety of a paclitaxel injection NK and Taxol injection in breast cancer patients].

A paclitaxel injection NK (NK) is a generic product containing the same amount of ingredient as a Taxol Injection. We examined the pharmacokinetics and safety of NK compared to the original product in breast cancer patients. As a result, the transition of plasma paclitaxel concentration and pharmacokinetic parameter in NK and the original drug were almost equal, which suggested that these products were bioequivalent. In adjuvant therapy, there was no significant difference in adverse events reported, and these products were approximately equally safe.

[Preoperative therapy with trastuzumab and paclitaxel in a stage IV advanced breast cancer with complete pathologic response].

A 53-year-old woman had a 105x100 mm tumor on her right breast with a 55x36 mm-sized bleeding ulcer of the skin and ipsilateral axillary and cervical lymph nodes swelling (T4bN3cM1, Stage IV). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor (ER-, PgR-) and overexpression of HER 2 (Hercep Test score 3+). She was treated with weekly trastuzumab (initially 4 mg/kg followed by 2 mg/kg every week), and a combination of tri-weekly paclitaxel (175 mg/m(2), 6 courses). After 3 courses of administration, the breast tumor subsided, the ulcer became flat, and axillary and cervical nodes completely disappeared. Clinical CR was obtained after 6 courses of treatment, and mastectomy with axillary clearance was then performed. Histopathology of the breast and lymph nodes showed complete disappearance of cancer cells (pCR, Grade 3+3 (d) +3 (n)). The combination of trastuzumab and paclitaxel is a promising regimen for HER 2 positive advanced breast cancer.

[A case of inflammatory breast cancer achieving pathological complete response by primary systemic therapy with CEF (cyclophosphamide, epirubicin, 5-fluorouracil) followed by docetaxel].

A 48-year-old woman noticed her right breast swelling since a few weeks earlier. Rigidity in the AC area, hotness, swelling and peau d'orange appearance of the right whole breast were recognized. She was diagnosed as inflammatory breast cancer clinically and invasive ductal carcinoma with lymphatic invasion pathologically. The patient underwent primary systemic therapy with 4 cycles of CEF (cyclophosphamide 500 mg/m(2), epirubicin 100 mg/m(2), 5-fluorouracil 500 mg/m(2)) followed by 4 cycles of docetaxel (70 mg/m(2)). The effect of chemotherapy showed a partial response evaluated by mammography and ultrasonography, and complete response by MRI before surgery. Right mastectomy with level II lymph node dissection was performed. Pathologically, complete response was confirmed (pCR). Although IBC has been known for its poor outcome, this case suggests IBC will show a better prognosis by chemotherapy such as CEF followed by docetaxel.

[Markedly effective regimen using bi-weekly trastuzumab and paclitaxel in an advanced breast cancer with multiple liver metastases].

A 69-year-old woman had a 7 x 6 cm tumor on her left breast with ipsilateral axillary lymph node swelling and multiple liver metastases as detected on CT scan (T 3 N 2 M 1 b, Stage IV). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor and overexpression of HER 2. After a treatment failure of 3 months weekly trastuzumab monotherapy, a combination of bi-weekly trastuzumab and paclitaxel (weekly 6, bi-weekly 9 courses), was given. Tumor markers became negative 4 months later, and multiple liver nodules, breast tumor and axillary nodes completely disappeared 9 months later. Breast surgery was avoided, and CR was maintained more than 8 months only with bi-weekly trastuzumab. From the standpoint of the patient's convenience,a bi-weekly schedule of trastuzumab and paclitaxel could be a promising treatment choice for metastatic breast cancer.

Rim enhancement of breast cancers on contrast-enhanced MR imaging: relationship with prognostic factors.

BACKGROUND: There is little evidence regarding associations between magnetic resonance imaging (MRI) features and other important histopathological prognostic factors of breast cancer. The purpose of our study was to investigate the relationship between rim enhancement on MRI and common histopathological prognostic factors of breast cancers. METHODS: We reviewed the contrast-enhanced MR images of 106 consecutive women with histopathologically verified invasive breast carcinomas. Three radiologists assessed the images of each lesion for the presence of rim enhancement on early and delayed images, which were classified into four patterns. Statistical analyses were performed to explore the associations of these patterns with common histopathological prognostic factors and patient age. RESULTS: Positive ratios of lymph node metastasis and blood vessel invasion and negative ratios of hormone receptors were higher in the invasive cancers with rim enhancement than those without rim enhancement. Rim enhancement was more frequent in invasive ductal cancers with a higher histological grade and larger invasive cancers. The pattern of rim enhancement with centripetal progression showed a significantly increased risk of lymph node metastasis and was associated with a larger size of invasive lesion when compared with the other patterns. Invasive cancers with rim enhancement and little change between the early and delayed images and with centrifugal progression showed significantly less hormone receptor positivity than those without rim enhancement. CONCLUSIONS: Rim enhancement patterns of breast cancers on contrast-enhanced MRI are related to common histopathological prognostic factors and these patterns may be valuable in the preoperative evaluation of breast cancers.

[Neoadjuvant endocrine therapy with anastrozole significantly downstaged an elderly breast cancer woman with locally-advanced breast cancer which became operable].

A 73-year-old postmenopausal woman had a 13 cm-sized huge tumor in her left breast with an extensive purple skin color change. She had sternal destruction, axillary and supraclavicular lymph node metastases (T4bN3M1, Stage IV). Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+++, PgR+++). She was treated with 1 mg per day of anastrozole. The tumor decreased in size gradually and became operable after 7.5 months of the anastrozole monotherapy. She underwent mastectomy and axillary node clearance. The resected specimen showed a 3.5 cm sized tumor with significant fibrosis and scanty viable tumor cells. We concluded that neoadjuvant therapy with anastrozole is a good choice for receptor-positive postmenopausal breast cancer, especially for elderly or poor risk women.

[Effective weekly paclitaxel therapy for massive metastatic breast cancer].

A 36-year-old woman with a 12-year disease free interval after radical mastectomy for breast cancer presented with dyspnea and lumbago. Chest CT and bone scintigraphy revealed numerous bilateral pulmonary metastatic nodules, pleural effusion and multiple bone metastases. We treated her with weekly paclitaxel therapy at a dose of 80 mg/m2, which was continued for 3 weeks followed by 1 week rest, and bisphosphonate biweekly. Lung lesions markedly decreased in number and size after 6 infusions, and disappeared after 12. Bone scintigraphy showed partial response. Lung effect (CR) and bone effect (PR) have been maintained after 30 infusions on an outpatient basis. The patient tolerated the treatment well without adverse effect, except for moderate alopecia.