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Background: Interest in the use of preoperative systemic treatment in the management of breast cancer has increased because such neoadjuvant therapy appears to reduce the extent of local surgery required. We compared the clinical end points of patients with breast cancer treated preoperatively with systemic therapy (neoadjuvant therapy) and of those treated postoperatively with the same regimen (adjuvant therapy) in a meta-analysis of randomized trials. Methods: We evaluated nine randomized studies, including a total of 3946 patients with breast cancer, that compared neoadjuvant therapy with adjuvant therapy regardless of what additional surgery and/or radiation treatment was used. Fixed and random effects methods were used to combine data. Primary outcomes were death, disease progression, distant disease recurrence, and loco-regional disease recurrence. Secondary outcomes were local response and conservative local treatment. All statistical tests were two-sided. Results: We found no statistically or clinically significant difference between neoadjuvant therapy and adjuvant therapy arms associated with death (summary risk ratio [RR] = 1.00, 95% confidence interval [CI] = 0.90 to 1.12), disease progression (summary RR = 0.99, 95% CI = 0.91 to 1.07), or distant disease recurrence (summary RR = 0.94, 95% CI = 0.83 to 1.06). However, neoadjuvant therapy was statistically significantly associated with an increased risk of loco-regional disease recurrences (RR = 1.22, 95% CI = 1.04 to 1.43), compared with adjuvant therapy, especially in trials where more patients in the neoadjuvant, than the adjuvant, arm received radiation therapy without surgery (RR = 1.53, 95% CI = 1.11 to 2.10). Across trials, we observed heterogeneity in the rates of complete clinical response (range = 7%-65%; P for heterogeneity of

Metastatic involvement of the gastrointestinal (G1) tract secondary to breast cancer is rare. Reported herein is the case of a 74-year-old woman with metastatic lobular breast carcinoma to the rectum presenting with obstruction. The breast tumour was diagnosed nine years prior to the presentation of rectal metastases. Endoscopy was repeated twice until a diagnosis was established. Examination of endoscopy material revealed infiltration of the rectum by malignant signet ring cells identical to those of the primary breast tumour. The patient did not respond to chemotherapy and underwent laparotomy with a defunctioning colostomy. Literature review revealed only a few more cases of metastatic breast carcinoma to the rectum. Awareness of this condition may lead to accurate diagnosis and early initiation of systemic treatment, thus avoiding surgical intervention. 12 5 715 718

BACKGROUND: We aimed to determine the frequency of fibromyalgia syndrome (FM) in operated breast cancer patients and to research the relationship between FM and the severity of fatigue and quality of life in these breast cancer patients. METHODS: The demographic data of 101 operated breast cancer patients were recorded. The patients who had pain were then classified as having regional pain (RP), widespread pain without FM (WP), and widespread pain with FM (WFM). The FM diagnosis was based on the American College of Rheumatology (ACR) criteria. The severity of fatigue was evaluated with the Brief Fatigue Inventory, the disease impact was evaluated with the Fibromyalgia Impact Questionnaire (FIQ), and the quality of life was evaluated with the European Organization for Research on Treatment of Cancer questionnaire Quality of Life-C30 (EORTC-QoL-C30). RESULTS: There was no pain in 38 (37.6%) patients, whereas there was pain in 63 (62.4%) patients (N = 42, 41.6% had RP, N = 21, 20.8% had WP). Ten (9.9%) of the entire patient cohort were diagnosed as having FM according to the ACR criteria. There were no differences among the 3 groups in respect to demographic characteristics when patients were classified as RP (N = 42), WP (N = 11), and WFM (N = 10) groups. While there were negative correlations between the FIQ and EORTC-QoL-C30-function score (r = -0.727) and EORTC-QoL-C30-global score (r = -0.488), there was a positive correlation between the FIQ and EORTC-QoL-C30-symptom score (r = 0.726). CONCLUSION: We note that the frequency of FM in the operated breast cancer patients in this study was higher than that reported in normal populations in the literature. Also, we found that the presence of FM had negative effects on the quality of life of the breast cancer patients. Accordingly, in the evaluation of widespread pain and complaints of fatigue in long-surviving breast cancer patients, after metastatic disease is excluded, the probability of FM should be kept in mind, so that appropriate treatment can be initiated to improve their functional status and quality of life.

Background Large-core needle biopsy of the breast (LCNB) and vacuum-assisted breast biopsy (VABB) are widely used as alternatives to open surgical biopsy (OSB) for initial diagnosis of mammographic abnormalities. Between 18% and 80% of cases in which such specimens show atypical lobular hyperplasia (ALH) or atypical ductal hyperplasia (ADH) are found to be malignant at surgery. Design From 1999 to 2005, 68 women with mammographic abnormalities were sampled by stereotactic VABB and presented atypical epithelial hyperplasia. Immunohistochemical staining with anti-cytokeratin 5/6 and anti-E-cadherin antibodies was performed. All women underwent a lumpectomy. Clinical, radiological or histological factors predictive of the risk of finding malignancy at surgery were sought. Results VABB initially showed 28 cases of ADH, 32 cases of ALH, one case of flat epithelial atypia, five cases of mixed atypia, and two cases of Lobular Carcinoma In Situ (LCIS). After slide review with immunohistochemical staining, two cases of ADH were reclassified as simple hyperplasia and two cases of ALH were reclassified as mixed atypia. Seven lesions (10.3%) that appeared to be benign on VABB were found to be malignant on OSB (Ductal Carcinoma In Situ (DCIS) in six cases and invasive ductal carcinoma in one case). ADH was the only predictive factor of malignancy on OSB ( p = 0.04 versus ALH). Conclusion ADH diagnosed by vacuum-assisted breast biopsy frequently corresponds to cancer on open surgical biopsy. Surgical excision of all breast lesions containing atypical hyperplasia on percutaneous biopsy can be recommended .

Ann Surg Oncol

Ann Surg Oncol

A 52-year-old woman presented with a palpable nodule in the right axilla. Physical examination revealed a 2.5 x 2.5 cm, nontender, firm, brownish, and peripherally hyperemic mass with overlying skin retraction on the right anterior axillary fold. Bilateral mammogram was negative. Ultrasonography of the right axillary region showed a 1.8 x 1.1 cm, poorly defined hypoechoic mass with irregular margins and posterior acoustic shadowing. Fine-needle aspiration biopsy of the mass revealed malignant epithelial cells. The patient underwent a wide local excision of the right axillary lesion with en bloc axillary lymph node dissection. Histopathological examination revealed an infiltrating ductal carcinoma. Here we report this case of carcinoma originating from aberrant breast tissue in the axilla. It is suggested that subcutaneous lesions of uncertain origin around the periphery of the breast should be suspected for breast carcinoma and treated appropriately.

Cryotherapy ablation is a minimally invasive procedure being investigated as an alternative to conventional surgery. There are few reports in breast cancer.Evaluate the histopathology of tumoral and normal breast tissue after cryotherapy.Eleven patients with clinically2.0cm and ultrasound visible tumors were studied. Invasive carcinoma was documented by preoperative mammography, magnetic resonance imaging and biopsies. Cryotherapy needles were inserted in the tumor under magnetic resonance guidance and deep freezed with a CRYO-HIT TM System-3. Lumpectomy was performed within 4-5 weeks following cryoablation and submitted for pathological examination including immunostaining of keratins.The tumoral response after cryoablation was variable. In 4 cases there was no viable invasive carcinoma left and focal DCIS only in 2. In 6 cases, residual invasive carcinoma of various size was present with DCIS inside or outside the cryozone. One case could not be evaluated because the cryozone was adjacent to the tumor due to technical problems. Histologically, the normal breast parenchyma of the cryozone showed dense fibrosis, fat necrosis, xanthogranulomatous reaction, endovascular fibrosis and haemorrhages in all cases. The positive immunostaining of keratins revealed remnants of cytoskeleton of carcinomatous cells in the necrotic areas without any viable tumoral cells on routine stains. Skin ulceration and/or necrosis were observed in five patients.Cryotherapy allows tumor destruction of variable extent in breast carcinomas2.0cm in diameter. Immunostaining of keratins is useful to identify cytoskeleton remnants of tumor cells in devitalized areas.

Preoperative diagnosis of fallopian tube carcinoma is difficult due to the rarity and silent course of this neoplasm. We present herein the case of a 58-year-old woman with primary fallopian tube carcinoma that was diagnosed preoperatively on the basis of a positive for adenocarcinoma Papanicolaou vaginal smear, repeated episodes of vaginal bleeding, negative endocervical and endometrial curettage, characteristic features on ultrasonography and elevated CA-125 levels. The patient was treated by total abdominal hysterectomy, bilateral salpigno-oophorectomy and omentectomy. Pathologic confirmation of primary serous papillary adenocarcinoma of the left fallopian tube was made. Peritoneal washings were positive for malignancy. FIGO stage was considered as IIIb and the patient received six courses of combined carboplatin-taxol chemotherapy. At two years from onset of therapy the patient underwent a modified radical mastectomy and lymphadenectomy because of primary carcinoma of the right breast. The patient was started on tamoxifen therapy, which she is still taking. At 60 months after initial surgery, the patient is alive and well. In conclusion, our study suggests an association between fallopian tube carcinoma and breast cancer and a good response of the patient to platinum-based chemotherapy. Eur J Gynaecol Oncol

The prognosis of patients with liver metastases from breast cancer has to be regarded as rather unfavorable. A 45-year-old woman with cancer of the left breast and multiple simultaneous liver metastases was initially treated with cyclophosphamide, methotrexate, and 5-fluorouracil. After two treatment cycles a sonogram of the left breast revealed reduction of the tumor size and she underwent a modified radical mastectomy and hepatic artery catheterization. There was no change in the multiple lesions of the liver on abdominal ultrasonography. One week later a regional chemotherapy regimen was given through a hepatic arterial catheter with subcutaneous implanted reservoir. After completion of the seventh course of chemotherapy, ultrasonography revealed that the multiple liver metastases had regressed completely. To date (July 2001) there has been no relapse during the seven-year follow-up period. In conclusion, we suggest that intra-arterial regional chemotherapy may have an important role to play in the management of breast cancer patients with isolated liver metastases.

Invasive micropapillary carcinoma of the breast is an uncommon variant of infiltrating ductal carcinoma. Observing its distinctive cytologic appearance and aggressive behavior is important for early diagnosis by fine-needle aspiration cytology (FNAC). There are only a few reported cases in the literature. Five women presented with breast masses. FNAC showed malignant epithelial tumors, and mastectomy materials showed invasive micropapillary carcinoma for all of them. Three patients had axillary lymph node metastases. Invasive micropapillary carcinoma, with its angulated papillary clusters lacking a fibrovascular core, and irregular crowded nuclei, has a distinctive cytologic appearance which correlates with its histological features. A differential diagnosis from other primary or metastatic papillary lesions of the breast may be possible using immunohistochemistry and some cytologic features. The limited experience with invasive micropapillary carcinoma should not discourage others from undetaking further studies. © 2002 Wiley-Liss, Inc.

PURPOSE: Tumor cell detection (TCD) in bone marrow is an outstanding prognostic factor in breast cancer. There is only one other study that has investigated more than 300 patients with a median follow-up of more than 5 years (J. L. Mansi et al., Lancet, 354:197-202, 1999). We report data from 727 patients with a median follow-up period of 6.5 years. EXPERIMENTAL DESIGN: In a prospective study, intraoperatively aspirated bone marrow was screened for micrometastatic cancer cells. We used an immunocytological method (monoclonal mucin antibody 2E11; the avidin-biotin complex method). RESULTS: Forty-three percent of the patients were TCD positive. Sixty percent of the patients with distant metastases were tumor cell positive (155 of 258 patients). Forty-nine percent of the patients with positive TCD developed distant metastases (155 of 315 patients). TCD was an independent prognostic factor for clinical outcome after a median follow-up time of 6.5 years. The prognostic impact of TCD and tumor size remains constant with the time, whereas the impact of grading and progesterone receptor on risk seems to decrease with longer follow-up time. CONCLUSIONS: TCD remains an independent prognostic factor The impact of TCD does not change with longer follow-up time. TCD is a reliable prognostic factor and provides important information about the process of metastasis. Clin Cancer Res

Matrix metalloprotease-9 (MMP-9; 92 kDa type IV collaganase, gelatinase B) is regarded as, important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodelling events. In this study we evaluate the prognostic value of MMP-9, by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 status was compared with the concentration of cytosolic Cathepsin-D and with other established prognostic factors, in terms of disease free survival and overall survival. The median follow-up period was 62 months. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger (P = 0.014), invasive ductal histologic (P = 0.037), progesterone receptor (PR)-negative and PR-strong positive tumours (P< 0.001), as well as samples belonging to patients with stage III-IV disease (P = 0.009) and age 45–55 years (P = 0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR = 0.45;P = 0.039) or death (RR = 0.32;P = 0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of OS (RR = 0.47;P = 0.034) in node-negative but not in node-positive patients. Our results suggest that MMP-9 may be an independent favourable prognostic factor in node-negative breast cancer patients. The overexpression of MMP-9 in breast cancer may be also used as a marker to subdivide node negative breast cancer patients in order to determine the optimal treatment modality. © 2001 Cancer Research Campaign http://www.bjcancer.com

The clinical relevance of quantitative assessment of tumor-tissue expression of the bcl-2 protein in operated stage II breast cancer was investigated in this study. Thirty-five cases were studied by immunohistochemistry for the expression of bcl-2 protein and analyzed for disease outcome. One fourth (25%) of the cases were negative and 57% demonstrated near-absolute expression of the bcl-2 protein. No association was found between immunohistochemical detection of the protein with age, hormonal receptor status and tumor grading other than between bcl-2 and estrogen receptor expression (p=0.01). An impressively positive impact of near-absolute expression of bcl-2 on clinical outcome was identified. Our results provide evidence that quantitative assessment of bcl-2 expression constitutes a new approach in early breast cancer with potential clinical implications. We consider that molecular sub-staging of patients with stage II breast cancer by level of bcl-2 expression provides additional important prognostic information and prompts for investigation of its clinical significance on the issue of adjuvant systemic therapy. J Exp Clin Cancer Res

The purpose of this study was to evaluate the activity and toxicity profile of dose-dense sequential chemotherapy with epirubicin (EPI) and paclitaxel in advanced breast cancer (ABC). From January to September 1997, 41 patients with recurrent or metastatic (stage IV) breast cancer were enrolled in the study. Their median age was 57 (range, 33-77) years and median performance status 0 (range, 0-2). Twenty patients had received adjuvant chemotherapy. The chemotherapeutic regimen consisted of 4 cycles of EPI 110 mg/m2 every 2 weeks followed by 4 cycles of paclitaxel, 225 mg/m2 over 3 hours every 2 weeks. G-CSF was administered prophylactically on days 2-10 of each cycle. 34 (83.0%) patients completed all 8 cycles of chemotherapy. A total of 304 cycles were administered, 259 (85.0%) of them at full dose. Thirty (10.0%) cycles were delivered with a delay. The relative median dose intensities of EPI and paclitaxel were 0.95. Most common grade 3-4 side effects were anemia (15.0%) neutropenia (12.0%), thrombocytopenia (5.0%), nausea/vomiting (10.0%), febrile neutropenia (7.5%), and alopecia (90.0%). Overall, 8 (19.5%) patients achieved a complete and 15 (36.5%) a partial response. Median duration of response was 8.4 (range, 3.1-15.5+) months. After a median follow-up of 18.5 months, median time to progression was 8.7 (range, 0.5-21+) months; median survival has not been reached yet. Dose-dense sequential chemotherapy with EPI and paclitaxel shows promising activity as first-line treatment in ABC. Randomized studies comparing this type of chemotherapy with the classical administration of the two drugs together every 3 weeks are ongoing. Cancer Invest