Docetaxel in the adjuvant therapy of HER-2 positive breast cancer patients.

Considering the clinical benefit of trastuzumab in advanced breast cancer, fi ve prospective adjuvant randomized trials have recently been completed and early results have been published. Two of them, (NSABP-B31 and NCCTG N9831), employed anthracycline-containing regimens with sequential paclitaxel, with or without trastuzumab. The third study, HERA trial, randomized patients after adjuvant chemotherapy into an observational arm, one or two years of trastuzumab. Results of these studies, after a median follow up of 2-3 years confirm a DFS and OS benefit for the experimental arms. The worst rate of cardiotoxicity, in terms of incidence of CHF, with the use of trastuzumab and anthracycline based regimens was 4.1% in the trastuzumab arm of the NSABP-B31 trial. Among the fi ve trastuzumab trials, two, BCIRG 006 and FinHer, employed docetaxel-based regimens. The innovative BCIRG 006 trial compared ACdocetaxel (T) with two trastuzumab-containing regimens, ACTH, and a non-anthracycline-containing regimens, TCH, with a clear advantage in DFS for both trastuzumab arms. Data from the second interim analysis indicate that, in the subgroup of patients without co-amplification of topoisomerase 2 (TOPO-2), the arm without trastuzumab (ACT) showed a DFS significantly poorer that in the other arms; moreover, if we consider the lower toxicity of TCH regimen in comparison with anthracycline-containing arms, the innovative statements offered by BCIRG 006 trial appear evident, and these findings opened an important question about the consolidated employment of anthracyclines in adjuvant setting.The FinHer trial was a small trial testing a short course of trastuzumab (9 weeks) concomitantly with a chemotherapy including docetaxel, and there was a significant advantage in DFS for the trastuzumab based arms, without relevant toxicity and without any cardiotoxicity. Although data from all trastuzumab adjuvant trials, and without particulary from BCIRG-006 and FinHer trials, appear very intriguing, further follow-up is required.

Optimal sequence of anthracyclines and taxanes as adjuvant breast cancer treatment.

Results from randomized trials evaluating taxane versus non-taxane containing regimens in adjuvant breast cancer treatment indicate an advantage in DFS and OS for the taxane-arms, but the best schedule of administration, in combination with anthracyclines or in sequence, is still a debated issue, even if the sequential strategy appears to be less toxic. Up to now, the majority of clinical trials employed the "standard" sequence, with anthracycline-based combinations fi rst, followed by taxanes. Few small phase II trials evaluated the reverse sequence, with taxanes administered fi rst, most of them in metastatic or neoadjuvant setting, suggesting efficacy and lower toxicity. An important issue to be considered is the hypothesized differences in the ability of the drugs to induce cross-resistance to each other, as suggested by data of a preclinical study, and from clinical study with a cross-over design; results of these trials suggest that the best strategy would be to administer a taxane prior to an anthracycline, also according to the Norton and Simon hypothesis. Moreover, trials evaluating the best sequence of anthracyclines and taxanes in adjuvant breast cancer setting are of small sample size, and an adequately powered randomized phase III trial is needed before definitive conclusions are reached.

Results of conservative surgery for limited-sized infiltrating breast cancer: analysis of 962 tested patients: 24 years of experience.

BACKGROUND AND OBJECTIVES: Breast-conserving treatment (BCT) is the elective approach to early stage breast cancer. We report on our 24 years of experience. METHODS: Between 1975 and 1998, 980 conservative surgical procedures in 962 patients for limited-sized infiltrating breast cancer (T1 to "small" T2, N0-N1, M0) were performed. BCT consisted of a local wide excision, axillary dissection and postoperative radiation therapy to the entire breast (50 Gy). An adjuvant systemic treatment (chemo- and/or hormonotherapy) was administered to the large majority of patients. Data on age, menopausal status, histologic subtype of tumor, quadrant site of cancer, tumor size (Tla, T1b, T1c, or T2), axillary nodal status (N- or N+, with involvement of 1-3 nodes, or more), and follow-up were stored for each patient. Overall, N+ patients constituted 29.2% of the total number. Survival data were analyzed using the Berkson-Gage actuarial method. RESULTS: The 15-year overall and disease-free survival rates were 72% and 67%, respectively. Nevertheless, the more interesting results concern survival rates in relation to T and N parameters. T-related survival showed a sharp distinction among the subgroups T1a + T1b and T1c, with values of 90% for the former versus 62% for the latter. Even more significative results were achieved by comparing N with survival. In fact, it was 84% for N-patients and 31% for N+ patients; for N+ patients, outcome was poor for the subgroup showing an involvement of more than 3 nodes, with no patient surviving at 15 years. None of the other evaluated parameters proved to be related to survival. The validity of our protocol is confirmed by the low number of local relapses: only 33 (3.4%) of 980 total treated cases. Cosmetic results were excellent or good in a high percentage of patients (>80%). CONCLUSIONS: These results unquestionably confirm the validity of BCT, provided certain prerequisites are fulfilled.

[Liver metastasis of breast carcinoma. Results of surgical resection. Analysis of 15 operated cases]. / Metastasi epatiche da carcinoma mammario. I risultati della resezione chirurgica. Analisi di 15 casi operati.

AIM OF THE STUDY: The aim of the study was to define the efficacy of liver resection for metastases from operated breast cancer by means of analysis of the results of a single institution compared to the literature data. MATERIALS AND METHODS: Over the period from 1990 to 1998, 15 patients with liver metastases from operated breast cancer were submitted to surgical resection. Thirteen patients were operated on for single metastases and two for multiple liver metastases. In the first group, a simple metastasectomy or wedge resection was sufficient, while in the second a bisegmentectomy and a right hepatectomy, respectively, were performed. Nine patients were subsequently submitted to adjuvant chemotherapy, two to chemo- and hormonotherapy, and two to hormonotherapy alone, while two other patients received no systemic treatment. RESULTS: No major complications or postoperative mortality were observed. Median survival was 44 months. The actuarial 5-year survival rate was 38.3%. Eight patients are still alive, and 7 patients have died as a result of their liver and systemic metastases. CONCLUSIONS: Hepatic metastasis from breast cancer is a good indication for surgical resection. Resection is capable of providing curative treatment and better results in terms of quality of life and survival rates, as compared to chemotherapy and hormonotherapy, especially in patients operated on for primary tumours more than three years earlier.

[Surgical resection of lung metastases from breast cancer. Report of 12 cases]. / Resezione di metastasi polmonari da carcinoma mammario. Analisi di 12 casi trattati.

Thirty-nine patients affected with lung metastases from different primary neoplastic sites have been treated between 1990 and 1998 at 2nd Surgical Division of "Regina Elena" National Cancer Institute of Rome. Among them, 12 were metastases from breast cancer-lung metastases were isolated in 9 cases and multifocal in 3 cases, although always in the same lung. Nine cases underwent a thoracotomic approach: in 6 patients we have performed a wedge resection, in 3 cases a lobectomy. Three patients underwent a wedge resection by means of a video-thoracoscopic approach. We have registered 2 post-operative complications and no deaths. Median survival rate was 40 months and 5 year actuarial survival rate was 42%. Surgery for isolated lung metastases seen to be a safe approach and to improve life expectancy in most of patients.

Potential use of monoclonal antibodies in the diagnostic distinction of gynecomastia from breast carcinoma in men.

Immunohistochemical (IHC) assays using the monoclonal antibodies (MoAbs) B72.3 and B6.2, recognizing two distinct and independently expressed breast tumor-associated antigens (BTAAs), recently have been shown to significantly improve the accuracy of cytodiagnosis of breast nodules by fine-needle aspiration (FNA). To evaluate whether the same method may be useful diagnostically in distinguishing gynecomastia from breast cancer in men, a retrospective avidin-biotin immunoperoxidase assay study was performed on 50 cases of gynecomastia and 30 cases of breast carcinoma in men, using a panel of five MoAbs known to recognize different BTAAs. The results of this study demonstrated that MoAbs B1.1, HMFG2, and MBr1 displayed a strong reactivity with gynecomastia and carcinoma, but MoAbs B72.3 and B6.2 separated benign and malignant lesions in a high percentage of cases. When used in combination, the latter two reagents reacted with 96% of the carcinomas that were analyzed but labeled only 67% of gynecomastia cases. Thus, the conjoint use of these two reagents may enhance the use of FNA biopsy as a valuable tool in the presurgical diagnosis of breast nodules in men.

Peritoneovenous shunt and neoplastic ascites: a 5-year experience report.

The cases of 42 patients with malignant ascites treated with a peritoneal venous shunt over a 5-year period are reviewed to establish the incidence of surgical and postsurgical complications. Although the yield of malignant cells found in the peripheral blood was increased after shunting, no new hematogenous metastases were observed after the operation. No evidence of disseminated intravascular coagulation was observed after shunt placement. While the shunt effectively relieved the discomfort due to abdominal distention and respiratory impairment, no restoration of cutaneous hypersensitivity was observed in the nine patients who were anergic prior to surgery. The median survival of patients with breast and gynecological cancer, after surgery, was significantly longer than the survival of patients with primary gastrointestinal neoplasma. In conclusion, peritoneal venous shunt appears to be an effective and safe method to improve the quality of life of patients with malignant ascites.