Pamela Guglielmini

Switching to Anastrozole Versus Continued Tamoxifen Treatment of Early Breast Cancer: Preliminary Results of the Italian Tamoxifen Anastrozole Trial

PURPOSE Tamoxifen, which is actually the gold standard adjuvant treatment in estrogen receptor-positive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy because of the development of resistance. Therefore new approaches are required. PATIENTS AND METHODS We conducted a prospective randomized trial to test the efficacy of switching postmenopausal patients who were already receiving tamoxifen to the aromatase inhibitor anastrozole. After 2 to 3 years of tamoxifen treatment, patients were randomly assigned either to receive anastrozole 1 mg/d or to continue receiving tamoxifen 20 mg/d, for a total duration of treatment of 5 years. Disease-free survival was the primary end point. Event-free survival, overall survival, and safety were secondary end points. RESULTS Four hundred forty-eight patients were enrolled. All women had node-positive, estrogen receptor-positive tumors. At a median follow-up time of 36 months, 45 events had been reported in the tamoxifen group compared with 17 events in the anastrozole group (P = .0002). Disease-free and local recurrence-free survival were also significantly longer in the anastrozole group (hazard ratio [HR] = 0.35; 95% CI, 0.18 to 0.68; P = .001 and HR = 0.15; 95% CI, 0.03 to 0.65; P = .003, respectively). Overall, more adverse events were recorded in the anastrozole group compared with the tamoxifen group (203 v 150, respectively; P = .04). However, more events were life threatening or required hospitalization in the tamoxifen group than in the anastrozole group (33 of 150 events v 28 of 203 events, P = .04). CONCLUSION Switching to anastrozole after the first 2 to 3 years of treatment is well tolerated and significantly improves event-free and recurrence-free survival in postmenopausal patients with early breast cancer.

HER2/neu oncoprotein overexpression in epithelial ovarian cancer : Evaluation of its prevalence and prognostic significance clinical study

Introduction: The HER2/neu proto-oncogene encodes a transmembrane receptor protein involved in the development and progression of the majority of cancers. Prior studies have shown that HER2/neu oncogene is overexpressed in approximately 15–30% of ovarian carcinomas. However findings regarding the overexpression and prognosis are still conflicting. Methods: Our retrospective study was performed on 194 ovarian carcinoma tissues obtained at the time of first surgery. The staining procedure for HER2/neu overexpression was performed using a polyclonal antibody. Results: HER2/neu overexpression was found in 53 out of 194 (27.3%) investigated cases of which 26 (13.4%) carcinomas were weakly positive (score 1+) and 27 (13.9%) moderately (score 2+) to intensely positive (score 3+). No significant relationship was found between HER2/neu score and main clinical and pathological features. Significant difference in overall survival was evident between negative women (0/1+) and positive women (2+/3+): 48 and 29 months, respectively (p = 0.04). In multivariate analysis HER2/neu overexpression appeared to be the only variable significantly correlated with progression and death. CA125 normalization at 3 and 6 months appeared a strong predictor of progression and survival. Conclusion: In this study HER2/neu overexpression was associated with an increased risk of progression and death, especially among women with FIGO Stage I and II ovarian carcinoma.

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: Long term results of the Italian Tamoxifen Anastrozole trial

The Italian Tamoxifen Anastrozole (ITA) trial investigated the efficacy of switching to anastrozole for women who were already on adjuvant tamoxifen since 2-3years. Relapse-free survival (RFS) was the primary end-point; event-free survival (EFS), overall survival (OS) and safety were secondary end-points. Herein, we report an update on the long term results of this trial. At a median follow-up time of 128 months (range 14-168 months), 94 events have been recorded in the tamoxifen group compared with 71 events in the anastrozole group (hazard ratio (HR)=0.71; 95% confidence interval (CI), 0.52-0.97; p=0.03). RFS was also significantly longer in the anastrozole group (HR=0.64; 95% CI, 0.44-0.94; p=0.023); no statistically significant difference between study arms concerning OS was shown, but the trial was not powered enough in respect to this end-point. The incidence of serious adverse events (SAE) like bone fractures was comparable (four in each arm), while gynaecological problems were still significantly more numerous among the women continued on tamoxifen (21 patients developed a SAE in this group, including eight endometrial cancers, compared to three patients who suffered from a SAE, including one endometrial cancer, in the anastrozole group: p<0.000). Present data confirm that switch is safe and can provide long-term gain in terms both of RFS and of EFS, which persists even several years since treatment discontinuation.

Complement C3f serum levels may predict breast cancer risk in women with gross cystic disease of the breast

UNLABELLED Gross cystic disease (GCDB) is a breast benign condition predisposing to breast cancer. Cryopreserved sera from GCDB patients, some of whom later developed a cancer (cases), were studied to identify potential risk markers. A MALDI-TOF mass spectrometry analysis found several complement C3f fragments having a significant increased abundance in cases compared to controls. After multivariate analysis, the full-length form of C3f maintained a predictive value of breast cancer risk. Higher levels of C3f in the serum of women affected by a benign condition like GCDB thus appears to be correlated to the development of breast cancer even 20 years later. BIOLOGICAL SIGNIFICANCE Increased complement system activation has been found in the sera of women affected by GCDB who developed a breast cancer, even twenty or more years later. C3f may predict an increased breast cancer risk in the healthy population and in women affected by predisposing conditions.

Epirubicin Followed by Cyclophosphamide, Methotrexate and 5-Fluorouracil versus Paclitaxel Followed by Epirubicin and Vinorelbine in Patients with High-Risk Operable Breast Cancer

Objective: Breast cancer patients with >3 involved nodes (N+) have a poor outcome. Chemotherapy (CT), alone or combined with endocrine therapy (ET) in hormone receptor (HOR)-positive patients, is the standard for these women. However, there are still questions surrounding the optimal adjuvant CT regimen. Methods: 244 patients with >3 N+ were randomized to receive either four 3-weekly courses of epirubicin (E: 100 mg/m2, day 1) followed by four 4-weekly cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF: 600, 40, 600 mg/m2, days 1, 8: n = 122) or four 3-weekly courses of paclitaxel (T: 175 mg/m2, day 1) followed by four 3-weekly cycles of epirubicin and vinorelbine (E: 75 mg/m2, day 1; V: 25 mg/m2, days 1, 8: n = 122). After CT, tamoxifen (plus an LH-RH analog in menstruating women) was given to all HOR-positive patients over a period of 5 years. Overall survival (OS) was the primary end point. Relapse-free survival (RFS) and toxicity were secondary end points. Results: At a median follow-up time of 102 months (range 3–146), OS and RFS did not differ significantly between groups (E-CMF vs. T-EV: OS, HR 0.94, 95% CI 0.59–1.48, p = 0.8; RFS, HR 0.86, 95% CI 0.57–1.29, p = 0.45). The lack of any difference between assigned treatments was confirmed by multivariate analysis (E-CMF vs. T-EV: RFS, HR 0.98, 95% CI 0.64–1.48, p = 0.9). The 2 regimens showed different toxicity profiles. In fact, significantly more women assigned to E-CMF were affected by stomatitis (p = 0.001) while significantly more women in the T-EV group developed peripheral neuropathy (p < 0.0001) and musculoskeletal disorders (p < 0.0001). However, side effects were moderate and manageable and no toxic death occurred in either arm of the study. Conclusions: T-EV was safe and moderately toxic but was not superior to E-CMF.