Massimo Rinaldo

Radiofrequency ablation in patients with primary breast carcinoma: a pilot study in 26 patients.

The authors performed a pilot trial of ultrasound‐guided percutaneous radiofrequency ablation (RFA) in patients with T1 and T2 breast tumors 1) to confirm complete coagulative necrosis of tumor tissue and 2) to determine the safety and complications related to this treatment.

Preoperative weekly cisplatin–epirubicin–paclitaxel with G-CSF support in triple-negative large operable breast cancer

BACKGROUND Findings from our previously published phase II study showed a high pathologic complete remission (pCR) rate in patients with triple-negative large operable breast cancer after the administration of eight cisplatin-epirubicin-paclitaxel (PET) weekly cycles. The safety and efficacy data of the initial population were updated, with inclusion of additional experience with the same therapy. METHODS Patients with triple-negative large operable breast cancer (T2-T3 N0-1; T > 3 cm) received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel (Taxol) 120 mg/m2, with granulocyte colony-stimulating factor (5 microg/kg days 3-5) support. RESULTS Overall 74 consecutive patients (T2/T3 = 35/39; N0/N+ = 26/48) were treated, from May 1999 to May 2008. At pathological assessment, 46 women (62%; 95% confidence interval 50-73) showed pCR in both breast and axilla. At a 41-month median follow-up (range 3-119), 13 events (nine distant metastases) had occurred, 5-year projected disease-free survival (DFS) and distant disease-free survival being 76% and 84%, respectively. Five-year DFS was 90% and 56% in pCRs and non-pCRs, respectively. Severe neutropenia and anemia occurred in 23 (31%) and eight (10.8%) patients, respectively. Severe non-hematological toxicity was recorded in <20% of patients. Peripheral neuropathy was quite frequent but never severe. CONCLUSIONS Eight weekly PET cycles are a highly effective primary treatment in women with triple-negative large operable breast cancer. This approach results in a very promising long-term DFS in this poor prognosis population. This triplet regimen is worthy of evaluation in phase III trials.

Compliance and toxicity of adjuvant CMF in elderly breast cancer patients: a single-center experience

BackgroundFew data are available on compliance and safety of adjuvant chemotherapy when indicated in elderly breast cancer patients; CMF (cyclophosphamide, methotrexate, fluorouracil) can be reasonably considered the most widely accepted standard of treatment.MethodsWe retrospectively reviewed compliance and safety of adjuvant CMF in patients older than 60. The treatment was indicated if patients had no severe comorbidity, a high-risk of recurrence, and were younger than 75. Toxicity was coded by NCI-CTC. Toxicity and compliance were compared between two age subgroups (<65, ≥ 65) by Fisher exact test and exact Wilcoxon rank-sum test.ResultsFrom March 1991 to March 2002, 180 patients were identified, 100 older than 60 and younger than 65, and 80 aged 65 or older. Febrile neutropenia was more frequent among older patients (p = 0.05). Leukopenia, neutropenia, nausea, cardiac toxicity and thrombophlebitis tended to be more frequent or severe among elderlies, while mucositis tended to be more evident among younger patients, all not significantly. Almost one half (47%) of the older patients receiving concomitant radiotherapy experienced grade 3–4 haematological toxicity. Compliance was similar in the two groups, with 6 cycles administered in 86% and 79%, day-8 chemotherapy omitted at least once in 36% and 39%, dose reduction in 27% and 38%, prolonged treatment duration (≥ 29 weeks) in 10% and 11% and need of G-CSF in 9% and 18%, among younger and older patients, respectively.ConclusionOur data show that, in a highly selected population of patients 65 or more years old, CMF is as feasible as in patients older than 60 and younger than 65, but with a relevant burden of toxicity. We suggest that prospective trials in elderly patients testing less toxic treatment schemes are mandatory before indicating adjuvant chemotherapy to all elderly patients with significant risk of breast cancer recurrence.

Endocrine Effects of Adjuvant Letrozole + Triptorelin Compared With Tamoxifen + Triptorelin in Premenopausal Patients With Early Breast Cancer

PURPOSE To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). PATIENTS AND METHODS Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. RESULTS Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. CONCLUSION Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series.

BackgroundStage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit.MethodsIn a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes.ResultsScreen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05).ConclusionsMolecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially.Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology.

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

BackgroundTo evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer.MethodsPatients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed.ResultsFrom February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm.ConclusionsIn this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer.Trial registrationClinicalTrials.gov NCT00540800.

Integration of DCE-MRI and DW-MRI Quantitative Parameters for Breast Lesion Classification

Objective. The purpose of our study was to evaluate the diagnostic value of an imaging protocol combining dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI) in patients with suspicious breast lesions. Materials and Methods. A total of 31 breast lesions (15 malignant and 16 benign proved by histological examination) in 26 female patients were included in this study. For both DCE-MRI and DW-MRI model free and model based parameters were computed pixel by pixel on manually segmented ROIs. Statistical procedures included conventional linear analysis and more advanced techniques for classification of lesions in benign and malignant. Results. Our findings indicated no strong correlation between DCE-MRI and DW-MRI parameters. Results of classification analysis show that combining of DCE parameters or DW-MRI parameter, in comparison of single feature, does not yield a dramatic improvement of sensitivity and specificity of the two techniques alone. The best performance was obtained considering a full combination of all features. Moreover, the classification results combining all features are dominated by DCE-MRI features alone. Conclusion. The combination of DWI and DCE-MRI does not show a potential to dramatically increase the sensitivity and specificity of breast MRI. DCE-MRI alone gave the same performance as in combination with DW-MRI.

Nuclear localization of cancer stem cell marker CD133 in triple-negative breast cancer: a case report

AIM AND BACKGROUND It has been recently demonstrated that the detection of stem cell niches in triple-negative (TN) breast cancer may provide good prognostic clues for this tumor. METHODS AND STUDY DESIGN We investigated the subcellular expression and localization of the cancer stem cell marker CD133 in a TN breast cancer biopsy from a 42-year-old Caucasian woman with a histological diagnosis of high-grade invasive ductal breast carcinoma by immunohistochemistry, flow cytometry and quantitative real-time PCR (qRT-PCR). RESULTS We describe for the first time in a TN breast cancer the nuclear mislocalization of CD133, which normally shows membrane localization and more sporadically cytoplasmic localization. We also found this aberrant expression with qRT-PCR analysis but not flow cytometry. CONCLUSIONS Nuclear localization of CD133 may be an indicator of poor prognosis in TN breast cancer, as it is known that surface molecules, when moving into the nucleus, can act as transcriptional regulators by interfering with molecular pathways directly connected to the proliferation and differentiation of tumor cells.

Gail Model Risk Factors: Impact of Adding an Extended Family History for Breast Cancer

Abstract:  An approach commonly used in estimating breast cancer risk is the Gail model. The objective of this study was to evaluate the feasibility and impact of adding extended family history as a new breast cancer risk factor into the Gail model. The data of the present study include cases with breast cancer and hospitalized controls recruited in the National Cancer Institute of Naples (southern Italy) between 1997 and 2000. We compared the first‐degree relative (FDR) risk factor (standard Gail model) with the second‐degree relative (SDR) information; and the FDR risk factor (standard Gail model) with the combination of FDR and SDR. We computed the c‐statistic by comparing the risks found in our population to those in Gail‐US population. The concordance for the model with FDR was 0.55 (95% CI 0.53–0.58), the model with SDR shows a modest but significant discriminatory accuracy (0.56, 95% CI 0.53–0.59), and the combination of FDR+SDR gave the concordance statistic of 0.57 (95% CI 0.54–0.60), indicating a good comparison between the two models. The results of our study show that extended family history information could be useful to improve the discriminatory power of the Gail model risk factors.

Added Value of Breast MRI for Preoperative Diagnosis of Ductal Carcinoma In Situ: Diagnostic Performance on 362 Patients

Introduction: The purpose of this study was to evaluate the added value of breast magnetic resonance imaging (MRI) in preoperative diagnosis of ductal carcinoma in situ (DCIS). We reviewed our institution database of 3499 consecutive patients treated for breast cancer. Patients and Methods: A total of 362 patients with histologically proven DCIS were selected from the institutional database. Of these, 245 (67.7%) preoperatively underwent conventional imaging (CI) (mammography/ultrasonography) (CI group), and 117 (32.3%) underwent CI and dynamic MRI (CI + MRI group). The pathology of surgical specimens served as a reference standard. The Mann‐Whitney U, χ2 test, and Spearman correlation coefficient were performed. Results: The CI + MRI group showed a sensitivity of 98.5% with an increase of 10.1% compared with the CI group to detect pure DCIS. Dynamic MRI identified 19.7% (n = 13) additional pure DCIS compared with CI. In the CI + MRI group, a single (1.5%) false negative was reported, whereas in the CI group, 11 (11.6%) false negatives were reported. Moreover, the CI + MRI group showed a sensitivity of 98.0% to detect DCIS + small invasive component. In this group, dynamic MRI identified 21.6% (n = 11) additional DCIS and a single (2.0%) false negative compared with the CI group, whereas in the CI group, 7 (4.7%) false negatives were reported. MRI and histopathologically measured lesion sizes, Breast Imaging Reporting and Data System MRI assessment categories, and enhancement signal intensity curve types showed a significant correlation. The MRI detection rate of DCIS increased significantly with increasing nuclear grade. Conclusions: Preoperative breast MRI showed a better accuracy then CI in preoperative diagnosis for both pure DCIS and DCIS + small invasive component with a precise assessment of lesion size. This can provide a more appropriate management of DCIS patients. To evaluate the added value of breast MRI in preoperative diagnosis of DCIS. A total of 362 patients with histologically proven DCIS were selected. Conventional imaging + MRI group showed a sensitivity of 98.5% with an increase of 10.1% compared with the conventional group to detect pure DCIS. Preoperative breast MRI showed a better accuracy than conventional imaging.