Neuroendocrine breast cancer: retrospective analysis of 96 patients and review of literature.

BACKGROUND AND PURPOSE: Primary neuroendocrine breast carcinomas (NEBC) are uncommon lesions; they constitute approximately 1% of all breast cancers and mostly affect elderly patients. According to the most recent World Health Organization classification, it concerns almost exclusively the female population between the sixth and seventh decades. The aim of this retrospective study is to analyze the clinicopathological aspects of 96 NEBC patients who had undergone surgical resection at a single institute. METHODS: We retrospectively analyzed a series of 96 patients who underwent surgical resection for NEBC between January 1992 and August 2013. RESULTS: The 96 patients with NEBC were divided into two categories: 61 (63.5%) in whom the expression of a neuroendocrine marker was present in more than 50% of neoplastic cells and 35 (36.5%) with a minor neuroendocrine component. Our data show a mean age of the patients at diagnosis of 70 years (range 42-87 years); the 10-year survival of the 96 patients was 87%, moreover we report tumor location, type of surgical operation, tumor size (average 2.1 cm), hormone therapy, chemotherapy and radiotherapy if used, recurrence sites, overall and disease free survival times. CONCLUSIONS: This study showed a better prognosis in patients with NEBC compared with breast carcinomas with a minor neuroendocrine component and with conventional invasive ductal or lobular cancers.

Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study.

PURPOSE: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes). PATIENTS AND METHODS: In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m(2)) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily. RESULTS: A total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B and C, respectively. The pCR rates were 25% (90% CI, 13.1% to 36.9%) in arm A, 26.3% (90% CI, 14.5% to 38.1%) in arm B, and 46.7% (90% CI, 34.4% to 58.9%) in arm C (exploratory P = .019). CONCLUSION: The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.

Serum cytokeratin fragment 21.1 (CYFRA 21.1) as tumour marker for breast cancer: comparison with carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA).

Serum carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA) are currently employed in clinical practice as markers for breast cancer, particularly in the follow-up and therapy monitoring. However, the American Society for Clinical Oncology (ASCO) stated in its clinical practice guidelines for the use of tumour markers in breast carcinoma that neither CA 15.3 nor CEA are recommended for routine use in screening, diagnosis and surveillance after primary treatment, or in monitoring response to treatment, because current literature data are insufficient. Cytokeratin fragment 21.1 (CYFRA 21.1) assay detects a serum fragment of cytokeratin 19 (CK19) and is employed in the diagnosis and management of lung cancer, particularly of squamous cell histotype. Breast carcinoma has been demonstrated to express CK19 fragments in the primary and metastatic lesions and CK19 mRNA is detectable in peripheral blood from patients affected by breast cancer. We measured serum markers CYFRA 21.1, CEA and CA 15.3 in the sera from 212 females affected by histologically proven breast carcinoma. Patients comprised 96 individuals with untreated primary disease (54 stage I-II, 18 stage III and 24 stage IV), 30 regional (chest-wall and/or lymph-nodes) relapsing disease and 68 metastatic (haematogenous metastases) relapsing disease. Forty-eight patients previously treated by surgery and without any evidence of disease were enrolled to evaluate the role of serum markers in the monitoring for recurrence of the disease. One hundred healthy age-matched females and 65 patients affected by benign mammary gland disease (including 38 patients with mastopathy and 27 with fibroadenoma) were enrolled as controls. Serum levels of all markers increased from controls to patients affected by breast cancer, from stage I-II to stage IV of the breast cancer and from local to advanced recurrence. The comparison of diagnostic accuracy in the detection of primary and relapsing breast cancer showed no significant differences between markers. Univariate and multivariate survival analysis showed a significant statistically prognostic value for CA 15.3 and CYFRA 21.1 but not for CEA. However, the factors N and M were confirmed to be very strong predictors of the patients' survival. Finally, CEA and CYFRA 21.1 detected less recurrences than CA 15.3. In conclusion, our data show no significant improvement in the diagnosis, prognostic evaluationand follow-up of breast cancer by CYFRA 21.1 and CEA assays compared to CA 15.3 assay. Considering the ASCO statement on tumour markers in breast cancer, the CYFRA 21.1 assay should not be employed in clinical practice.