Prospective cohort study of febrile neutropenia in breast cancer patients administered with neoadjuvant and adjuvant chemotherapies: CSPOR-BC FN study.

BACKGROUND: As Asians are more vulnerable to febrile neutropenia (FN) than Caucasians, evaluations of FN incidence and risk factors in Asians are important for the appropriate use of primary pegfilgrastim (PEG-G). PATIENTS AND METHODS: Japanese breast cancer patients receiving standard adjuvant chemotherapies were prospectively enrolled in multicenter institutions from August 2015 to July 2017. FN was evaluated from 2 treatment policies: true FN (T-FN): ≥37.5 °C, grade 4 neutropenia, mandatory hospital visit (visiting); surrogate FN (S-FN): ≥37.5 °C, oral antibiotic, no mandatory visit (non-visiting). PEG-G was used at the physicians' discretion. The primary endpoint was FN incidence during all cycles. Multivariate logistic regression analysis was performed to identify T-FN risk factors. RESULTS: Of 1005 enrolled patients, 980 women treated with FEC, E(A)C, and TC were analyzed. The FN incidence proportions in all patients were 22.5%, 27.5%, and 33.9% for FEC, E(A)C, and TC, respectively. Those of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5% with more frequent primary PEG-G usage. The relative dose intensity (RDI) of the 3 regimens was ≥0.85 in both groups. In the analysis of risk factors, TC (odds ratio = 2.67), age ≥ 65 years (2.24), and pretreatment absolute neutrophil count (ANC)/1000 µl (0.8) remained significant. CONCLUSIONS: FN incidences were above 20% in the 3 regimens, with TC showing the highest. RDI was maintained at a high level in both visiting and non-visiting groups. Patient-related risk factors were age and pretreatment ANC.

De-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low-risk pure HER2 breast cancer.

PURPOSE: Neoadjuvant trastuzumab combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse. METHODS: We treated patients with tumors measuring ≤ 3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for four cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted. RESULTS: Eighteen patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low. CONCLUSION: This less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk.

Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes.

BACKGROUND: Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. METHODS: A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. RESULTS: The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005-2.245 for CEA; HR 2.088, 95% CI 1.457-2.901 for CA15-3). CONCLUSIONS: These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

[A Case of Synchronous Double Cancers of the Liver and Pancreas Treated Using Pancreaticoduodenectomy and Liver Resection].

A 50-year-old woman had a 12mm liver tumor at segment 4 and was diagnosed with hemangioma. Two years later, the liver tumor had grown to 27mm in diameter, and a new pancreatic tumor was detected using CT examination. The pancreatic tumor was suspected of being pancreatic carcinoma, based on the results of endoscopic-ultrasound-guided fine-needlebiopsy( EUS-FNA)of the pancreas. The liver tumor was diagnosed as adenocarcinoma using liver biopsy. Because of its slow growth and the solitary liver tumor, synchronous pancreatic cancer and intrahepatic cancer were suspected. We therefore performed pancreaticoduodenectomy with portal vein resection and partial liver resection of segment 4. Upon histological analysis, carcinoma in situ was detected in the liver tumor and the patient was diagnosed with synchronous double cancers of the liver(cholangiocellular carcinoma)and pancreas(invasive ductal carcinoma). Our case indicated that it is very difficult to distinguish cholangiocellular carcinoma from metastatic liver tumor using diagnostic images. We should therefore consider the possibility of cholangiocellular carcinoma when a solitary tumor in the liver is detected at the same time as pancreatic cancer.

A Pleural Solitary Fibrous Tumor, Multiple Gastrointestinal Stromal Tumors, Moyamoya Disease, and Hyperparathyroidism in a Patient Associated with NF1.

Neurofibromatosis type 1 (NF1), also called von Recklinghausen's disease, is a multisystemic disease caused by an alteration of the NF1 gene, a tumor suppressor located on the long arm of chromosome 17 (17q11.2). Loss of the gene function, due to a point mutation, leads to an increase in cell proliferation and the development of several tumors. We report a 60-year-old female patient manifesting hypercalcemia due to hyperparathyroidism, a solitary fibrous tumor (SFT) of the pleura, multiple gastrointestinal stromal tumors (GISTs), and moyamoya disease associated with NF1. The SFT and GISTs were removed by staged operations. Then, hypercalcemia was successfully controlled after resection of the parathyroid adenoma. Based on a literature review, these combinations have never been reported, and the relevant literature is briefly discussed.

Prediction of pathological complete response to neoadjuvant chemotherapy by magnetic resonance imaging in breast cancer patients.

The purpose of this study was to evaluate whether the baseline breast MRI findings would be useful for the prediction for pathological complete response (pCR) by breast cancer patients to neoadjuvant chemotherapy. Primary breast cancer patients (stage II-III) preoperatively treated with sequential paclitaxel (12 cycles) and fluorouracil, epirubicin, and cyclophosphamide (4 cycles), followed by surgery were retrospectively enrolled, and 229 patients were eligible. Before chemotherapy, breast MRI studies were performed. Breast tumors were dichotomized into round + oval and irregular types based on MRI morphology. The round + oval tumors showed a significantly higher pCR rate than the irregular tumors (42.0% vs 17.3%; P < 0.001). In addition, PAM50 analysis revealed that basal and HER2-enriched tumors were significantly more prevalent among round + oval than irregular type tumors (P = 0.015). Baseline MRI morphology appears to be a significant predictor for pCR. The higher rate of the basal and HER2-enriched tumors among the round + oval tumors may explain their better chemo-sensitivity.