The value of sentinel lymph-node biopsy in women with node-positive breast cancer at diagnosis and node-negative tumour after neoadjuvant therapy: a systematic review.

PURPOSE: To conduct a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) in women with node-positive breast cancer at diagnosis and node-negative tumour after neoadjuvant therapy, compared to axillary lymph-node dissection. METHODS: The more relevant databases were searched. Main outcomes were false-negative rate (FNR), sentinel lymph-node identification rate (SLNIR), negative predictive value (NPV), and accuracy. We conducted meta-analyses when appropriate. RESULTS: Twenty studies were included. The pooled FNR was 0.14 (95% CI 0.11-0.17), the pooled SLNIR was 0.89 (95% CI 0.86-0.92), NPV was 0.83 (95% CI 0.79-0.87), and summary accuracy was 0.92 (95% CI 0.90-0.94). SLNB performed better when more than one node was removed and double mapping was used. CONCLUSIONS: SLNB can be performed in women with a node-negative tumour after neoadjuvant therapy. It has a better performance when used with previous marking of the affected node and with double tracer.

Dual neoadjuvant blockade plus chemotherapy versus monotherapy for the treatment of women with non-metastatic HER2-positive breast cancer: a systematic review and meta-analysis.

BACKGROUND: We aimed to determine the effect of dual anti-HER2 blockade compared to monotherapy on clinically important outcomes. METHODS: We carried out a systematic review updated until July 2022. The outcomes included pathological complete response (pCR), clinical response, event-free survival, and overall survival. RESULTS: We identified eleven randomized clinical trials (2836 patients). When comparing paclitaxel plus dual treatment versus paclitaxel plus trastuzumab or lapatinib, dual treatment was associated with a higher probability of achieving a pathological complete response (OR 2.88, 95% CI 2.02-4.10). Addition of a taxane to an anthracycline plus cyclophosphamide and fluorouracil, plus lapatinib or trastuzumab, showed that the dual treatment was better than lapatinib alone (OR 2.47, 95% CI 1.41-4.34), or trastuzumab alone (OR 1.89, 95% CI 1.13-3.16). Dual treatment may result in an increase in survival outcomes and tumour clinical response, although such benefits are not consistent for all the combinations studied. CONCLUSIONS: The use of dual blockade with combinations of trastuzumab and pertuzumab can be recommended for the neoadjuvant treatment of women with HER2-positive breast cancer. PROSPERO Registration number: CRD42018110273.

The value of sentinel lymph-node biopsy after neoadjuvant therapy: an overview.

PURPOSE: We conducted a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) after the neoadjuvant chemotherapy, compared to axillary lymph-node dissection, in terms of false-negative rate (FNR) and sentinel lymph-node identification rate (SLNIR), sensitivity, negative predictive value (NPV), need for axillary lymph-node dissection (ALND), morbidity, preferences, and costs. METHODS: MEDLINE, Embase, Scopus, and The Cochrane Library were searched. We assessed the quality of the included systematic reviews using AMSTAR2 tool, and estimated the degree of overlapping of the individual studies on the included reviews. RESULTS: Six systematic reviews with variable quality were selected. We observed a very high overlapping degree across the included reviews. The FNR and the SLNIR were quite consistent (FNR 13-14%; SLNIR ~ 90% or higher). In women with initially clinically node-negative breast cancer, the FNR was better (6%), with similar SLNIR (96%). The included reviews did not consider the other prespecified outcomes. CONCLUSIONS: It would be reasonable to suggest performing an SLNB in patients treated with NACT, adjusting the procedure to the previous marking of the affected lymph node, using double tracer, and biopsy of at least three sentinel lymph nodes. More well-designed research is needed. PROSPERO registration number: CRD42020114403.

Chemotherapy-induced nausea and vomiting: pathophysiology and therapeutic principles.

Chemotherapy-induced nausea and vomiting (CINV) is a major determinant of quality of life in cancer patients. In addition, the perceptions that oncology professionals have about CINV quite often do not coincide with reality. Antineoplastic agents and their combinations can be categorised according to their emetogenic level, and this categorisation is helpful for classifying the severity of CINV and treating it. All CINV treatment guidelines emphasise the need to administer prophylaxis to patients who receive highly or moderately emetogenic chemotherapy. With the introduction of NK1 receptor antagonists, the control of acute and delayed CINV after highly or moderately emetogenic chemotherapy schedules has improved in the great majority of patients. NK1 receptor antagonists have been demonstrated to improve the control of CINV in all risk subgroups of patients.

Classical markers like ER and ki-67, but also survivin and pERK, could be involved in the pathological response to gemcitabine, adriamycin and paclitaxel (GAT) in locally advanced breast cancer patients: results from the GEICAM/2002-01 phase II study.

INTRODUCTION: The identification and validation of biomarkers of chemotherapy sensitivity is critical in order to individualise therapy in breast cancer. We evaluated pathological complete response (pCR) to GAT, and its correlation with tumour biomarkers before and after neoadjuvant chemotherapy. MATERIALS AND METHODS: Stage III (and stage II with T≥5 cm) breast cancer patients were included. Treatment consisted of adriamycin (40 mg/m(2)) day 1, and paclitaxel (150 mg/ m(2)) followed by gemcitabine (2000 mg/m(2)) day 2, every 14 days for six cycles. Tissue from pre-treatment biopsy and surgery was evaluated for biologic markers by immunohistochemistry. Two XPD single nucleotide polymorphisms (SNP) were also analysed. RESULTS: Forty-six patients entered the trial. Median age was 49.5 years (range 31-72); 25 patients (54%) were pre-menopausal; 12 (26%) were ER-PgR-negative; pCR was observed in 17% (95% CI: 6.4-28.4) of patients. Significant differences in marker expression (mean±SD) in correlation to pathological response were only found in Ki- 67. After treatment, tumours showed lower Ki-67-, surviving- and pERK-positive cells. No correlation between XPD polymorphisms and pCR was found. The overall response rate was 89% (95% CI: 80.1-98.1). Fifteen patients (33%) underwent breast-conserving surgery. The most frequent grade 3 or 4 toxicities were neutropenia (with one febrile neutropenia) and asthenia. CONCLUSION: These results show an effective regimen with acceptable tolerability. Our data suggest that not only classical markers (ER, Ki-67), but also survivin and pERK could be involved in the response to GAT, which may contribute to therapy individualisation in future study designs.

Phase I/II docetaxel plus concurrent hyperfractionated radiotherapy in locally advanced unresectable head and neck cancer (TAX.ES1.102 study).

INTRODUCTION: Concurrent chemotherapy and radiotherapy is recommended for the treatment of locally advanced unresectable head and neck (H&N) cancer. OBJECTIVE: The primary purpose of the Phase I part of the study was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose (RD) of docetaxel with hyperfractionation radiotherapy. The primary objective of the Phase II part was to determine the response rate to the RD of treatment and, secondarily, to assess the toxicity of the schedule, time to progression, duration of response and overall survival (OS). MATERIALS AND METHODS: Patients (n=9 in Phase I; n=19 in Phase II) had unresectable H&N cancer. The starting docetaxel dose was 20 mg/m(2) plus hyperfractionated radiotherapy. Ramping of docetaxel was 5 mg/m(2) if MTD was not reached. RESULTS: MTD of docetaxel was 20 mg/m(2). Limiting toxicities were grade 4 pneumonia and grade 4 mucositis. The RD was 15 mg/m(2). Phase II initial response was 76% (CR=18%; PR=9%); updated response was 89% (CR=59%; PR=29%). The median progression-free survival was 7.8 months (95%CI: 0-22.3) and the median OS was 15.1 months (95%CI: 0-35.9). Grade 3-4 toxicities included mucositis (91%), pneumonia (27%) and fatigue (27%). There were 5 toxic deaths (2 from intestinal perforation, 3 from pneumonia). CONCLUSIONS: Weekly docetaxel+hyperfractionation radiotherapy is active but with high toxicity rates and, hence, this treatment regimen would be difficult to justify.

Biweekly vinorelbine and tegafur/uracil in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: GEICAM 2000-02 phase II study.

INTRODUCTION: To assess the efficacy and safety profile of biweekly vinorelbine and tegafur/uracil (UFT) as treatment in patients with metastatic breast cancer previously treated with anthracyclines and taxanes. PATIENTS AND METHODS: Patients with histologically confirmed breast cancer, measurable disease, no more than one prior chemotherapy regimen for metastatic disease, an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and adequate bone marrow, renal and liver function were eligible. Patients received vinorelbine (30 mg/m(2) on day 1) and UFT (250 mg/m(2) daily) every two weeks for 12 cycles unless progression or unacceptable toxicity was observed. RESULTS: Thirty-seven patients were included and received 311 cycles of chemotherapy. Efficacy and toxicity analyses were carried out on an intention-to-treat basis. The overall response rate was 35% (95% CI: 20-53). With a median follow-up of 18.6 months (95% CI: 1.0-74.3), the median time to progression was 7.0 months (96% CI: 5.2-8.9) and the median overall survival was 19.4 months (95% CI: 11.1-27.8). The most common severe toxicities were neutropenia (38% of patients) and asthenia (11% of patients). CONCLUSION: The combination of biweekly vinorelbine and UFT in patients with metastatic breast cancer pretreated with anthracyclines and taxanes is a well tolerated and effective regimen. AEMPS Trial Registration No.: 00-0534.

Diagnosis and medical treatment of breast cancer. Cordoba Consensus of 2007.

Many important studies have changed the perspective from which breast cancer is approached, and they may change what have to date been the standards applicable to the diagnosis and treatment of breast cancer. In 2007, just over 200 oncologists from all over Spain met in Cordoba in order to review the latest evidence related to breast cancer and reach a consensus on the most important aspects of its diagnosis and treatment in different clinical situations: neoadjuvance, adjuvance and advanced disease. In view of these important changes, opinions on some specific aspects may be varied and all are justified. This document represents a review of the current state of the evidence.

Serum endostatin and bFGF as predictive factors in advanced breast cancer patients treated with letrozole.

INTRODUCTION: To investigate the value of baseline serum levels of VEGF, bFGF, endostatin and their ratio as predictive factors of response to endocrine therapy in patients with metastatic breast cancer (MBC) and positive ER treated with letrozole after tamoxifen failure. MATERIALS AND METHOD: The serum levels of endostatin, VEGF and bFGF were determined in postmenopausal patients with progressing MBC from serum samples obtained before initiation of letrozole. The relation between serum angiogenic factor levels and TTP was investigated. RESULTS: Seventy-six patients (45.2%) presented a high endostatin level (> 24.6 ng/ml), 40% low bFGF levels (0 pg/ml) and 50.4% low VEGF (=/< 187 ng/ml). With a median follow-up of 22 months, the median TTP was 12.3 months. Median TTP was worse in patients with high endostatin concentration as well as in the low bFGF group, but was not affected when VEGF was considered. When the two factors were combined, the median TTP of patients with endostatin > 24.6 ng/ml and bFGF equal 0 pg/ml was 9.5 months versus 19.5 months in patients with endostatin =/< 24.6 ng/ml and bFGF > 0 pg/ml. CONCLUSIONS: The baseline levels of bFGF and endostatin are predictive factors of efficacy in patients with MBC treated with letrozole and can select groups with different TTP.