Pathological complete response following cisplatin or carboplatin-based neoadjuvant chemotherapy for triple-negative breast cancer: A systematic review and meta-analysis.

The addition of platinum compounds to standard neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) is highly controversial. Platinum agents, such as cisplatin and carboplatin, are DNA-damaging agents which exhibit activity in breast cancer, particularly in the TNBC subgroup. In order to assess the efficacy of each most representative platinum agent (cisplatin and carboplatin) in patients with TNBC treated with NACT, the present study performed a systematic review and meta-analysis of all available published studies on TNBC. A search of PubMed was performed to identify studies that investigated platinum-based NACT in patients with TNBC. The primary endpoints were the pooled rate of the pathological complete response (pCR) between cisplatin vs. carboplatin-based NACT. A total of 24 studies were selected (17 studies for carboplatin and 6 studies for cisplatin and 1 study with both carboplatin and cisplatin, with 20 prospective studies) for the analysis of 1,711 patients with TNBC. Overall, the pooled rate of pCR in patients treated with platinum-based NACT was 48%. No significant differences were observed between the rates of pCR obtained under carboplatin vs cisplatin treatment. The carboplatin pCR rate was 0.470 [95% confidence interval (CI), 0.401-0.539], while the cisplatin pCR rate was 0.473 (95% CI, 0.379-0.568). The comparison between these two categories revealed no significant differences (P=0.959). In the whole, the present study demonstrates that neoadjuvant platinum-based chemotherapy improves the pCR rate in patients with TNBC, regardless of the platinum agent used. Carboplatin may thus represent a viable option due to its more favorable toxicity profile.

Follow-up protocol for oncological patients at risk of developing multiple primary neoplasms.

PURPOSE: Multiple primary neoplasms (MPN) have a growing impact in the outcome of oncological patients given the rising incidence of these entities in daily practice. The early diagnosis of secondary tumors could translate into better survival of patients with MPN. The final objective of this study was the elaboration of a follow-up protocol for oncological patients at risk of developing multiple primary neoplasms. METHODS: Patients with MPN diagnosed and treated in the Oncology Institute "Prof.Dr.Ion Chiricuta" Cluj-Napoca (OICN) between 2008-2012 were included in this nonrandomized, retrospective study and the clinicopathological characteristics of these patients and the prognostic factors possibly involved in the occurrence of MPN were analyzed. RESULTS: 278 patients with MPN were included in this study. The median age at diagnosis was 60 years. The median interval between the diagnosis of the primary and secondary neoplasm was 30.98 months. Smoking and alcohol consumption were the most frequent environmental factors observed in patients with MPN. Patients diagnosed with breast cancers, head and neck cancers, colorectal cancer, prostate cancer, ovarian cancer or uterine body cancer were the patients with the highest risk of developing MPN. CONCLUSION: This first follow-up protocol for oncological patients at risk of developing multiple primary neoplasms could be implemented in daily practice with further validation of the protocol.

The impact of multiple primary neoplasms in daily practicea systematic review of the literature.

Multiple primary neoplasms (MPN) represent particular entities with growing impact in our daily practice due to their increasing incidence and implications in the treatment and outcome of oncological patients. MPN have a specific deffinition and can be classified as synchronous or metachronous depending on the time of diagnosis of the first and latter malignancies. We review in this article the possible risk factors involved in the etiology of MPN, the most frequent cancer associations, the incidence of synchronous and metachronous tumors, the stage at diagnosis, the treatment administered to the patients with MPN and the survival of patients with MPN.

Clinicopathological characteristics of patients with multiple primary neoplasms-a retrospective analysis.

PURPOSE: Multiple primary neoplasms (MPN) represent the occurrence of two or more primary neoplasms in the same individual during lifetime and today there is an increased interest in studying the implications of MPN in the outcome of oncological patients. In this study we aimed to evaluate the clinicopathological characteristics of patients with MPN. METHODS: In this nonrandomized, retrospective study patients with MPN treated in the Oncology Institute "Prof.Dr.Ion Chiricuta" Cluj-Napoca between 2008-2012 were included. Data were collected from the medical charts. RESULTS: 278 patients with MPN were treated in our institute between 2008-2012: 120 patients with synchronous tumors and 158 with metachronous tumors. Of them, 260 patients presented with two MPN and 13 with three MPN. Fifty four percent (n=151) of the patients were females and 127 (46%) males, with a median age at diagnosis of 60 years. Most patients presented with early stage tumors, both for the initial primary tumor (54%) and for the second tumor (55%). The most frequent initial primary tumors were breast, head and neck, colorectal, ovarian, prostate and uterine body cancers and the most frequent second tumors were breast, colorectal, uterine body, head and neck, lung and thyroid cancers. Five-year survival was higher for patients with metachronous tumors (68%) compared with patients with synchronous tumors (54%; p=0.02). CONCLUSION: MPN represent a real challenge in daily practice and their occurrence should not be overlooked. Lack of solid data from the literature makes it difficult to establish which patients are at risk for developing multiple neoplasms and should be closely followed up.

The androgen receptor remains a key player in metastatic hormone-refractory prostate cancer. Implications for new treatments.

Metastatic castration-resistant prostate cancer (mCRPC) shows a number of adaptive mechanisms that facilitate continued androgen receptor (AR) dependent tumor growth. In this article we reviewed the subsequent hormonal manipulation in mCRPC, including the recently approved new drugs, in relation to the AR dependent and independent growth mechanisms. Maintaining castrate levels of testosterone is mandatory. The AR amplification, a process that can occur within the hypersensitive AR escape route, can be fought by using high dose antiandrogen (bicalutamide 150mg), change in antiandrogen preparation or the use of enzalutamide. Switch to another antiandrogen, the use of LHRH antagonists, change to another LHRH agonist, bilateral orchidectomy, adrenals' inhibition and the blockade of intratumor testosterone synthesis are several ways to counter the increased AR sensitivity. Increased androgen levels can be reduced by the use of ketoconazole, dexamethasone, abiraterone acetate or 5α-reductase inhibitors. Antiandrogen withdrawal and enzalutamide can be used to counter the promiscuous AR escape route. The use of metformin, cetuximab or cabozantinib could represent ways to overcome the outlaw pathway, but further studies are needed to show the efficacy of these drugs in mCRPC. Bcl-2 inhibitors, emerging drugs still in experimental phase, show great potential in counteracting the bypass pathway. Docetaxel and cabazitaxel, the standard chemotherapy of mCRPC, are the treatment of choice when androgen-independent prostate cancer cells are selected (as supported by the lurker cell pathway).The correct and rational use of all these drugs may delay by months or even years the need to administer chemotherapy in patients with mCRPC but some AR targeted therapies may impair the subsequent response to chemotherapy.