Papers by Francesco Boccardo
Journal of Oncology, 2020
Despite chemotherapy and novel androgen-receptor signalling inhibitors (ARSi) have been approved ... more Despite chemotherapy and novel androgen-receptor signalling inhibitors (ARSi) have been approved during the last decades, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with poor clinical outcomes. Several studies found that germline or acquired DNA damage repair (DDR) defects affect a high percentage of mCRPC patients. Among DDR defects, BRCA mutations show relevant clinical implications. BRCA mutations are associated with adverse clinical features in primary tumors and with poor outcomes in patients with mCRPC. In addition, BRCA mutations predict good response to poly-ADP ribose polymerase (PARP) inhibitors, such as olaparib, rucaparib, and niraparib. However, concerns still remain on the role of extensive mutational testing in prostate cancer patients, given the implications for patients and for their progeny. The present comprehensive review attempts to provide an overview of BRCA mutations in prostate cancer, focusing on their prognostic and pr...
Expert Opinion on Orphan Drugs, 2015
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Cancers, Oct 3, 2020
In randomized trials, both chemotherapy and androgen-receptor signaling inhibitors provided signi... more In randomized trials, both chemotherapy and androgen-receptor signaling inhibitors provided significant survival benefits in patients with metastatic prostate cancer (mPCa). However, it is largely unknown to what extent these therapeutic advances have impacted the general, real-world survival of patients with de novo mPCa. Here, we analyzed more than 26,000 patients included in the U.S. Surveillance, Epidemiology, and End Results (SEER) database to describe potential recent improvements in overall and cancer-specific survival. We found that patients diagnosed in the latest years showed a modest reduction in the risk of death and cancer-specific death, compared with those diagnosed in 2000-2003 and 2004-2010. Although our analysis was not adjusted for many confounders, the overall population of patients diagnosed in 2011-2014 only showed a survival gain of 4 months. Patients' ineligibility or refusal of anticancer treatments, insurance issues, intrinsic disease aggressiveness, or prior unavailability of drugs in a hormone-sensitive setting might contribute to these disappointing results.
Clinical Genitourinary Cancer, 2016
Tumori
Metronomic chemotherapy refers to the administration of low doses of cytotoxic agents over a prol... more Metronomic chemotherapy refers to the administration of low doses of cytotoxic agents over a prolonged period of time with no or only short drug-free intervals. It is designed to overcome acquired tumor resistance to chemotherapy and reduce neo-angiogenesis despite a lower toxicity than with standard chemotherapy. The role of metronomic chemotherapy remains controversial, and its optimal therapeutic use has not yet been defined. The present survey was designed as a short questionnaire and was sent to the medical oncologists registered with Medikey, a national database listing all the Italian oncology specialists linked with the Italian Council of Medical Oncology Hospital Consultants (Collegio Italiano Primari Oncologi Medici Ospedalieri, CIPOMO) and the Italian Association of Medical Oncology (Associazione Italiana di Oncologia Medica, AIOM). The questionnaire was completed on a voluntary basis and it was totally anonymous. The questionnaire was sent to 3,289 oncologists, and 191 (...
Oncology, 2008
Background: Abnormal epidermal growth factor receptor expression and pre-clinical data prompted u... more Background: Abnormal epidermal growth factor receptor expression and pre-clinical data prompted us to investigate the activity of gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, in hormone-refractory prostate cancer. Methods: Eighty-two patients were randomly assigned to receive prednisone plus gefitinib (pG; n = 44) or prednisone plus placebo (ppl; n = 38). On progression, patients initially assigned to placebo were offered the possibility to receive gefitinib. Best prostate-specific antigen response was the primary endpoint. Results: At a median follow-up time of 29.0 months (26.0–32.0), 77 patients progressed and 51 died. Prostate-specific antigen response was recorded in 6/38 (15.8%; 95% CI 4.2–27.4) and in 5/44 (11.4%; 95% CI 2.0–20.8) patients in pG and ppl groups, respectively. There was no difference between groups in time to progression (median pG 4.0 months, range 3.5–4.5; median ppl 4.5 months, range 3.5–5.0) and survival (median pG 26.5...
Annals of Oncology, 2008
Advance directives, acceleration of death, euthanasia and 'life-sustaining treatment&... more Advance directives, acceleration of death, euthanasia and 'life-sustaining treatment' have sparked much heated debate among the media, the public, doctors and political leaders. We evaluate the personal opinions of Italian Association of Medical Oncology (AIOM) members. A 30-item questionnaire was developed and delivered to all 1,832 AIOM members. Six-hundred and eighty-five (37%) oncologists completed and returned the questionnaires. Sixty-three per cent felt culturally and psychologically prepared to face these issues. Fifty-four per cent believed that what had been decided while the patient enjoyed good health is no longer applicable in an advanced state of terminal illness. Thirty-nine per cent believed that doctors should abide by these directives, while 49% believed that this should be discussed on a case-by-case basis. Fourteen per cent of oncologists were favourable towards euthanasia and 42% only in particular circumstances. Fifty-six per cent had received at least one request for accelerating death: 15% consented, 50% discussed it with the patient and 31% refused. Advance directives, euthanasia, accelerated death and life-sustaining treatment represent considerable challenges for Italian oncologists. Although prepared to face these issues, AIOM members ask for a debate within the medical world and for a shared judicial regulation.
Translational Cancer Research, 2017
Approximately 70% of breast cancers (BC) are classified as hormone receptor-positive (HRpositive)... more Approximately 70% of breast cancers (BC) are classified as hormone receptor-positive (HRpositive), comprising those expressing estrogen receptors and/or progesterone receptors. BC deaths are ultimately caused by metastatic disease. In this setting, although estrogen pathway blockade is an initially highly effective therapy, virtually all patients will develop resistance to endocrine therapy (de novo or acquired). Further understanding of the underlying mechanisms related to endocrine therapy resistance is vital and can ultimately lead to new therapies for this population. Recently, cyclin-dependent kinase (CDK) 4/6 inhibitors have emerged as one of the most important groups of drugs that synergize with endocrine therapy. In this perspective article we will discuss the recent data from the phase III MONALEESA-2 trial, which evaluated the addition of ribociclib with letrozole in the first line of treatment for patients with advanced HR-positive BC, and we will put the results in context with clinical data of other CDK 4/6 inhibitors. In addition, we will discuss future directions in the field.
Journal of Clinical Oncology, 2001
PURPOSE: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonist... more PURPOSE: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. PATIENTS AND METHODS: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tamoxifen were identified. Meta-analytic techniques were used to analyze individual patient data from these trials. RESULTS: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank tes...
Journal of Thoracic Oncology, 2015
Letters to the Editor FIGURE 1. A, Computed tomography (CT)-scan showing left lower pleural effus... more Letters to the Editor FIGURE 1. A, Computed tomography (CT)-scan showing left lower pleural effusion at baseline, although no measureable lesions were reported. B, CT-scan during gefitinib treatment revealed a progressive increase of the sub-centimetric nodules and increase pleural effusion.
Cancer research, Jan 15, 1993
We studied the effect of fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)], a synthetic analogu... more We studied the effect of fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)], a synthetic analogue of retinoic acid, on plasma insulin-like growth factor I (IGF-I) levels in a consecutive cohort of stage I breast cancer patients belonging to a randomized phase III trial of breast cancer chemoprevention. Thirty-two women receiving 4-HPR 200 mg/daily and 28 untreated controls entered the study. IGF-I levels were determined after acid-ethanol extraction, on plasma obtained at randomization and after a mean time of 10.8 +/- 0.3 months. At baseline, there was no difference in IGF-I levels between the two groups [152.9 +/- 9.4 versus 159.2 +/- 7.0 ng/ml in treated and control group (P = 0.59), respectively]. After follow-up time, while plasma IGF-I levels were unchanged in control patients (163.3 +/- 7.4 ng/ml; P = 0.5), they were significantly reduced to 134.6 +/- 8.1 ng/ml in the patients treated with 4-HPR (P = 0.003 and P = 0.011 versus baseline and control values, respectively). Mult...
Anticancer research
Solid tumors develop resistance to retinoids during carcinogenesis. One of the strategies to over... more Solid tumors develop resistance to retinoids during carcinogenesis. One of the strategies to overcome this resistance may include the combination of these molecules with other differentiating, cytotoxic or chromatin-remodelling agents. We analysed the anti-proliferative activity of two histone-deacetylase inhibitors (HDACIs), Trichostatin A (TSA) and sodium phenylbutyrate (PB), alone or combined with retinoids, all-trans retinoic acid (ATRA) and Ro 41-5253, on two human breast cancer cell lines: the hormone-dependent MCF-7 and the hormone-independent MDA-MB-231. These lines responded differently to retinoids: MCF-7 were sensitive, whilst MDA-MB-231 were rather resistant. When the retinoids were combined with HDACIs, these molecules potentiated the retinoid activity on growth inhibition, especially for the association Ro 41-5253 and TSA. By FACS analysis, we observed that the anti-proliferative effects were only partially due to pro-apopotic mechanisms, suggesting a cell-cycle block....
Anticancer research
Angiosarcoma of the breast is a malignant tumour of vascular endothelial cells. It is a rare and ... more Angiosarcoma of the breast is a malignant tumour of vascular endothelial cells. It is a rare and difficult tumour to treat. The authors report a case of cutaneous radiation-associated angiosarcoma treated with paclitaxel chemotherapy. A few days after drug administration, bleeding of skin lesions was observed and the patient died.
Oncology Reports, 2006
The process of carcinogenesis is characterized by definite changes in the protein composition of ... more The process of carcinogenesis is characterized by definite changes in the protein composition of the nuclear matrix. We have recently found that lamins form, in addition to the nuclear lamina, an intranuclear web of thin fibrils. This finding prompted us to address the question of whether changes in the expression of lamins occur in the course of tumor development. In prostate cancer, lamin B undergoes a significant increase; interestingly, its nuclear content strongly correlates with tumor differentiation. Moreover, all the lamins show reproducible alterations in the distribution of the isoelectric variants, suggesting that dephosphorylation events could trigger changes in the pattern of gene expression by inducing structural rearrangements of the nuclear scaffold.
The Lancet Oncology, 2006
The Lancet, 1996
The aim of the paper is clearly stated under the heading of background as "to find out whether th... more The aim of the paper is clearly stated under the heading of background as "to find out whether the benefit of adding chemotherapy to tamoxifen outweighs its cost in terms of toxic effects for postmenopausal patients. This is a reasonable question to ask. In the context of good palliation, the null result is still of value.
Journal of Proteomics, 2013
Gross cystic disease (GCDB) is a breast benign condition predisposing to breast cancer. Cryoprese... more Gross cystic disease (GCDB) is a breast benign condition predisposing to breast cancer. Cryopreserved sera from GCDB patients, some of whom later developed a cancer (cases), were studied to identify potential risk markers. A MALDI-TOF mass spectrometry analysis found several complement C3f fragments having a significant increased abundance in cases compared to controls. After multivariate analysis, the full-length form of C3f maintained a predictive value of breast cancer risk. Higher levels of C3f in the serum of women affected by a benign condition like GCDB thus appears to be correlated to the development of breast cancer even 20 years later. Biological significance Increased complement system activation has been found in the sera of women affected by GCDB who developed a breast cancer, even twenty or more years later. C3f may predict an increased breast cancer risk in the healthy population and in women affected by predisposing conditions.
Journal of Clinical Oncology, 2010
Purpose To conduct meta-analyses of randomized trials of aromatase inhibitors (AIs) compared with... more Purpose To conduct meta-analyses of randomized trials of aromatase inhibitors (AIs) compared with tamoxifen either as initial monotherapy (cohort 1) or after 2 to 3 years of tamoxifen (cohort 2). Materials and Methods Data submitted to the Early Breast Cancer Trialists' Collaborative Group were used in separate meta-analyses of two cohorts. Primary analyses involve postmenopausal women with tumors reported to be estrogen receptor positive. Log-rank P values are two-sided. Results Cohort 1 comprised 9,856 patients with a mean of 5.8 years of follow-up. At 5 years, AI therapy was associated with an absolute 2.9% (SE = 0.7%) decrease in recurrence (9.6% for AI v 12.6% for tamoxifen; 2P < .00001) and a nonsignificant absolute 1.1% (SE = 0.5%) decrease in breast cancer mortality (4.8% for AI v 5.9% for tamoxifen; 2P = .1). Cohort 2 comprised 9,015 patients with a mean of 3.9 years of follow-up. At 3 years from treatment divergence (ie, approximately 5 years after starting hormonal...
Acta Endocrinologica, 1993
The claimed ability of non-steroidal antiandrogens to preserve libido and sexual potency is sough... more The claimed ability of non-steroidal antiandrogens to preserve libido and sexual potency is sought as a potential improvement in the palliative management of prostate cancer. A critical issue for the clinical use of these compounds is, however, the reported evidence in the rat of an excessive increase in testosterone concentrations as a consequence of the androgen negative feedback interruption. On the other hand, the recovery of testicular function after long-term inhibition by luteinizing hormone-releasing hormone (LHRH) analogs is also an important concern in view of the proposed use of these compounds for the treatment of several non-malignant conditions. We addressed these issues by studying the long-term endocrine effects induced by the administration of either the non-steroidal antiandrogen nilutamide or the depot preparation of d-Trp6-LHRH in men with prostate cancer. Treatment with the antiandrogen induced a marked increase in gonadotropin levels, LH concentrations rising f...
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Papers by Francesco Boccardo