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43 results on '"Di Rella, F."'

1. Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients

Author

Gravina, A., Gargiulo, P., De Laurentiis, M., Arenare, L., De Placido, S., Orditura, M., Cinieri, S., Riccardi, F., Ribecco, A.S., Putzu, C., Del Mastro, L., Rossi, E., Ciardiello, F., Di Rella, F., Nuzzo, F., Pacilio, C., Caputo, R., Cianniello, D., Forestieri, V., Giuliano, M., Arpino, G., Orlando, L., Mocerino, C., Schettino, C., Piccirillo, M.C., Gallo, C., and Perrone, F.

Published
2025
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2. Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial

Author

Perrone, F., Nuzzo, F., Di Rella, F., Gravina, A., Iodice, G., Labonia, V., Landi, G., Pacilio, C., Rossi, E., De Laurentiis, M., D'Aiuto, M., Botti, G., Forestieri, V., Lauria, R., De Placido, S., Tinessa, V., Daniele, B., Gori, S., Colantuoni, G., Barni, S., Riccardi, F., De Maio, E., Montanino, A., Morabito, A., Daniele, G., Di Maio, M., Piccirillo, M.C., Signoriello, S., Gallo, C., and de Matteis, A.

Published
2015
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6. Correction: The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: A systematic review and meta-analysis (Reproductive Biology and Endocrinology (2019) 17:18 DOI: 10.1186/s12958-019-0460-4)

Author

Conforti A., Esteves S. C., Di Rella F., Strina I., De Rosa P., Fiorenza A., Zullo F., De Placido G., Alviggi C., Conforti, A., Esteves, S. C., Di Rella, F., Strina, I., De Rosa, P., Fiorenza, A., Zullo, F., De Placido, G., and Alviggi, C.

Abstract

Following publication of the original article [1], the authors would like to apologize for an error in Fig. 2 describing clinical pregnancy rate comparison between treatment arms. The authors would like to reassure the readers that this minor type error does not affect any other content and the main findings of the article. The correct figure is presented below.

Published
2019

7. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, Zoboli, A, De Placido S., Gallo C., De Laurentiis M., Bisagni G., Arpino G., Sarobba M. G., Riccardi F., Russo A., Del Mastro L., Cogoni A. A., Cognetti F., Gori S., Foglietta J., Frassoldati A., Amoroso D., Laudadio L., Moscetti L., Montemurro F., Verusio C., Bernardo A., Lorusso V., Gravina A., Moretti G., Lauria R., Lai A., Mocerino C., Rizzo S., Nuzzo F., Carlini P., Perrone F., Accurso A., Agostara B., Aieta M., Alabiso O., Alicicco M. G., Amadori D., Amaducci L., Amiconi G., Antuzzi G., Ardine M., Ardizzoia A., Aversa C., Badalamenti G., Barni S., Basurto C., Berardi R., Bergamasco C., Bidoli P., Bighin C., Biondi E., Boni C., Borgonovo K., Botta M., Bravi S., Bruzzi P., Buono G., Butera A., Caldara A., Candeloro G., Cappelletti C., Cardalesi C., Carfora E., Cariello A., Carrozza F., Carteni G., Caruso M., Casadei V., Casanova C., Castori L., Cavanna L., Cavazzini G., Cazzaniga M., Chilelli M., Chiodini P., Chiorrini S., Ciardiello F., Ciccarese M., Cinieri S., Clerico M., Coccaro M., Comande M., Corbo C., Cortino G., Cusenza S., Daniele G., D'arco A. M., D'auria G., Dazzi C., De Angelis C., de Braud F., De Feo G., De Matteis A., De Tursi M., Di Blasio A., di Lucca G., Di Lullo L., Di Rella F., Di Renzo G., Di Stefano P., Di Stefano A., Diana A., Donati S., Fabbri A., Fabi A., Faedi M., Farina G., Farris A., Febbraro A., Fedele P., Federico P., Ferrau F., Ferretti G., Ferro A., Floriani I., Forcignano R., Forciniti S., Forestieri V., Fornari G., Frisinghelli M., Fusco V., Gallizzi G., Galvano A., Gambardella A., Gambi A., Gebbia V., Gervasi E., Ghilardi M., Giacobino A., Giardina G., Giotta F., Giraudi S., Giuliano M., Grassadonia A., Grasso D., Grosso F., Guizzaro L., Incoronato P., Incorvaia L., Iodice G., La Verde N., Labonia V., Landi G., Latorre A., Leonardi V., Levaggi A., Limite G., Lina Bascialla L., Livi L., Maiello E., Mandelli D., Marcon I., Menon D., Montedoro M., Moraca L., Moretti A., Morritti M. G., Morselli P., Mura A., Mura S., Musacchio M., Muzio A., Natale D., Natoli C., Nigro C., Nistico C., Nuzzo A., Orditura M., Orlando L., Pacilio C., Palumbo G., Palumbo R., Pasini F., Paterno E., Pazzola A., Pelliccioni S., Pensabene M., Perroni D., Pesenti Gritti A., Petrelli F., Piccirillo M. C., Pinotti G., Pogliani C., Poli D., Prader S., Recchia F., Rizzi D., Romano C., Rossello R., Rossini C., Salvucci G., Sanna V., Santini A., Saracchini S., Savastano C., Scambia G., Schettini F., Schiavone P., Schirone A., Seles E., Signoriello S., Signoriello G., Silva R. R., Silvestri A., Simeon V., Spagnoletti I., Tamberi S., Teragni C., Thalmann V., Thomas R., Thomas G., Tienghi A., Tinari N., Tinessa V., Tomei F., Tonini G., Torri V., Traficante D., Tudini M., Turazza M., Vignoli R., Vitale M. G., Zacchia A., Zagarese P., Zanni A., Zavallone L., Zavettieri M., Zoboli A., De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, Zoboli, A, De Placido S., Gallo C., De Laurentiis M., Bisagni G., Arpino G., Sarobba M. G., Riccardi F., Russo A., Del Mastro L., Cogoni A. A., Cognetti F., Gori S., Foglietta J., Frassoldati A., Amoroso D., Laudadio L., Moscetti L., Montemurro F., Verusio C., Bernardo A., Lorusso V., Gravina A., Moretti G., Lauria R., Lai A., Mocerino C., Rizzo S., Nuzzo F., Carlini P., Perrone F., Accurso A., Agostara B., Aieta M., Alabiso O., Alicicco M. G., Amadori D., Amaducci L., Amiconi G., Antuzzi G., Ardine M., Ardizzoia A., Aversa C., Badalamenti G., Barni S., Basurto C., Berardi R., Bergamasco C., Bidoli P., Bighin C., Biondi E., Boni C., Borgonovo K., Botta M., Bravi S., Bruzzi P., Buono G., Butera A., Caldara A., Candeloro G., Cappelletti C., Cardalesi C., Carfora E., Cariello A., Carrozza F., Carteni G., Caruso M., Casadei V., Casanova C., Castori L., Cavanna L., Cavazzini G., Cazzaniga M., Chilelli M., Chiodini P., Chiorrini S., Ciardiello F., Ciccarese M., Cinieri S., Clerico M., Coccaro M., Comande M., Corbo C., Cortino G., Cusenza S., Daniele G., D'arco A. M., D'auria G., Dazzi C., De Angelis C., de Braud F., De Feo G., De Matteis A., De Tursi M., Di Blasio A., di Lucca G., Di Lullo L., Di Rella F., Di Renzo G., Di Stefano P., Di Stefano A., Diana A., Donati S., Fabbri A., Fabi A., Faedi M., Farina G., Farris A., Febbraro A., Fedele P., Federico P., Ferrau F., Ferretti G., Ferro A., Floriani I., Forcignano R., Forciniti S., Forestieri V., Fornari G., Frisinghelli M., Fusco V., Gallizzi G., Galvano A., Gambardella A., Gambi A., Gebbia V., Gervasi E., Ghilardi M., Giacobino A., Giardina G., Giotta F., Giraudi S., Giuliano M., Grassadonia A., Grasso D., Grosso F., Guizzaro L., Incoronato P., Incorvaia L., Iodice G., La Verde N., Labonia V., Landi G., Latorre A., Leonardi V., Levaggi A., Limite G., Lina Bascialla L., Livi L., Maiello E., Mandelli D., Marcon I., Menon D., Montedoro M., Moraca L., Moretti A., Morritti M. G., Morselli P., Mura A., Mura S., Musacchio M., Muzio A., Natale D., Natoli C., Nigro C., Nistico C., Nuzzo A., Orditura M., Orlando L., Pacilio C., Palumbo G., Palumbo R., Pasini F., Paterno E., Pazzola A., Pelliccioni S., Pensabene M., Perroni D., Pesenti Gritti A., Petrelli F., Piccirillo M. C., Pinotti G., Pogliani C., Poli D., Prader S., Recchia F., Rizzi D., Romano C., Rossello R., Rossini C., Salvucci G., Sanna V., Santini A., Saracchini S., Savastano C., Scambia G., Schettini F., Schiavone P., Schirone A., Seles E., Signoriello S., Signoriello G., Silva R. R., Silvestri A., Simeon V., Spagnoletti I., Tamberi S., Teragni C., Thalmann V., Thomas R., Thomas G., Tienghi A., Tinari N., Tinessa V., Tomei F., Tonini G., Torri V., Traficante D., Tudini M., Turazza M., Vignoli R., Vitale M. G., Zacchia A., Zagarese P., Zanni A., Zavallone L., Zavettieri M., and Zoboli A.

Abstract

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is regist

Published
2018

8. The cyto-protective effects of LH on ovarian reserve and female fertility during exposure to gonadotoxic alkylating agents in an adult mouse model.

Author

Castillo, L M Del, Buigues, A, Rossi, V, Soriano, M J, Martinez, J, Felici, M De, Lamsira, H K, Rella, F Di, Klinger, F G, Pellicer, A, Herraiz, S, Del Castillo, L M, De Felici, M, and Di Rella, F

Subjects
OVARIAN reserve, OVARIES, LABORATORY mice, ALKYLATING agents, INDUCED ovulation, FERTILITY preservation, ADULTS, WARNING labels, RESEARCH, ANIMAL experimentation, RESEARCH methodology, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, RESEARCH funding, MICE
Abstract

Study Question: Does LH protect mouse oocytes and female fertility from alkylating chemotherapy?Summary Answer: LH treatment before and during chemotherapy prevents detrimental effects on follicles and reproductive lifespan.What Is Known Already: Chemotherapies can damage the ovary, resulting in premature ovarian failure and reduced fertility in cancer survivors. LH was recently suggested to protect prepubertal mouse follicles from chemotoxic effects of cisplatin treatment.Study Design, Size, Duration: This experimental study investigated LH effects on primordial follicles exposed to chemotherapy. Seven-week-old CD-1 female mice were randomly allocated to four experimental groups: Control (n = 13), chemotherapy (ChT, n = 15), ChT+LH-1x (n = 15), and ChT+LH-5x (n = 8). To induce primary ovarian insufficiency (POI), animals in the ChT and ChT+LH groups were intraperitoneally injected with 120 mg/kg of cyclophosphamide and 12 mg/kg of busulfan, while control mice received vehicle. For LH treatment, the ChT+LH-1x and ChT+LH-5x animals received a 1 or 5 IU LH dose, respectively, before chemotherapy, then a second LH injection administered with chemotherapy 24 h later. Then, two animals/group were euthanized at 12 and 24 h to investigate the early ovarian response to LH, while remaining mice were housed for 30 days to evaluate short- and long-term reproductive outcomes. The effects of LH and chemotherapy on growing-stage follicles were analyzed in a parallel experiment. Seven-week-old NOD-SCID female mice were allocated to control (n = 5), ChT (n = 5), and ChT+LH-1x (n = 6) groups. Animals were treated as described above, but maintained for 7 days before reproductive assessment.Participants/materials, Setting, Methods: In the first experiment, follicular damage (phosphorylated H2AX histone (γH2AX) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay), apoptotic biomarkers (western blot), and DNA repair pathways (western blot and RT-qPCR) were assessed in ovaries collected at 12 and 24 h to determine early ovarian responses to LH. Thirty days after treatments, remaining mice were stimulated (10 IU of pregnant mare serum gonadotropin (PMSG) and 10 IU of hCG) and mated to collect ovaries, oocytes, and embryos. Histological analysis was performed on ovarian samples to investigate follicular populations and stromal status, and meiotic spindle and chromosome alignment was measured in oocytes by confocal microscopy. Long-term effects were monitored by assessing pregnancy rate and litter size during six consecutive breeding attempts. In the second experiment, mice were stimulated and mated 7 days after treatments and ovaries, oocytes, and embryos were collected. Follicular numbers, follicular protection (DNA damage and apoptosis by H2AX staining and TUNEL assay, respectively), and ovarian stroma were assessed. Oocyte quality was determined by confocal analysis.Main Results and the Role Of Chance: LH treatment was sufficient to preserve ovarian reserve and follicular development, avoid atresia, and restore ovulation and meiotic spindle configuration in mature oocytes exposed at the primordial stage. LH improved the cumulative pregnancy rate and litter size in six consecutive breeding rounds, confirming the potential of LH treatment to preserve fertility. This protective effect appeared to be mediated by an enhanced early DNA repair response, via homologous recombination, and generation of anti-apoptotic signals in the ovary a few hours after injury with chemotherapy. This response ameliorated the chemotherapy-induced increase in DNA-damaged oocytes and apoptotic granulosa cells. LH treatment also protected growing follicles from chemotherapy. LH reversed the chemotherapy-induced depletion of primordial and primary follicular subpopulations, reduced oocyte DNA damage and granulosa cell apoptosis, restored mature oocyte cohort size, and improved meiotic spindle properties.Large Scale Data: N/A.Limitations, Reasons For Caution: This was a preliminary study performed with mouse ovarian samples. Therefore, preclinical research with human samples is required for validation.Wider Implications Of the Findings: The current study tested if LH could protect the adult mouse ovarian reserve and reproductive lifespan from alkylating chemotherapy. These findings highlight the therapeutic potential of LH as a complementary non-surgical strategy for preserving fertility in female cancer patients.Study Funding/competing Interest(s): This study was supported by grants from the Regional Valencian Ministry of Education (PROMETEO/2018/137), the Spanish Ministry of Science and Innovation (CP19/00141), and the Spanish Ministry of Education, Culture and Sports (FPU16/05264). The authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

Published
2021
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10. The HOBOE-2 multicenter randomized phase III trial in premenopausal patients with hormone-receptor positive early breast cancer comparing triptorelin plus either tamoxifen or letrozole or letrozole + zoledronic acid

Author

Perrone, F., primary, De Laurentiis, M., additional, de Placido, S., additional, Orditura, M., additional, Cinieri, S., additional, Riccardi, F., additional, Ribecco, A.S., additional, Putzu, C., additional, Del Mastro, L., additional, Rossi, E., additional, Daniele, B., additional, Mosconi, A.M., additional, Di Rella, F., additional, Landi, G., additional, Nuzzo, F., additional, Pacilio, C., additional, Lauria, R., additional, Arenare, L., additional, Piccirillo, M.C., additional, and Gallo, C., additional

Published
2018
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11. PerTe: efficacy and safety of pertuzumab in “real life setting” for the neoadjuvant treatment of HER2-positive breast cancer patients

Author

Cianniello, D., primary, Prudente, A., additional, Caputo, R., additional, Piezzo, M., additional, Riemma, M., additional, Savastano, B., additional, Cocco, S., additional, Licenziato, M., additional, De Stefano, B., additional, Di Gioia, G., additional, Fusco, G., additional, Buonfanti, G., additional, Gravina, A., additional, Landi, G., additional, Di Rella, F., additional, Pacilio, C., additional, Nuzzo, F., additional, Iodice, G., additional, De Laurentiis, M., additional, and Del Prete, S., additional

Published
2017
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12. LBA14_PR - The HOBOE-2 multicenter randomized phase III trial in premenopausal patients with hormone-receptor positive early breast cancer comparing triptorelin plus either tamoxifen or letrozole or letrozole + zoledronic acid

Author

Perrone, F., De Laurentiis, M., de Placido, S., Orditura, M., Cinieri, S., Riccardi, F., Ribecco, A.S., Putzu, C., Del Mastro, L., Rossi, E., Daniele, B., Mosconi, A.M., Di Rella, F., Landi, G., Nuzzo, F., Pacilio, C., Lauria, R., Arenare, L., Piccirillo, M.C., and Gallo, C.

Published
2018
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13. High progesterone levels during the luteal phase related to the use of an aromatase inhibitor in breast cancer patients.

Author

ALVIGGI, C., MARCI, R., VALLONE, R., CONFORTI, A., DI RELLA, F., STRINA, I., PICARELLI, S., DE ROSA, P., DE LAURENTIIS, M., ANDERSEN, C. YDING, and DE PLACIDO, G.

Abstract

To evaluate the hormonal profile in three breast cancer patients who underwent controlled ovarian stimulation in the presence of the aromatase inhibitor letrozole. PATIENTS AND METHODS: In IVF University referral center, a case series of three breast cancer patients who underwent controlled ovarian stimulation (COS) with recombinant FSH and letrozole were investigated. Ovulation was induced with hCG (case No. 1) or with GnRH agonist (case No. 2-3). The primary outcome of our study was the detection of progesterone levels in the luteal phase. RESULTS: Very high progesterone values (mean 186.6 ± 43.6 ng/mL) during the luteal phase were recorded in all three cases. CONCLUSIONS: High progesterone levels can be related to the use of letrozole independently of the most commonly used trigger regimen. Although progesterone has long been considered a protective factor against breast cancer, several studies have demonstrated that progesterone could expand a transformation-sensitive stem cell population in the mammary glands. The estrogen negative feedback effect on the hypothalamus-pituitary axis and the disruption of steroid biosynthesis and could represent an intriguing reason behind this phenomenon. Our results highlight the need to evaluate further the increase in progesterone levels in the luteal phase in women with breast cancer undergoing COS with letrozole. [ABSTRACT FROM AUTHOR]

Published
2017

14. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmela Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone, Antonello Accurso, Biagio Agostara, Michele Aieta, Oscar Alabiso, Maria Grazia Alicicco, Dino Amadori, Laura Amaducci, Gianna Amiconi, Giustino Antuzzi, Mara Ardine, Antonio Ardizzoia, Caterina Aversa, Giuseppe Badalamenti, Sandro Barni, Carlo Basurto, Rossana Berardi, Cinzia Bergamasco, Paolo Bidoli, Claudia Bighin, Edoardo Biondi, Corrado Boni, Karen Borgonovo, Mario Botta, Stefano Bravi, Paolo Bruzzi, Giuseppe Buono, Alfredo Butera, Alessia Caldara, Giampiero Candeloro, Claudia Cappelletti, Cinzia Cardalesi, Elisabetta Carfora, Anna Cariello, Francesco Carrozza, Giacomo Cartenì, Michele Caruso, Virginia Casadei, Claudia Casanova, Luigi Castori, Luigi Cavanna, Giovanna Cavazzini, Marina Cazzaniga, Mario Chilelli, Paolo Chiodini, Silvia Chiorrini, Fortunato Ciardiello, Mariangela Ciccarese, Saverio Cinieri, Mario Clerico, Mariarosa Coccaro, Mario Comande, Claudia Corbo, Giuseppina Cortino, Stefania Cusenza, Gennaro Daniele, Alfonso Maria D'arco, Giuliana D'auria, Claudio Dazzi, Carmine De Angelis, Filippo de Braud, Gianfranco De Feo, Andrea De Matteis, Michele De Tursi, Anna Di Blasio, Giuseppe di Lucca, Liberato Di Lullo, Francesca Di Rella, Gianfranco Di Renzo, Pia Di Stefano, Aida Di Stefano, Anna Diana, Sara Donati, Agnese Fabbri, Alessandra Fabi, Marina Faedi, Gabriella Farina, Antonio Farris, Antonio Febbraro, Palma Fedele, Piera Federico, Francesco Ferraù, Gianluigi Ferretti, Antonella Ferro, Irene Floriani, Rosachiara Forcignanò, Samantha Forciniti, Valeria Forestieri, Gianni Fornari, Michela Frisinghelli, Vittorio Fusco, Giulia Gallizzi, Antonio Galvano, Antonio Gambardella, Angelo Gambi, Vittorio Gebbia, Erika Gervasi, Mara Ghilardi, Alice Giacobino, Giovanni Giardina, Francesco Giotta, Sara Giraudi, Mario Giuliano, Antonino Grassadonia, Donatella Grasso, Federica Grosso, Lorenzo Guizzaro, Pasquale Incoronato, Lorena Incorvaia, Giovanni Iodice, Nicla La Verde, Vincenzo Labonia, Gabriella Landi, Agnese Latorre, Vita Leonardi, Alessia Levaggi, Gennaro Limite, Linda Lina Bascialla, Lorenzo Livi, Evaristo Maiello, Daniela Mandelli, Ilaria Marcon, Daniela Menon, Michele Montedoro, Lucia Moraca, Anna Moretti, Maria Grazia Morritti, Patrizia Morselli, Antonella Mura, Silvia Mura, Michela Musacchio, Alberto Muzio, Donato Natale, Clara Natoli, Cinzia Nigro, Cecilia Nisticò, Antonio Nuzzo, Michele Orditura, Laura Orlando, Carmen Pacilio, Giuliano Palumbo, Raffaella Palumbo, Felice Pasini, Emanuela Paterno, Antonio Pazzola, Silvia Pelliccioni, Matilde Pensabene, Davide Perroni, Angela Pesenti Gritti, Fausto Petrelli, Maria Carmela Piccirillo, Graziella Pinotti, Claudia Pogliani, Davide Poli, Sonia Prader, Francesco Recchia, Daniele Rizzi, Carmen Romano, Rosalba Rossello, Chiara Rossini, Giuseppina Salvucci, Valeria Sanna, Alessandra Santini, Silvana Saracchini, Clementina Savastano, Giovanni Scambia, Francesco Schettini, Paola Schiavone, Alessio Schirone, Elena Seles, Simona Signoriello, Giuseppe Signoriello, Rosa Rita Silva, Antonia Silvestri, Vittorio Simeon, Ilaria Spagnoletti, Stefano Tamberi, Cristina Teragni, Verena Thalmann, Renato Thomas, Guglielmo Thomas, Amelia Tienghi, Nicola Tinari, Vincenza Tinessa, Federica Tomei, Giuseppe Tonini, Valter Torri, Divina Traficante, Marianna Tudini, Monica Turazza, Roberto Vignoli, Maria Giuseppa Vitale, Alessandra Zacchia, Pasquale Zagarese, Alda Zanni, Laura Zavallone, Maria Zavettieri, Alessandra Zoboli, De Placido, S., Gallo, C., De Laurentiis, M., Bisagni, G., Arpino, G., Sarobba, M. G., Riccardi, F., Russo, A., Del Mastro, L., Cogoni, A. A., Cognetti, F., Gori, S., Foglietta, J., Frassoldati, A., Amoroso, D., Laudadio, L., Moscetti, L., Montemurro, F., Verusio, C., Bernardo, A., Lorusso, V., Gravina, A., Moretti, G., Lauria, R., Lai, A., Mocerino, C., Rizzo, S., Nuzzo, F., Carlini, P., Perrone, F., Accurso, A., Agostara, B., Aieta, M., Alabiso, O., Alicicco, M. G., Amadori, D., Amaducci, L., Amiconi, G., Antuzzi, G., Ardine, M., Ardizzoia, A., Aversa, C., Badalamenti, G., Barni, S., Basurto, C., Berardi, R., Bergamasco, C., Bidoli, P., Bighin, C., Biondi, E., Boni, C., Borgonovo, K., Botta, M., Bravi, S., Bruzzi, P., Buono, G., Butera, A., Caldara, A., Candeloro, G., Cappelletti, C., Cardalesi, C., Carfora, E., Cariello, A., Carrozza, F., Carteni, G., Caruso, M., Casadei, V., Casanova, C., Castori, L., Cavanna, L., Cavazzini, G., Cazzaniga, M., Chilelli, M., Chiodini, P., Chiorrini, S., Ciardiello, F., Ciccarese, M., Cinieri, S., Clerico, M., Coccaro, M., Comande, M., Corbo, C., Cortino, G., Cusenza, S., Daniele, G., D'Arco, A. M., D'Auria, G., Dazzi, C., De Angelis, C., de Braud, F., De Feo, G., De Matteis, Ma., De Tursi, M., Di Blasio, A., di Lucca, G., Di Lullo, L., Di Rella, F., Di Renzo, G., Di Stefano, P., Di Stefano, A., Diana, A., Donati, S., Fabbri, A., Fabi, A., Faedi, M., Farina, G., Farris, A., Febbraro, A., Fedele, P., Federico, P., Ferrau, F., Ferretti, G., Ferro, A., Floriani, I., Forcignano, R., Forciniti, S., Forestieri, V., Fornari, G., Frisinghelli, M., Fusco, V., Gallizzi, G., Galvano, A., Gambardella, A., Gambi, A., Gebbia, V., Gervasi, E., Ghilardi, M., Giacobino, A., Giardina, G., Giotta, F., Giraudi, S., Giuliano, M., Grassadonia, A., Grasso, D., Grosso, F., Guizzaro, L., Incoronato, P., Incorvaia, L., Iodice, G., La Verde, N., Labonia, V., Landi, G., Latorre, A., Leonardi, V., Levaggi, A., Limite, G., Lina Bascialla, L., Livi, L., Maiello, E., Mandelli, D., Marcon, I., Menon, D., Montedoro, M., Moraca, L., Moretti, A., Morritti, M. G., Morselli, P., Mura, A., Mura, S., Musacchio, M., Muzio, A., Natale, D., Natoli, C., Nigro, C., Nistico, C., Nuzzo, A., Orditura, M., Orlando, L., Pacilio, C., Palumbo, G., Palumbo, R., Pasini, F., Paterno, E., Pazzola, A., Pelliccioni, S., Pensabene, M., Perroni, D., Pesenti Gritti, A., Petrelli, F., Piccirillo, M. C., Pinotti, G., Pogliani, C., Poli, D., Prader, S., Recchia, F., Rizzi, D., Romano, C., Rossello, R., Rossini, C., Salvucci, G., Sanna, V., Santini, A., Saracchini, S., Savastano, C., Scambia, G., Schettini, F., Schiavone, P., Schirone, A., Seles, E., Signoriello, S., Signoriello, G., Silva, R. R., Silvestri, A., Simeon, V., Spagnoletti, I., Tamberi, S., Teragni, C., Thalmann, V., Thomas, R., Thomas, G., Tienghi, A., Tinari, N., Tinessa, V., Tomei, F., Tonini, G., Torri, V., Traficante, D., Tudini, M., Turazza, M., Vignoli, R., Vitale, M. G., Zacchia, A., Zagarese, P., Zanni, A., Zavallone, L., Zavettieri, M., Zoboli, A., De Placido, Sabino, Gallo, Ciro, De Laurentiis, Michelino, Bisagni, Giancarlo, Arpino, Grazia, Sarobba, Maria Giuseppa, Riccardi, Ferdinando, Russo, Antonio, Del Mastro, Lucia, Cogoni, Alessio Aligi, Cognetti, Francesco, Gori, Stefania, Foglietta, Jennifer, Frassoldati, Antonio, Amoroso, Domenico, Laudadio, Lucio, Moscetti, Luca, Montemurro, Filippo, Verusio, Claudio, Bernardo, Antonio, Lorusso, Vito, Gravina, Adriano, Moretti, Gabriella, Lauria, Rossella, Lai, Antonella, Mocerino, Carmen, Rizzo, Sergio, Nuzzo, Francesco, Carlini, Paolo, Perrone, Francesco, Accurso, Antonello, Agostara, Biagio, Aieta, Michele, Alabiso, Oscar, Alicicco, Maria Grazia, Amadori, Dino, Amaducci, Laura, Amiconi, Gianna, Antuzzi, Giustino, Ardine, Mara, Ardizzoia, Antonio, Aversa, Caterina, Badalamenti, Giuseppe, Barni, Sandro, Basurto, Carlo, Berardi, Rossana, Bergamasco, Cinzia, Bidoli, Paolo, Bighin, Claudia, Biondi, Edoardo, Boni, Corrado, Borgonovo, Karen, Botta, Mario, Bravi, Stefano, Bruzzi, Paolo, Buono, Giuseppe, Butera, Alfredo, Caldara, Alessia, Candeloro, Giampiero, Cappelletti, Claudia, Cardalesi, Cinzia, Carfora, Elisabetta, Cariello, Anna, Carrozza, Francesco, Cartenì, Giacomo, Caruso, Michele, Casadei, Virginia, Casanova, Claudia, Castori, Luigi, Cavanna, Luigi, Cavazzini, Giovanna, Cazzaniga, Marina, Chilelli, Mario, Chiodini, Paolo, Chiorrini, Silvia, Ciardiello, Fortunato, Ciccarese, Mariangela, Cinieri, Saverio, Clerico, Mario, Coccaro, Mariarosa, Comande, Mario, Corbo, Claudia, Cortino, Giuseppina, Cusenza, Stefania, Daniele, Gennaro, D'arco, Alfonso Maria, D'auria, Giuliana, Dazzi, Claudio, De Angelis, Carmine, de Braud, Filippo, De Feo, Gianfranco, De Matteis, Andrea, De Tursi, Michele, Di Blasio, Anna, di Lucca, Giuseppe, Di Lullo, Liberato, Di Rella, Francesca, Di Renzo, Gianfranco, Di Stefano, Pia, Di Stefano, Aida, Diana, Anna, Donati, Sara, Fabbri, Agnese, Fabi, Alessandra, Faedi, Marina, Farina, Gabriella, Farris, Antonio, Febbraro, Antonio, Fedele, Palma, Federico, Piera, Ferraù, Francesco, Ferretti, Gianluigi, Ferro, Antonella, Floriani, Irene, Forcignanò, Rosachiara, Forciniti, Samantha, Forestieri, Valeria, Fornari, Gianni, Frisinghelli, Michela, Fusco, Vittorio, Gallizzi, Giulia, Galvano, Antonio, Gambardella, Antonio, Gambi, Angelo, Gebbia, Vittorio, Gervasi, Erika, Ghilardi, Mara, Giacobino, Alice, Giardina, Giovanni, Giotta, Francesco, Giraudi, Sara, Giuliano, Mario, Grassadonia, Antonino, Grasso, Donatella, Grosso, Federica, Guizzaro, Lorenzo, Incoronato, Pasquale, Incorvaia, Lorena, Iodice, Giovanni, La Verde, Nicla, Labonia, Vincenzo, Landi, Gabriella, Latorre, Agnese, Leonardi, Vita, Levaggi, Alessia, Limite, Gennaro, Lina Bascialla, Linda, Livi, Lorenzo, Maiello, Evaristo, Mandelli, Daniela, Marcon, Ilaria, Menon, Daniela, Montedoro, Michele, Moraca, Lucia, Moretti, Anna, Morritti, Maria Grazia, Morselli, Patrizia, Mura, Antonella, Mura, Silvia, Musacchio, Michela, Muzio, Alberto, Natale, Donato, Natoli, Clara, Nigro, Cinzia, Nisticò, Cecilia, Nuzzo, Antonio, Orditura, Michele, Orlando, Laura, Pacilio, Carmen, Palumbo, Giuliano, Palumbo, Raffaella, Pasini, Felice, Paterno, Emanuela, Pazzola, Antonio, Pelliccioni, Silvia, Pensabene, Matilde, Perroni, Davide, Pesenti Gritti, Angela, Petrelli, Fausto, Piccirillo, Maria Carmela, Pinotti, Graziella, Pogliani, Claudia, Poli, Davide, Prader, Sonia, Recchia, Francesco, Rizzi, Daniele, Romano, Carmen, Rossello, Rosalba, Rossini, Chiara, Salvucci, Giuseppina, Sanna, Valeria, Santini, Alessandra, Saracchini, Silvana, Savastano, Clementina, Scambia, Giovanni, Schettini, Francesco, Schiavone, Paola, Schirone, Alessio, Seles, Elena, Signoriello, Simona, Signoriello, Giuseppe, Silva, Rosa Rita, Silvestri, Antonia, Simeon, Vittorio, Spagnoletti, Ilaria, Tamberi, Stefano, Teragni, Cristina, Thalmann, Verena, Thomas, Renato, Thomas, Guglielmo, Tienghi, Amelia, Tinari, Nicola, Tinessa, Vincenza, Tomei, Federica, Tonini, Giuseppe, Torri, Valter, Traficante, Divina, Tudini, Marianna, Turazza, Monica, Vignoli, Roberto, Vitale, Maria Giuseppa, Zacchia, Alessandra, Zagarese, Pasquale, Zanni, Alda, Zavallone, Laura, Zavettieri, Maria, Zoboli, Alessandra, Mocerino, Carmela, D'Arco, Alfonso Maria, D'Auria, Giuliana, De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, and Zoboli, A

Subjects
Oncology, Receptor, ErbB-2, Settore MED/06 - Oncologia Medica, letrozole, law.invention, Adjuvant anastrozole, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Exemestane, law, exemestane, tamoxifen, breast cancer, Antineoplastic Combined Chemotherapy Protocols, 030212 general & internal medicine, Aromatase Inhibitors, Letrozole, Hazard ratio, Middle Aged, Receptors, Estrogen, Tolerability, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Receptors, Progesterone, Breast Neoplasm, Human, medicine.drug, medicine.medical_specialty, Socio-culturale, Anastrozole, Breast Neoplasms, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Aromatase Inhibitor, Humans, Aged, Antineoplastic Combined Chemotherapy Protocol, Androstadiene, business.industry, medicine.disease, Androstadienes, chemistry, business, Tamoxifen
Abstract

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

Published
2018

15. Epigenetics: An opportunity to shape innate and adaptive immune responses

Author

Antonietta Liotti, Anne Lise Ferrara, Stefania Loffredo, Maria Rosaria Galdiero, Gilda Varricchi, Francesca Di Rella, Giorgia Teresa Maniscalco, Martina Belardo, Roberta Vastano, Rosaria Prencipe, Laura Pignata, Roberta Romano, Giuseppe Spadaro, Paola de Candia, Antonio Pezone, Veronica De Rosa, Liotti, A, Ferrara, Al, Loffredo, S, Galdiero, Mr, Varricchi, G, Di Rella, F, Maniscalco, Gt, Belardo, M, Vastano, R, Prencipe, R, Pignata, L, Romano, R, Spadaro, G, de Candia, P, Pezone, A, De Rosa, V., Liotti, Antonietta, Ferrara, Anne Lise, Loffredo, Stefania, Galdiero, Maria Rosaria, Varricchi, Gilda, Di Rella, Francesca, Maniscalco, Giorgia Teresa, Belardo, Martina, Vastano, Roberta, Prencipe, Rosaria, Pignata, Laura, Romano, Roberta, Spadaro, Giuseppe, de Candia, Paola, Pezone, Antonio, and De Rosa, Veronica

Subjects
Epidrug, adaptive immunity, autoimmunity, epidrugs, epigenetics, Foxp3, innate immunity, T-celldifferentiation, Treg cell, Immunology, T cell differentiation, Immunity, Epigenetic, Autoimmunity, Cell Differentiation, Adaptive Immunity, DNA Methylation, Innate Immunity, Immunity, Innate, Epigenesis, Genetic, Histones, Foxp3, Immunology and Allergy, Treg cells
Abstract

Epigenetics connects genetic and environmental factors: it includes DNA methylation, histone post-translational modifications and the regulation of chromatin accessibility by non-coding RNAs, all of which control constitutive or inducible gene transcription. This plays a key role in harnessing the transcriptional programs of both innate and adaptive immune cells due to its plasticity and environmental-driven nature, piloting myeloid and lymphoid cell fate decision with no change in their genomic sequence. In particular, epigenetic marks at the site of lineage specific transcription factors and maintenance of cell type-specific epigenetic modifications, referred to as "epigenetic memory", dictate cell differentiation, cytokine production and functional capacity following repeated antigenic exposure in memory T cells. Moreover, metabolic and epigenetic reprogramming occurring during a primary innate immune response leads to enhanced responses to secondary challenges, a phenomenon known as "trained immunity". Here we discuss how stable and dynamic epigenetic states control immune cell identity and plasticity in physiological and pathological conditions. Dissecting the regulatory circuits of cell fate determination and maintenance is of paramount importance for understanding the delicate balance between immune cell activation and tolerance, in healthy conditions and in autoimmune diseases. This article is protected by copyright. All rights reserved.

Published
2022
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16. Incidence of nausea and vomiting in breast cancer patients treated with anthracycline plus cyclophosphamide-based chemotherapy regimens in Italy: NAVY observational study

Author

Domenico Amoroso, Manuela Otero, Francesca Di Rella, Giuseppe Altavilla, Chiara Bonfadini, Giorgia Peverelli, Paolo Marchetti, Elena Fiorio, Stefania Vecchio, Simona Orecchia, Giuseppina Cilenti, Vito Lorusso, Michelino De Laurentiis, Antonio Ardizzoia, De Laurentiis, M., Bonfadini, C., Lorusso, V., Cilenti, G., Di Rella, F., Altavilla, G., Otero, M., Ardizzoia, A., Marchetti, P., Peverelli, G., Amoroso, D., Vecchio, S., Fiorio, E., and Orecchia, S.

Subjects
vomiting, Antiemetic Agent, medicine.medical_specialty, Nausea, medicine.drug_class, Guideline, Anthracycline, outcomes, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, middle aged, breast neoplasms, medicine, Antiemetic, guidelines, 030212 general & internal medicine, humans, Adverse effect, Aprepitant, Outcome, anthracyclines, business.industry, adult, nausea, medicine.disease, prospective studies, Prospective Studie, aged, Regimen, antiemetics, female, Italy, Oncology, Cancer chemotherapy, guidelines, nausea, outcomes, vomiting, adult, aged, anthracyclines, antiemetics, breast neoplasms, cyclophosphamide, female, humans, incidence, Italy, middle aged, prospective studies, 030220 oncology & carcinogenesis, incidence, Vomiting, cyclophosphamide, Cancer chemotherapy, medicine.symptom, business, Breast Neoplasm, Human, medicine.drug
Abstract

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event with cancer chemotherapy, despite the availability of effective antiemetic agents. This is a prospective observational study of Italian breast cancer patients treated with anthracycline plus cyclophosphamide (AC), assessed CINV incidence, adherence to national antiemetic guidelines (AIOM 2012), and the relationship with CINV outcomes. Methods: Patients with breast cancer scheduled to receive their first cycle of an AC-based regimen were enrolled at 12 Italian centers and their clinical data prospectively recorded. CINV incidence was assessed from patient diaries after the first chemotherapy cycle. The relationship between guideline adherence and CINV outcomes was examined using multiple logistic regression. Results: The overall incidence rates of nausea and vomiting among 246 evaluable patients were 63.0 and 25.4%, respectively. Most patients received a 5-HT3-RA agent and dexamethasone for acute phase CINV prophylaxis, whereas a triple combination including aprepitant (NK1-RA), consistent with national guidelines, was used in only 45.5% of cases. In the delayed phase, the guideline adherence was 48.8%, while the overall adherence was 43.5%. After adjusting for confounding factors, adherence to antiemetic prophylaxis guidelines was associated with a significant reduction in the odds of three endpoints, namely any nausea, “significant nausea,” and vomiting (OR = 0.49, OR = 0.54, and OR = 0.48, respectively), and a 90% increase in the odds of overall complete protection (OR = 1.90). Conclusions: CINV is still a critical issue in AC-treated patients, despite antiemetic treatment. Non-adherence to antiemetic guidelines may lead to poorer outcomes and indicates the need for strategies to enhance the use of guidelines in clinical practice.

Published
2018
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17. Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation

Author

Alessandra Colamatteo, Fortunata Carbone, Sara Bruzzaniti, Mario Galgani, Clorinda Fusco, Giorgia Teresa Maniscalco, Francesca Di Rella, Paola de Candia, Veronica De Rosa, Colamatteo, A., Carbone, F., Bruzzaniti, S., Galgani, M., Fusco, C., Maniscalco, G. T., Di Rella, F., de Candia, P., and De Rosa, V.

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, genetic structures, Cellular differentiation, Immunology, chemical and pharmacologic phenomena, Review, [object Object], Biology, T-Lymphocytes, Regulatory, epigenetic regulation, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, T-Lymphocyte Subsets, Transcriptional regulation, Immunology and Allergy, Animals, Humans, Epigenetics, Enhancer, Transcription factor, Regulation of gene expression, Foxp3 stability, autoimmunity, FOXP3, Cell Differentiation, Forkhead Transcription Factors, hemic and immune systems, Chromatin, Cell biology, 030104 developmental biology, Gene Expression Regulation, Foxp3, lcsh:RC581-607, Treg cells, 030215 immunology
Abstract

The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4+T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors. Progetto giovani ricercatori [GR-2016-02363725] dal titolo: "Immune Tolerance, Metabolism and Multiple Sclerosis: Novel Molecular Tools to Monitor Disease Pathogenesis and Progression" &nbsp

Published
2020
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18. Metabolism and Autoimmune Responses: The microRNA Connection

Author

Alessandra Colamatteo, Teresa Micillo, Sara Bruzzaniti, Clorinda Fusco, Silvia Garavelli, Veronica De Rosa, Mario Galgani, Maria Immacolata Spagnuolo, Francesca Di Rella, Annibale A. Puca, Paola de Candia, Giuseppe Matarese, Colamatteo, A., Micillo, T., Bruzzaniti, S., Fusco, C., Garavelli, S., De Rosa, V., Galgani, M., Spagnuolo, M. I., Di Rella, F., Puca, A. A., de Candia, P., and Matarese, G.

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, T cell, Immunology, immunometabolism, T cells, Inflammation, Autoimmunity, Review, Biology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Immune system, T-Lymphocyte Subsets, Autoimmune disease, microRNA, Gene expression, medicine, Immunology and Allergy, Animals, Humans, autoimmune diseases, metabolic regulation, miRNAs, Effector, Cellular Reprogramming, Autoimmune diseases, Immunometabolism, Metabolic regulation, MiRNAs, Cell biology, Metabolic pathway, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, RNA Interference, Disease Susceptibility, medicine.symptom, MiRNA, Energy Metabolism, lcsh:RC581-607, 030215 immunology
Abstract

Distinct metabolic pathways are known to regulate growth, differentiation, survival, and activation of immune cells by providing energy and specific biosynthetic precursors. Compelling experimental evidence demonstrates that effector T cell functions are coupled with profound changes in cellular metabolism. Importantly, the effector T cell-dependent "anti-self" response characterizing the autoimmune diseases is accompanied by significant metabolic alterations. MicroRNAs (miRNAs), evolutionary conserved small non-coding RNA molecules that affect gene expression by binding to target messenger RNAs, are now known to regulate multiple functions of effector T cells, including the strength of their activation, thus contributing to immune homeostasis. In this review, we will examine the most recent studies that describe miRNA direct involvement in the metabolic reprogramming that marks effector T cell functions. In particular, we will focus on the work showing a connection between miRNA regulatory function and the molecular network dysregulation that leads to metabolic pathway derangement in autoimmunity. Finally, we will also speculate on the possibility that the interplay between miRNAs and metabolism in T cells may help identify novel miRNA-based therapeutic strategies to treat effector T cell immunometabolic alterations in pathological conditions such as autoimmunity and chronic inflammation.

Published
2019
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19. Management of Women With an Unexpected Low Ovarian Response to Gonadotropin

Author

Alessandro Conforti, Sandro C. Esteves, Danilo Cimadomo, Alberto Vaiarelli, Francesca Di Rella, Filippo Maria Ubaldi, Fulvio Zullo, Giuseppe De Placido, Carlo Alviggi, Conforti, A., Esteves, S. C., Cimadomo, D., Vaiarelli, A., Di Rella, F., Ubaldi, F. M., Zullo, F., De Placido, G., and Alviggi, C.

Subjects
0301 basic medicine, Suboptimal response, medicine.drug_class, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Urinary system, 030209 endocrinology & metabolism, Stimulation, Review, Bioinformatics, Assisted Reproductive Technology, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Gonadotropin preparations, ovarian reserve, 03 medical and health sciences, Follicle, 0302 clinical medicine, Endocrinology, suboptimal response, ART calculator, medicine, Ovarian reserve, hypo-response, Hypo-response, Assisted reproductive technology, lcsh:RC648-665, business.industry, Follicleto-oocyte index, Oocyte, ovarian stimulation, POSEIDON criteria, 030104 developmental biology, medicine.anatomical_structure, follicle-to-oocyte index, ART calculato, Ovarian stimulation, Gonadotropin, business
Abstract

POSEIDON groups 1 and 2 patients respond poorly (

Published
2019
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20. Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

Author

Francesca Di Rella, Paolo Chiodini, Carmen Pacilio, Giovanni Iodice, Michelino De Laurentiis, Daniela Cianniello, Matilde Pensabene, Giuseppina Fusco, Germira Di Gioia, Stefania Cocco, Vincenzo Di Lauro, Roberta Caputo, Francesco Nuzzo, Michela Piezzo, Maria Antonietta Riemma, Piezzo, M., Chiodini, P., Riemma, M., Cocco, S., Caputo, R., Cianniello, D., Di Gioia, G., Di Lauro, V., Di Rella, F., Fusco, G., Iodice, G., Nuzzo, F., Pacilio, C., Pensabene, M., and De Laurentiis, M.

Subjects
0301 basic medicine, Oncology, Review, CDK4/6 inhibitor, lcsh:Chemistry, 0302 clinical medicine, Neoplasm Metastasis, subgroup analysis, lcsh:QH301-705.5, Spectroscopy, Hazard ratio, General Medicine, Prognosis, Metastatic breast cancer, Computer Science Applications, Survival Rate, 030220 oncology & carcinogenesis, Meta-analysis, epidemiology, Female, metastatic breast cancer, medicine.medical_specialty, Antineoplastic Agents, Hormonal, medicine.drug_class, overall survival, therapies, Breast Neoplasms, Palbociclib, Hormone receptor, Catalysis, Inorganic Chemistry, Subgroup analysi, CDK4/6 inhibitors, 03 medical and health sciences, Internal medicine, medicine, cancer, Humans, Progression-free survival, Physical and Theoretical Chemistry, Protein Kinase Inhibitors, Molecular Biology, Survival analysis, Aromatase inhibitor, hormone therapy, business.industry, Organic Chemistry, hormone receptors, Cyclin-Dependent Kinase 4, Cancer, Cyclin-Dependent Kinase 6, medicine.disease, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, business
Abstract

The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).

Published
2020
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21. Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial

Author

Emanuela Rossi, Francesca Di Rella, Carlo Putzu, Francesco Perrone, Rossella Lauria, Lucia Del Mastro, Gennaro Daniele, Vittorio Simeon, Vincenza Tinessa, Ermelinda De Maio, Sabino De Placido, G. Landi, Sandro Barni, Francesco Nuzzo, Saverio Cinieri, Giovanni Iodice, Andrea de Matteis, Nicola Normanno, A. Fabbri, Carmen Pacilio, Laura Arenare, Maria Carmela Piccirillo, Toni Ibrahim, Valeria Forestieri, Angela Stefania Ribecco, Adriano Gravina, Ciro Gallo, Stefania Gori, Anna Maria Mosconi, Ferdinando Riccardi, Michele Orditura, Michelino De Laurentiis, Perrone, Francesco, De Laurentiis, Michelino, De Placido, Sabino, Orditura, Michele, Cinieri, Saverio, Riccardi, Ferdinando, Ribecco, Angela Stefania, Putzu, Carlo, Del Mastro, Lucia, Rossi, Emanuela, Tinessa, Vincenza, Mosconi, Anna Maria, Nuzzo, Francesco, Di Rella, Francesca, Gravina, Adriano, Iodice, Giovanni, Landi, Gabriella, Pacilio, Carmen, Forestieri, Valeria, Lauria, Rossella, Fabbri, Agnese, Ibrahim, Toni, De Maio, Ermelinda, Barni, Sandro, Gori, Stefania, Simeon, Vittorio, Arenare, Laura, Daniele, Gennaro, Piccirillo, Maria Carmela, Normanno, Nicola, de Matteis, Andrea, Gallo, Ciro, Perrone, F., De Laurentiis, M., De Placido, S., Orditura, M., Cinieri, S., Riccardi, F., Ribecco, A. S., Putzu, C., Del Mastro, L., Rossi, E., Tinessa, V., Mosconi, A. M., Nuzzo, F., Di Rella, F., Gravina, A., Iodice, G., Landi, G., Pacilio, C., Forestieri, V., Lauria, R., Fabbri, A., Ibrahim, T., De Maio, E., Barni, S., Gori, S., Simeon, V., Arenare, L., Daniele, G., Piccirillo, M. C., Normanno, N., de Matteis, A., and Gallo, C.

Subjects
0301 basic medicine, Cancer Research, Time Factors, Gastroenterology, Zoledronic Acid, 0302 clinical medicine, Breast cancer, Antineoplastic Combined Chemotherapy Protocols, education.field_of_study, Triptorelin Pamoate, Bone Density Conservation Agents, Aromatase Inhibitors, Letrozole, Hazard ratio, Estrogen Antagonists, Middle Aged, Triptorelin, Oncology, Italy, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Adjuvant endocrine treatment, Aromatase inhibitors, Breast cancer, Phase 3, Premenopausal patients, Zoledronic acid, Disease Progression, Female, medicine.drug, Adult, medicine.medical_specialty, Population, Breast Neoplasms, Phase 3, Adjuvant endocrine treatment, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, Humans, education, Premenopausal patients, business.industry, Ovary, Premenopausal patient, Cancer, Aromatase inhibitor, medicine.disease, Tamoxifen, 030104 developmental biology, Zoledronic acid, Premenopause, business
Abstract

Aim The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor–positive (HR+) tumours. Patients and methods In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis. Results With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3–4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively. Conclusion HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. ( NCT00412022 )

Published
2019

22. Unexpected ovarian activity in premenopausal breast cancer survivors treated with exemestane and GnRH analogues

Author

Giovanni Nazzaro, Alessandro Conforti, Rossella Lauria, Francesca Di Rella, Roberta Caputo, Irene De Santo, Sabino De Placido, Grazia Arpino, Roberta Vallone, Michelino De Laurentiis, Mario Giuliano, Mariavittoria Locci, Pasquale De Rosa, Giuseppe De Placido, Francesco Schettini, Carlo Alviggi, Conforti, A., Schettini, F., Vallone, R., Di Rella, F., De Rosa, P., De Santo, I., Giuliano, M., Arpino, G., Lauria, R., De Placido, S., Caputo, R., De Laurentiis, M., Nazzaro, G., De Placido, G., Locci, M., and Alviggi, C.

Subjects
Oncology, Adult, medicine.medical_specialty, Antineoplastic Agents, Hormonal, medicine.medical_treatment, MEDLINE, Breast Neoplasms, Gonadotropin-Releasing Hormone, Premenstrual Syndrome, chemistry.chemical_compound, Text mining, Exemestane, Cancer Survivors, Internal medicine, Internal Medicine, medicine, Humans, Ovarian Function Tests, Chemotherapy, Estradiol, business.industry, Ovary, Androstadienes, Tamoxifen, chemistry, Chemotherapy, Adjuvant, Premenopausal breast cancer, Surgery, Female, Uterine Hemorrhage, Drug Monitoring, business
Published
2019

23. The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: A systematic review and meta-analysis

Author

Sandro C. Esteves, Pasquale De Rosa, Fulvio Zullo, Alessia Fiorenza, Alessandro Conforti, Carlo Alviggi, Ida Strina, Giuseppe De Placido, Francesca Di Rella, Conforti, A., Esteves, S. C., Di Rella, F., Strina, I., De Rosa, P., Fiorenza, A., Zullo, F., De Placido, G., and Alviggi, C.

Subjects
0301 basic medicine, LH, Pregnancy Rate, medicine.medical_treatment, Hypo-responders, Physiology, Stimulation, Review, Miscarriage, 0302 clinical medicine, Endocrinology, Pregnancy, In vitro fertilization, lcsh:Reproduction, Prospective Studies, Gonadotropin, Clinical Trials as Topic, 030219 obstetrics & reproductive medicine, Recombinant LH, Obstetrics and Gynecology, Recombinant Proteins, Meta-analysis, Hypo-responder, Female, Assisted reproductive technologies, Human, medicine.medical_specialty, lcsh:QH471-489, Ovulation induction, Reproductive medicine, lcsh:Gynecology and obstetrics, 03 medical and health sciences, medicine, Assisted reproductive technologie, Humans, Embryo Implantation, lcsh:RG1-991, In vitro fertilisation, business.industry, Correction, Odds ratio, Luteinizing Hormone, medicine.disease, Clinical trial, Prospective Studie, 030104 developmental biology, Reproductive Medicine, Follicle Stimulating Hormone, business, Gonadotropins, Developmental Biology
Abstract

Objective To study the role of recombinant human LH supplementation in women with hypo-response to ovarian stimulation. Methods We performed a systematic review and meta-analysis of prospective clinical trials in which recombinant FSH monotherapy protocols were compared with LH-supplemented protocols in hypo-responders. A search was conducted of the Scopus, MEDLINE databases without time or language restrictions. Primary outcome was clinical pregnancy rate. Results Significantly higher clinical pregnancy rates (odds ratio: 2.03, P = 0.003), implantation rates (odds ratio: 2.62, P = 0.004) and number of oocytes retrieved (weight mean differences: 1.98, P = 0.03) were observed in hypo-responders supplemented with recombinant LH versus hypo-responders who underwent FSH monotherapy. No differences in terms of mature oocytes or miscarriage rates were found between the two groups. Conclusion In conclusion, our analysis confirms that women with a hypo-response to exogenous gonadotropins might benefit from LH supplementation. However, more trials are required before a definitive conclusion can be drawn. Electronic supplementary material The online version of this article (10.1186/s12958-019-0460-4) contains supplementary material, which is available to authorized users.

Published
2019

24. CD4 + FOXP3Exon2 + regulatory T cell frequency predicts breast cancer prognosis and survival.

Author

Fusco C, Di Rella F, Liotti A, Colamatteo A, Ferrara AL, Gigantino V, Collina F, Esposito E, Donzelli I, Porcellini A, Feola A, Micillo T, Perna F, Garziano F, Maniscalco GT, Varricchi G, Mottola M, Zuccarelli B, De Simone B, di Bonito M, Matarese G, Accurso A, Pontillo M, Russo D, Insabato L, Spaziano A, Cantone I, Pezone A, and De Rosa V

Subjects
Humans, Female, Prognosis, Tumor Microenvironment immunology, Biomarkers, Tumor, Receptors, CXCR4 metabolism, Receptors, CXCR4 genetics, Exons, Chemokine CXCL12 metabolism, Gene Expression Regulation, Neoplastic, Forkhead Transcription Factors metabolism, Forkhead Transcription Factors genetics, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Breast Neoplasms immunology, Breast Neoplasms mortality, Breast Neoplasms pathology, Breast Neoplasms metabolism
Abstract

CD4 + FOXP3 + regulatory T cells (T regs ) suppress immune responses to tumors, and their accumulation in the tumor microenvironment (TME) correlates with poor clinical outcome in several cancers, including breast cancer (BC). However, the properties of intratumoral T regs remain largely unknown. Here, we found that a functionally distinct subpopulation of T regs , expressing the FOXP3 Exon2 splicing variants, is prominent in patients with hormone receptor-positive BC with poor prognosis. Notably, a comprehensive examination of the TCGA validated FOXP3E2 as an independent prognostic marker in all other BC subtypes. We found that FOXP3E2 expression underlies BCs with defective mismatch repair and a stem-like signature and highlights pathways involved in tumor survival. Last, we found that the TME induces FOXP3E2 through the CXCL12/CXCR4 axis and confirmed the higher immunosuppressive capacity of FOXP3E2 + T regs derived from patients with BC. Our study suggests that FOXP3E2 + T regs might be used as an independent biomarker to predict BC prognosis and survival and to develop super-targeted immunotherapies.

Published
2025
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25. Ovarian reserve, metabolic and neuroendocrine profiles of cadets from Air Force Academy: a pilot study.

Author

Conforti A, Guadalupi GA, Perruolo G, Auriemma RS, DI Girolamo R, Carbone L, Cariati F, Orsi MG, Raffone A, Strina I, Formisano P, Guida M, Capuano G, DI Rella F, Longobardi S, Alviggi C, and Mollo A

Abstract

Background: Intensive physical activity and rigid dietary regimes can act as modifiers of neuroendocrine axes in women, inducing hormonal disorders and related menstrual irregularities such as functional hypothalamic amenorrhea (FHA). It would be important to evaluate if such disturbances may worsen female fertility. The aim of this study was to evaluate ovarian reserve markers and neuroendocrine axis in young military academy female cadets with years of training and occurrence of FHA., Methods: This is a prospective pilot study involving young female cadets from the Military Academy training program. Ovarian reserve markers and metabolic and neuroendocrine factors in the early follicular phase were measured with blood tests and transvaginal ultrasound., Results: The study group consisted of 11 women belonging to the first year of training and the control group of 33 women belonging to the second to sixth year of training. No differences were found about ovarian reserve markers between the two groups. Moreover, the occurrence of FHA did not modify the ovarian reserve compared to eumenorrhea in both groups. Women from the study group showed significantly higher levels of fasting Insulin (42.18±26.14 uUI/mL versus 11.9±10.2 ng/mL, P value <0.001) and insulin-like growth factor 1 (310.06±67.90 uUI/mL versus 248.67±61.57 uUI/mL, P value = 0.015) compared with control group., Conclusions: Both intense physical training and FHA do not appear to impact the ovarian reserve of young female cadets. Although preliminary, these findings seem reassuring about the reproductive health of these women and their future fertility.

Published
2024
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26. Psychometric properties of patient-reported outcomes Common Terminology Criteria for adverse events (PRO-CTCAE®) in breast cancer patients: The prospective observational multicenter VIP study.

Author

Caminiti C, Maglietta G, Arenare L, Di Liello R, Migliaccio G, Barberio D, De Laurentiis M, Di Rella F, Nuzzo F, Pacilio C, Iodice G, Orditura M, Ciardiello F, Di Bella S, Cavanna L, Porta C, Giovanardi F, Ripamonti CI, Bilancia D, Aprile G, Ruelle T, Diodati F, Piccirillo MC, Iannelli E, Pinto C, and Perrone F

Subjects
Humans, Female, Middle Aged, Prospective Studies, Aged, Adult, Drug-Related Side Effects and Adverse Reactions psychology, Surveys and Questionnaires, Self Report, Reproducibility of Results, Breast Neoplasms psychology, Patient Reported Outcome Measures, Psychometrics, Quality of Life
Abstract

Patients' self-reporting is increasingly considered essential to measure quality-of-life and treatment-related side-effects. However, if multiple patient-reported instruments are used, redundancy may represent an overload for patients. Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) are a tool allowing direct patients' reporting of side-effects. We tested psychometric properties of a selected list of PRO-CTCAE items, in a cohort of 303 breast cancer patients, using validated instruments for quality of life assessment as anchors. The analysis of convergent validity with HADS (Hospital Anxiety and Depression Scale) and EORTC BR-23 sub-scales, and the analysis of responsiveness with the PGIC (Patients Global Impression of Change) score supported that a selected list of PRO-CTCAE symptoms might represent a standardized, agile tool for both research and practice settings to reduce patient burden without missing relevant information on patient perceptions. Among patients using digital devices, those with a higher education levels required shorter time to fulfil questionnaires. In conclusion, a selected list of PRO-CTCAE items can be considered as a standardized, agile tool for capturing crucial domains of side-effects and quality of life in patients with breast cancer. The study is registered on clinicaltrials.gov (NCT04416672)., Competing Interests: Declaration of competing interest Michelino De Laurentiis declares: honoraria or consultation fees for speaker, consultancy or advisory roles from Eli Lilly, Seagen, Therapeutics, GSK, Roche, Novartis, Genetic, Pfizer, Pierre Fabre, MSD, Menarini Stemline, Sophos Biotech, Max Farma, Celltrion Healthcare, Gilead, Daiichi Sankyo; institutional financial interests, financial support for clinical trials or contracted research, from: Novartis, Pierre Fabre, Pfizer, Roche, Stemline Therapeutics. Fortunato Ciardiello declares: honoraria or consultation fees for speaker, consultancy or advisory roles from Amgen, Merck KGaA, MSD, Pierre Fabre, Pfizer, Roche, Servier; institutional financial interests, financial support for clinical trials or contracted research, from: Amgen, Merck KGaA, MSD, Pierre Fabre, Pfizer, Roche, Servier. Lugi Cavanna declares honoraria from Roche and Pfizer. Filippo Giovanardi declares honoraria from Eli Lilly, AstraZeneca, Roche, Seagen, Novartis. Maria Carmela Piccirillo declares: honoraria for speaker activities from Astellas, Pfizer, Ipsen, Astrazeneca; financial support to institutional research activities from AstraZeneca, Bayer, Roche. Francesco Perrone declares: institutional grants or contracts from Roche, Bayer, AstraZeneca, Pfizer, Incyte, Tesaro/GSK, Merck; consulting fees from Bayer, Pierre Fabre, Astra Zeneca, Incyte, Ipsen, Clovis, Astellas, Sanofi, Roche, Pfizer; leadership in scientific society: President of AIOM 2023–2025. All the other authors declares no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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27. Neratinib as adjuvant therapy in patients with HER2 positive breast cancer: expert opinion.

Author

Caputo R, Buono G, Di Lauro V, Cianniello D, Von Arx C, Pensabene M, Pagliuca M, Pacilio C, Di Rella F, Verrazzo A, Martinelli C, Nuzzo F, and De Laurentiis M

Subjects
Humans, Female, Combined Modality Therapy, Trastuzumab adverse effects, Protein Kinase Inhibitors adverse effects, Breast Neoplasms drug therapy
Abstract

Neratinib is a tyrosine kinase receptor inhibitor used in the extended adjuvant therapy of early-stage breast cancer. After adjuvant trastuzumab therapy, neratinib reduces the risk of recurrence and, if taken within 1 year from trastuzumab, significantly improves the invasive disease-free survival of patients with early-stage human epidermal growth factor receptor-2 positive (HER2+) breast cancer with no increased risk of long-term toxicity. Diarrhea, the most common adverse event associated with neratinib use, deters some clinicians from prescribing this drug. However, neratinib-related toxicity is predictable, short-lived, mostly limited to the first month of treatment and can be managed with dose-escalation and prophylactic strategies. Thus, close surveillance and prompt management, relying on supportive care and administration schedule modification, allows discontinuation of treatment to be avoided.

Published
2023
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28. An Overview of the Roles of CDK4/6 Inhibitors in Metastatic Breast Cancer Elderly Patients.

Author

Pacilio C, Rosati G, Crispo A, Bimonte S, DI Rella F, Nuzzo F, and DE Laurentiis M

Subjects
Humans, Female, Aged, Protein Kinase Inhibitors adverse effects, Cyclin-Dependent Kinase 6, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Receptor, ErbB-2, Cyclin-Dependent Kinase 4 therapeutic use, Breast Neoplasms pathology
Abstract

Breast cancer is the most common type of cancer in women worldwide. Many studies indicate that breast cancer increases in elderly patients (≥70 years) and suggest that the higher cancer mortality in this population relative to that observed in younger women could be related to organ dysfunction, an advanced and delayed diagnosis, and other morbidities. Endocrine therapy (ET) represents the favorite treatment for patients affected by hormone receptor positive (HR+) metastatic breast cancer (MBC). Unfortunately, half of these patients are resistant to ET. In recent years, new therapeutic options, such as orally highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6), have been widely investigated in patients suffering from MBC with good outcomes. They are able to bypass resistance from hormonal therapy, by restoring hormone sensitivity and by delaying chemotherapeutic agent use. Thus, CDK4/6 inhibitors, combined with hormonal therapy, represent an alternative treatment for MBC. Unfortunately, the elderly population with MBC remains mostly excluded from clinical trials. Moreover, few data on the efficacy, safety, and short and longterm outcomes of therapies based on the combined treatment of ET and CDK4/6 inhibitors are available. This narrative review highlights the use of CDK 4/6 inhibitor-based therapy for MBC in elderly patients and suggests new therapeutic perspectives., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Published
2023
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29. Sperm Oxidative Stress during In Vitro Manipulation and Its Effects on Sperm Function and Embryo Development.

Author

Gualtieri R, Kalthur G, Barbato V, Longobardi S, Di Rella F, Adiga SK, and Talevi R

Abstract

Reactive oxygen species (ROS) generated at low levels during mitochondrial respiration have key roles in several signaling pathways. Oxidative stress (OS) arises when the generation of ROS exceeds the cell's antioxidant scavenging ability and leads to cell damage. Physiological ROS production in spermatozoa regulates essential functional characteristics such as motility, capacitation, acrosome reaction, hyperactivation, and sperm-oocyte fusion. OS can have detrimental effects on sperm function through lipid peroxidation, protein damage, and DNA strand breakage, which can eventually affect the fertility of an individual. Substantial evidence in the literature indicates that spermatozoa experiencing OS during in vitro manipulation procedures in human- and animal-assisted reproduction are increasingly associated with iatrogenic ROS production and eventual impairment of sperm function. Although a direct association between sperm OS and human assisted reproductive techniques (ART) outcomes after in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) is still a matter of debate, studies in animal models provide enough evidence on the adverse effects of sperm OS in vitro and defective fertilization and embryo development. This review summarized the literature on sperm OS in vitro, its effects on functional ability and embryo development, and the approaches that have been proposed to reduce iatrogenic sperm damage and altered embryonic development.

Published
2021
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30. Identification and Relative Quantification of hFSH Glycoforms in Women's Sera via MS-PRM-Based Approach.

Author

Melchiorre C, Chhuon C, Jung V, Lipecka J, Di Rella F, Conforti A, Amoresano A, Carpentieri A, and Guerrera IC

Abstract

Follicle-stimulating hormone (FSH) is a glycohormone synthesized by adenohypophysis, and it stimulates ovulation in women and spermatogenesis in men by binding to its receptor (FSHR). FSHR is involved in several mechanisms to transduce intracellular signals in response to the FSH stimulus. Exogenous FSH is currently used in the clinic for ovarian hyperstimulation during in vitro fertilization in women, and for treatment of infertility caused by gonadotropin deficiency in men. The glycosylation of FSH strongly affects the binding affinity to its receptor, hence significantly influencing the biological activity of the hormone. Therefore, the accurate measurement and characterization of serum hFSH glycoforms will contribute to elucidating the complex mechanism of action by which different glycoforms elicit distinct biological activity. Nowadays ELISA is the official method with which to monitor serum hFSH, but the test is unable to distinguish between the different FSH glycovariants and is therefore unsuitable to study the biological activity of this hormone. This study presents a preliminary alternative strategy for identifying and quantifying serum hFSH glycoforms based on immunopurification assay and mass spectrometry (MS), and parallel reaction monitoring (PRM) analysis. In this study, we provide an MS-PRM data acquisition method for hFSH glycopeptides identification with high specificity and their quantification by extracting the chromatographic traces of selected fragments of glycopeptides. Once set up for all its features, the proposed method could be transferred to the clinic to improve fertility treatments and follow-ups in men and women.

Published
2021
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31. Targeting Autophagy in Breast Cancer.

Author

Cocco S, Leone A, Piezzo M, Caputo R, Di Lauro V, Di Rella F, Fusco G, Capozzi M, Gioia GD, Budillon A, and De Laurentiis M

Subjects
Antineoplastic Agents therapeutic use, Autophagy physiology, Breast Neoplasms metabolism, Clinical Trials as Topic, Female, Humans, Molecular Targeted Therapy methods, Phosphatidylinositol 3-Kinases metabolism, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism, TOR Serine-Threonine Kinases metabolism, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms metabolism, Triple Negative Breast Neoplasms pathology, Tumor Microenvironment, Antineoplastic Agents pharmacology, Autophagy drug effects, Breast Neoplasms drug therapy, Breast Neoplasms pathology
Abstract

Breast cancer is a heterogeneous disease consisting of different biological subtypes, with differences in terms of incidence, response to diverse treatments, risk of disease progression, and sites of metastases. In the last years, several molecular targets have emerged and new drugs, targeting PI3K/Akt/mTOR and cyclinD/CDK/pRb pathways and tumor microenvironment have been integrated into clinical practice. However, it is clear now that breast cancer is able to develop resistance to these drugs and the identification of the underlying molecular mechanisms is paramount to drive further drug development. Autophagy is a highly conserved homeostatic process that can be activated in response to antineoplastic agents as a cytoprotective mechanism. Inhibition of autophagy could enhance tumor cell death by diverse anti-cancer therapies, representing an attractive approach to control mechanisms of drug resistance. In this manuscript, we present a review of autophagy focusing on its interplay with targeted drugs used for breast cancer treatment.

Published
2020
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32. Distinct effects of epirubicin, cisplatin and cyclophosphamide on ovarian somatic cells of prepuberal ovaries.

Author

Marcozzi S, Rossi V, Salvatore G, Di Rella F, De Felici M, and Klinger FG

Subjects
Animals, Apoptosis drug effects, Cellular Senescence drug effects, Female, Mice, Antineoplastic Agents toxicity, Cisplatin toxicity, Cyclophosphamide toxicity, Epirubicin toxicity, Granulosa Cells drug effects, Theca Cells drug effects
Abstract

In vitro culture models were used to characterize the effects of chemotherapeutic drugs and of LH on somatic cells from prepuberal mouse ovaries. All cell types (pre- and granulosa cells, pre-thecal and OSE cells) underwent apoptosis following Epirubicin (0.5μM) exposure for 24hrs (about 60%) and 48hrs (>80%). Cisplatin (10μM) and the Cyclophosphamide active metabolite, Phosphoramide Mustard (10μM), didn't cause apoptosis in 90% of pre-thecal and pre-granulosa cells up to 72hrs of exposure, although they suffered extensive DNA damage and cell cycle arrest, and acquired stress induced premature senescence (SIPS) features. Cultured granulosa cells didn't show evident DNA damage and remained viable without acquiring SIPS features; OSE cells were resistant to apoptosis and SIPS but not to DNA damage. These latter, like pre-thecal and pre-granulosa cells, were able of efficient DNA repair involving MLH1-dependent MMR pathways. SIPS features were also observed in ovary after in vivo treatment with Cisplatin. LH (200mIU/mL) didn't significantly influence apoptosis, SIPS and DNA damage but favoured DNA repair. These results show that somatic cells of prepuberal ovary response to drugs in different ways, either undergoing apoptosis or SIPS, either showing resistance to Cisplatin and Phosphoramide Mustard. Moreover, a new role of LH in promoting DNA repair was shown.

Published
2019
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33. Unexpected ovarian activity in premenopausal breast cancer survivors treated with exemestane and GnRH analogues.

Author

Conforti A, Schettini F, Vallone R, Di Rella F, De Rosa P, De Santo I, Giuliano M, Arpino G, Lauria R, De Placido S, Caputo R, De Laurentiis M, Nazzaro G, De Placido G, Locci M, and Alviggi C

Subjects
Adult, Antineoplastic Agents, Hormonal administration & dosage, Antineoplastic Agents, Hormonal adverse effects, Cancer Survivors statistics & numerical data, Chemotherapy, Adjuvant adverse effects, Chemotherapy, Adjuvant methods, Female, Humans, Ovary drug effects, Ovary metabolism, Ovary physiopathology, Premenstrual Syndrome diagnosis, Uterine Hemorrhage diagnosis, Androstadienes administration & dosage, Androstadienes adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Drug Monitoring methods, Drug Monitoring standards, Estradiol blood, Gonadotropin-Releasing Hormone agonists, Ovarian Function Tests methods, Ovarian Function Tests standards, Tamoxifen administration & dosage, Tamoxifen adverse effects
Published
2019
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34. Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial.

Author

Perrone F, De Laurentiis M, De Placido S, Orditura M, Cinieri S, Riccardi F, Ribecco AS, Putzu C, Del Mastro L, Rossi E, Tinessa V, Mosconi AM, Nuzzo F, Di Rella F, Gravina A, Iodice G, Landi G, Pacilio C, Forestieri V, Lauria R, Fabbri A, Ibrahim T, De Maio E, Barni S, Gori S, Simeon V, Arenare L, Daniele G, Piccirillo MC, Normanno N, de Matteis A, and Gallo C

Subjects
Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Aromatase Inhibitors adverse effects, Bone Density Conservation Agents adverse effects, Breast Neoplasms mortality, Breast Neoplasms physiopathology, Chemotherapy, Adjuvant, Disease Progression, Disease-Free Survival, Estrogen Antagonists adverse effects, Female, Humans, Italy, Letrozole adverse effects, Middle Aged, Ovary physiopathology, Tamoxifen adverse effects, Time Factors, Triptorelin Pamoate adverse effects, Zoledronic Acid adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Aromatase Inhibitors therapeutic use, Bone Density Conservation Agents therapeutic use, Breast Neoplasms drug therapy, Estrogen Antagonists therapeutic use, Letrozole therapeutic use, Ovary drug effects, Premenopause, Tamoxifen therapeutic use, Triptorelin Pamoate therapeutic use, Zoledronic Acid therapeutic use
Abstract

Aim: The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor-positive (HR+) tumours., Patients and Methods: In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis., Results: With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3-4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively., Conclusion: HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. (NCT00412022)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Published
2019
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35. Metabolism and Autoimmune Responses: The microRNA Connection.

Author

Colamatteo A, Micillo T, Bruzzaniti S, Fusco C, Garavelli S, De Rosa V, Galgani M, Spagnuolo MI, Di Rella F, Puca AA, de Candia P, and Matarese G

Subjects
Animals, Cellular Reprogramming, Disease Susceptibility, Gene Expression Regulation, Humans, MicroRNAs genetics, RNA Interference, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Autoimmune Diseases etiology, Autoimmune Diseases metabolism, Autoimmunity genetics, Energy Metabolism genetics, Energy Metabolism immunology
Abstract

Distinct metabolic pathways are known to regulate growth, differentiation, survival, and activation of immune cells by providing energy and specific biosynthetic precursors. Compelling experimental evidence demonstrates that effector T cell functions are coupled with profound changes in cellular metabolism. Importantly, the effector T cell-dependent "anti-self" response characterizing the autoimmune diseases is accompanied by significant metabolic alterations. MicroRNAs (miRNAs), evolutionary conserved small non-coding RNA molecules that affect gene expression by binding to target messenger RNAs, are now known to regulate multiple functions of effector T cells, including the strength of their activation, thus contributing to immune homeostasis. In this review, we will examine the most recent studies that describe miRNA direct involvement in the metabolic reprogramming that marks effector T cell functions. In particular, we will focus on the work showing a connection between miRNA regulatory function and the molecular network dysregulation that leads to metabolic pathway derangement in autoimmunity. Finally, we will also speculate on the possibility that the interplay between miRNAs and metabolism in T cells may help identify novel miRNA-based therapeutic strategies to treat effector T cell immunometabolic alterations in pathological conditions such as autoimmunity and chronic inflammation.

Published
2019
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36. Type 2 Diabetes: How Much of an Autoimmune Disease?

Author

de Candia P, Prattichizzo F, Garavelli S, De Rosa V, Galgani M, Di Rella F, Spagnuolo MI, Colamatteo A, Fusco C, Micillo T, Bruzzaniti S, Ceriello A, Puca AA, and Matarese G

Abstract

Type 2 diabetes (T2D) is characterized by a progressive status of chronic, low-grade inflammation (LGI) that accompanies the whole trajectory of the disease, from its inception to complication development. Accumulating evidence is disclosing a long list of possible "triggers" of inflammatory responses, many of which are promoted by unhealthy lifestyle choices and advanced age. Diabetic patients show an altered number and function of immune cells, of both innate and acquired immunity. Reactive autoantibodies against islet antigens can be detected in a subpopulation of patients, while emerging data are also suggesting an altered function of specific T lymphocyte populations, including T regulatory (Treg) cells. These observations led to the hypothesis that part of the inflammatory response mounting in T2D is attributable to an autoimmune phenomenon. Here, we review recent data supporting this framework, with a specific focus on both tissue resident and circulating Treg populations. We also propose that selective interception (or expansion) of T cell subsets could be an alternative avenue to dampen inappropriate inflammatory responses without compromising immune responses.

Published
2019
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37. Management of Women With an Unexpected Low Ovarian Response to Gonadotropin.

Author

Conforti A, Esteves SC, Cimadomo D, Vaiarelli A, Di Rella F, Ubaldi FM, Zullo F, De Placido G, and Alviggi C

Abstract

POSEIDON groups 1 and 2 patients respond poorly (<4 oocytes retrieved) or sub-optimally (4-9 oocytes retrieved) to gonadotropin stimulation despite the presence of adequate ovarian parameters, which negatively affect their cumulative chances of delivering a baby using Assisted Reproductive Technology. A polygenic trait involving gonadotropins and/or their receptors seems to be the primary pathophysiology mechanism explaining this phenomenon. The clinical management is mainly focused on maximizing oocyte yield as to increase the likelihood of having at least one euploid embryo for transfer. Indices such as FORT (follicle output rate) and FOI (follicle-to-oocyte index) may be used to determine if the ovarian reserve was properly explored during a previous ovarian stimulation. Testing for the presence of common polymorphisms affecting gonadotropins and/or their receptors can also be considered to identify patients at risk of hypo-response. An individualized estimation of the minimum number of oocytes needed to obtain at least one euploid embryo can assist counseling and treatment planning. Among currently existing pharmacological interventions, use of recombinant FSH in preference over urinary gonadotropin preparations, FSH dosage increase, and use of rLH supplementation may be considered -alone or combined- for optimally managing POSEIDON's groups 1 and 2 patients. However, given the recent introduction of the POSEIDON criteria, there is still a lack of studies examining the role of interventions specifically to patients classified as groups 1 and 2, thus making it an area for open research.

Published
2019
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38. Pharmacogenetics of FSH Action in the Female.

Author

Conforti A, Vaiarelli A, Cimadomo D, Bagnulo F, Peluso S, Carbone L, Di Rella F, De Placido G, Ubaldi FM, Huhtaniemi I, and Alviggi C

Abstract

The purpose of a pharmacogenomic approach is to tailor treatment on the basis of an individual human genotype. This strategy is becoming increasingly common in medicine, and important results have been obtained in oncologic and antimicrobial therapies. The rapid technological developments and availability of innovative methodologies have revealed the existence of numerous genotypes that can influence the action of medications and give rise to the idea that a true "individualized" approach could become in the future a reality in clinical practice. Moreover, compared to the past, genotype analyses are now more easily available at accessible cost. Concerning human reproduction, there is ample evidence that several variants of gonadotropins and their receptors influence female reproductive health and ovarian response to exogenous gonadotropins. In more detail, variants in genes of follicle-stimulating hormone β -chain (FSH-B) and its receptor (FSH-R) seem to be the most promising candidates for a pharmacogenomic approach to controlled ovarian stimulation in assisted reproductive technologies. In the present review, we summarize the evidence regarding FSH-B and FSH-R variants, with special reference to their impact on reproductive health and assisted reproductive technology treatments.

Published
2019
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41. The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: a systematic review and meta-analysis.

Author

Conforti A, Esteves SC, Di Rella F, Strina I, De Rosa P, Fiorenza A, Zullo F, De Placido G, and Alviggi C

Subjects
Clinical Trials as Topic, Embryo Implantation drug effects, Female, Humans, Luteinizing Hormone genetics, Pregnancy, Pregnancy Rate, Prospective Studies, Follicle Stimulating Hormone therapeutic use, Gonadotropins therapeutic use, Luteinizing Hormone therapeutic use, Ovulation Induction methods, Recombinant Proteins therapeutic use
Abstract

Objective: To study the role of recombinant human LH supplementation in women with hypo-response to ovarian stimulation., Methods: We performed a systematic review and meta-analysis of prospective clinical trials in which recombinant FSH monotherapy protocols were compared with LH-supplemented protocols in hypo-responders. A search was conducted of the Scopus, MEDLINE databases without time or language restrictions. Primary outcome was clinical pregnancy rate., Results: Significantly higher clinical pregnancy rates (odds ratio: 2.03, P = 0.003), implantation rates (odds ratio: 2.62, P = 0.004) and number of oocytes retrieved (weight mean differences: 1.98, P = 0.03) were observed in hypo-responders supplemented with recombinant LH versus hypo-responders who underwent FSH monotherapy. No differences in terms of mature oocytes or miscarriage rates were found between the two groups., Conclusion: In conclusion, our analysis confirms that women with a hypo-response to exogenous gonadotropins might benefit from LH supplementation. However, more trials are required before a definitive conclusion can be drawn.

Published
2019
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42. Regulatory T cells as suppressors of anti-tumor immunity: Role of metabolism.

Author

De Rosa V, Di Rella F, Di Giacomo A, and Matarese G

Subjects
Animals, Apoptosis, Cell Proliferation, Glucose metabolism, Glycolysis, Humans, Immunotherapy, Mice, Mitochondria metabolism, Neoplasms therapy, Oxidative Phosphorylation, T-Lymphocytes immunology, Tumor Microenvironment immunology, Neoplasms immunology, Neoplasms metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Tumor Microenvironment physiology
Abstract

Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response. Current experimental evidence suggests that tumor-derived metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance. For example, several glycolytic enzymes, deregulated in cancer, contribute to tumor progression independently from their canonical metabolic activity. Indeed, they can control apoptosis, gene expression and activation of specific intracellular pathways, thus suggesting a direct link between metabolic switches and pro-tumorigenic transcriptional programs. Focus of this review is to define the specific metabolic pathways controlling Treg cell immunobiology in the context of anti-tumor immunity and tumor progression., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2017
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43. LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility in mouse.

Author

Rossi V, Lispi M, Longobardi S, Mattei M, Di Rella F, Salustri A, De Felici M, and Klinger FG

Subjects
Androstadienes pharmacology, Animals, Cells, Cultured, Chromones pharmacology, Cyclic AMP metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, DNA Damage drug effects, Female, Fertility drug effects, Follicle Stimulating Hormone pharmacology, Mice, Mice, Transgenic, Morpholines pharmacology, Oocytes cytology, Oocytes drug effects, Oocytes metabolism, Ovarian Follicle cytology, Ovarian Follicle drug effects, Ovarian Follicle metabolism, Phosphoproteins metabolism, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Proto-Oncogene Proteins c-akt metabolism, Receptors, LH metabolism, Signal Transduction, Trans-Activators metabolism, Wortmannin, Apoptosis drug effects, Cisplatin toxicity, Luteinizing Hormone pharmacology
Abstract

Premature ovarian failure and female infertility are frequent side effects of anticancer therapies, owing to the extreme sensitivity of the ovarian reserve oocytes to the damaging effects of irradiation and chemotherapy on DNA. We report here a robust protective effect of luteinizing hormone (LH) on the primordial follicle pool of prepubertal ovaries against the cisplatin (Cs)-induced apoptosis. In vitro LH treatment of prepubertal ovarian fragments generated anti-apoptotic signals by a subset of ovarian somatic cells expressing LH receptor (LHR) through cAMP/PKA and Akt pathways. Such signals, reducing the oocyte level of pro-apoptotic TAp63 protein and favoring the repair of the Cs-damaged DNA in the oocytes, prevented their apoptosis. Noteworthy, in vivo administration to prepubertal female mice of a single dose of LH together with Cs inhibited the depletion of the primordial follicle reserve caused by the drug and preserved their fertility in reproductive age, preventing significant alteration in the number of pregnancy and of delivered pups. In conclusion, these findings establish a novel ovoprotective role for LH and further support the very attracting prospective to use physiological 'fertoprotective' approaches for preventing premature infertility and risks linked to precocious menopause in young patients who survived cancer after chemotherapy.

Published
2017
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