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2,686 results on '"Paris I"'

1. The diverse landscape of AB5-type toxins

Author

Paris I. Brown, Adaobi Ojiakor, Antonio J. Chemello, and Casey C. Fowler

Subjects
Bacterial pathogenesis, Pathogen evolution, Ab-type toxins, Ab5-type toxins, Shiga toxin, Cholera toxin, Biotechnology, TP248.13-248.65, Microbiology, QR1-502
Abstract

AB5-type toxins are a group of secreted protein toxins that are central virulence factors for bacterial pathogens such as Shigella dysenteriae, Vibrio cholerae, Bordetella pertussis, and certain lineages of pathogenic Escherichia coli and Salmonella enterica. AB5 toxins are composed of an active (A) subunit that manipulates host cell biology in complex with a pentameric binding/delivery (B) subunit that mediates the toxin's entry into host cells and its subsequent intracellular trafficking. Broadly speaking, all known AB5-type toxins adopt similar structural architectures and employ similar mechanisms of binding, entering and trafficking within host cells. Despite this, there is a remarkable amount of diversity amongst AB5-type toxins; this includes different toxin families with unrelated activities, as well as variation within families that can have profound functional consequences. In this review, we discuss the diversity that exists amongst characterized AB5-type toxins, with an emphasis on the genetic and functional variability within AB5 toxin families, how this may have evolved, and its impact on human disease.

Published
2023
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3. The Sloan Digital Sky Survey Quasar Catalog: Fourteenth Data Release

Author

Pâris, I., Petitjean, P., Aubourg, E., Myers, A. D., Streblyanska, A., Lyke, B. W., Anderson, S. F., Armengaud, E., Bautista, J., Blanton, M. R., Blomqvist, M., Brinkmann, J., Brownstein, J. R., Brandt, W. N., Burtin, E., Dawson, K., de la Torre, S., Georgakakis, A., Gil-Marin, H., Green, P. J., Hall, P. B., Kneib, J. -P., LaMassa, S. M., Goff, J. -M. Le, MacLeod, C., Mariappan, V., McGreer, I. D., Merloni, A., Noterdaeme, P., Delabrouille, N. Palanque, Percival, W. J., Ross, A. J., Rossi, G., Schneider, D. P., Seo, H. -J., Tojeiro, R., Weaver, B. A., Weijmans, A. -M., Yèche, C., Zarrouk, P., and Zhao, G. -B.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present the Data Release 14 Quasar catalog (DR14Q) from the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV). This catalog includes all SDSS-IV/eBOSS objects that were spectroscopically targeted as quasar candidates and that are confirmed as quasars via a new automated procedure combined with a partial visual inspection of spectra, have luminosities $M_{\rm i} \left[ z=2 \right] < -20.5$ (in a $\Lambda$CDM cosmology with $H_0 = 70 \ {\rm km \ s^{-1} \ Mpc ^{-1}}$, $\Omega_{\rm M} = 0.3$, and $\Omega_{\rm \Lambda} = 0.7$), and either display at least one emission line with a full width at half maximum (FWHM) larger than $500 \ {\rm km \ s^{-1}}$ or, if not, have interesting/complex absorption features. The catalog also includes previously spectroscopically-confirmed quasars from SDSS-I, II and III. The catalog contains 526,356 quasars 144,046 are new discoveries since the beginning of SDSS-IV) detected over 9,376 deg$^2$ (2,044 deg$^2$ having new spectroscopic data available) with robust identification and redshift measured by a combination of principal component eigenspectra. The catalog is estimated to have about 0.5% contamination. The catalog identifies 21,877 broad absorption line quasars and lists their characteristics. For each object, the catalog presents SDSS five-band CCD-based photometry with typical accuracy of 0.03 mag. The catalog also contains X-ray, ultraviolet, near-infrared, and radio emission properties of the quasars, when available, from other large-area surveys., Comment: Accepted for publication in A&A. The catalog is available at https://data.sdss.org/sas/dr14/eboss/qso/DR14Q/DR14Q_v4_4.fits

Published
2017
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4. WEAVE-QSO: A Massive Intergalactic Medium Survey for the William Herschel Telescope

Author

Pieri, M. M., Bonoli, S., Chaves-Montero, J., Paris, I., Fumagalli, M., Bolton, J. S., Viel, M., Noterdaeme, P., Miralda-Escudé, J., Busca, N. G., Rahmani, H., Peroux, C., Font-Ribera, A., Trager, S. C., and Collaboration, The WEAVE

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

In these proceedings we describe the WEAVE-QSO survey, which will observe around 400,000 high redshift quasars starting in 2018. This survey is part of a broader WEAVE survey to be conducted at the 4.2m William Herschel Telescope. We will focus on chiefly on the science goals, but will also briefly summarise the target selection methods anticipated and the expected survey plan. Understanding the apparent acceleration in the expansion of the Universe is one of the key scientific challenges of our time. Many experiments have been proposed to study this expansion, using a variety of techniques. Here we describe a survey that can measure this acceleration and therefore help elucidate the nature of dark energy: a survey of the Lyman-alpha forest (and quasar absorption in general) in spectra towards z>2 quasars (QSOs). Further constraints on neutrino masses and warm dark matter are also anticipated. The same data will also shed light on galaxy formation via study of the properties of inflowing/outflowing gas associated with nearby galaxies and in a cosmic web context. Gas properties are sensitive to density, temperature, UV radiation, metallicity and abundance pattern, and so constraint galaxy formation in a variety of ways. WEAVE-QSO will study absorbers with a dynamic range spanning more than 8 orders of magnitude in column density, their thermal broadening, and a host of elements and ionization species. A core principal of the WEAVE-QSO survey is the targeting of QSOs with near 100% efficiency principally through use of the J-PAS (r < 23.2) and Gaia (r < 20) data., Comment: 8 pages, 2 figures, proceedings of the SF2A conference, Lyon, 2016

Published
2016

5. Discovery of a Perseus-like cloud in the early Universe: HI-to-H2 transition, carbon monoxide and small dust grains at zabs=2.53 towards the quasar J0000+0048

Author

Noterdaeme, P., Krogager, J. -K., Balashev, S., Ge, J., Gupta, N., Krühler, T., Ledoux, C., Murphy, M. T., Pâris, I., Petitjean, P., Rahmani, H., Srianand, R., and Ubachs, W.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present the discovery of a molecular cloud at zabs=2.5255 along the line of sight to the quasar J0000+0048. We perform a detailed analysis of the absorption lines from ionic, neutral atomic and molecular species in different excitation levels, as well as the broad-band dust extinction. We find that the absorber classifies as a Damped Lyman-alpha system (DLA) with logN(HI)(cm^-2)=20.8+/-0.1. The DLA has super-Solar metallicity with a depletion pattern typical of cold gas and an overall molecular fraction ~50%. This is the highest f-value observed to date in a high-z intervening system. Most of the molecular hydrogen arises from a clearly identified narrow (b~0.7 km/s), cold component in which CO molecules are also found, with logN(CO)~15. We study the chemical and physical conditions in the cold gas. We find that the line of sight probes the gas deep after the HI-to-H2 transition in a ~4-5 pc-size cloud with volumic density nH~80 cm^-3 and temperature of only 50 K. Our model suggests that the presence of small dust grains (down to about 0.001 {\mu}m) and high cosmic ray ionisation rate (zeta_H a few times 10^-15 s^-1) are needed to explain the observed atomic and molecular abundances. The presence of small grains is also in agreement with the observed steep extinction curve that also features a 2175 A bump. The properties of this cloud are very similar to what is seen in diffuse molecular regions of the nearby Perseus complex. The high excitation temperature of CO rotational levels towards J0000+0048 betrays however the higher temperature of the cosmic microwave background. Using the derived physical conditions, we correct for a small contribution (0.3 K) of collisional excitation and obtain TCMB(z = 2.53)~9.6 K, in perfect agreement with the predicted adiabatic cooling of the Universe. [abridged], Comment: 24 pages, 24 figures, accepted for publication in A&A

Published
2016
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6. XQ-100: A legacy survey of one hundred 3.5 < z < 4.5 quasars observed with VLT/XSHOOTER

Author

Lopez, S., D'Odorico, V., Ellison, S. L., Becker, G. D., Christensen, L., Cupani, G., Denney, K. D., Paris, I., Worseck, G., Berg, T. A. M., Cristiani, S., Dessauges-Zavadsky, M., Haehnelt, M., Hamann, F., Hennawi, J., Irsic, V., Kim, T. -S., Lopez, P., Saust, R. Lund, Menard, B., Perrotta, S., Prochaska, J. X., Sanchez-Ramirez, R., Vestergaard, M., Viel, M., and Wisotzki, L.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

We describe the execution and data reduction of the European Southern Observatory Large Programme "Quasars and their absorption lines: a legacy survey of the high-redshift universe with VLT/XSHOOTER" (hereafter `XQ-100'). XQ-100 has produced and made publicly available an homogeneous and high-quality sample of echelle spectra of 100 QSOs at redshifts z~3.5-4.5 observed with full spectral coverage from 315 to 2500 nm at a resolving power ranging from R~4000 to 7000, depending on wavelength. The median signal-to-noise ratios are 33, 25 and 43, as measured at rest-frame wavelengths 1700, 3000 and 3600 Angstrom, respectively. This paper provides future users of XQ-100 data with the basic statistics of the survey, along with details of target selection, data acquisition and data reduction. The paper accompanies the public release of all data products, including 100 reduced spectra. XQ-100 is the largest spectroscopic survey to date of high-redshift QSOs with simultaneous rest-frame UV/optical coverage, and as such enables a wide range of extragalactic research, from cosmology and galaxy evolution to AGN astrophysics., Comment: In press at A&A. Table A.2 updated to match the summary table in the ESO archive

Published
2016
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7. The evolution of neutral gas in damped Lyman $\alpha$ systems from the XQ-100 survey

Author

Sánchez-Ramírez, R., Ellison, S. L., Prochaska, J. X., Berg, T. A. M., López, S., D'Odorico, V., Becker, G. D., Christensen, L., Cupani, G., Denney, K. D., Pâris, I., Worseck, G., and Gorosabel, J.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, Astrophysics - Astrophysics of Galaxies
Abstract

We present a sample of 38 intervening Damped Lyman $\alpha$ (DLA) systems identified towards 100 $z>3.5$ quasars, observed during the XQ-100 survey. The XQ-100 DLA sample is combined with major DLA surveys in the literature. The final combined sample consists of 742 DLAs over a redshift range approximately $1.6 < z_{\rm abs} < 5.0$. We develop a novel technique for computing $\Omega_{\rm HI}^{\rm DLA}$ as a continuous function of redshift, and we thoroughly assess and quantify the sources of error therein, including fitting errors and incomplete sampling of the high column density end of the column density distribution function. There is a statistically significant redshift evolution in $\Omega_{\rm HI}^{\rm DLA}$ ($\geq 3 \sigma$) from $z \sim 2$ to $z \sim$ 5. In order to make a complete assessment of the redshift evolution of $\Omega_{\rm HI}$, we combine our high redshift DLA sample with absorption surveys at intermediate redshift and 21cm emission line surveys of the local universe. Although $\Omega_{\rm HI}^{\rm DLA}$, and hence its redshift evolution, remains uncertain in the intermediate redshift regime ($0.1 < z_{\rm abs} < 1.6$), we find that the combination of high redshift data with 21cm surveys of the local universe all yield a statistically significant evolution in $\Omega_{\rm HI}$ from $z \sim 0$ to $z \sim 5$ ($\geq 3 \sigma$). Despite its statistical significance, the magnitude of the evolution is small: a linear regression fit between $\Omega_{\rm HI}$ and $z$ yields a typical slope of $\sim$0.17$\times 10^{-3}$, corresponding to a factor of $\sim$ 4 decrease in $\Omega_{\rm HI}$ between $z=5$ and $z=0$., Comment: Submitted to MNRAS, this version follows the referee's report and minor revisions. Large tables are included in the source file tarball

Published
2015
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8. Les évêques et les abbés devant la faim

Author

Séminaire du Laboratoire de Médiévistique de Paris I (23-01-2024: Paris-1, Sorbonne), Wilkin, Alexis, Séminaire du Laboratoire de Médiévistique de Paris I (23-01-2024: Paris-1, Sorbonne), and Wilkin, Alexis

Abstract

info:eu-repo/semantics/nonPublished

Published
2024

9. The Extended Baryon Oscillation Spectroscopic Survey: Variability Selection and Quasar Luminosity Function

Author

Palanque-Delabrouille, N., Magneville, Ch., Yèche, Ch., Pâris, I., Petitjean, P., Burtin, E., Dawson, K., McGreer, I., Myers, A. D., Rossi, G., Schlegel, D., Schneider, D., Streblyanska, A., and Tinker, J.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The SDSS-IV/eBOSS has an extensive quasar program that combines several selection methods. Among these, the photometric variability technique provides highly uniform samples, unaffected by the redshift bias of traditional optical-color selections, when $z= 2.7 - 3.5$ quasars cross the stellar locus or when host galaxy light affects quasar colors at $z < 0.9$. Here, we present the variability selection of quasars in eBOSS, focusing on a specific program that led to a sample of 13,876 quasars to $g_{\rm dered}=22.5$ over a 94.5 deg$^2$ region in Stripe 82, an areal density 1.5 times higher than over the rest of the eBOSS footprint. We use these variability-selected data to provide a new measurement of the quasar luminosity function (QLF) in the redshift range $0.682.2$. Both models are constrained to be continuous at $z=2.2$. They present a flattening of the bright-end slope at large redshift. The LEDE model indicates a reduction of the break density with increasing redshift, but the evolution of the break magnitude depends on the parameterization. The models are in excellent accord, predicting quasar counts that agree within 0.3\% (resp., 1.1\%) to $g<22.5$ (resp., $g<23$). The models are also in good agreement over the entire redshift range with models from previous studies., Comment: 15 pages, 12 figures, accepted for publication in A&A

Published
2015
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10. The Sloan Digital Sky Survey Reverberation Mapping Project: Rapid CIV Broad Absorption Line Variability

Author

Grier, C. J., Hall, P. B., Brandt, W. N., Trump, J. R., Shen, Yue, Vivek, M., Ak, N. Filiz, Chen, Yuguang, Dawson, K. S., Denney, K. D., Green, Paul. J., Jiang, Linhua, Kochanek, C. S., McGreer, Ian D., Pâris, I., Peterson, B. M., Schneider, D. P., Tao, Charling, Wood-Vasey, W. M., Bizyaev, Dmitry, Ge, Jian, Kinemuchi, Karen, Oravetz, Daniel, Pan, Kaike, and Simmons, Audrey

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We report the discovery of rapid variations of a high-velocity CIV broad absorption line trough in the quasar SDSS J141007.74+541203.3. This object was intensively observed in 2014 as a part of the Sloan Digital Sky Survey Reverberation Mapping Project, during which 32 epochs of spectroscopy were obtained with the Baryon Oscillation Spectroscopic Survey spectrograph. We observe significant (>4sigma) variability in the equivalent width of the broad (~4000 km/s wide) CIV trough on rest-frame timescales as short as 1.20 days (~29 hours), the shortest broad absorption line variability timescale yet reported. The equivalent width varied by ~10% on these short timescales, and by about a factor of two over the duration of the campaign. We evaluate several potential causes of the variability, concluding that the most likely cause is a rapid response to changes in the incident ionizing continuum. If the outflow is at a radius where the recombination rate is higher than the ionization rate, the timescale of variability places a lower limit on the density of the absorbing gas of n_e > 3.9 x 10^5 cm^-3. The broad absorption line variability characteristics of this quasar are consistent with those observed in previous studies of quasars, indicating that such short-term variability may in fact be common and thus can be used to learn about outflow characteristics and contributions to quasar/host-galaxy feedback scenarios., Comment: 15 pages, 14 figures. Accepted for publication in the Astrophysical Journal

Published
2015
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11. VLT/UVES observations of extremely strong intervening damped Lyman-alpha systems: Molecular hydrogen and excited carbon, oxygen and silicon at log N(HI)=22.4

Author

Noterdaeme, P., Srianand, R., Rahmani, H., Petitjean, P., Pâris, I., Ledoux, C., Gupta, N., and López, S.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present a detailed analysis of three extremely strong intervening DLAs (log N(HI)>=21.7) observed towards quasars with VLT/UVES. We measure overall metallicities of [Zn/H]~-1.2, -1.3 and -0.7 at respectively zabs=2.34 towards SDSS J2140-0321 (log N(HI) = 22.4+/-0.1), zabs=3.35 towards SDSS J1456+1609 (log N(HI) = 21.7+/-0.1) and zabs=2.25 towards SDSS J0154+1935 (log N(HI) = 21.75+/-0.15). We detect H2 towards J2140-0321 (log N(H2) = 20.13+/-0.07) and J1456+1609 (log N(H2) = 17.10+/-0.09) and argue for a tentative detection towards J0154+1935. Absorption from the excited fine-structure levels of OI, CI and SiII are detected in the system towards J2140-0321, that has the largest HI column density detected so far in an intervening DLA. This is the first detection of OI fine-structure lines in a QSO-DLA, that also provides us a rare possibility to study the chemical abundances of less abundant atoms like Co and Ge. Simple single phase photo-ionisation models fail to reproduce all the observed quantities. Instead, we suggest that the cloud has a stratified structure: H2 and CI likely originate from both a dense (log nH~2.5-3) cold (80K) and warm (250K) phase containing a fraction of the total HI while a warmer (T>1000 K) phase probably contributes significantly to the high excitation of OI fine-structure levels. The observed CI/H2 column density ratio is surprisingly low compared to model predictions and we do not detect CO molecules: this suggests a possible underabundance of C by 0.7 dex compared to other alpha elements. The absorber could be a photo-dissociation region close to a bright star (or a star cluster) where higher temperature occurs in the illuminated region. Direct detection of on-going star formation through e.g. NIR emission lines in the surrounding of the gas would enable a detailed physical modelling of the system., Comment: accepted for publication in A&A

Published
2015
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12. The time-domain spectroscopic survey: Understanding the optically variable sky with sequels in SDSS-III

Author

Ruan, JJ, Anderson, SF, Green, PJ, Morganson, E, Eracleous, M, Myers, AD, Badenes, C, Bershady, MA, Brandt, WN, Chambers, KC, Davenport, JRA, Dawson, KS, Flewelling, H, Heckman, TM, Isler, JC, Kaiser, N, Kneib, JP, MacLeod, CL, Paris, I, Ross, NP, Runnoe, JC, Schlafly, EF, Schmidt, SJ, Schneider, DP, Schwope, AD, Shen, Y, Stassun, KG, Szkody, P, Waters, CZ, and York, DG

Subjects
quasars: general, stars: variables: general, surveys, astro-ph.GA, astro-ph.CO, astro-ph.SR, Astronomy & Astrophysics, Astronomical and Space Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Physical Chemistry, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Physical Chemistry (incl. Structural)
Abstract

The Time-Domain Spectroscopic Survey (TDSS) is an SDSS-IV eBOSS subproject primarily aimed at obtaining identification spectra of ∼220,000 optically variable objects systematically selected from SDSS/Pan-STARRS1 multi-epoch imaging. We present a preview of the science enabled by TDSS, based on TDSS spectra taken over ∼320 deg2 of sky as part of the SEQUELS survey in SDSS-III, which is in part a pilot survey for eBOSS in SDSS-IV. Using the 15,746 TDSS-selected single-epoch spectra of photometrically variable objects in SEQUELS, we determine the demographics of our variability-selected sample and investigate the unique spectral characteristics inherent in samples selected by variability. We show that variability-based selection of quasars complements color-based selection by selecting additional redder quasars and mitigates redshift biases to produce a smooth quasar redshift distribution over a wide range of redshifts. The resulting quasar sample contains systematically higher fractions of blazars and broad absorption line quasars than from color-selected samples. Similarly, we show that M dwarfs in the TDSS-selected stellar sample have systematically higher chromospheric active fractions than the underlying M-dwarf population based on their Hα emission. TDSS also contains a large number of RR Lyrae and eclipsing binary stars with main-sequence colors, including a few composite-spectrum binaries. Finally, our visual inspection of TDSS spectra uncovers a significant number of peculiar spectra, and we highlight a few cases of these interesting objects. With a factor of ∼15 more spectra, the main TDSS survey in SDSS-IV will leverage the lessons learned from these early results for a variety of time-domain science applications.

Published
2016

13. The extended Baryon Oscillation Spectroscopic Survey: Variability selection and quasar luminosity function (vol 587, A41, 2016)

Author

Palanque-Delabrouille, N, Magneville, Ch, Yeche, Ch, Paris, I, Petitjean, P, Burtin, E, Dawson, K, McGreer, I, Myers, AD, Rossi, G, Schlegel, D, Schneider, D, Streblyanska, A, and Tinker, J

Subjects
quasars: general, large-scale structure of Universe, surveys, errata, addenda, errata, addenda, Astronomical and Space Sciences, Astronomy & Astrophysics
Published
2016

15. The Dependence of C IV Broad Absorption Line Properties on Accompanying Si IV and Al III Absorption: Relating Quasar-Wind Ionization Levels, Kinematics, and Column Densities

Author

Ak, N. Filiz, Brandt, W. N., Hall, P. B., Schneider, D. P., Trump, J. R., Anderson, S. F., Hamann, F., Myers, Adam D., Paris, I., Petitjean, P., Ross, Nicholas P., Shen, Yue, and York, Don

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

We consider how the profile and multi-year variability properties of a large sample of C IV Broad Absorption Line (BAL) troughs change when BALs from Si IV and/or Al III are present at corresponding velocities, indicating that the line-of-sight intercepts at least some lower ionization gas. We derive a number of observational results for C IV BALs separated according to the presence or absence of accompanying lower ionization transitions, including measurements of composite profile shapes, equivalent width (EW), characteristic velocities, composite variation profiles, and EW variability. We also measure the correlations between EW and fractional-EW variability for C IV, Si IV, and Al III. Our measurements reveal the basic correlated changes between ionization level, kinematics, and column density expected in accretion-disk wind models; e.g., lines-of-sight including lower ionization material generally show deeper and broader C IV troughs that have smaller minimum velocities and that are less variable. Many C IV BALs with no accompanying Si IV or Al III BALs may have only mild or no saturation., Comment: 26 pages, 16 figures. Accepted for publication in ApJ

Published
2014
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16. A connection between extremely strong Damped Lyman-alpha Systems and Lyman-alpha Emitting Galaxies at small impact parameters

Author

Noterdaeme, P., Petitjean, P., Paris, I., Cai, Z., Finley, H., Ge, J., Pieri, M. M., and York, D. G.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present a study of ~100 high redshift (z~2-4) extremely strong damped Lyman-alpha systems (ESDLA, with N(HI)>0.5x10^22 cm^-2) detected in quasar spectra from the Baryon Oscillation Spectroscopic Survey SDSS-III DR11. We study the neutral hydrogen, metal, and dust content of this elusive population of absorbers and confirm our previous finding that the high column density end of the N(HI) frequency distribution has a relatively shallow slope with power-law index -3.6, similar to what is seen from 21-cm maps in nearby galaxies. The stacked absorption spectrum indicates a typical metallicity ~1/20th solar, similar to the mean metallicity of the overall DLA population. The relatively small velocity extent of the low-ionisation lines suggests that ESDLAs do not arise from large-scale flows of neutral gas. The high column densities involved are in turn more similar to what is seen in DLAs associated with gamma-ray burst afterglows (GRB-DLAs), which are known to occur close to star forming regions. This indicates that ESDLAs arise from lines of sight passing at very small impact parameters from the host galaxy, as observed in nearby galaxies. This is also supported by simple theoretical considerations and recent high-z hydrodynamical simulations. We strongly substantiate this picture by the first statistical detection of Lya emission with ~(0.6+/-0.2)x10^42 erg/s in the core of ESDLAs (corresponding to about 0.1 L* at z~2-3), obtained through stacking the fibre spectra (of radius 1" corresponding to ~8 kpc at z~2.5). [truncated], Comment: 20 pages, 21 figures, 2 tables. Accepted for publication in A&A

Published
2014
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17. Clustering of intermediate redshift quasars using the final SDSS III-BOSS sample

Author

Eftekharzadeh, S, Myers, AD, White, M, Weinberg, DH, Schneider, DP, Shen, Y, Font-Ribera, A, Ross, NP, Paris, I, and Streblyanska, A

Subjects
galaxies: quasars: general, cosmology: observations, dark matter, large-scale, structure of Universe, astro-ph.CO, Astronomy & Astrophysics, Astronomical and Space Sciences
Abstract

We measure the two-point clustering of spectroscopically confirmed quasars from the final sample of the Baryon Oscillation Spectroscopic Survey (BOSS) on comoving scales of 4 ≲ s ≲ 22 h-1 Mpc. The sample covers 6950 deg2 [~19 (h-1Gpc)3] and, over the redshift range 2.2 ≲ z ≲ 2.8, contains 55 826 homogeneously selected quasars, which is twice as many as in any similar work. We deduce bQ = 3.54 ± 0.10; the most precise measurement of quasar bias to date at these redshifts. This corresponds to a host halo mass of ~2 × 1012 h-1M⊙ with an implied quasar duty cycle of ~1 per cent. The real-space projected correlation function is well fitted by a power law of index 2 and correlation length r0 = (8.12 ± 0.22) h-1 Mpc over scales of 4 ≲ rp ≲ 25 h-1 Mpc. To better study the evolution of quasar clustering at moderate redshift, we extend the redshift range of our study to z ~ 3.4 and measure the bias and correlation length of three subsamples over 2.2 ≲ z ≲ 3.4. We find no significant evolution of r0 or bias over this range, implying that the host halo mass of quasars decreases somewhat with increasing redshift. We find quasar clustering remains similar over a decade in luminosity, contradicting a scenario in which quasar luminosity is monotonically related to halo mass at z ≈ 2.5. Our results are broadly consistent with previous BOSS measurements, but they yield more precise constraints based upon a larger and more uniform data set.

Published
2015

18. Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study

Author

Di Lisa, F, Krasniqi, E, Pizzuti, L, Barba, M, Cannita, K, De Giorgi, U, Borella, F, Foglietta, J, Cariello, A, Ferro, A, Picardo, E, Mitidieri, M, Sini, V, Stani, S, Tonini, G, Santini, D, La Verde, N, Gambaro, A, Grassadonia, A, Tinari, N, Garrone, O, Sarobba, G, Livi, L, Meattini, I, D'Auria, G, Vergati, M, Gamucci, T, Pistelli, M, Berardi, R, Risi, E, Giotta, F, Lorusso, V, Rinaldi, L, Artale, S, Cazzaniga, M, Zustovich, F, Cappuzzo, F, Landi, L, Torrisi, R, Scagnoli, S, Botticelli, A, Michelotti, A, Fratini, B, Saltarelli, R, Paris, I, Muratore, M, Cassano, A, Gianni, L, Gaspari, V, Veltri, E, Zoratto, F, Fiorio, E, Fabbri, M, Mazzotta, M, Ruggeri, E, Pedersini, R, Valerio, M, Filomeno, L, Minelli, M, Scavina, P, Raffaele, M, Astone, A, De Vita, R, Pozzi, M, Riccardi, F, Greco, F, Moscetti, L, Giordano, M, Maugeri-Sacca, M, Zennaro, A, Botti, C, Pelle, F, Cappelli, S, Cavicchi, F, Vizza, E, Sanguineti, G, Tomao, F, Cortesi, E, Marchetti, P, Tomao, S, Speranza, I, Sperduti, I, Ciliberto, G, Vici, P, Di Lisa F. S., Krasniqi E., Pizzuti L., Barba M., Cannita K., De Giorgi U., Borella F., Foglietta J., Cariello A., Ferro A., Picardo E., Mitidieri M., Sini V., Stani S., Tonini G., Santini D., La Verde N., Gambaro A. R., Grassadonia A., Tinari N., Garrone O., Sarobba G., Livi L., Meattini I., D'Auria G., Vergati M., Gamucci T., Pistelli M., Berardi R., Risi E., Giotta F., Lorusso V., Rinaldi L., Artale S., Cazzaniga M. E., Zustovich F., Cappuzzo F., Landi L., Torrisi R., Scagnoli S., Botticelli A., Michelotti A., Fratini B., Saltarelli R., Paris I., Muratore M., Cassano A., Gianni L., Gaspari V., Veltri E. M., Zoratto F., Fiorio E., Fabbri M. A., Mazzotta M., Ruggeri E. M., Pedersini R., Valerio M. R., Filomeno L., Minelli M., Scavina P., Raffaele M., Astone A., De Vita R., Pozzi M., Riccardi F., Greco F., Moscetti L., Giordano M., Maugeri-Sacca M., Zennaro A., Botti C., Pelle F., Cappelli S., Cavicchi F., Vizza E., Sanguineti G., Tomao F., Cortesi E., Marchetti P., Tomao S., Speranza I., Sperduti I., Ciliberto G., Vici P., Di Lisa, F, Krasniqi, E, Pizzuti, L, Barba, M, Cannita, K, De Giorgi, U, Borella, F, Foglietta, J, Cariello, A, Ferro, A, Picardo, E, Mitidieri, M, Sini, V, Stani, S, Tonini, G, Santini, D, La Verde, N, Gambaro, A, Grassadonia, A, Tinari, N, Garrone, O, Sarobba, G, Livi, L, Meattini, I, D'Auria, G, Vergati, M, Gamucci, T, Pistelli, M, Berardi, R, Risi, E, Giotta, F, Lorusso, V, Rinaldi, L, Artale, S, Cazzaniga, M, Zustovich, F, Cappuzzo, F, Landi, L, Torrisi, R, Scagnoli, S, Botticelli, A, Michelotti, A, Fratini, B, Saltarelli, R, Paris, I, Muratore, M, Cassano, A, Gianni, L, Gaspari, V, Veltri, E, Zoratto, F, Fiorio, E, Fabbri, M, Mazzotta, M, Ruggeri, E, Pedersini, R, Valerio, M, Filomeno, L, Minelli, M, Scavina, P, Raffaele, M, Astone, A, De Vita, R, Pozzi, M, Riccardi, F, Greco, F, Moscetti, L, Giordano, M, Maugeri-Sacca, M, Zennaro, A, Botti, C, Pelle, F, Cappelli, S, Cavicchi, F, Vizza, E, Sanguineti, G, Tomao, F, Cortesi, E, Marchetti, P, Tomao, S, Speranza, I, Sperduti, I, Ciliberto, G, Vici, P, Di Lisa F. S., Krasniqi E., Pizzuti L., Barba M., Cannita K., De Giorgi U., Borella F., Foglietta J., Cariello A., Ferro A., Picardo E., Mitidieri M., Sini V., Stani S., Tonini G., Santini D., La Verde N., Gambaro A. R., Grassadonia A., Tinari N., Garrone O., Sarobba G., Livi L., Meattini I., D'Auria G., Vergati M., Gamucci T., Pistelli M., Berardi R., Risi E., Giotta F., Lorusso V., Rinaldi L., Artale S., Cazzaniga M. E., Zustovich F., Cappuzzo F., Landi L., Torrisi R., Scagnoli S., Botticelli A., Michelotti A., Fratini B., Saltarelli R., Paris I., Muratore M., Cassano A., Gianni L., Gaspari V., Veltri E. M., Zoratto F., Fiorio E., Fabbri M. A., Mazzotta M., Ruggeri E. M., Pedersini R., Valerio M. R., Filomeno L., Minelli M., Scavina P., Raffaele M., Astone A., De Vita R., Pozzi M., Riccardi F., Greco F., Moscetti L., Giordano M., Maugeri-Sacca M., Zennaro A., Botti C., Pelle F., Cappelli S., Cavicchi F., Vizza E., Sanguineti G., Tomao F., Cortesi E., Marchetti P., Tomao S., Speranza I., Sperduti I., Ciliberto G., and Vici P.

Abstract

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning ef

Published
2023

19. Broad Absorption Line Variability on Multi-Year Timescales in a Large Quasar Sample

Author

Ak, N. Filiz, Brandt, W. N., Hall, P. B., Schneider, D. P., Anderson, S. F., Hamann, F., Lundgren, B. F., Myers, Adam D., Paris, I., Petitjean, P., Ross, Nicholas P., Shen, Yue, and York, Don

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present a detailed investigation of the variability of 428 C IV and 235 Si IV Broad Absorption Line (BAL) troughs identified in multi-epoch observations of 291 quasars by the Sloan Digital Sky Survey-I/II/III. These observations primarily sample rest-frame timescales of 1-3 yr over which significant rearrangement of the BAL wind is expected. We derive a number of observational results on, e.g., the frequency of BAL variability, the velocity range over which BAL variability occurs, the primary observed form of BAL-trough variability, the dependence of BAL variability upon timescale, the frequency of BAL strengthening vs. weakening, correlations between BAL variability and BAL-trough profiles, relations between C IV and Si IV BAL variability, coordinated multi-trough variability, and BAL variations as a function of quasar properties. We assess implications of these observational results for quasar winds. Our results support models where most BAL absorption is formed within an order-of-magnitude of the wind-launching radius, although a significant minority of BAL troughs may arise on larger scales. We estimate an average lifetime for a BAL trough along our line-of-sight of a few thousand years. BAL disappearance and emergence events appear to be extremes of general BAL variability, rather than being qualitatively distinct phenomena. We derive the parameters of a random-walk model for BAL EW variability, finding that this model can acceptably describe some key aspects of EW variability. The coordinated trough variability of BAL quasars with multiple troughs suggests that changes in "shielding gas" may play a significant role in driving general BAL variability., Comment: 34 pages, 29 figures. Review study. ApJ, in press

Published
2013
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20. Broad Absorption Line Quasars with Redshifted Troughs: High-Velocity Infall or Rotationally Dominated Outflows?

Author

Hall, Patrick B., Brandt, W. N., Petitjean, P., Paris, I., Ak, N. Filiz, Shen, Yue, Gibson, R. R., Aubourg, E., Anderson, S. F., Schneider, D. P., Bizyaev, D., Brinkmann, J., Malanushenko, E., Malanushenko, V., Myers, A. D., Oravetz, D. J., Ross, N. P., Shelden, A., Simmons, A. E., Streblyanska, A., Weaver, B. A., and York, D. G.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We report the discovery in the Sloan Digital Sky Survey and the SDSS-III Baryon Oscillation Spectroscopic Survey of seventeen broad absorption line (BAL) quasars with high-ionization troughs that include absorption redshifted relative to the quasar rest frame. The redshifted troughs extend to velocities up to v=12,000 km/s and the trough widths exceed 3000 km/s in all but one case. Approximately 1 in 1000 BAL quasars with blueshifted C IV absorption also has redshifted C IV absorption; objects with C IV absorption present only at redshifted velocities are roughly four times rarer. In more than half of our objects, redshifted absorption is seen in C II or Al III as well as C IV, making low-ionization absorption at least ten times more common among BAL quasars with redshifted troughs than among standard BAL quasars. However, the C IV absorption equivalent widths in our objects are on average smaller than those of standard BAL quasars with low-ionization absorption. We consider several possible ways of generating redshifted absorption. The two most likely possibilities may be at work simultaneously, in the same objects or in different ones. Rotationally dominated outflows seen against a quasar's extended continuum source can produce redshifted and blueshifted absorption, but variability consistent with this scenario is seen in only one of the four objects with multiple spectra. The infall of relatively dense and low-ionization gas to radii as small as 400 Schwarzschild radii can in principle explain the observed range of trough profiles, but current models do not easily explain the origin and survival of such gas. Whatever the origin(s) of the absorbing gas in these objects, it must be located at small radii to explain its large redshifted velocities, and thus offers a novel probe of the inner regions of quasars., Comment: MNRAS in press. 40 pages, 17 figures (a few of reduced quality); for full-resolution figures see http://www.yorku.ca/phall/RESEARCH/rsub3-aas.pdf

Published
2013
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22. Column density distribution and cosmological mass density of neutral gas: Sloan Digital Sky Survey-III Data Release 9

Author

Noterdaeme, P., Petitjean, P., Carithers, W. C., Pâris, I., Font-Ribera, A., Bailey, S., Aubourg, E., Bizyaev, D., Ebelke, G., Finley, H., Ge, J., Malanushenko, E., Malanushenko, V., Miralda-Escudé, J., Myers, A. D., Oravetz, D., Pan, K., Pieri, M. M., Ross, N. P., Schneider, D. P., Simmons, A., and York, D. G.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present the first results from an ongoing survey for Damped Lyman-alpha systems (DLAs) in the spectra of z>2 quasars observed in the course of the Baryon Oscillation Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey (SDSS) III. Our full (non-statistical) sample, based on Data Release 9, comprises 12,081 systems with log N(HI)>=20, out of which 6,839 have log N(HI)>=20.3. This is the largest DLA sample ever compiled, superseding that from SDSS-II by a factor of seven. Using a statistical sub-sample and estimating systematics from realistic mock data, we probe the N(HI) distribution at = 2.5. Contrary to what is generally believed, the distribution extends beyond 10^22 cm^-2 with a moderate slope of index\approx-3.5. This result matches surprisingly well the opacity-corrected distribution observed at z = 0. The cosmological mass density of neutral gas in DLAs is found to be Omega_g_DLA~10^-3, evolving only mildly over the past 12 billion years., Comment: Accepted for publication as Letter to the Editor in A&A

Published
2012
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23. Luminosity Function from dedicated SDSS-III and MMT data of quasars in 0.7<z<4.0 selected with a new approach

Author

Palanque-Delabrouille, N., Magneville, Ch., Yeche, Ch., Eftekharzadeh, S., Myers, A. D., Petitjean, P., Paris, I., Aubourg, E., McGreer, I., Fan, X., Dey, A., Schlegel, D., Bailey, S ., Bizayev, D., Bolton, A., Dawson, K., Ebelke, G., Malanushenko, E., Malanushenko, V., Oravetz, D., Pan, K., Ross, N. P., Schneider, D. P., Sheldon, E., Simmons, A., Tinker, J., White, M., and Willmer, Ch.

Subjects
Astrophysics - Cosmology and Extragalactic Astrophysics
Abstract

We present a measurement of the quasar luminosity function in the range 0.682.15. Using pure luminosity evolution models, we fitted our LF measurements, and predicted quasar number counts as a function of redshift and observed magnitude. These predictions are useful inputs for future cosmology surveys such as those relying on the observation of quasars to measure baryon acoustic oscillations., Comment: 15 pages, 14 figs, accepted for publication in A&A

Published
2012
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24. The clustering of intermediate redshift quasars as measured by the Baryon Oscillation Spectroscopic Survey

Author

White, Martin, Myers, Adam D., Ross, Nicholas P., Schlegel, David J., Hennawi, Joseph F., Shen, Yue, McGreer, Ian, Strauss, Michael A., Bolton, Adam S., Bovy, Jo, Fan, X., Miralda-Escude, Jordi, Palanque-Delabrouille, N., Paris, I., Petitjean, P., Schneider, D. P., Viel, M., Weinberg, David H., Yeche, Ch., Zehavi, I., Pan, K., Snedden, S., Bizyaev, D., Brewington, H., Brinkman, J., Malanushenko, V., Malanushenko, E., Oravetz, D., Simmons, A., Sheldon, A., and Weaver, Benjamin A.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We measure the quasar two-point correlation function over the redshift range 2.2~10^{12}Msun/h with a duty cycle for the quasar activity of 1 per cent., Comment: 20 pages, 18 figures. Minor modifications to match version accepted by journal

Published
2012
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25. Simulations of BAO reconstruction with a quasar Lyman-alpha survey

Author

Goff, J. -M. Le, Magneville, C., Rollinde, E., Peirani, S., Petitjean, P., Pichon, C., Rich, J., Yeche, C., Aubourg, E., Busca, N., Charlassier, R., Delubac, T., Hamilton, J. C., Delabrouille, N. Palanque, Paris, I., and Vargas, M.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The imprint of Baryonic Acoustic Oscillations (BAO) on the matter power spectrum can be constrained using the neutral hydrogen density in the intergalactic medium as a tracer of the matter density. One of the goals of the Baryon Oscillation Spectroscopic Survey (BOSS) of the Sloan Digital Sky Survey (SDSS-III) is to derive the Hubble expansion rate and the angular scale from the BAO signal in the IGM. To this aim, the Lyman-alpha forest of 10^5 quasars will be observed in the redshift range 2.2

Published
2011
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26. A Principal Component Analysis of quasar UV spectra at z~3

Author

Pâris, I., Petitjean, P., Rollinde, E., Aubourg, E., Busca, N., Charlassier, R., Delubac, T., Hamilton, J. -Ch., Goff, J. -M. Le, Palanque-Delabrouille, N., Peirani, S., Pichon, Ch., Rich, J., Vargas-Magaña, M., and Yèche, Ch.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

From a Principal Component Analysis (PCA) of 78 z~3 high quality quasar spectra in the SDSS-DR7, we derive the principal components characterizing the QSO continuum over the full wavelength range available. The shape of the mean continuum, is similar to that measured at low-z (z~1), but the equivalent width of the emission lines are larger at low redshift. We calculate the correlation between fluxes at different wavelengths and find that the emission line fluxes in the red part of the spectrum are correlated with that in the blue part. We construct a projection matrix to predict the continuum in the Lyman-$\alpha$ forest from the red part of the spectrum. We apply this matrix to quasars in the SDSS-DR7 to derive the evolution with redshift of the mean flux in the Lyman-$\alpha$ forest due to the absorption by the intergalactic neutral hydrogen. A change in the evolution of the mean flux is apparent around z~3 in the sense of a steeper decrease of the mean flux at higher redshifts. The same evolution is found when the continuum is estimated from the extrapolation of a power-law continuum fitted in the red part of the quasar spectrum if a correction, derived from simple simulations, is applied. Our findings are consistent with previous determinations using high spectral resolution data. We provide the PCA eigenvectors over the wavelength range 1020-2000 \AA\ and the distribution of their weights that can be used to simulate QSO mock spectra., Comment: 15 pages, 18 figures, accepted for publication in A&A

Published
2011
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27. Variability selected high-redshift quasars on SDSS Stripe 82

Author

Palanque-Delabrouille, N., Yeche, Ch., Myers, A. D., Petitjean, P., Ross, Nicholas P., Sheldon, E., Aubourg, E., Delubac, T., Goff, J. -M. Le, Paris, I., Rich, J., Dawson, K. S., Schneider, D. P., and Weaver, B. A.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The SDSS-III BOSS Quasar survey will attempt to observe z>2.15 quasars at a density of at least 15 per square degree to yield the first measurement of the Baryon Acoustic Oscillations in the Ly-alpha forest. To help reaching this goal, we have developed a method to identify quasars based on their variability in the u g r i z optical bands. The method has been applied to the selection of quasar targets in the SDSS region known as Stripe 82 (the Southern equatorial stripe), where numerous photometric observations are available over a 10-year baseline. This area was observed by BOSS during September and October 2010. Only 8% of the objects selected via variability are not quasars, while 90% of the previously identified high-redshift quasar population is recovered. The method allows for a significant increase in the z>2.15 quasar density over previous strategies based on optical (ugriz) colors, achieving a density of 24.0 deg^{-2} on average down to g~22 over the 220 deg^2 area of Stripe 82. We applied this method to simulated data from the Palomar Transient Factory and from Pan-STARRS, and showed that even with data that have sparser time sampling than what is available in Stripe 82, including variability in future quasar selection strategies would lead to increased target selection efficiency in the z>2.15 redshift range. We also found that Broad Absorption Line quasars are preferentially present in a variability than in a color selection., Comment: 14 pages, 21 figures, accepted for publication in A&A

Published
2010
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28. QSO Selection and Photometric Redshifts with Neural Networks

Author

Yeche, Ch., Petitjean, P., Rich, J., Aubourg, E., Busca, N., Hamilton, J. -Ch., Goff, J. -M. Le, Paris, I., Peirani, S., Pichon, Ch., Rollinde, E., and Vargas-Magana, M.

Subjects
Astrophysics - Cosmology and Extragalactic Astrophysics
Abstract

Baryonic Acoustic Oscillations (BAO) and their effects on the matter power spectrum can be studied by using the Lyman-alpha absorption signature of the matter density field along quasar (QSO) lines of sight. A measurement sufficiently accurate to provide useful cosmological constraints requires the observation of ~100000 quasars in the redshift range 2.2

Published
2009

29. 199P Correlation of circulating tumor DNA (ctDNA) or thymidine kinase activity (TKa) dynamic patterns with tumor response in patients (pts) with hormone receptor (HR)+ human epidermal growth factor 2 (HER2)– advanced breast cancer (ABC) on ribociclib (RIB) + letrozole (LET) in BioItaLEE trial

Author

Arpino, G., primary, Bianchini, G., additional, Malorni, L., additional, Caputo, R., additional, Zambelli, A., additional, Puglisi, F., additional, Del Mastro, L., additional, Colleoni, M.A., additional, Montemurro, F., additional, Bianchi, G.V., additional, Paris, I., additional, Allegrini, G., additional, Tamberi, S., additional, Cazzaniga, M.E., additional, Orditura, M., additional, Zamagni, C., additional, Suter, M.B., additional, Fenderico, N., additional, and De Laurentiis, M., additional

Published
2023
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30. 174P Endocrine disruptors and life STILe in patients carrying BRCA pathogenic VAriants with breast and/or ovarian CAncer and women without neoplasm: The STILVARCA study

Author

Fabi, A., primary, Franco, A., additional, Cordisco, E. Lucci, additional, Rossi, A., additional, Terribile, D.A., additional, Fiorio, E., additional, Paris, I., additional, Muratore, M., additional, Terrana, G., additional, Salutari, V., additional, Pavese, F., additional, L'Erario, F.F., additional, Palazzo, A., additional, Di Guglielmo, E., additional, Giontella, E., additional, Cardinali, L., additional, Ferretti, E., additional, Carcagnì, A., additional, Scambia, G., additional, and Migliaccio, S., additional

Published
2023
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31. 138P Activity and efficacy of neoadjuvant chemotherapy (NACT) in luminal-HER2-negative early breast cancer (EBC) according to HER2 score (low vs score 0): A retrospective study

Author

Garufi, G., primary, Carbognin, L., additional, Mastrantoni, L., additional, Maliziola, N., additional, Di Monte, E., additional, Arcuri, G., additional, Frescura, V., additional, Rotondi, A., additional, Fabi, A., additional, Paris, I., additional, Marazzi, F., additional, Franco, A., additional, Mulè, A., additional, Franceschini, G., additional, Orlandi, A., additional, Palazzo, A., additional, Scambia, G., additional, Tortora, G., additional, and Bria, E., additional

Published
2023
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32. 108P Safety results of post-neoadjuvant T-DM1 in the Italian compassionate use program (GIM26-TRASTHER study)

Author

Poggio, F., primary, Tagliamento, M., additional, Favero, D., additional, De Laurentiis, M., additional, Tonini, G., additional, Bernardo, A., additional, Ferraris, E., additional, Paris, I., additional, Riccardi, F., additional, Bianchi, G.V., additional, Cancello, G., additional, Chini, C., additional, Fontana, A., additional, Bisagni, G., additional, Crippa, A., additional, Gennari, A., additional, Berardi, R., additional, Musolino, A., additional, Lambertini, M., additional, and Del Mastro, L., additional

Published
2023
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34. Prospective Study Investigating the Efficacy and Safety of a Scalp Cooling Device for the Prevention of Alopecia in Women Undergoing (Neo)Adjuvant Chemotherapy for Breast Cancer

Author

Carbognin, L., Accetta, C., Di Giorgio, D., Fuso, P., Muratore, M., Tiberi, G., Pavese, F., D'Angelo, T., Fabi, A., Giannarelli, D., Di Leone, A., Magno, S., Garganese, G., Sanchez, A. M., Terribile, D. A., Franceschini, G., Masetti, R., Scambia, G., Paris, I., Fuso P., Muratore M., Giannarelli D., Di Leone A., Magno S., Garganese G. (ORCID:0000-0002-4209-5285), Terribile D. A. (ORCID:0000-0002-3511-0010), Franceschini G. (ORCID:0000-0002-2950-3395), Masetti R. (ORCID:0000-0002-7520-9111), Scambia G. (ORCID:0000-0003-2758-1063), Paris I., Carbognin, L., Accetta, C., Di Giorgio, D., Fuso, P., Muratore, M., Tiberi, G., Pavese, F., D'Angelo, T., Fabi, A., Giannarelli, D., Di Leone, A., Magno, S., Garganese, G., Sanchez, A. M., Terribile, D. A., Franceschini, G., Masetti, R., Scambia, G., Paris, I., Fuso P., Muratore M., Giannarelli D., Di Leone A., Magno S., Garganese G. (ORCID:0000-0002-4209-5285), Terribile D. A. (ORCID:0000-0002-3511-0010), Franceschini G. (ORCID:0000-0002-2950-3395), Masetti R. (ORCID:0000-0002-7520-9111), Scambia G. (ORCID:0000-0003-2758-1063), and Paris I.

Abstract

The prevention of chemotherapy-induced alopecia still represents an urgent need for every day clinical practice. In this regard, this prospective single-center study included breast cancer (BC) patients who underwent a scalp cooling device (Dignicap®) during (neo)adjuvant chemotherapy with the aim to evaluate the efficacy and safety of this device in preventing alopecia. One hundred and seventy-eight patients (median age 43 years) were enrolled. The chemotherapy regimen included anthracycline and taxane-based chemotherapy (68.1%), docetaxel and cyclophosphamide (25.8%), anthracycline and taxane-based plus carboplatin (3.9%), and paclitaxel alone (2.2%). In 25.3% of cases, a dose dense schedule was used. Overall, the success rate was 68.0%: 100% in paclitaxel alone, 87.0% in docetaxel-cyclophosphamide, 59.5% in anthracycline and taxane, and 71.4% in the sequential regimen plus carboplatin group (anthracycline and taxane-based chemotherapy versus taxane-based chemotherapy, p ≤ 001. No difference in terms of hair preservation between dose-dense or standard schedule was found (p = 0.557). Early discontinuation of the scalp cooling was observed in 50 patients (28.1%). Although 138 patients (77.5%) experienced adverse events, 70.2% of patients were satisfied with this device. In conclusion, this large prospective study confirmed the helpful effect of the scalp cooling system in preventing alopecia in BC patients also undergoing sequential anthracyclines and taxane-based chemotherapy.

Published
2022

35. An Innovative Scoring System to Select the Optimal Surgery in Breast Cancer after Neoadjuvant Chemotherapy

Author

Franco, Alessio, Di Leone, Alba, Conti, Marco, Fabi, A., Carbognin, L., Terribile, A. D., Belli, Paolo, Orlandi, Armando, Sanchez, Alejandro Martin, Moschella, F., Mason, Elena Jane, Cimino, G., De Filippis, Alessandra, Marazzi, Fabio, Paris, Ida, Visconti, Giuseppe, Barone Adesi, Liliana, Scardina, L., D'Archi, S., Salgarello, Marzia, Giannarelli, Diana, Masetti, Riccardo, Franceschini, Gianluca, Franco A., Di Leone A., Conti M., Belli P. (ORCID:0000-0001-7979-2466), Orlandi A. (ORCID:0000-0001-5253-4678), Sanchez M. A., Mason E. J., De Filippis A., Marazzi F., Paris I., Visconti G. (ORCID:0000-0002-0041-5420), Barone Adesi L., Salgarello M. (ORCID:0000-0003-4296-4214), Giannarelli D., Masetti R. (ORCID:0000-0002-7520-9111), Franceschini G. (ORCID:0000-0002-2950-3395), Franco, Alessio, Di Leone, Alba, Conti, Marco, Fabi, A., Carbognin, L., Terribile, A. D., Belli, Paolo, Orlandi, Armando, Sanchez, Alejandro Martin, Moschella, F., Mason, Elena Jane, Cimino, G., De Filippis, Alessandra, Marazzi, Fabio, Paris, Ida, Visconti, Giuseppe, Barone Adesi, Liliana, Scardina, L., D'Archi, S., Salgarello, Marzia, Giannarelli, Diana, Masetti, Riccardo, Franceschini, Gianluca, Franco A., Di Leone A., Conti M., Belli P. (ORCID:0000-0001-7979-2466), Orlandi A. (ORCID:0000-0001-5253-4678), Sanchez M. A., Mason E. J., De Filippis A., Marazzi F., Paris I., Visconti G. (ORCID:0000-0002-0041-5420), Barone Adesi L., Salgarello M. (ORCID:0000-0003-4296-4214), Giannarelli D., Masetti R. (ORCID:0000-0002-7520-9111), and Franceschini G. (ORCID:0000-0002-2950-3395)

Abstract

Introduction: The selection of surgery post-neoadjuvant chemotherapy (NACT) is difficult and based on surgeons’ expertise. The aim of this study was to create a post-NEoadjuvant Score System (pNESSy) to choose surgery, optimizing oncological and aesthetical outcomes. Methods: Patients (stage I–III) underwent surgery post-NACT (breast-conserving surgery (BCS), oncoplastic surgery (OPS), and conservative mastectomy (CMR) were included. Data selected were BRCA mutation, ptosis, breast volume, radiological response, MRI, and mammography pre- and post-NACT prediction of excised breast area. pNESSy was created using the association between these data and surgery. Area under the curve (AUC) was assessed. Patients were divided into groups according to correspondence (G1) or discrepancy (G2) between score and surgery; oncological and aesthetic outcomes were analyzed. Results: A total of 255 patients were included (118 BCS, 49 OPS, 88 CMR). pNESSy between 6.896–8.724 was predictive for BCS, 8.725–9.375 for OPS, and 9.376–14.245 for CMR; AUC was, respectively, 0.835, 0.766, and 0.825. G1 presented a lower incidence of involved margins (5–14.7%; p = 0.010), a better locoregional disease-free survival (98.8–88.9%; p < 0.001) and a better overall survival (96.1–86.5%; p = 0.017), and a better satisfaction with breasts (39.8–27.5%; p = 0.017) and physical wellbeing (93.5–73.6%; p = 0.001). Conclusion: A score system based on clinical and radiological features was created to select the optimal surgery post-NACT and improve oncological and aesthetic outcomes.

Published
2023

36. Conservative Surgery in cT4 Breast Cancer: Single-Center Experience in the Neoadjuvant Setting

Author

Franco, Alessio, Di Leone, Alba, Fabi, A., Belli, Paolo, Carbognin, L., Gambaro, Elisabetta, Marazzi, Fabio, Mason, Elena Jane, Mule, A., Orlandi, Armando, Palazzo, Antonella, Paris, Ida, Rossi, A., Scardina, L., Terribile, Daniela Andreina, Tiberi, G., Giannarelli, Diana, Scambia, Giovanni, Masetti, Riccardo, Franceschini, Gianluca, Franco A., Di Leone A., Belli P. (ORCID:0000-0001-7979-2466), Gambaro E., Marazzi F., Mason E. J., Orlandi A. (ORCID:0000-0001-5253-4678), Palazzo A., Paris I., Terribile D. A. (ORCID:0000-0002-3511-0010), Giannarelli D., Scambia G. (ORCID:0000-0003-2758-1063), Masetti R. (ORCID:0000-0002-7520-9111), Franceschini G. (ORCID:0000-0002-2950-3395), Franco, Alessio, Di Leone, Alba, Fabi, A., Belli, Paolo, Carbognin, L., Gambaro, Elisabetta, Marazzi, Fabio, Mason, Elena Jane, Mule, A., Orlandi, Armando, Palazzo, Antonella, Paris, Ida, Rossi, A., Scardina, L., Terribile, Daniela Andreina, Tiberi, G., Giannarelli, Diana, Scambia, Giovanni, Masetti, Riccardo, Franceschini, Gianluca, Franco A., Di Leone A., Belli P. (ORCID:0000-0001-7979-2466), Gambaro E., Marazzi F., Mason E. J., Orlandi A. (ORCID:0000-0001-5253-4678), Palazzo A., Paris I., Terribile D. A. (ORCID:0000-0002-3511-0010), Giannarelli D., Scambia G. (ORCID:0000-0003-2758-1063), Masetti R. (ORCID:0000-0002-7520-9111), and Franceschini G. (ORCID:0000-0002-2950-3395)

Abstract

Background: The diffusion of screening programs has resulted in a decrease of cT4 breast cancer diagnosis. The standard care for cT4 was neoadjuvant chemotherapy (NA), surgery, and locoregional or adjuvant systemic therapies. NA allows two outcomes: 1. improve survival rates, and 2. de-escalation of surgery. This de-escalation has allowed the introduction of conservative breast surgery (CBS). We evaluate the possibility of submitting cT4 patients to CBS instead of radical breast surgery (RBS) by assessing the risk of locoregional disease-free survival, (LR-DFS) distant disease-free survival (DDFS), and overall survival (OS). Methods: This monocentric, retrospective study evaluated cT4 patients submitted to NA and surgery between January 2014 and July 2021. The study population included patients undergoing CBS or RBS without immediate reconstruction. Survival curves were obtained using the Kaplan-Meyer method and compared using a Log Rank test. Results: At a follow-up of 43.7 months, LR-DFS was 70% and 75.9%, respectively, in CBS and RBS (p = 0.420). DDFS was 67.8% and 29.7%, respectively, (p = 0.122). OS was 69.8% and 59.8%, respectively, (p = 0.311). Conclusions: In patients with major or complete response to NA, CBS can be considered a safe alternative to RBS in the treatment of cT4a-d stage. In patients with poor response to NA, RBS remained the best surgical choice.

Published
2023

39. The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial

Author

Pizzuti, L, Barba, M, Mazzotta, M, Krasniqi, E, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Sergi, D, Marinelli, D, Paoletti, G, Tomao, S, Botticelli, A, Marchetti, P, Tinari, N, Grassadonia, A, Valerio, M, Mirabelli, R, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Meattini, I, Pistelli, M, Giotta, F, Lorusso, V, Garufi, C, Russo, A, Cazzaniga, M, Del Medico, P, Roselli, M, Vaccaro, A, Perracchio, L, di Benedetto, A, Daralioti, T, Sperduti, I, De Maria, R, Di Leo, A, Sanguineti, G, Ciliberto, G, Vici, P, Pizzuti L., Barba M., Mazzotta M., Krasniqi E., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Sergi D., Marinelli D., Paoletti G., Tomao S., Botticelli A., Marchetti P., Tinari N., Grassadonia A., Valerio M. R., Mirabelli R., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Meattini I., Pistelli M., Giotta F., Lorusso V., Garufi C., Russo A., Cazzaniga M., Del Medico P., Roselli M., Vaccaro A., Perracchio L., di Benedetto A., Daralioti T., Sperduti I., De Maria R., Di Leo A., Sanguineti G., Ciliberto G., Vici P., Pizzuti, L, Barba, M, Mazzotta, M, Krasniqi, E, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Sergi, D, Marinelli, D, Paoletti, G, Tomao, S, Botticelli, A, Marchetti, P, Tinari, N, Grassadonia, A, Valerio, M, Mirabelli, R, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Meattini, I, Pistelli, M, Giotta, F, Lorusso, V, Garufi, C, Russo, A, Cazzaniga, M, Del Medico, P, Roselli, M, Vaccaro, A, Perracchio, L, di Benedetto, A, Daralioti, T, Sperduti, I, De Maria, R, Di Leo, A, Sanguineti, G, Ciliberto, G, Vici, P, Pizzuti L., Barba M., Mazzotta M., Krasniqi E., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Sergi D., Marinelli D., Paoletti G., Tomao S., Botticelli A., Marchetti P., Tinari N., Grassadonia A., Valerio M. R., Mirabelli R., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Meattini I., Pistelli M., Giotta F., Lorusso V., Garufi C., Russo A., Cazzaniga M., Del Medico P., Roselli M., Vaccaro A., Perracchio L., di Benedetto A., Daralioti T., Sperduti I., De Maria R., Di Leo A., Sanguineti G., Ciliberto G., and Vici P.

Abstract

In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world setting at 45 Italian cancer centers were retrospectively collected and analyzed. From 2003 to 2017, 491 HER2‐positive mBC patients were included. Of these, 102 (20.7%) had been initially diagnosed as HER2-negative early BC. Estrogen and/or progesterone receptor were more expressed in patients with HER2-discordance compared to patients with HER2-concordant status (p < 0.0001 and p = 0.006, respectively). HER2-discordant tumors were characterized also by a lower rate of brain metastases (p = 0.01) and a longer disease free interval (p < 0.0001). Median overall survival was longer, although not statistically significant, in the subgroup of patients with HER2-discordant cancer with respect to patients with HER2-concordant status (140 vs 78 months, p = 0.07). Our findings suggest that patients with HER2-positive mBC with discordant HER2 status in early BC may have different clinical, biological and prognostic behavior compared to HER2-concordant patients.

Published
2021

40. Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study

Author

Bon, G, Pizzuti, L, Laquintana, V, Loria, R, Porru, M, Marchio, C, Krasniqi, E, Barba, M, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Barchiesi, G, Mazzotta, M, Marinelli, D, Tomao, S, Marchetti, P, Valerio, M, Mirabelli, R, Russo, A, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Giotta, F, Garufi, C, Cazzaniga, M, Del Medico, P, Roselli, M, Sanguineti, G, Sperduti, I, Sapino, A, De Maria, R, Leonetti, C, Di Leo, A, Ciliberto, G, Falcioni, R, Vici, P, Bon G., Pizzuti L., Laquintana V., Loria R., Porru M., Marchio C., Krasniqi E., Barba M., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Barchiesi G., Mazzotta M., Marinelli D., Tomao S., Marchetti P., Valerio M. R., Mirabelli R., Russo A., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Giotta F., Garufi C., Cazzaniga M., Del Medico P., Roselli M., Sanguineti G., Sperduti I., Sapino A., De Maria R., Leonetti C., Di Leo A., Ciliberto G., Falcioni R., Vici P., Bon, G, Pizzuti, L, Laquintana, V, Loria, R, Porru, M, Marchio, C, Krasniqi, E, Barba, M, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Barchiesi, G, Mazzotta, M, Marinelli, D, Tomao, S, Marchetti, P, Valerio, M, Mirabelli, R, Russo, A, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Giotta, F, Garufi, C, Cazzaniga, M, Del Medico, P, Roselli, M, Sanguineti, G, Sperduti, I, Sapino, A, De Maria, R, Leonetti, C, Di Leo, A, Ciliberto, G, Falcioni, R, Vici, P, Bon G., Pizzuti L., Laquintana V., Loria R., Porru M., Marchio C., Krasniqi E., Barba M., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Barchiesi G., Mazzotta M., Marinelli D., Tomao S., Marchetti P., Valerio M. R., Mirabelli R., Russo A., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Giotta F., Garufi C., Cazzaniga M., Del Medico P., Roselli M., Sanguineti G., Sperduti I., Sapino A., De Maria R., Leonetti C., Di Leo A., Ciliberto G., Falcioni R., and Vici P.

Abstract

Background: HER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to different drugs sequences including pertuzumab and T-DM1 in HER2 positive cell lines. Methods: The biology of HER2 was investigated in vitro through sequential exposure of resistant HER2 + breast cancer cell lines to trastuzumab, pertuzumab, and their combination. In vitro experiments were paralleled by the analysis of data from 555 HER2 + ABC patients treated with T-DM1 and evaluation of T-DM1 efficacy in the 371 patients who received it in second line. Survival estimates were graphically displayed in Kaplan Meier curves, compared by log rank test and, when possibile, confirmed in multivariate models. Results: We herein show evidence of lower activity of T-DM1 in two HER2+ breast cancer cell lines resistant to trastuzumab+pertuzumab, as compared to trastuzumab-resistant cells. Lower T-DM1 efficacy was associated with a marked reduction of HER2 expression on the cell membrane and its nuclear translocation. HER2 downregulation at the membrane level was confirmed in biopsies of four trastuzumab/pertuzumab-pretreated patients. Among the 371 patients treated with second-line T-DM1, median overall survival (mOS) from diagnosis of advanced disease and median progression-free survival to second-line treatment (mPFS2) were 52 and 6 months in 177 patients who received trastuzumab/pertuzumab in f

Published
2020

41. Netupitant/palonosetron (NEPA) and dexamethasone for prevention of emesis in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide: A multi-cycle, phase II study

Author

Caputo, R, Cazzaniga, M, Sbrana, A, Torrisi, R, Paris, I, Giordano, M, Montesarchio, V, Guarneri, V, Amaducci, L, Bilancia, D, Cilenti, G, Fabi, A, Collova, E, Schirone, A, Bonizzoni, E, Celio, L, De Placido, S, De Laurentiis, M, Caputo R., Cazzaniga M. E., Sbrana A., Torrisi R., Paris I., Giordano M., Montesarchio V., Guarneri V., Amaducci L., Bilancia D., Cilenti G., Fabi A., Collova E., Schirone A., Bonizzoni E., Celio L., De Placido S., De Laurentiis M., Caputo, R, Cazzaniga, M, Sbrana, A, Torrisi, R, Paris, I, Giordano, M, Montesarchio, V, Guarneri, V, Amaducci, L, Bilancia, D, Cilenti, G, Fabi, A, Collova, E, Schirone, A, Bonizzoni, E, Celio, L, De Placido, S, De Laurentiis, M, Caputo R., Cazzaniga M. E., Sbrana A., Torrisi R., Paris I., Giordano M., Montesarchio V., Guarneri V., Amaducci L., Bilancia D., Cilenti G., Fabi A., Collova E., Schirone A., Bonizzoni E., Celio L., De Placido S., and De Laurentiis M.

Abstract

Background: NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle. Methods: In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-to-severe nausea) were also examined. Results: Of the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all 4 cycles. The proportion of patients with an overall CR was 70.5% (90% CI, 64.1 to 76.9) in cycle 1, and this was maintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was 53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better control of very late CINV events than those who experienced no CR. Among the patients with CR, the only predictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea (adjusted odds ratio = 0.65-0.50 for no CINV events on cycles 3 and 4). Conclusion: The high anti-emetic efficacy seen with the NEPA regimen in the first cycle was m

Published
2020

42. Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting

Author

Pizzuti, L, Krasniqi, E, Barchiesi, G, Della Giulia, M, Izzo, F, Sanguineti, G, Marchetti, P, Mazzotta, M, Giusti, R, Botticelli, A, Gamucci, T, Natoli, C, Grassadonia, A, Tinari, N, Iezzi, L, Tomao, S, Tomao, F, Tonini, G, Santini, D, Astone, A, Michelotti, A, De Angelis, C, Mentuccia, L, Vaccaro, A, Magnolfi, E, Gelibter, A, Magri, V, Cortesi, E, D'Onofrio, L, Cassano, A, Rossi, E, Cazzaniga, M, Moscetti, L, Omarini, C, Piacentini, F, Fabbri, M, Scinto, A, Corsi, D, Carbognin, L, Bria, E, La Verde, N, Samaritani, R, Garufi, C, Barni, S, Mirabelli, R, Sarmiento, R, Veltri, E, D'Auria, G, Paris, I, Giotta, F, Lorusso, V, Cardillo, F, Landucci, E, Mauri, M, Ficorella, C, Roselli, M, Adamo, V, Ricciardi, G, Russo, A, Berardi, R, Pistelli, M, Fiorio, E, Cannita, K, Sini, V, D'Ostilio, N, Foglietta, J, Greco, F, Zamagni, C, Garrone, O, Di Cocco, B, Baldini, E, Livi, L, Desideri, I, Meattini, I, Sarobba, G, Del Medico, P, De Tursi, M, Generali, D, De Maria, R, Risi, E, Ciliberto, G, Sperduti, I, Villa, A, Barba, M, Di Leo, A, Vici, P, Pizzuti L., Krasniqi E., Barchiesi G., Della Giulia M., Izzo F., Sanguineti G., Marchetti P., Mazzotta M., Giusti R., Botticelli A., Gamucci T., Natoli C., Grassadonia A., Tinari N., Iezzi L., Tomao S., Tomao F., Tonini G., Santini D., Astone A., Michelotti A., De Angelis C., Mentuccia L., Vaccaro A., Magnolfi E., Gelibter A., Magri V., Cortesi E., D'Onofrio L., Cassano A., Rossi E., Cazzaniga M., Moscetti L., Omarini C., Piacentini F., Fabbri M. A., Scinto A. F., Corsi D., Carbognin L., Bria E., La Verde N., Samaritani R., Garufi C., Barni S., Mirabelli R., Sarmiento R., Veltri E. M., D'Auria G., Paris I., Giotta F., Lorusso V., Cardillo F., Landucci E., Mauri M., Ficorella C., Roselli M., Adamo V., Ricciardi G. R. R., Russo A., Berardi R., Pistelli M., Fiorio E., Cannita K., Sini V., D'Ostilio N., Foglietta J., Greco F., Zamagni C., Garrone O., Di Cocco B., Baldini E., Livi L., Desideri I., Meattini I., Sarobba G., Del Medico P., De Tursi M., Generali D., De Maria R., Risi E., Ciliberto G., Sperduti I., Villa A., Barba M., Di Leo A., Vici P., Pizzuti, L, Krasniqi, E, Barchiesi, G, Della Giulia, M, Izzo, F, Sanguineti, G, Marchetti, P, Mazzotta, M, Giusti, R, Botticelli, A, Gamucci, T, Natoli, C, Grassadonia, A, Tinari, N, Iezzi, L, Tomao, S, Tomao, F, Tonini, G, Santini, D, Astone, A, Michelotti, A, De Angelis, C, Mentuccia, L, Vaccaro, A, Magnolfi, E, Gelibter, A, Magri, V, Cortesi, E, D'Onofrio, L, Cassano, A, Rossi, E, Cazzaniga, M, Moscetti, L, Omarini, C, Piacentini, F, Fabbri, M, Scinto, A, Corsi, D, Carbognin, L, Bria, E, La Verde, N, Samaritani, R, Garufi, C, Barni, S, Mirabelli, R, Sarmiento, R, Veltri, E, D'Auria, G, Paris, I, Giotta, F, Lorusso, V, Cardillo, F, Landucci, E, Mauri, M, Ficorella, C, Roselli, M, Adamo, V, Ricciardi, G, Russo, A, Berardi, R, Pistelli, M, Fiorio, E, Cannita, K, Sini, V, D'Ostilio, N, Foglietta, J, Greco, F, Zamagni, C, Garrone, O, Di Cocco, B, Baldini, E, Livi, L, Desideri, I, Meattini, I, Sarobba, G, Del Medico, P, De Tursi, M, Generali, D, De Maria, R, Risi, E, Ciliberto, G, Sperduti, I, Villa, A, Barba, M, Di Leo, A, Vici, P, Pizzuti L., Krasniqi E., Barchiesi G., Della Giulia M., Izzo F., Sanguineti G., Marchetti P., Mazzotta M., Giusti R., Botticelli A., Gamucci T., Natoli C., Grassadonia A., Tinari N., Iezzi L., Tomao S., Tomao F., Tonini G., Santini D., Astone A., Michelotti A., De Angelis C., Mentuccia L., Vaccaro A., Magnolfi E., Gelibter A., Magri V., Cortesi E., D'Onofrio L., Cassano A., Rossi E., Cazzaniga M., Moscetti L., Omarini C., Piacentini F., Fabbri M. A., Scinto A. F., Corsi D., Carbognin L., Bria E., La Verde N., Samaritani R., Garufi C., Barni S., Mirabelli R., Sarmiento R., Veltri E. M., D'Auria G., Paris I., Giotta F., Lorusso V., Cardillo F., Landucci E., Mauri M., Ficorella C., Roselli M., Adamo V., Ricciardi G. R. R., Russo A., Berardi R., Pistelli M., Fiorio E., Cannita K., Sini V., D'Ostilio N., Foglietta J., Greco F., Zamagni C., Garrone O., Di Cocco B., Baldini E., Livi L., Desideri I., Meattini I., Sarobba G., Del Medico P., De Tursi M., Generali D., De Maria R., Risi E., Ciliberto G., Sperduti I., Villa A., Barba M., Di Leo A., and Vici P.

Abstract

We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression-free survival at first-line (mPFS1) was 12 months. Pertuzumab as first-line conferred longer mPFS1 compared to other first-line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second-line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T-DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs-negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T-DM1 in second-line after pertuzumab were significantly lower compared to pertuzumab-naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment-related outcomes of HER2-positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2-positive (mbc) patients

Published
2020

43. Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer

Author

Schettini, F., Venturini, Sergio, Giuliano, M., Lambertini, M., Pinato, D. J., Onesti, C. E., De Placido, P., Harbeck, N., Luftner, D., Denys, H., Van Dam, P., Arpino, G., Zaman, K., Mustacchi, G., Gligorov, J., Awada, A., Campone, M., Wildiers, H., Gennari, Alessandro, Tjan-Heijnen, V., Bartsch, R., Cortes, J., Paris, Ida, Martin, M., De Placido, S., Del Mastro, L., Jerusalem, G., Curigliano, G., Prat, A., Generali, Daniele, Venturini S. (ORCID:0000-0002-6574-3337), Gennari A., Paris I., Generali D. (ORCID:0000-0003-2480-3855), Schettini, F., Venturini, Sergio, Giuliano, M., Lambertini, M., Pinato, D. J., Onesti, C. E., De Placido, P., Harbeck, N., Luftner, D., Denys, H., Van Dam, P., Arpino, G., Zaman, K., Mustacchi, G., Gligorov, J., Awada, A., Campone, M., Wildiers, H., Gennari, Alessandro, Tjan-Heijnen, V., Bartsch, R., Cortes, J., Paris, Ida, Martin, M., De Placido, S., Del Mastro, L., Jerusalem, G., Curigliano, G., Prat, A., Generali, Daniele, Venturini S. (ORCID:0000-0002-6574-3337), Gennari A., Paris I., and Generali D. (ORCID:0000-0003-2480-3855)

Abstract

Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and un-certain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel +/- bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1 -positive mTNBC, performed similar to paclitaxel +/- bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, ac-cording to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).

Published
2022

44. Level II Oncoplastic Surgery as an Alternative Option to Mastectomy with Immediate Breast Reconstruction in the Neoadjuvant Setting: A Multidisciplinary Single Center Experience

Author

Di Leone, A., Franco, Antonio, Terribile, Daniela Andreina, Magno, Stefano, Fabi, A., Sanchez, A. M., D'Archi, S., Scardina, L., Natale, Maria, Mason, Elena Jane, Murando, F., Marazzi, Fabio, Orlandi, Armando, Paris, Ida, Visconti, Giuseppe, Palazzo, Antonella, Masiello, V., Adesi, L. B., Salgarello, Marzia, Masetti, Riccardo, Franceschini, Gianluca, Franco A., Terribile D. A. (ORCID:0000-0002-3511-0010), Magno S., Natale M., Mason E. J., Marazzi F., Orlandi A. (ORCID:0000-0001-5253-4678), Paris I., Visconti G. (ORCID:0000-0002-0041-5420), Palazzo A., Salgarello M. (ORCID:0000-0003-4296-4214), Masetti R. (ORCID:0000-0002-7520-9111), Franceschini G. (ORCID:0000-0002-2950-3395), Di Leone, A., Franco, Antonio, Terribile, Daniela Andreina, Magno, Stefano, Fabi, A., Sanchez, A. M., D'Archi, S., Scardina, L., Natale, Maria, Mason, Elena Jane, Murando, F., Marazzi, Fabio, Orlandi, Armando, Paris, Ida, Visconti, Giuseppe, Palazzo, Antonella, Masiello, V., Adesi, L. B., Salgarello, Marzia, Masetti, Riccardo, Franceschini, Gianluca, Franco A., Terribile D. A. (ORCID:0000-0002-3511-0010), Magno S., Natale M., Mason E. J., Marazzi F., Orlandi A. (ORCID:0000-0001-5253-4678), Paris I., Visconti G. (ORCID:0000-0002-0041-5420), Palazzo A., Salgarello M. (ORCID:0000-0003-4296-4214), Masetti R. (ORCID:0000-0002-7520-9111), and Franceschini G. (ORCID:0000-0002-2950-3395)

Abstract

Oncoplastic surgery level II techniques (OPSII) are used in patients with operable breast cancer. There is no evidence regarding their safety and efficacy after neoadjuvant chemotherapy (NAC). The aim of this study was to compare the oncological and aesthetic outcomes of this technique compared with those observed in mastectomy with immediate breast reconstruction (MIBR), in post-NAC patients undergoing surgery between January 2016 and March 2021. Local disease-free survival (L-DFS), regional disease-free survival (R-DFS), distant disease-free survival (D-DFS), and overall survival (OS) were compared; the aesthetic results and quality of life (QoL) were evaluated using BREAST-Q. A total of 297 patients were included, 87 of whom underwent OPSII and 210 of whom underwent MIBR. After a median follow-up of 39.5 months, local recurrence had occurred in 3 patients in the OPSII group (3.4%), and in 13 patients in the MIBR group (6.1%) (p = 0.408). The three-year L-DFS rates were 95.1% for OPSII and 96.2% for MIBR (p = 0.286). The three-year R-DFS rates were 100% and 96.4%, respectively (p = 0.559). The three-year D-DFS rate were 90.7% and 89.7% (p = 0.849). The three-year OS rates were 95.7% and 95% (p = 0.394). BREAST-Q highlighted significant advantages in physical well-being for OPSII. No difference was shown for satisfaction with breasts (p = 0.656) or psychosocial well-being (p = 0.444). OPSII is safe and effective after NAC. It allows oncological and aesthetic outcomes with a high QoL, and is a safe alternative for locally advanced tumors which are partial responders to NAC.

Published
2022

46. C5 - Efficacy of pertuzumab in combination with trastuzumab and a taxane in in first line treatment for metastatic breast cancer (MBC): a multicenter retrospective observational study

Author

Mentuccia, L., Gelibter, A., Sperduti, I., D'Onofrio, L., Botticelli, A., Vici, P., Cassano, A., Moscetti, L., Carbognin, L., Graziano, V., Barchiesi, G., Rossi, E., Cursano, M.C., Pizzuti, L., Paris, I., Vaccaro, A., Fabbri, A., Rossi, L., Samaritani, R., Sarmiento, R., and Gamucci, T.

Published
2017
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48. Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience

Author

Pizzuti, L, Giordano, A, Michelotti, A, Mazzotta, M, Natoli, C, Gamucci, T, De Angelis, C, Landucci, E, Diodati, L, Iezzi, L, Mentuccia, L, Fabbri, A, Barba, M, Sanguineti, G, Marchetti, P, Tomao, S, Mariani, L, Paris, I, Lorusso, V, Vallarelli, S, Cassano, A, Airoldi, F, Orlandi, A, Moscetti, L, Sergi, D, Sarobba, M, Tonini, G, Santini, D, Sini, V, Veltri, E, Vaccaro, A, Ferrari, L, De Tursi, M, Tinari, N, Grassadonia, A, Greco, F, Botticelli, A, La Verde, N, Zamagni, C, Rubino, D, Cortesi, E, Magri, V, Pomati, G, Scagnoli, S, Capomolla, E, Kayal, R, Scinto, A, Corsi, D, Cazzaniga, M, Laudadio, L, Forciniti, S, Mancini, M, Carbognin, L, Seminara, P, Barni, S, Samaritani, R, Roselli, M, Portarena, I, Russo, A, Ficorella, C, Cannita, K, Carpano, S, Pistelli, M, Berardi, R, De Maria, R, Sperduti, I, Ciliberto, G, Vici, P, Pizzuti L., Giordano A., Michelotti A., Mazzotta M., Natoli C., Gamucci T., De Angelis C., Landucci E., Diodati L., Iezzi L., Mentuccia L., Fabbri A., Barba M., Sanguineti G., Marchetti P., Tomao S., Mariani L., Paris I., Lorusso V., Vallarelli S., Cassano A., Airoldi F., Orlandi A., Moscetti L., Sergi D., Sarobba M. G., Tonini G., Santini D., Sini V., Veltri E., Vaccaro A., Ferrari L., De Tursi M., Tinari N., Grassadonia A., Greco F., Botticelli A., La Verde N., Zamagni C., Rubino D., Cortesi E., Magri V., Pomati G., Scagnoli S., Capomolla E., Kayal R., Scinto A. F., Corsi D., Cazzaniga M., Laudadio L., Forciniti S., Mancini M., Carbognin L., Seminara P., Barni S., Samaritani R., Roselli M., Portarena I., Russo A., Ficorella C., Cannita K., Carpano S., Pistelli M., Berardi R., De Maria R., Sperduti I., Ciliberto G., Vici P., Pizzuti, L, Giordano, A, Michelotti, A, Mazzotta, M, Natoli, C, Gamucci, T, De Angelis, C, Landucci, E, Diodati, L, Iezzi, L, Mentuccia, L, Fabbri, A, Barba, M, Sanguineti, G, Marchetti, P, Tomao, S, Mariani, L, Paris, I, Lorusso, V, Vallarelli, S, Cassano, A, Airoldi, F, Orlandi, A, Moscetti, L, Sergi, D, Sarobba, M, Tonini, G, Santini, D, Sini, V, Veltri, E, Vaccaro, A, Ferrari, L, De Tursi, M, Tinari, N, Grassadonia, A, Greco, F, Botticelli, A, La Verde, N, Zamagni, C, Rubino, D, Cortesi, E, Magri, V, Pomati, G, Scagnoli, S, Capomolla, E, Kayal, R, Scinto, A, Corsi, D, Cazzaniga, M, Laudadio, L, Forciniti, S, Mancini, M, Carbognin, L, Seminara, P, Barni, S, Samaritani, R, Roselli, M, Portarena, I, Russo, A, Ficorella, C, Cannita, K, Carpano, S, Pistelli, M, Berardi, R, De Maria, R, Sperduti, I, Ciliberto, G, Vici, P, Pizzuti L., Giordano A., Michelotti A., Mazzotta M., Natoli C., Gamucci T., De Angelis C., Landucci E., Diodati L., Iezzi L., Mentuccia L., Fabbri A., Barba M., Sanguineti G., Marchetti P., Tomao S., Mariani L., Paris I., Lorusso V., Vallarelli S., Cassano A., Airoldi F., Orlandi A., Moscetti L., Sergi D., Sarobba M. G., Tonini G., Santini D., Sini V., Veltri E., Vaccaro A., Ferrari L., De Tursi M., Tinari N., Grassadonia A., Greco F., Botticelli A., La Verde N., Zamagni C., Rubino D., Cortesi E., Magri V., Pomati G., Scagnoli S., Capomolla E., Kayal R., Scinto A. F., Corsi D., Cazzaniga M., Laudadio L., Forciniti S., Mancini M., Carbognin L., Seminara P., Barni S., Samaritani R., Roselli M., Portarena I., Russo A., Ficorella C., Cannita K., Carpano S., Pistelli M., Berardi R., De Maria R., Sperduti I., Ciliberto G., and Vici P.

Abstract

Data from 423 human epidermal growth factor receptor 2-negative (HER2−), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6–35.4) and clinical benefit was 52.7% (95% CI, 48–57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (p = 0.002) and favorably influenced by early line-treatment (p < 0.0001). At 6 months, median progression-free survival was 12 months (95% CI, 8–16) and median overall survival was 24 months (95% CI, 17–30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2−, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained.

Published
2019

49. Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success

Author

Cazzaniga, M, Danesi, R, Girmenia, C, Invernizzi, P, Elvevi, A, Uguccioni, M, Amaducci, L, Atzori, F, Blasi, L, Butti, C, Collova, E, De Conciliis, E, Fabi, A, Febbraro, A, Garrone, O, Gianni, L, Giotta, F, La Verde, N, Michelotti, A, Palumbo, R, Paris, I, Pistelli, M, Pizzuti, L, Rubino, D, Valerio, M, Zustovich, F, Cazzaniga M. E., Danesi R., Girmenia C., Invernizzi P., Elvevi A., Uguccioni M., Amaducci L., Atzori F., Blasi L., Butti C., Collova E., De Conciliis E., Fabi A., Febbraro A., Garrone O., Gianni L., Giotta F., La Verde N., Michelotti A., Palumbo R., Paris I., Pistelli M., Pizzuti L., Rubino D., Valerio M. R., Zustovich F., Cazzaniga, M, Danesi, R, Girmenia, C, Invernizzi, P, Elvevi, A, Uguccioni, M, Amaducci, L, Atzori, F, Blasi, L, Butti, C, Collova, E, De Conciliis, E, Fabi, A, Febbraro, A, Garrone, O, Gianni, L, Giotta, F, La Verde, N, Michelotti, A, Palumbo, R, Paris, I, Pistelli, M, Pizzuti, L, Rubino, D, Valerio, M, Zustovich, F, Cazzaniga M. E., Danesi R., Girmenia C., Invernizzi P., Elvevi A., Uguccioni M., Amaducci L., Atzori F., Blasi L., Butti C., Collova E., De Conciliis E., Fabi A., Febbraro A., Garrone O., Gianni L., Giotta F., La Verde N., Michelotti A., Palumbo R., Paris I., Pistelli M., Pizzuti L., Rubino D., Valerio M. R., and Zustovich F.

Abstract

Purpose: Agents targeting HR-positive, HER2-negative locally advanced or metastatic breast cancer have improved patient outcomes compared with conventional single-agent endocrine therapy. Currently, approved targeted agents include everolimus and three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Unlike the well-characterized and easily manageable safety profile of endocrine therapies, adverse events associated with targeted therapies are complex and potentially severe. Their prompt recognition and treatment, crucial for prolonged endocrine sensitivity and survival, may be challenging and requires a multidisciplinary effort and a good knowledge of drug interactions. Methods: We reviewed the current evidence on the drug safety of targeted agents for metastatic breast cancer currently used in clinical practice in Italy, supported by the clinical experience of Italian oncologists with expertise in the field. Results: All oncologists had used CDK4/6 inhibitors in clinical practice and/or within a clinical trial. The clinical management of toxicities, including dose adjustments, treatment interruptions, and concerns regarding special populations is discussed, and the management of relevant adverse events, related to individual agents and class-specific, toxicities is reviewed. Hematologic toxicities have the greatest impact on clinical management of the disease and on patients. Although toxicities associated with the new treatments result in more visits to the physician and more time and attention with patients, they are manageable, with no need for the oncologist to consult with specialist physicians. Conclusions: Based on the available evidence and current guidelines, we propose a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy.

Published
2019

50. Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success

Author

Cazzaniga M. E., Danesi R., Girmenia C., Invernizzi P., Elvevi A., Uguccioni M., Amaducci L., Atzori F., Blasi L., Butti C., Collova E., De Conciliis E., Fabi A., Febbraro A., Garrone O., Gianni L., Giotta F., La Verde N., Michelotti A., Palumbo R., Paris I., Pistelli M., Pizzuti L., Rubino D., Valerio M. R., Zustovich F., Cazzaniga M.E., Danesi R., Girmenia C., Invernizzi P., Elvevi A., Uguccioni M., Amaducci L., Atzori F., Blasi L., Butti C., Collova E., De Conciliis E., Fabi A., Febbraro A., Garrone O., Gianni L., Giotta F., La Verde N., Michelotti A., Palumbo R., Paris I., Pistelli M., Pizzuti L., Rubino D., Valerio M.R., Zustovich F., Cazzaniga, M, Danesi, R, Girmenia, C, Invernizzi, P, Elvevi, A, Uguccioni, M, Amaducci, L, Atzori, F, Blasi, L, Butti, C, Collova, E, De Conciliis, E, Fabi, A, Febbraro, A, Garrone, O, Gianni, L, Giotta, F, La Verde, N, Michelotti, A, Palumbo, R, Paris, I, Pistelli, M, Pizzuti, L, Rubino, D, Valerio, M, and Zustovich, F

Subjects
0301 basic medicine, Cancer Research, Review, Disease, chemistry.chemical_compound, 0302 clinical medicine, Ribociclib, Molecular Targeted Therapy, Abemaciclib, Clinical Trials as Topic, Disease Management, Metastatic breast cancer, Everolimu, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, Advanced breast cancer, Receptors, Progesterone, Breast Neoplasm, medicine.drug, Human, medicine.medical_specialty, Neutropenia, Drug-Related Side Effects and Adverse Reactions, Antineoplastic Agents, Hormonal, Protein Kinase Inhibitor, Breast Neoplasms, Palbociclib, 03 medical and health sciences, Breast cancer, medicine, Biomarkers, Tumor, Humans, Everolimus, Intensive care medicine, Adverse effect, Protein Kinase Inhibitors, business.industry, medicine.disease, Clinical trial, 030104 developmental biology, chemistry, MED/06 - ONCOLOGIA MEDICA, business, Drug-Related Side Effects and Adverse Reaction
Abstract

Purpose: Agents targeting HR-positive, HER2-negative locally advanced or metastatic breast cancer have improved patient outcomes compared with conventional single-agent endocrine therapy. Currently, approved targeted agents include everolimus and three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Unlike the well-characterized and easily manageable safety profile of endocrine therapies, adverse events associated with targeted therapies are complex and potentially severe. Their prompt recognition and treatment, crucial for prolonged endocrine sensitivity and survival, may be challenging and requires a multidisciplinary effort and a good knowledge of drug interactions. Methods: We reviewed the current evidence on the drug safety of targeted agents for metastatic breast cancer currently used in clinical practice in Italy, supported by the clinical experience of Italian oncologists with expertise in the field. Results: All oncologists had used CDK4/6 inhibitors in clinical practice and/or within a clinical trial. The clinical management of toxicities, including dose adjustments, treatment interruptions, and concerns regarding special populations is discussed, and the management of relevant adverse events, related to individual agents and class-specific, toxicities is reviewed. Hematologic toxicities have the greatest impact on clinical management of the disease and on patients. Although toxicities associated with the new treatments result in more visits to the physician and more time and attention with patients, they are manageable, with no need for the oncologist to consult with specialist physicians. Conclusions: Based on the available evidence and current guidelines, we propose a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy.

Published
2019

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