Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT

PURPOSEThe Tamoxifen and Exemestane Trial (TEXT)/Suppression of Ovarian Function Trial (SOFT) showed superior outcomes for premenopausal women with hormone receptor (HR)-positive breast cancer treated with adjuvant exemestane plus ovarian function suppression (OFS) or tamoxifen plus OFS versus tamoxifen alone. We previously reported the magnitude of absolute improvements in freedom from any recurrence across a continuous, composite measure of recurrence risk to tailor decision making. With longer follow-up, we now focus on distant recurrence.METHODSThe TEXT/SOFT HR-positive/human epidermal growth factor receptor 2 (HER2)-negative analysis population included 4,891 women stratified by predetermined chemotherapy use. Kaplan-Meier estimates of 8-year freedom from distant recurrence were analyzed using subpopulation treatment effect pattern plot (STEPP) methodology across subpopulations defined by the continuous composite measure of recurrence risk. For each patient, the composite risk value was obtained from a Cox model that incorporated age; nodal status; tumor size; grade; and estrogen receptor, progesterone receptor, and Ki-67 labeling index expression levels.RESULTSThe overall rate of 8-year freedom from distant recurrence was 91.1% and ranged from approximately 100% to 63% across lowest to highest composite risks. TEXT patients who received chemotherapy had an average absolute improvement with exemestane plus OFS versus tamoxifen plus OFS of 5.1%, and STEPP analysis showed improvements from less than 1% to more than 15% from lowest to highest composite risks. SOFT patients who remained premenopausal after chemotherapy had an average 5.2% absolute improvement with exemestane plus OFS versus tamoxifen and reached 10% across composite risks; for tamoxifen plus OFS versus tamoxifen, the maximum improvement was approximately 3.5%. Women who did not receive chemotherapy had a more than 97% rate of 8-year freedom from distant recurrence, and improvements with exemestane plus OFS ranged from 1% to 4%.CONCLUSIONPremenopausal women with HR-positive/HER2-negative breast cancer and high recurrence risk, as defined by clinicopathologic characteristics, may experience a 10% to 15% absolute improvement in 8-year freedom from distant recurrence with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone. The potential benefit of escalating endocrine therapy versus tamoxifen alone is minimal for those at low recurrence risk. (c) 2019 by American Society of Clinical Oncolog

A PMT-Block test bench

The front-end electronics of the ATLAS hadronic calorimeter (Tile Cal) is housed in a unit, called {\it PMT-Block}. The PMT-Block is a compact instrument comprising a light mixer, a PMT together with its divider and a {\it 3-in-1} card, which provides shaping, amplification and integration for the signals. This instrument needs to be qualified before being assembled on the detector. A PMT-Block test bench has been developed for this purpose. This test bench is a system which allows fast, albeit accurate enough, measurements of the main properties of a complete PMT-Block. The system, both hardware and software, and the protocol used for the PMT-Blocks characterisation are described in detail in this report. The results obtained in the test of about 10000 PMT-Blocks needed for the instrumentation of the ATLAS (LHC-CERN) hadronic Tile Calorimeter are also reported.Comment: 23 pages, 10 figure

Planck early results. XXII. The submillimetre properties of a sample of Galactic cold clumps

We perform a detailed investigation of sources from the Cold Cores Catalogue of Planck Objects (C3PO). Our goal is to probe the reliability of the detections, validate the separation between warm and cold dust emission components, provide the first glimpse at the nature, internal morphology and physical characterictics of the Planck-detected sources. We focus on a sub-sample of ten sources from the C3PO list, selected to sample different environments, from high latitude cirrus to nearby (150 pc) and remote (2 kpc) molecular complexes. We present Planck surface brightness maps and derive the dust temperature, emissivity spectral index, and column densities of the fields. With the help of higher resolution Herschel and AKARI continuum observations and molecular line data, we investigate the morphology of the sources and the properties of the substructures at scales below the Planck beam size. The cold clumps detected by Planck are found to be located on large-scale filamentary (or cometary) structures that extend up to 20 pc in the remote sources. The thickness of these filaments ranges between 0.3 and 3 pc, for column densities NH2 ∼ 0.1 to 1.6 × 1022 cm−2, and with linear mass density covering a broad range, between 15 and 400 M pc−1. The dust temperatures are low (between 10 and 15K) and the Planck cold clumps correspond to local minima of the line-of-sight averaged dust temperature in these fields. These low temperatures are confirmed when AKARI and Herschel data are added to the spectral energy distributions. Herschel data reveal a wealth of substructure within the Planck cold clumps. In all cases (except two sources harbouring young stellar objects), the substructures are found to be colder, with temperatures as low as 7 K. Molecular line observations provide gas column densities which are consistent with those inferred from the dust. The linewidths are all supra-thermal, providing large virial linear mass densities in the range 10 to 300 M pc−1, comparable within factors of a few, to the gas linear mass densities. The analysis of this small set of cold clumps already probes a broad variety of structures in the C3PO sample, probably associated with different evolutionary stages, from cold and starless clumps, to young protostellar objects still embedded in their cold surrounding cloud. Because of the all-sky coverage and its sensitivity, Planck is able to detect and locate the coldest spots in massive elongated structures that may be the long-searched for progenitors of stellar clusters

Frequency of αS1-casein variants in the Italian goat breeds Sarda and Verzaschese

The alpha(s1)-casein pattern was studied in 104 individual milk samples from goats of the Italian breeds Verzaschese and Sarda. Analysis of the alpha(s1)-casein variants was performed by combining isoelectric focusing and reverse-phase HPLC. The most frequent alpha(s1)-casein variants in Sarda goats were the "strong" A and B variants. The majority of Verzaschese goats bore the "weak" F variant, and B was the only strong variant in this breed. In both breeds, the total casein content was correlated to the variant distribution. This finding could be useful for rapid screening purposes, given the different technological properties of goat milks containing different alpha(s1)-casein variants

Premenopausal endocrine-responsive early breast cancer : who receives chemotherapy?

BACKGROUND: The role of chemotherapy in addition to combined endocrine therapy for premenopausal women with endocrine-responsive early breast cancer remains an open question, yet trials designed to answer it have repeatedly failed to adequately accrue. The International Breast Cancer Study Group initiated two concurrent trials in this population: in Premenopausal Endocrine Responsive Chemotherapy (PERCHE), chemotherapy use is determined by randomization and in Tamoxifen and Exemestane Trial (TEXT) by physician choice. PERCHE closed with inadequate accrual; TEXT accrued rapidly. METHODS: From 2003 to 2006, 1317 patients (890 with baseline data) were randomly assigned to receive ovarian function suppression (OFS) plus tamoxifen or OFS plus exemestane for 5 years in TEXT. We explore patient-related factors according to whether or not chemotherapy was given using descriptive statistics and classification and regression trees. RESULTS: Adjuvant chemotherapy was chosen for 64% of patients. Lymph node status was the predominant determinant of chemotherapy use (88% of node positive treated versus 46% of node negative). Geography, patient age, tumor size and grade were also determinants, but degree of receptor positivity and human epidermal growth factor receptor 2 status were not. CONCLUSIONS: The perceived estimation of increased risk of relapse is the primary determinant for using chemotherapy despite uncertainties regarding the degree of benefit it offers when added to combined endocrine therapy in this population