Systemic treatments for women with breast cancer: outcome with relation to screening for the disease

Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warrante

A phase II study of primary dose-dense sequential doxorubicin plus cyclophosphamide and docetaxel in cT4 breast cancer

Background: Dose-dense chemotherapy with anthracyclines and taxanes has improved either disease free survival or overall survival in high risk patients with early breast cancer. Patients and Methods: The activity and safety of a dose-dense schedule (q14 days) of adriamycin 60 mg/sqm and cyclophosphamide 600 mg/sqm (AC) x 4 cycles followed by docetaxel 75 mg/sqm for 4 cycles with hematopoietic support in patients with stage IIIB breast cancer was explored. Patients with ER >= 10% tumors received concomitant endocrine therapy with 3-month triptorelin and letrozole. Results: Fifteen patients with histologically proven cT4b (three patients) and cT4d (twelve patients) MO breast cancer were enrolled. Median age was 48 years (range 25-66). Eight clinical responses including one pathological complete remission (pCR), three stable disease (including minor responses) and four progression of disease, one during AC and three during taxotere, were observed. Four patients had grade 3-4 non hematological toxicities and all except one discontinued treatment. Conclusion: Due to the high rate of progressive disease, this schedule should not represent a standard option in cT4 breast cancer

Time-domain phenomenological model of gravitational-wave subdominant harmonics for quasicircular nonprecessing binary black hole coalescences

In this work we present an extension of the time domain phenomenological model IMRPhenomT for gravitational wave signals from binary black hole coalescences to include subdominant harmonics, specifically the $(l=2, m=\pm 1)$, $(l=3, m=\pm 3)$, $(l=4, m=\pm 4)$ and $(l=5, m=\pm 5)$ spherical harmonics. We also improve our model for the dominant $(l=2, m=\pm 2)$ mode and discuss mode mixing for the $(l=3, m=\pm 2)$ mode. The model is calibrated to numerical relativity solutions of the full Einstein equations up to mass ratio 18, and to numerical solutions of the Teukolsky equations for higher mass ratios. This work complements the latest generation of traditional frequency domain phenomenological models (IMRPhenomX), and provides new avenues to develop computationally efficient models for gravitational wave signals from generic compact binaries

Systemic treatments for women with breast cancer: outcome with relation to screening for the disease

Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warranted

Parameter estimation with the current generation of phenomenological waveform models applied to the black hole mergers of GWTC-1

We consider the ten confidently detected gravitational-wave signals in theGWTC-1 catalog which are consistent with mergers of binary black hole systems,and perform a thorough parameter estimation re-analysis. This is made possibleby using computationally efficient waveform models of the current (fourth)generation of the IMRPhenom family of phenomenological waveform models, whichconsists of the IMRPhenomX frequency-domain modelsand the IMRPhenomTtime-domain models. The analysis is performed with both precessing andnon-precessing waveform models with and without subdominant spherical harmonicmodes. Results for all events are validated with convergence tests, discussingin particular the events GW170729 and GW151226. For the latter and the othertwo lowest-mass events, we also compare results between two independentsampling codes, Bilby and LALInference. We find overall consistent results withthe original GWTC-1 results, with all Jensen-Shannon divergences between theprevious results using IMRPhenomPv2 and our default IMRPhenomXPHM posteriorsbelow 0.045 bits, but we also discuss cases where including subdominantharmonics and/or precession influences the posteriors.<br

New twists in compact binary waveform modeling: A fast time-domain model for precession

We present IMRPhenomTPHM, a phenomenological model for the gravitational wave signals emitted by the coalescence of quasi-circular precessing binary black holes systems. The model is based on the "twisting up" approximation, which maps non-precessing signals to precessing ones in terms of a time dependent rotation described by three Euler angles, and which has been utilized in several frequency domain waveform models that have become standard tools in gravitational wave data analysis. Our model is however constructed in the time domain, which allows several improvements over the frequency domain models: we do not use the stationary phase approximation, we employ a simple approximation for the precessing Euler angles for the ringdown signal, and we implement a new method for computing the Euler angles through the evolution of the spin dynamics of the system, which is more accurate and also computationally efficient

Factors that predict early treatment failure for patients with locally advanced (T4) breast cancer

Locally advanced breast cancer (LABC) is associated with dire prognosis despite progress in multimodal treatments. We evaluated several clinical and pathological features of patients with either noninflammatory (NIBC, cT4a-c) or inflammatory (IBC, cT4d) breast cancer to identify subset groups of patients with high risk of early treatment failure. Clinical and pathological features of 248 patients with LABC, who were treated with multimodality treatments including neoadjuvant chemotherapy followed by radical surgery and radiotherapy were reassessed. Tumour samples obtained at surgery were evaluated using standard immunohistochemical methods. Overall, 141 patients (57%) presented with NIBC (cT4a-c, N0-2, M0) and 107 patients (43%) with IBC (cT4d, N0-2, M0). Median follow-up time was 27.5 months (range: 1.6–87.8). No significant difference in terms of recurrence-free survival (RFS) (P=0.72), disease-free survival (DFS) (P=0.98) and overall survival (OS) (P=0.35) was observed between NIBC and IBC. At the multivariate analysis, patients with ER- and PgR-negative diseases had a significantly worse RFS than patients with ER- and/or PgR-positive diseases (hazard ratio: 2.47, 95% CI: 1.33–4.59 for overall). The worst RFS was observed for the subgroup of patients with endocrine nonresponsive and HER2-negative breast cancer (2-year RFS: 57% in NIBC and 57% in IBC) A high Ki-67 labelling index (>20% of the invasive tumour cells) and the presence of peritumoral vascular invasion (PVI) significantly correlated with poorer RFS in overall (HR 2.69, 95% CI: 1.61–4.50 for Ki-67>20% and HR 2.27, 95% CI: 1.42–3.62 for PVI). Patients with endocrine nonresponsive LABC had the most dire treatment outcome. High degree of Ki-67 staining and presence of PVI were also indicators of higher risk of early relapse. These factors should be considered in therapeutic algorithms for LABC

A detailed analysis of GW190521 with phenomenological waveform models

In this paper we present an extensive analysis of the GW190521 gravitational wave event with the current (fourth) generation of phenomenological waveform models for binary black hole coalescences. GW190521 stands out from other events since only a few wave cycles are observable. This leads to a number of challenges, one being that such short signals are prone to not resolve approximate waveform degeneracies, which may result in multi-modal posterior distributions. The family of waveform models we use includes a new fast time-domain model IMRPhenomTPHM, which allows us extensive tests of different priors and robustness with respect to variations in the waveform model, including the content of spherical harmonic modes. We clarify some issues raised in a recent paper [Nitz&Capano], associated with possible support for a high-mass ratio source, but confirm their finding of a multi-modal posterior distribution, albeit with important differences in the statistical significance of the peaks. In particular, we find that the support for both masses being outside the PISN mass-gap, and the support for an intermediate mass ratio binary are drastically reduced with respect to what Nitz&Capano found. We also provide updated probabilities for associating GW190521 to the potential electromagnetic counterpart from ZTF

Who are the women who enrolled in the POSITIVE trial: A global study to support young hormone receptor positive breast cancer survivors desiring pregnancy

Càncer de mama; Desig d'embaràs; Dones jovesBreast cancer; Pregnancy desire; Young womenCáncer de mama; Deseo de embarazo; Mujeres jóvenesBackground Premenopausal women with early hormone-receptor positive (HR+) breast cancer receive 5–10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and fertility may wane. The POSITIVE study investigates the impact of temporary ET interruption to allow pregnancy. Methods POSITIVE enrolled women with stage I-III HR + early breast cancer, ≤42 years, who had received 18–30 months of adjuvant ET and wished to interrupt ET for pregnancy. Treatment interruption for up to 2 years was permitted to allow pregnancy, delivery and breastfeeding, followed by ET resumption to complete the planned duration. Findings From 12/2014 to 12/2019, 518 women were enrolled at 116 institutions/20 countries/4 continents. At enrolment, the median age was 37 years and 74.9 % were nulliparous. Fertility preservation was used by 51.5 % of women. 93.2 % of patients had stage I/II disease, 66.0 % were node-negative, 54.7 % had breast conserving surgery, 61.9 % had received neo/adjuvant chemotherapy. Tamoxifen alone was the most prescribed ET (41.8 %), followed by tamoxifen + ovarian function suppression (OFS) (35.4 %). A greater proportion of North American women were <35 years at enrolment (42.7 %), had mastectomy (59.0 %) and received tamoxifen alone (59.8 %). More Asian women were nulliparous (81.0 %), had node-negative disease (76.2%) and received tamoxifen + OFS (56.0 %). More European women had received chemotherapy (69.3 %). Interpretation The characteristics of participants in the POSITIVE study provide insights to which patients and doctors considered it acceptable to interrupt ET to pursue pregnancy. Similarities and variations from a regional, sociodemographic, disease and treatment standpoint suggest specific sociocultural attitudes across the world.The POSITIVE trial and this work are sponsored by the IBCSG in non-North American countries and by the Alliance for Clinical Trials in Oncology in North America, with collaboration of the Breast International Group (BIG) cooperative groups and US National Clinical Trials Network groups