Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer.

BACKGROUND: Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. METHODS: We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. RESULTS: Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. CONCLUSIONS: Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).

Influence of an "Electroencephalogram-Based" Monitor Choice on the Delay Between the Predicted Propofol Effect-Site Concentration and the Measured Drug Effect.

BACKGROUND: Clinicians can optimize propofol titration by using 2 sources of pharmacodynamic (PD) information: the predicted effect-site concentration for propofol (Ceprop) and the electroencephalographically (EEG) measured drug effect. Relation between these sources should be time independent, that is, perfectly synchronized. In reality, various issues corrupt time independency, leading to asynchrony or, in other words, hysteresis. This asynchrony can lead to conflicting information, making effective drug dosing challenging. In this study, we tried to quantify and minimize the hysteresis between the Ceprop (calculated using the Schnider model for propofol) and EEG measured drug effect, using nonlinear mixed-effects modeling (NONMEM). Further, we measured the influence of EEG-based monitor choice, namely Bispectral index (BIS) versus qCON index (qCON) monitor, on propofol PD hysteresis. METHODS: We analyzed the PD data from 165 patients undergoing propofol-remifentanil anesthesia for outpatient surgery. Drugs were administered using target-controlled infusion (TCI) pumps. Pumps were programmed with Schnider model for propofol and Minto model for remifentanil. We constructed 2 PD models (direct models) relating the Schnider Ceprop to the measured BIS and qCON monitor values. We quantified the models' misspecification due to hysteresis, on an individual level, using the root mean squared errors (RMSEs). Subsequently, we optimized the PD models' predictions by adding a lag term to both models (lag-time PD models) and quantified the optimization using the RMSE. RESULTS: There is a counterclockwise hysteresis between Ceprop and BIS/qCON values. Not accounting for this hysteresis results in a direct PD model with an effect-site concentration which produces 50% of the maximal drug effect (Ce50) of 6.24 and 8.62 µg/mL and RMSE (median and interquartile range [IQR]) of 9.38 (7.92-11.23) and 8.41(7.04-10.2) for BIS and qCON, respectively. Adding a modeled lag factor of 49 seconds to the BIS model and 53 seconds to the qCON model improved both models' prediction, resulting in similar Ce50 (3.66 and 3.62 µg/mL for BIS and qCON) and lower RMSE (median (IQR) of 7.87 (6.49-9.90) and 6.56 (5.28-8.57) for BIS and qCON. CONCLUSIONS: There is a significant "Ceprop versus EEG measured drug effect" hysteresis. Not accounting for it leads to conflicting PD information and false high Ce50 for propofol in both monitors. Adding a lag term improved the PD model performance, improved the "pump-monitor" synchrony, and made the estimates of Ce50 for propofol more realistic and less monitor dependent.

External cavity diode laser based upon an FBG in an integrated optical fiber platform.

An external cavity diode laser is demonstrated using a Bragg grating written into a novel integrated optical fiber platform as the external cavity. The cavity is fabricated using flame-hydrolysis deposition to bond a photosensitive fiber to a silica-on-silicon wafer, and a grating written using direct UV-writing. The laser operates on a single mode at the acetylene P13 line (1532.83 nm) with 9 mW output power. The noise properties of the laser are characterized demonstrating low linewidth operation (< 14 kHz) and superior relative intensity noise characteristics when compared to a commercial tunable external cavity diode laser.

(87)Rb-stabilized 375-MHz Yb:fiber femtosecond frequency comb.

We report a fully stabilized 1030-nm Yb-fiber frequency comb operating at a pulse repetition frequency of 375 MHz. The comb spacing was referenced to a Rb-stabilized microwave synthesizer and the comb offset was stabilized by generating a super-continuum containing a coherent component at 780.2 nm which was heterodyned with a (87)Rb-stabilized external cavity diode laser to produce a radio-frequency beat used to actuate the carrier-envelope offset frequency of the Yb-fiber laser. The two-sample frequency deviation of the locked comb was 235 kHz for an averaging time of 50 seconds, and the comb remained locked for over 60 minutes with a root mean squared deviation of 236 kHz.

[A lump in the breast]. / Un bulto en la mama.

The statistics seem to indicate that at some point in their lives, one in nine women must face breast cancer. The author recounts hi personal way of moving forward and sharing the questions and answers that have been found in this way. She is the author of the book with the same title that his article.

Frequency stability of a femtosecond optical parametric oscillator frequency comb.

Carrier-envelope-offset (CEO) and pulse-repetition frequencies of a Ti:sapphire-pumped femtosecond optical parametric oscillator were locked to uncertainties of 0.09 Hz and 0.16 mHz respectively, with the CEO beat signal linewidth being stabilized to 15 Hz (instrument limited). In-loop phase-noise power spectral density measurements showed a contribution of our servo electronics to the comb-line frequency uncertainty of up to 110 Hz. Complementary time-series data implied an in-loop comb instability of 2 x 10(-11) (1-s gate time), matching the Rb-stabilized reference used and verifying that dual servo-control of the CEO and repetition frequencies was effective in stabilizing the comb to at least this precision.

Locking the carrier-envelope-offset frequency of an optical parametric oscillator without f-2f self-referencing.

The carrier-envelope-offset (CEO) frequency of pulses from a femtosecond optical parametric oscillator (OPO) was stabilized for 30 min without the need for f-2f self-referencing in either the OPO or its pump laser. Interference between the high-frequency modes of the pump supercontinuum and the modes of the non-phase-matched pump+signal sum-frequency-mixing pulses provided the beat signal used for locking. The -3 dB bandwidth of the locked CEO-frequency was measured as 1.1 kHz, and the cumulative phase error recorded over 1 s was 0.38 rad, representing 1-order-of-magnitude improvement in comparison to previous results.