PurposeIndications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion.MethodsThe panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology.ResultsConsensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference.ConclusionsIn case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.Electronic supplementary materialThe online version of this article (10.1007/s10549-018-4937-1) contains supplementary material, which is available to authorized users.

This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment. We evaluated the effects of melatonin on cognition, depressive symptoms and sleep quality, and whether these effects were related to serum levels of Brain Derived Neurotrophic Factor (BDNF) and its receptor, tropomyosin kinase B (TrkB). Thirty-six women were randomly assigned to receive melatonin or placebo for 10 days. To evaluate cognitive performance, we used the Trail-Making-Test Parts A and B (A-B), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and an inhibitory task type Go / No-Go. Our results revealed that melatonin improved executive function on TMT scores, enhanced episodic memory (immediate and delayed) and recognition on RAVLT, and increased verbal fluency in the orthographic COWAT. The TMT-A-B(A-B) were negatively correlated with baseline levels of TrkB and BDNF, respectively. At the end of treatment, changes in TrkB and BDNF were inversely associated with depressive symptoms and sleep quality, but not with the TMT scores. These results suggest a neuroprotective effect of melatonin to counteract the adverse effects of ACBC on cognitive function, sleep quality and depressive symptoms.

A LC-MSMS method for the simultaneous determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots samples was developed and validated. The method employs an ultrasound-assisted liquid extraction and a reversed phase separation in an Acquity(®) C18 column (150×2.1 mm, 1.7 µm). Mobile phase was a mixture of formic acid 0.1% (v/v) pH 2.7 and acetonitrile (gradient from 60:40 to 50:50, v/v). Total analytical run time was 8 min. Precision assays showed CV % lower than 10.75% and accuracy in the range 94.5 to 110.3%. Mean analytes recoveries from DBS ranged from 40% to 92%. The method was successfully applied to 91 paired clinical DBS and plasma samples. Dried blood spots concentrations were highly correlated to plasma, with rs>0.83 (P<0.01). Median estimated plasma concentrations after hematocrit and partition factor adjustment were: TAM 123.3 ng mL(-1); NDT 267.9 ng mL(-1), EDF 10.0 ng mL(-1) and HTF 1.3 ng mL(-1,) representing in average 98 to 104% of the actually measured concentrations. The DBS method was able to identify 96% of patients with plasma EDF concentrations below the clinical threshold related to better prognosis (5.9 ng mL(-1)). The procedure has adequate analytical performance and can be an efficient tool to optimize adjuvant breast cancer treatment, especially in resource limited settings.

BackgroundThis cross-sectional, nested cohort study assessed Female Sexual Function Index (FSFI) scores in postmenopausal women with breast cancer receiving primary chemotherapy.MethodsThe FSFI questionnaire was administered to 24 postmenopausal women one month after diagnosis of breast cancer (post-diagnosis group) and one month after completion of the first cycle of primary anthracyclin-based chemotherapy (post-chemotherapy group). Scores were compared to those of 24 healthy postmenopausal women seeking routine gynecological care (control group). All patients were sexually active at the time of enrollment. Mean age was 57.29 ± 11.82 years in the breast cancer group and 52.58 ± 7.19 years in the control group.ResultsScores in all domains of the FSFI instrument were significantly lower in the post-diagnosis group than in controls (−41.3%, p < 0.001). A further major reduction in FSFI scores was evident on completion of one cycle of primary chemotherapy (down 46.7% from post-diagnosis scores, p < 0.003), again in all domains. Six patients (25%) ceased all sexual relations, in a significant change from baseline (p < 0.001). After one chemotherapy cycle, a further five patients ceased sexual activity, for a total of 11 (45.8%) participants – a borderline significant difference (p = 0.063).ConclusionThe present study shows that female sexual function as assessed by the FSFI declines significantly at two distinct points in time: upon diagnosis of breast cancer and after administration of systemic chemotherapy.

CYP3A4 contributes to the bioactivation of TAM through formation of HTF and becomes increasingly important in case of reduced or absent CYP2D6 activity. EDF and HTF exposure were associated to seasonal variations, with considerable higher plasma concentrations during summer.

No abstract

The presence of CYP3A4*22 might compensate the reduction of EDF concentrations related to CYP2D6 inactivity, especially due to increased HTF concentrations.

Background: Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS). We tested the hypothesis that melatonin use before and during the first cycle of ACBC is better than placebo at improving the DPMS function assessed by changes in the 0–10 Numerical Pain Scale (NPS) during the conditioned pain modulating task (CPM-task) (primary outcome). The effects of melatonin were evaluated in the following secondary endpoints: heat pain threshold (HPT), heat pain tolerance (HPTo), and neuroplasticity state assessed by serum brain-derived neurotrophic factor (BDNF), tropomyosin kinase receptor B, and S100B-protein and whether melatonin’s effects on pain and neuroplasticity state are due more so to its impact on sleep quality. Methods: Thirty-six women, ages 18 to 75 years old, scheduled for their first cycle of ACBC were randomized to receive 20mg of oral melatonin (n = 18) or placebo (n = 18). The effect of treatment on the outcomes was analyzed by delta (Δ)-values (from pre to treatment end). Results: Multivariate analyses of covariance revealed that melatonin improved the function of the DPMS. The Δ-mean (SD) on the NPS (0–10) during the CPM-task in the placebo group was −1.91 [−1.81 (1.67) vs. −0.1 (1.61)], and in the melatonin group was −3.5 [−0.94 (1.61) vs. −2.29 (1.61)], and the mean difference (md) between treatment groups was 1.59 [(95% CI, 0.50 to 2.68). Melatonin’s effect increased the HPTo and HPT while reducing the (Δ)-means of the serum neuroplasticity marker in placebo vs. melatonin. The Δ-BDNF is 1.87 (7.17) vs. −20.44 (17.17), respectively, and the md = 22.31 [(95% CI = 13.40 to 31.22)]; TrKB md = 0.61 [0.46 (0.17) vs. −0.15 (0.18); 95% CI = 0.49 to 0.73)] and S00B-protein md = −8.27[(2.89 (11.18) vs. −11.16 (9.75); 95% CI = −15.38 to −1.16)]. However, melatonin’s effect on pain and the neuroplastic state are not due to its effect on sleep quality. Conclusions: These results suggest that oral melatonin, together with the first ACBC counteracts the dysfunction in the inhibitory DPMS and improves pain perception measures. Also, it shows that changes in the neuroplasticity state mediate the impact of melatonin on pain. Clinical Trial Registration: , identifier NCT03205033.