The optimal adjuvant endocrine therapy for HR-positive/HER2-positive breast cancer patients is unknown. We included in this analysis 784 patients with HR-positive/HER2-positive BC from the randomized ShortHER trial of adjuvant trastuzumab (1 year vs 9 weeks) + chemotherapy. At a median follow-up of 8.7 years, patients who received AI had a significantly better DFS vs patients who received TAM or TAM-AI: 8-yr DFS 86.4 vs 79.7%, log-rank P = 0.013 (HR 1.52, 95% CI 1.09-2.11). In multivariate analysis, the type of endocrine therapy maintained a significant association with DFS (HR 1.64, 95% CI 1.07-2.52, p = 0.025 for TAM/TAM-AI vs AI). Among premenopausal patients aged ≤45 years, the use of GnRHa was associated with longer DFS: 8-yr DFS rate 85.2 vs 62.6% (log-rank p = 0.019, HR 0.41, 95% CI 0.19-0.88). In this post-hoc analysis of the ShortHER trial adjuvant treatment with AI was independently associated with improved DFS. Subgroup analysis in premenopausal patients suggests benefits with ovarian suppression.Trial registration: NCI ClinicalTrials.gov number: NCT00629278.
How common is the use of herbal supplements during pregnancy and does it adversely affect the pregnancy outcome? The use of herbal products during pregnancy is very common and daily almond oil spreading is associated with preterm birth (PTB). Herbal drugs are often promoted as 'natural' and 'safe' and such claims attract pregnant women. More than a quarter of Italian pregnant women consume herbs every day for at least 3 months during pregnancy. We raise an alert over the habit of daily almond oil spreading since it seems to be associated with PTB. A multicenter retrospective cohort study performed over a 15-month period. Seven hundred women interviewed within 3 days of childbirth, in three public hospitals in northern Italy. One hundred and eighty-nine women were considered 'regular users', since they consumed herbs every day, for at least 3 months. Almond oil, chamomile and fennel were the most commonly used herbs. Both length of gestation and birthweight were affected by herb consumption. Almond oil users showed more pre-term birth (29 of 189) than non-users (51 of 511). After adjusting for multiple pregnancies, smoking, advanced age and drug intake, almond oil users maintained an increased risk to give birth <37th week (odds ratio = 2.09, 95% confidence interval: 1.08–4.08). The association between daily spreading of almond oil and PTB only raises a hypothesis that requires confirmation in larger trials devoted to this topic. The relatively small sample size did not allow the investigation of other adverse pregnancy outcomes in herb users. The population under investigation did not significantly differ from the general population attending the same hospitals. No conflict of interest exists. The study has been supported by a public grant from the University of Modena and Reggio Emilia. None
Objective To investigate whether different antenatal care models could account for differences in operative delivery rates and adverse neonatal outcomes among low-risk pregnant women, and to identify independent variables associated with delivery modes and adverse neonatal outcomes. Study design Retrospective cohort from a single center of singleton, term, live births between January 2012 and June 2014. Rates of cesarean deliveries, operative vaginal deliveries, and neonatal morbidities were analyzed among women followed by private obstetrician-gynecologists versus national health system providers (certified nurse midwifes supervised by obstetrician-gynecologists), and adjusted for potential confounders. Results Among the 2,831 women in our cohort, obstetric and neonatal outcomes were independent of obstetric providers. After we controlled for confounders, private patients having more than four antenatal ultrasound examinations were more likely to undergo cesarean delivery than public patients with four or fewer sonographic assessments (five to eight prenatal scans: relative risk ratio, 3.3; 95% confidence interval [CI] 1.4–8; nine or more prenatal scans: relative risk ratio, 4.1; 95% CI 1.2–14). Conclusions Multiple prenatal ultrasound examinations in low-risk obstetric populations appear to be an independent and potentially modifiable risk factor for cesarean deliveries.
Abstract Background: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery. Methods: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2). Conclusions: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.
Abstract Background The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial. Methods The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death. Results A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% ( n = 517) of patients to a more favorable stage category. Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% ( P < 0.001). Five-year DDFS according to prognostic stage was as follows: IA 95.7%, IB 91.4%, IIA 86.9%, IIB 85.0%, IIIA 77.6%, IIIC 67.7% ( P < 0.001). The C index was similar (0.69209 and 0.69249, P = 0.975). Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080). Conclusions The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment. Trial registration EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278 .
1097 Background: Oligometastatic breast cancer (OMBC) is a clinical entity with favorable prognosis compared to MBC in general, but the optimal treatment for individual patients remains unclear. We compared high dose chemotherapy (HDCT) to conventional dose chemotherapy (CDCT) in patients receiving local ablative therapy (LAT) of all disease sites in HER2-negative OMBC that harbors homologous recombination deficiency (HRD). Methods: In this open-label phase 3 study, we randomly assigned patients with OMBC after 3 cycles of induction CDCT to either continue with CDCT (up to a maximum total of 8 cycles) or switch to HDCT. OMBC was defined as 1-3 distant metastatic lesions, with or without locoregional disease, all amenable to LAT. Main eligibility criteria included pathologic proof of a distant metastatic lesion, HRD (based on either germline BRCA1/2 mutation and/or a BRCA-like profile in the tumor), and a favorable response to induction CDCT. The primary endpoint was event-free survival (EFS), defined as time since randomization to recurrence or death. Overall survival (OS), safety and quality of life (QoL) were key secondary endpoints. Following the advice of the independent data monitoring committee, analyses were performed before the prespecified number of events was reached. Results: Between November 2012 and May 2022, 36 patients were allocated to HDCT and 39 to CDCT. 52 (69%) tumors were triple negative and 23 (31%) were hormone receptor positive; 39 patients (52%) had a solitary metastasis and 43 (57%) had synchronous OMBC. After a median follow-up of 52 months (interquartile range 28-97), 42 EFS-events had occurred. Median EFS in the HDCT-group was 28 months (95% CI 21 – not reached (NR)) compared to 25 months (95% CI 14 – NR) in the CDCT-group (hazard ratio (HR) 0.78 (95% CI 0.42 – 1.42, p = 0.411). Median OS was 67 months (95% CI 37 – NR) in the HDCT-group versus 36 months (95% CI 26 – NR) in the CDCT-group (HR 0.74, 95% CI 0.37 – 1.48, p = 0.398). 5-year EFS was 40% and 30%, and 5-year OS was 51% and 49% in the HDCT- and CDCT-group, respectively. 34 (94%) patients in the HDCT-group experienced grade 3 or higher adverse events, compared to 25 (64%) patients in the CDCT-group; no grade 5 adverse events occurred. QoL was comparable between groups at 12 months. Conclusions: HDCT does not improve outcome compared to CDCT in patients with OMBC harboring HRD and can therefore not be recommended. Survival in this highly selected group of patients with OMBC, all receiving LAT, compares favorably to survival in the overall MBC population. The optimal systemic therapy for patients with OMBC requires further study. Clinical trial information: NCT01646034 .
Background . When the bivalent and the quadrivalent HPV vaccines were marketed they were presented as having comparable efficacy against cervical cancer. Differences between the vaccines are HPV types included and formulation of the adjuvant. Method . A systematic review was conducted to assess the efficacy of the two vaccines against cervical cancer. Outcomes considered were CIN2+, CIN3+, and AIS. Results . Nine reports (38,419 women) were included. At enrolment mean age of women was 20 years, 90% had negative cytology, and 80% were seronegative and/or DNA negative for HPV 16 or 18 (naïve women). In the TVC-naïve, VE against CIN2+ was 58% (95% CI: 35, 72); heterogeneity was detected, VE being 65% (95% CI: 54, 74) for the bivalent and 43% (95% CI: 23, 57) for the quadrivalent. VE against CIN3+ was 78% (95% CI: <0, 97); heterogeneity was substantial, VE being 93% (95% CI: 77, 98) for the bivalent and 43% (95% CI: 12, 63) for the quadrivalent. VE in the TVC was much lower. No sufficient data were available on AIS. Conclusions . In naïve girls bivalent vaccine shows higher efficacy, even if the number of events detected is low. In women already infected the benefit of the vaccination seems negligible.
