Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Trends in use of neoadjuvant systemic therapy in patients with clinically node-positive breast cancer in Europe: prospective TAXIS study (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

PURPOSE: The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe. METHODS: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery. The TAXIS study's pragmatic design allowed both the neoadjuvant and adjuvant setting according to the preferences of the local investigators who were encouraged to register eligible patients consecutively. RESULTS: A total of 500 patients were included at 44 breast centers in six European countries from August 2018 to June 2022, 165 (33%) of whom underwent NST. Median age was 57 years (interquartile range [IQR], 48-69). Most patients were postmenopausal (68.4%) with grade 2 and 3 hormonal receptor-positive and human epidermal growth factor receptor 2-negative breast cancer with a median tumor size of 28 mm (IQR 20-40). The use of NST varied significantly across the countries (p < 0.001). Austria (55.2%) and Switzerland (35.8%) had the highest percentage of patients undergoing NST and Hungary (18.2%) the lowest. The administration of NST increased significantly over the years (OR 1.42; p < 0.001) and more than doubled from 20 to 46.7% between 2018 and 2022. CONCLUSION: Substantial heterogeneity in the use of NST with HR+/HER2-breast cancer exists in Europe. While stringent guidelines are available for its use in triple-negative and HER2+ breast cancer, there is a need for the development of and adherence to well-defined recommendations for HR+/HER2-breast cancer.

Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

AIM: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS. METHODS: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load. RESULTS: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3-7) nodes, two (IQR 1-4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10-17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%. CONCLUSIONS: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.

Breech delivery in the all fours position: a prospective observational comparative study with classic assistance.

OBJECTIVE: Vaginal delivery of fetal breech presentation is considered to be a challenge for obstetricians. The purpose of this study was to show that vaginal delivery in all fours position is feasible and safe for mother and child compared with vaginal breech and classic support. METHODS: A single-center prospective observational case series of breech delivery (n=41) in all fours position was compared to a retrospective cohort of breech deliveries in the form of a matched-pair analysis. RESULTS: Deliveries in the all fours position successfully took place without obstetric intervention in 70.7% of deliveries (n=29/41), and those including intervention in 90.2% (n=37/41). The rate of maternal perineal injuries was reduced (14.6% vs. 58.5%, P<0.001). Newborns delivered in all fours position had increased prenatal hypoxic stress with a pH of 7.19 [95% confidence interval (CI) 7.16-7.22] vs. a pH of 7.24 (95% CI 7.21-7.27; P=0.016). With n=24 vs. n=16, a higher number of newborns had a pH of <7.20 (P=0.03) and decreased base excess of -7.2 mmol/L (95% CI -8.2-6.2) vs. -4.8 mmol/L (95% CI -5.7-4.0; P<0.001). However, this had no clinical consequences for the newborns (5 min Apgar score <9: n=5 vs. n=4, not significant; transfer rate to neonatal intensive care unit n=7 vs. n=6, not significant). CONCLUSION: This is the first clinical evaluation of breech delivery in the all fours position. It is a feasible non-interventional obstetric delivery method. It seems to be safe for the fetus with reduced maternal morbidity. Vaginal delivery of fetal breech presentation, even in the all fours position, creates stress for the newborn.

Patient satisfaction with childbirth after external cephalic version.

PURPOSE: To assess acceptance and impact of external cephalic version (ECV) for breech presentation at term on maternal satisfaction with childbirth. METHODS: Retrospective study on n = 131 women with breech presentation comparing maternal satisfaction after ECV and consecutive childbirth (n = 66; 50.4% of these successful attempts in n = 33; 50%) against the group without ECV and primary caesarean section (CS) (n = 65; 49.6%) instead using a questionnaire. RESULTS: Women with successful ECV tolerated side effects of the intervention better than after unsuccessful ECV (pain, tocolytics, mental and physical state, for all p < 0.001). They were not more satisfied with childbirth than women who experienced an unsuccessful ECV (p = 0.37). However, they would undergo the procedure again (p = 0.003) and would recommend it to other women (p < 0.001). Only women with spontaneous vaginal deliveries after successful version were more satisfied with childbirth than women with planned CS (p = 0.05). Women with version attempts tend to perceive childbirth as being less problematic with fewer complications (9.5 vs. 19%, p = 0.12). Unsuccessful ECVs had no negative impact on satisfaction with childbirth (p = 0.072). CONCLUSION: Attempting ECV seems to be an option for increasing the rate of vaginal births with breech presentation without negative impact on maternal satisfaction regarding consecutive childbirth.

Single-institute experience, management, success rate, and outcome after external cephalic version at term.

OBJECTIVE: To determine obstetric outcomes after external cephalic version (ECV) performed at term. METHODS: In a retrospective study of ECV among pregnant women at term at Klinikum Kreuzschwestern Wels between January 1999 and June 2010, univariate and multivariate logistic regression was used to analyze factors influencing success rate. RESULTS: Among 379 ECV attempts, 49.1% (95% confidence interval, 44.1-54.1) were successful. Success rate was dependent on parity, gestational age, and performing physician. Increasing parity was associated with increasing success rate (P=0.05). Gestational age had no influence until week 39, after which the success rate increased (success after completion of week 35, 48.1%; week 37, 43.7%; week 38, 43.5%; week 39, 64.9%; week 40 or more, 90.9%; P=0.19). The performing physician had a significant influence (P<0.0005). Regarding obstetric outcome, spontaneous re-version occurred in 8.1% of women, 81.1% of women delivered vaginally, 7.9% had unplanned cesarean delivery, and 4.9% had vacuum extraction. No harm to fetal or maternal health resulted from ECV. CONCLUSION: ECV was found to be a safe procedure at term. The skill of the physician significantly affected the success rate. The rate of surgical delivery after successful ECV was low. A trial of ECV at term and beyond is feasible.

Placental passage of clarithromycin surpasses other macrolide antibiotics.

OBJECTIVE: Infection of the amnion cavity with Ureaplasma urealyticum continues to be a therapeutic challenge. The transplacental transfer rates of macrolide antibiotics are low, and tetracyclines and quinolones are contraindicated in pregnancy. The aim of this study was to investigate placental transfer of clarithromycin in a well-studied placental perfusion model to determine whether clarithromycin surpasses the transfer rate of other macrolide antibiotics in similar models. STUDY DESIGN: Ten placentas that were obtained immediately after delivery were perfused with clarithromycin (3 microg/mL) plus a reference substance (antipyrine). Open circulation placental preparations were used to evaluate steady-state pharmacodynamics and transplacental gradient formation. Drug concentrations were measured by high-performance liquid chromatography. RESULTS: The mean transplacental transfer of clarithromycin was 6.1% (95% CI, 1.8%). CONCLUSION: Because of its enhanced placental passage compared with other macrolide antibiotics, clarithromycin that is given after the first trimester (after embryogenesis) may be an appropriate candidate in treatment trials of genital mycoplasma and ureaplasma infections during pregnancy.