Current status of ultrasound-guided surgery in the treatment of breast cancer

The primary goal of breast-conserving surgery (BCS) is to obtain tumour-free resection margins. Margins positive or focally positive for tumour cells are associated with a high risk of local recurrence, and in the case of tumour-positive margins, re-excision or even mastectomy are sometimes needed to achieve definite clear margins. Unfortunately, tumour-involved margins and re-excisions after lumpectomy are still reported in up to 40% of patients and additionally, unnecessary large excision volumes are described. A secondary goal of BCS is the cosmetic outcome and one of the main determinants of worse cosmetic outcome is a large excision volume. Up to 30% of unsatisfied cosmetic outcome is reported. Therefore, the search for better surgical techniques to improve margin status, excision volume and consequently, cosmetic outcome has continued. Nowadays, the most commonly used localization methods for BCS of non-palpable breast cancers are wire-guided localization (WGL) and radio-guided localization (RGL). WGL and RGL are invasive procedures that need to be performed pre-operatively with technical and scheduling difficulties. For palpable breast cancer, tumour excision is usually guided by tactile skills of the surgeon performing "blind" surgery. One of the surgical techniques pursuing the aims of radicality and small excision volumes includes intra-operative ultrasound (IOUS). The best evidence available demonstrates benefits of IOUS with a significantly high proportion of negative margins compared with other localization techniques in palpable and non-palpable breast cancer. Additionally, IOUS is non-invasive, easy to learn and can centralize the tumour in the excised specimen with low amount of healthy breast tissue being excised. This could lead to better cosmetic results of BCS. Despite the advantages of IOUS, only a small amount of surgeons are performing this technique. This review aims to highlight the position of ultrasound-guided surgery for malignant breast tumours in the search for better oncological and cosmetic outcomes

Breast conserving therapy after neoadjuvant chemotherapy; data from the Dutch Breast Cancer Audit

Introduction: NAC has led to an increase in breast conserving surgery (BCS) worldwide. This study aims to analyse trends in the use of neoadjuvant chemotherapy (NAC) and the impact on surgical outcomes. Methods: We reviewed all records of cT1-4N0-3M0 breast cancer patients diagnosed between July 2011 and June 2016 who have been registered in the Dutch National Breast Cancer Audit (NBCA) (N = 57.177). The surgical outcomes of ‘BCS after NAC′ were compared with ‘primary BCS′ using a multivariable logistic regression model. Results: Between 2011 and 2016, the use of NAC increased from 9% to 18% and ‘BCS after NAC’ (N = 4170) increased from 43% to 57%. We observed an involved invasive margin rate (IMR) of 6,7% and a re-excision rate of 6,6%. As compared to ‘primary BCS′ the IMR of ‘BCS after NAC′ is higher for cT1 (12,3% versus 8,3%; p < 0.005), equal for cT2 (14% versus 14%; p = 0.046) and lower for cT3 breast cancer (28,3% versus 31%; p < 0.005). Prognostic factors associated with IMR for both ‘primary BCS′ as for ‘BCS after NAC′ are: lobular invasive breast cancer and a hormone receptor positive receptor status (all p < 0,005). Conclusion: The use of NAC and the incidence of ‘BCS after NAC′ increased exponentially in time for all stages of invasive breast cancer in the Netherlands. This nationwide data confirms that ‘BCS after NAC′ compared to ‘primary BCS′ leads to equal surgical outcomes for cT2 and improved surgical outcomes for cT3 breast cancer. These promising results encourage current developments towards de-escalation of surgical treatment

Cosmetic outcome and quality of life are inextricably linked in breast-conserving therapy

Introduction: Cosmetic results and quality of life (QoL) are increasingly important in the treatment of breast cancer. This study was designed to determine the relationship between QoL and both subjectively and objectively measured cosmetic outcomes of breast-conserving therapy (BCT), and its course over time. Methods: A total of 128 breast cancer patients who underwent BCT as part of a prospective randomized controlled trial were included. QoL was measured using the EORTC QLQ-C30 and QLQ-BR23 at baseline, 3, 6, 12, and 36 months. Cosmetic outcome was determined by patient self-evaluation, panel evaluation, and BCCT.core software. Results: By 36 months, all QoL factors except arm symptoms had returned to baseline or improved. After adjustment for patient and tumor characteristics, a significantly better QoL in terms of body image, pain, and arm and breast symptoms was found for good/excellent cosmetic outcomes compared to fair/poor outcomes, as measured by both patient self-evaluation and panel evaluation. The BCCT.core showed no correlation with any QoL factors. Conclusion: There is a high correlation between poor cosmetic outcome and low scores on quality of life indicators, underlining the importance of achieving a good cosmetic outcome after BCT

Breast-specific factors determine cosmetic outcome and patient satisfaction after breast-conserving therapy: Results from the randomized COBALT study

Background and Objectives: To identify breast-specific factors and the role of tumor, treatment, and patient-related items in influencing patient opinion on cosmesis and satisfaction after breast-conserving therapy (BCT). Methods: Data from the randomized COBALT study was used. At 3, 12, and 36 months, 128 patients with T1-T2 breast cancer completed a questionnaire on breast-specific factors and overall cosmetic outcome and patient satisfaction, using a 4-point Likert scale. Results: There was a strong positive correlation between breast-specific factors, overall cosmetic outcome,and satisfaction at all time-points. Excellent/good cosmetic outcomes and satisfaction decreased during follow-up. A shift was noted in the degree of influence of the various breast-specific factors. At 3 years, symmetry factors such as size, shape, and nipple position largely determined a patient's opinion on the final cosmesis, followed by firmness. The risk of an unacceptable outcome was associated with young age and large excision volumes. Conclusion: A questionnaire including breast-specific questions provides important information on final cosmetic results and satisfaction after BCT. These outcomes can also be of great value as quality indicators and pre-operative counseling. The major influence of breast-specific factors on asymmetry underlines the importance of achieving an optimal excision volume at the initial procedure

Breast-conserving surgery following neoadjuvant therapy-a systematic review on surgical outcomes

Purpose: Neoadjuvant chemotherapy (NACT) is increasingly used in breast cancer treatment. One of the main goals of NACT is to reduce the extent of local surgery of the breast and axilla. The aim of this study was to determine surgical outcomes for patients receiving breast-conserving therapy (BCT) after NACT, including margin status plus secondary surgeries, excision volumes, and cosmetic outcomes. Methods: A systematic review was performed in accordance with PRISMA principles. Pubmed, MEDLINE, Embase, and the Cochrane Library were searched for studies investigating the results of BCT following NACT. The main study outcomes were margin status, additional local therapies, excision volumes, and cosmetic outcomes. Non-comparative studies on NACT were also included. Exclusion criteria were studies with less than 25 patients, and studies excluding secondary mastectomy patients. Findings: Of the 1219 studies screened, 26 studies were deemed eligible for analysis, including data from 5379 patients treated with NACT and 10,110 patients treated without NACT. Included studies showed wide ranges of tumor-involved margins (2–39.8%), secondary surgeries (0–45.4%), and excision volumes (43.2–268 cm3) or specimen weight (26.4–233 g) after NACT. Most studies were retrospective, with a high heterogeneity and a high risk of bias. Cosmetic outcomes after NACT were reported in two single-center cohort studies. Both studies showed acceptable cosmetic outcomes. Interpretation: There is currently insufficient evidence to suggest that NACT improves surgical outcomes of BCT. It is imperative that clinical trials include patient outcome measures in order to allow monitoring and meaningful comparison of treatment outcomes in breast cancer

Breast-conserving therapy for breast cancer: Cosmetic results and options for delayed reconstruction

OBJECTIVES: Optimisation of the cosmetic outcome after breast-conserving therapy (BCT) is important. We aimed to determine the cosmetic outcome following BCT and factors influencing this cosmesis and identify the most favourable options for delayed breast reconstruction. MATERIALS AND METHODS: Four reconstructive surgeons evaluated the cosmetic outcome of 109 patients after BCT. Additionally, the surgeons indicated which patients were amenable for delayed reconstruction and the preferred type of reconstruction. The inter- and intra-observer agreement of the surgeons was rated. RESULTS: The mean overall cosmetic outcome was rated as fair (2.7/4.0, SD 0.9, 1.0-4.0). Risk factors for a poor cosmesis were larger breast size (OR 3.81, p = 0.040), larger tumour (OR 1.63, p = 0.028) and axillary lymph node dissection (ALND) (OR 3.09, p = 0.013). Reconstruction of the ipsilateral side was recommended in 55.6% and 94.5% and contralateral reconstruction in 16.7% and 73.3% of patients with good and poor cosmesis, respectively. Flap reconstruction and lipofilling were most commonly reported for the ipsilateral, and breast reduction for the contralateral breast, with reasonable improvement expected (2.2/4.0, SD 0.5, 1.08-3.3). The inter- (0.5-0.7) and intra-observer (0.63-0.79) agreement of the cosmesis was moderate to good, however, poor regarding the recommended reconstruction techniques (mainly < 0.50). CONCLUSION: Cosmetic outcome after BCT is influenced by breast and tumour size and ALND. Although several reconstructive options are available, the optimal method for revision surgery has not yet been determined. Future studies are necessary to obtain evidence-based guidelines for reconstructive surgery after BCT

Intraoperative Ultrasound Guidance in Breast-Conserving Surgery Improves Cosmetic Outcomes and Patient Satisfaction: Results of a Multicenter Randomized Controlled Trial (COBALT)

BACKGROUND: Ultrasound-guided breast-conserving surgery (USS) results in a significant reduction in both margin involvement and excision volumes (COBALT trial). Objective. The aim of the present study was to determine whether USS also leads to improvements in cosmetic outcome and patient satisfaction when compared with standard palpation-guided surgery (PGS). METHODS: A total of 134 patients with T1–T2 invasive breast cancer were included in the COBALT trial (NTR2579) and randomized to either USS (65 patients) or PGS (69 patients). Cosmetic outcomes were assessed by a three-member panel using computerized software Breast Cancer Conservative Treatment cosmetic results (BCCT.- core) and by patient self-evaluation, including patient satisfaction. Time points for follow-up were 3, 6, and 12 months after surgery. Overall cosmetic outcome and patient satisfaction were scored on a 4-point Likert scale (excellent, good, fair, or poor), and outcomes were analyzed using a multilevel, mixed effect, proportional odds model for ordinal responses. RESULTS: Ultrasound-guided breast-conserving surgery achieved better cosmetic outcomes, with 20 % excellence overall and only 6 % rated as poor, whereas 14 % of PGS outcomes were rated excellent and 13 % as poor. USS also had consistently lower odds for worse cosmetic outcomes (odds ratio 0.55, p = 0.067) than PGS. The chance of having a worse outcome was significantly increased by a larger lumpectomy volume (ptrend = 0.002); a volume [40 cc showed odds 2.78-fold higher for a worse outcome than a volume B40 cc. USS resulted in higher patient satisfaction compared with PGS. CONCLUSION: Ultrasound-guided breast-conserving surgery achieved better overall cosmetic outcomes and patient satisfaction than PGS. Lumpectomy volumes[40 cc resulted in significantly worse cosmetic outcomes

Blockade of I(Ks) by HMR 1556 increases the reverse rate-dependence of refractoriness prolongation by dofetilide in isolated rabbit ventricles

1. The rate-dependent contributions of the rapid and slow components of the cardiac delayed rectifier K(+) current (I(Kr) and I(Ks), respectively) to repolarization are not fully understood. It is unclear whether the addition of I(Ks) block will attenuate reverse rate-dependence seen after I(Kr) block. 2. The individual and combined electrophysiological effects of selective I(Kr) and I(Ks) blockers, dofetilide and HMR 1556, respectively, were evaluated using Langendorff-perfused rabbit hearts. Monophasic action potential duration at 90% repolarization (MAPD(90)) and ventricular effective refractory period (VERP) were determined at cycle lengths (CLs) of 200–500 ms (at 50 ms intervals). 3. Dofetilide (1–100 nM) prolonged MAPD(90) in a concentration-dependent manner (P<0.001, n=6) with reverse rate-dependence (P<0.0001). In contrast, HMR 1556 (10–240 nM) alone did not prolong MAPD(90). However, in the presence of 7.5 nM dofetilide, HMR 1556 (100 nM) increased the extent of reverse rate-dependence by further prolonging MAPD(90) at CLs of 400, 450 and 500 ms (P<0.05, n=9) and, to a lesser extent, at shorter CLs (e.g. by 17±4 ms at CL 500 vs 2±3 ms at CL 200 ms). 4. Effects of dofetilide and HMR 1556 on VERP were similar to those on MAPD(90). The slope of the VERP vs CL relation was steeper after the combination (0.081±0.013) than after dofetilide alone (0.028±0.018, P<0.01, n=9). 5. Blockade of rabbit I(Ks) increased reverse rate-dependence of I(Kr) block