Is Autologous Fat Grafting an Oncologically Safe Procedure following Breast Conserving Surgery for Breast Cancer? A Comprehensive Review.

BACKGROUND: Autologous fat grafting (AFG) is a recognized surgical procedure to correct deformities following breast conservation surgery (BCS) for breast cancer. However, there are concerns about the oncological safety of this technique. In this study we have reviewed the current literature to assess whether AFG adversely influences the oncological outcome after BCS for breast cancer. METHODS: We have searched the medical literature using the Embase and PubMed search engines from conception until May 2019 to identify all relevant studies of patients who underwent AFG after BCS. Meta-analysis and meta-regression methodologies were used to calculate the overall relative risk (RR) of loco-regional recurrence (LRR) rates for case-control and case series studies (with historical controls) respectively. RESULTS: We have identified 26 eligible studies with a total of 1640 patients who had undergone fat transfer after lumpectomy for breast cancer. The meta-analysis of 11 studies revealed an overall RR for LRR of 0.82 [95% confidence interval (CI):0.14-1.66]. The meta-regression of case series revealed an overall incidence of LRR of 1.85% compared with 2.53% for historical controls. CONCLUSIONS: Our study lends further support to the notion that fat transfer after lumpectomy for breast cancer does not seem to increase the risk of LRR. However further prospective research is required in order to confirm this.

A multicentre prospective feasibility study of carbon dye tattooing of biopsied axillary node and surgical localisation in breast cancer patients.

BACKGROUND: The primary aim of this prospective, multicentre feasibility study was to determine whether the biopsied axillary node can be marked using black carbon dye and successfully identified at the time of surgery. METHODS: We included breast cancer patients undergoing needle biopsy of the axillary node. The biopsied node was tattooed at the time of needle biopsy (fine needle aspiration or core biopsy) or at a separate visit with black carbon dye (Spot® or Black Eye™). Participants underwent primary surgery or neoadjuvant chemotherapy (NACT) and axillary surgery (SNB or ALND) as per routine care. RESULTS: 110 patients were included. Median age of the women was 59 (range 31-88) years. 48 (44%) underwent SNB and 62 (56%) ALND. Median volume of dye injected was 2.0 ml (range 0.2-4.2). Tattooed node was identified intra-operatively in 90 (82%) patients. The identification rate was higher (76 of 88, 86%) in the primary surgery group compared with NACT (14 of 22, 64%) (p = 0.03). Of those undergoing NACT, the identification rate was better in the patients undergoing SNB (3 of 4, 75%) compared with ALND (11 of 18, 61%) (p > 0.99). The tattooed node was the sentinel node in 78% (28 of 36) patients in the primary surgery group and 100% (3 of 3) in the NACT group. There was no learning curve for surgeons or radiologists. The identification rate did not vary with timing between dye injection and surgery (p = 0.56), body mass index (p = 0.62) or volume of dye injected (p = 0.25). CONCLUSION: It is feasible to mark the axillary node with carbon dye and identify it intra-operatively. ClinicalTrials.gov: NCT03640819.

Opportunities and priorities for breast surgical research.

The 2013 Breast Cancer Campaign gap analysis established breast cancer research priorities without a specific focus on surgical research or the role of surgeons on breast cancer research. This Review aims to identify opportunities and priorities for research in breast surgery to complement the 2013 gap analysis. To identify these goals, research-active breast surgeons met and identified areas for breast surgery research that mapped to the patient pathway. Areas included diagnosis, neoadjuvant treatment, surgery, adjuvant therapy, and attention to special groups (eg, those receiving risk-reducing surgery). Section leads were identified based on research interests, with invited input from experts in specific areas, supported by consultation with members of the Association of Breast Surgery and Independent Cancer Patients' Voice groups. The document was iteratively modified until participants were satisfied that key priorities for surgical research were clear. Key research gaps included issues surrounding overdiagnosis and treatment; optimising treatment options and their selection for neoadjuvant therapies and subsequent surgery; reducing rates of re-operations for breast-conserving surgery; generating evidence for clinical effectiveness and cost-effectiveness of breast reconstruction, and mechanisms for assessing novel interventions; establishing optimal axillary management, especially post-neoadjuvant treatment; and defining and standardising indications for risk-reducing surgery. We propose strategies for resolving these knowledge gaps. Surgeons are ideally placed for a central role in breast cancer research and should foster a culture of engagement and participation in research to benefit patients and health-care systems. Development of infrastructure and surgical research capacity, together with appropriate allocation of research funding, is needed to successfully address the key clinical and translational research gaps that are highlighted in this Review within the next two decades.

Downregulation of aquaporin 3 inhibits cellular proliferation, migration and invasion in the MDA-MB-231 breast cancer cell line.

Aquaporins are membrane proteins that regulate cellular water flow. Recently, aquaporins have been proposed as mediators of cancer cell biology. A subset of aquaporins, referred to as aquaglyceroporins are known to facilitate the transport of glycerol. The present study describes the effect of gene knockdown of the aquaglyceroporin AQP3 on MDA-MB-231 breast cancer cell proliferation, migration, invasion, adherence and response to the chemotherapeutic agent 5-fluorouracil. shRNA mediated AQP3 gene knockdown induced a 28% reduction in cellular proliferation (P<0.01), a 39% decrease in migration (P<0.0001), a 24% reduction in invasion (P<0.05) and a 25% increase in cell death at 100 µM 5-FU (P<0.01). Analysis of cell permeability to water and glycerol revealed that MDA-MB-231 cells with knocked down AQP3 demonstrated a modest decrease in water permeability (17%; P<0.05) but a more marked decrease in glycerol permeability (77%; P<0.001). These results suggest that AQP3 has a role in multiple aspects of breast cancer cell pathophysiology and therefore represents a novel target for therapeutic intervention.

Physical activity for women with breast cancer after adjuvant therapy.

BACKGROUND: Women with a diagnosis of breast cancer may experience short- and long-term disease and treatment-related adverse physiological and psychosocial outcomes. These outcomes can negatively impact prognosis, health-related quality of life (HRQoL), and psychosocial and physical function. Physical activity may help to improve prognosis and may alleviate the adverse effects of adjuvant therapy. OBJECTIVES: To assess effects of physical activity interventions after adjuvant therapy for women with breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group (CBCG) Specialised Registry, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Physiotherapy Evidence Database (PEDro), SPORTDiscus, PsycINFO, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform, on 18 September 2015. We also searched OpenGrey and Healthcare Management Information Consortium databases. SELECTION CRITERIA: We searched for randomised and quasi-randomised trials comparing physical activity interventions versus control (e.g. usual or standard care, no physical activity, no exercise, attention control, placebo) after adjuvant therapy (i.e. after completion of chemotherapy and/or radiation therapy, but not hormone therapy) in women with breast cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when needed. We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome and used GRADE to assess the quality of evidence for the most important outcomes. MAIN RESULTS: We included 63 trials that randomised 5761 women to a physical activity intervention (n = 3239) or to a control (n = 2524). The duration of interventions ranged from 4 to 24 months, with most lasting 8 or 12 weeks (37 studies). Twenty-eight studies included aerobic exercise only, 21 involved aerobic exercise and resistance training, and seven used resistance training only. Thirty studies described the comparison group as usual or standard care, no intervention, or control. One-fifth of studies reported at least 20% intervention attrition and the average physical activity adherence was approximately 77%.No data were available on effects of physical activity on breast cancer-related and all-cause mortality, or on breast cancer recurrence. Analysis of immediately postintervention follow-up values and change from baseline to end of intervention scores revealed that physical activity interventions resulted in significant small-to-moderate improvements in HRQoL (standardised mean difference (SMD) 0.39, 95% CI 0.21 to 0.57, 22 studies, 1996 women; SMD 0.78, 95% CI 0.39 to 1.17, 14 studies, 1459 women, respectively; low-quality evidence), emotional function (SMD 0.21, 95% CI 0.10 to 0.32, 26 studies, 2102 women, moderate-quality evidence; SMD 0.31, 95% CI 0.09 to 0.53, 15 studies, 1579 women, respectively; low-quality evidence), perceived physical function (SMD 0.33, 95% CI 0.18 to 0.49, 25 studies, 2129 women; SMD 0.60, 95% CI 0.23 to 0.97, 13 studies, 1433 women, respectively; moderate-quality evidence), anxiety (SMD -0.57, 95% CI -0.95 to -0.19, 7 studies, 326 women; SMD -0.37, 95% CI -0.63 to -0.12, 4 studies, 235 women, respectively; low-quality evidence), and cardiorespiratory fitness (SMD 0.44, 95% CI 0.30 to 0.58, 23 studies, 1265 women, moderate-quality evidence; SMD 0.83, 95% CI 0.40 to 1.27, 9 studies, 863 women, respectively; very low-quality evidence).Investigators reported few minor adverse events.Small improvements in physical activity interventions were sustained for three months or longer postintervention in fatigue (SMD -0.43, 95% CI -0.60 to -0.26; SMD -0.47, 95% CI -0.84 to -0.11, respectively), cardiorespiratory fitness (SMD 0.36, 95% CI 0.03 to 0.69; SMD 0.42, 95% CI 0.05 to 0.79, respectively), and self-reported physical activity (SMD 0.44, 95% CI 0.17 to 0.72; SMD 0.51, 95% CI 0.08 to 0.93, respectively) for both follow-up values and change from baseline scores.However, evidence of heterogeneity across trials was due to variation in intervention components (i.e. mode, frequency, intensity, duration of intervention and sessions) and measures used to assess outcomes. All trials reviewed were at high risk of performance bias, and most were also at high risk of detection, attrition, and selection bias. In light of the aforementioned issues, we determined that the evidence was of very low, low, or moderate quality. AUTHORS' CONCLUSIONS: No conclusions regarding breast cancer-related and all-cause mortality or breast cancer recurrence were possible. However, physical activity interventions may have small-to-moderate beneficial effects on HRQoL, and on emotional or perceived physical and social function, anxiety, cardiorespiratory fitness, and self-reported and objectively measured physical activity. The positive results reported in the current review must be interpreted cautiously owing to very low-to-moderate quality of evidence, heterogeneity of interventions and outcome measures, imprecision of some estimates, and risk of bias in many trials. Future studies with low risk of bias are required to determine the optimal combination of physical activity modes, frequencies, intensities, and durations needed to improve specific outcomes among women who have undergone adjuvant therapy.

The effects of a home-based physical activity intervention on cardiorespiratory fitness in breast cancer survivors; a randomised controlled trial.

The aim of this current randomised controlled trial was to evaluate the effects of a home-based physical activity (PA) intervention on cardiorespiratory fitness in breast cancer survivors. Thirty-two post-adjuvant therapy breast cancer survivors (age = 52 ± 10 years; BMI = 27.2 ± 4.4 kg∙m2) were randomised to a six-month home-based PA intervention with face-to-face and telephone PA counselling or usual care. Cardiorespiratory fitness and self-reported PA were assessed at baseline and at six-months. Participants had a mean relative V̇O2max of 25.3 ± 4.7 ml∙kg-1∙min-1, which is categorised as "poor" according to age and gender matched normative values. Magnitude-based inference analyses revealed likely at least small beneficial effects (effect sizes ≥.20) on absolute and relative V̇O2 max (d = .44 and .40, respectively), and total and moderate PA (d = .73 and .59, respectively) in the intervention compared to the usual care group. We found no likely beneficial improvements in any other outcome. Our home-based PA intervention led to likely beneficial, albeit modest, increases in cardiorespiratory fitness and self-reported PA in breast cancer survivors. This intervention has the potential for widespread implementation and adoption, which could considerably impact on post-treatment recovery in this population.

Clinical outcome and patient satisfaction with the use of bovine-derived acellular dermal matrix (SurgiMend™) in implant based immediate reconstruction following skin sparing mastectomy: A prospective observational study in a single centre.

INTRODUCTION: The advent of acellular dermal matrix devices (ADMs) has enhanced both the scope of implant-based immediate breast reconstruction (IBR) following skin sparing mastectomy (SSM) for the treatment or risk reduction of breast cancer. Currently, there are a wide range of options available for the use of ADMs. METHODS: This is a prospective observational single institution study of 118 consecutive patients undergoing a total of 164 SSM and IBR procedures either for treatment for breast cancer or for risk reduction, between 2012 and 2014. IBR was performed using an implant and bovine-derived ADM (SurgiMend™). Nipple sparing mastectomy (NSM) accounted for 103 procedures. IBR was performed as a single stage procedure in 23% of patients. The primary endpoint of this prospective study was the explantation rate and secondary endpoints included quality of life, patient satisfaction, aesthetic outcome assessed objectively, surgical complications, overall and disease free survival. RESULTS: Forty-six patients (39%) had a bilateral and 72 underwent a unilateral SSM. Of those who underwent a unilateral SSM, 25 had a contralateral adjustment procedure. Out of 164 procedures, 117 (71%) were for the treatment of breast cancer. Sixty-one patients received chemotherapy (52%) and 32 (27%) had radiotherapy. In this study 27 patients underwent post-mastectomy radiotherapy. At a mean follow of 21 months, the explantation rate was 1.2%, 4% (6 patients) developed wound complications. The patient satisfaction with the procedure was found to be very high. The mean Breast Q Score was 85 and the mean overall patient satisfaction rating was 9 out of a possible 10. The mean objective assessment score was 8.9 out of a possible 10 and the mean subjective capsular contracture severity score was 2.9 out of 10. There were two cases of local recurrence (1.7%), one distant recurrence (0.8%) and one patient died of metastatic breast cancer (0.8%). Overall survival was 99.2% and locoregional disease free survival (LRFS) was 98.3%. One patient (0.8%) developed a mild inflammatory reaction secondary to the underlying mesh. CONCLUSIONS: SurgiMend™ is an effective adjunct to implant based IBR following SSM. It is associated with a very low rate of implant loss and a high level of patient satisfaction and is associated with a very low incidence of inflammatory reaction. Neither prior radiotherapy nor post-mastectomy radiotherapy (PMRT) represents a contraindication to its use.

Randomised controlled trial of a home-based physical activity intervention in breast cancer survivors.

BACKGROUND: To improve adherence to physical activity (PA), behavioural support in the form of behavioural change counselling may be necessary. However, limited evidence of the effectiveness of home-based PA combined with counselling in breast cancer patients exists. The aim of this current randomised controlled trial with a parallel group design was to evaluate the effectiveness of a home-based PA intervention on PA levels, anthropometric measures, health-related quality of life (HRQoL), and blood biomarkers in breast cancer survivors. METHODS: Eighty post-adjuvant therapy invasive breast cancer patients (age = 53.6 ± 9.4 years; height = 161.2 ± 6.8 cm; mass = 68.7 ± 10.5 kg) were randomly allocated to a 6-month home-based PA intervention or usual care. The intervention group received face-to-face and telephone PA counselling aimed at encouraging the achievement of current recommended PA guidelines. All patients were evaluated for our primary outcome, PA (International PA Questionnaire) and secondary outcomes, mass, BMI, body fat %, HRQoL (Functional assessment of Cancer Therapy-Breast), insulin resistance, triglycerides (TG) and total (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol were assessed at baseline and at 6-months. RESULTS: On the basis of linear mixed-model analyses adjusted for baseline values performed on 40 patients in each group, total, leisure and vigorous PA significantly increased from baseline to post-intervention in the intervention compared to usual care (between-group differences, 578.5 MET-min∙wk(-1), p = .024, 382.2 MET-min∙wk(-1), p = .010, and 264.1 MET-min∙wk(-1), p = .007, respectively). Both body mass and BMI decreased significantly in the intervention compared to usual care (between-group differences, -1.6 kg, p = .040, and -.6 kg/m(2), p = .020, respectively). Of the HRQoL variables, FACT-Breast, Trial Outcome Index, functional wellbeing, and breast cancer subscale improved significantly in the PA group compared to the usual care group (between-group differences, 5.1, p = .024; 5.6, p = .001; 1.9 p = .025; and 2.8, p = .007, respectively). Finally, TC and LDL-C was significantly reduced in the PA group compared to the usual care group (between-group differences, -.38 mmol∙L(-1), p = .001; and -.3 mmol∙L(-1), p = .023, respectively). CONCLUSIONS: We found that home-based PA resulted in significant albeit small to moderate improvements in self-reported PA, mass, BMI, breast cancer specific HRQoL, and TC and LDL-C compared with usual care. CLINICALTRIALS. GOV IDENTIFIER: NCT02408107 (March 25, 2015).

Physical activity and awareness in breast screening attendees in Black Country, UK.

This study aimed to determine the physical activity levels and awareness of the influence of physical activity and overweight/obesity on breast cancer risk among NHS breast screening programme (NHSBSP) attendees. One hundred and eighty-eight (white British = 95%; post-menopausal = 80%) attendees completed a demographic and anthropometric data questionnaire, International Physical Activity Questionnaire (IPAQ) and awareness of breast cancer risk factors questionnaire. IPAQ data were reported as continuous measures (MET-min · week(-1)) and as categorical variables (low, moderate and high activities). The highest median physical activity levels were reported in the domestic physical activity domain (756 MET-min · week(-1)). Most participants were categorized as 'moderately active' (45%), while 30% were classified in the 'high activity' and 25% as 'low activity' categories. Almost a third of participants (30%) reported no leisure-time physical activity and 83% reported no vigorous physical activity. There was high awareness of the effects of physical activity (75%) and obesity (80%) on breast cancer risk. No significant differences were found between physical activity categories and awareness that physical activity can reduce breast cancer risk (p > 0.05). However, compared with moderate and high activity categories, participants in the 'low activity' category were significantly more likely to respond that they thought they achieved recommended physical activity levels (p < 0.05). Participants who are unaware of their inadequate physical activity levels may have a less positive intention to increase physical activity levels. Practical strategies aimed to increase knowledge of the recommended physical activity guidelines and facilitate the achievement of these guidelines may be required for NHSBSP attendees.