Combined breast conservation therapy versus mastectomy for BRCA mutation carriers – A systematic review and meta-analysis

BackgroundThe non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers.AimsTo evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis.MethodsA systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel–Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method.ResultsTwenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77–7.42, P < 0.001, heterogeneity (I²) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44–5.11, P = 0.510, I² = 80%), disease recurrence (HR:1.16, 95%CI: 0.78–1.72, P = 0.470, I² = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79–3.15, P = 0.200, I² = 38%) and death (HR:1.10, 95%CI: 0.72–1.69, P = 0.660, I² = 38%) were equivalent for combined BCT and mastectomy.ConclusionsSurvival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.     

Identification of intermediate risk breast cancer patients with1–3 positive lymph nodes and excellent survival after tamoxifen as only systemic adjuvant therapy by use of markers of proliferation and apoptosis

BackgroundAccording to current guidelines, patients with primary breast cancer and 1–3 lymph node metastases will in general be offered adjuvant chemotherapy.AimOur objective was to investigate the relationship between markers of proliferation and apoptosis with survival for patients subjected to adjuvant tamoxifen solely.Material and methodsTumour cytosol samples from 409 consecutive patients with operable oestrogen receptor positive BC, stage I–III and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase-cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival analyses were performed according to levels of ccCK18 and SPF separately, as well as combined.ResultsA wide range of ccCK18 protein levels was found, median 9.97, range 0.0–87.3 pg/μgDNA. Increasing SPFs were significantly associated with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p = 0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed. Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p = 0.038) and when divided into quartiles; DRFS (p < 0.001) and BCS (p = 0.0012). A similar correlation was found in patients with 1–3 lymph node metastases; DRFS (p = 0.089) and BCS (p = 0.019). A Cox's proportional hazard model including age, tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR = 0.47 (0.22–0.98), p = 0.043), and BCS (HR = 0.39 (0.16–1.00), p = 0.049), respectively.ConclusionBy use of a proliferation index based on markers of proliferation and apoptosis, a group of patients with 1–3 lymph node metastases with good outcome following adjuvant tamoxifen was identified; this group could possibly be spared adjuvant chemotherapy.     

High prevalence of vitamin D deficiency in women with breast cancer: The first Chilean study

BackgroundBreast cancer (BC) is the leading cause of female death from malignancy worldwide. One factor that has been associated to a higher incidence and poor prognosis is a Vitamin D deficiency (measured as 25-Hydroxi-Vitamin D (25OHD)). Our aim was to determine 25OHD levels in serum samples of Chilean BC patients before endocrine therapy and its association to clinical parameters at the time of diagnosis.MethodsWe analyzed clinical records of 105 women, evaluated at the Cancer Center of the Pontificia Universidad Católica de Chile. Serum levels of 25OHD were determined using a chemiluminescent microparticle immunoassay.ResultsThe prevalence of vitamin D deficiency before endocrine therapy was of 70.5%. Only 7% of our patients showed sufficient vitamin D levels at the beginning of the endocrine treatment. There was a significant correlation found between age and 25OHD levels, and also between body fat percentage and 25OHD levels (r² = 0.04; p = 0.021; r² = 0.028; p = 0.0432, respectively). Summer 25OHD levels were significantly higher than winter levels (p = 0.0322).ConclusionVitamin D deficiency is highly prevalent in Chilean BC women before endocrine therapy and 25OHD levels are inversely correlated to the age and body fat percentage of patients. Further studies are needed to determine causal relationship between vitamin D levels and BC development and outcome.     

Adjuvant regional nodal irradiation did not improve outcomes in T1-2N1 breast cancer after breast-conserving surgery: A propensity score matching analysis of BIG02/98 and BCIRG005 trials

AimTo determine whether the addition of regional nodal irradiation (RNI) to whole-breast irradiation (WBI) would improve outcomes over WBI alone in T1-2N1 breast cancer after breast-conserving surgery (BCS) and adjuvant systematic therapy.MethodsData were obtained from two randomized controlled trials (NCT00174655 and NCT00312208). Univariate and multivariate Cox-regression analysis were performed to investigate predictors for overall survival and disease-free survival. A 1:1 propensity score matching (PSM) analysis was applied to eliminate selection bias.ResultsWith median follow-up 80 months (range: 3–155 months), the 5-year local regional recurrence in the WBI group was 2% vs. 5% (p = 0.28) in the WBI + supraclavicular radiotherapy, and the rate of 5-year distant metastasis in the WBI group was 7% vs. 13% in the WBI + supraclavicular radiotherapy (p = 0.0748); In addition, the 5-year local regional recurrence in the WBI group was 3% vs. 9% (p = 0.19) in the WBI + internal mammary irradiation (IMI); However, the rate of 5-year distant metastasis in the in the WBI group was significantly lower than that in the WBI + IMI (8% vs. 24%, p = 0.036). After PSM, cox-regression analysis indicated that neither RNI nor IMI in combination with WBI in T1-2N1 breast cancer was associated with an improved overall survival and disease-free survival when compared to WBI alone.ConclusionThe addition of RNI to WBI in T1-2N1 breast cancer after BCS and adjuvant systematic therapy did not improve outcomes in comparison with WBI alone. Further studies are still needed to identify patients who would most benefit from RNI in this patient population.     

Routine shave margins are not necessary in early stage breast cancer treated with Breast Conserving Surgery

Introduction

Breast Conserving Surgery (BCS) is considered standard of care for women with early stage breast cancer. Between 20 and 50% of women treated with BCS will require re-operation for positive or close margins and it has been suggested that routine cavity shave margins may reduce the frequency of positive margins.

Higher body mass index is a more important risk factor than sarcopenia for complications in reconstruction of the deep inferior epigastric perforator

BackgroundIn recent years, breast reconstruction using autologous tissue after breast cancer surgery has become a common procedure. This study investigated the association between the occurrence of complications in breast reconstruction using deep inferior epigastric perforator (DIEP) flaps and patient risk factors among Asian women.MethodsThis study included cases of breast reconstruction using DIEP flaps performed at our institution. We retrospectively investigated the relationship between preoperative and operative patient factors and postoperative complications by collecting data from medical records. Sarcopenia was also evaluated by calculating psoas muscle index from the area of the iliopsoas muscle at the level of the third lumbar vertebra using images from preoperative computed tomography. Postoperative complications were compared between a low-body mass index (BMI) group and a high-BMI group, defined using BMI values of <25 kg/m² and ≥25 kg/m², respectively.ResultsA total of 129 cases of breast reconstruction using DIEP flaps were included in this analysis. The frequency of postoperative complications was significantly higher in the high-BMI group, including for skin flap necrosis of the breast (p = 0.03), recipient-site infection (p = 0.03), and donor-site seroma (p = 0.003). Moreover, abdominal circumference correlated significantly with recipient-site infection (p = 0.01) and donor-site seroma (p = 0.002). Sarcopenia did not show significant correlations with any complications.ConclusionBMI was identified as a risk factor for the occurrence of postoperative complications in breast reconstruction using the DIEP flap, but sarcopenia was not.     

The impact of tamoxifen brand switch on side effects and patient compliance in hormone receptor positive breast cancer patients

BackgroundIn 2006 Nolvadex was discontinued and replaced by a variety of alternative generic tamoxifen brands for the adjuvant treatment of breast cancer. Anecdotally, patients are switching brands and taking alternative medications to reduce treatment related symptoms. Nevertheless, more severe side effects may equate to better relapse prevention. This study evaluates generic tamoxifen adherence and its correlation with side effects and brand switch.MethodsConsecutive disease free ER positive patients (stage I–III) were invited to respond to a questionnaire. 165 of 327 questionnaires were returned (50% response). Pearson's Chi Square test was used for data analysis.Results63 patients (38%) reported a switch between generic tamoxifen. 59% of all patients experienced side effects associated with tamoxifen treatment of which 53% were severe. Patients experiencing differential symptoms dependent on tamoxifen brand reported more severe side effects (p = 0.02). Non-prescribed supplements were taken by 42% of all patients with no significant improvement in climacteric symptoms (p = 0.05). The concomitant use of SSRIs appeared to have no effect on symptoms. A significant number of patients considered discontinuing tamoxifen because of the side effects (p = 0.001), yet this did not translate into discontinuation or non-adherence (p = 0.8 and 0.08 respectively).ConclusionSevere tamoxifen side effects are commonly experienced by breast cancer patients and can be significantly altered by change in tamoxifen brand.Most patients will continue to take tamoxifen, despite side effects to avoid cancer relapse. Supplementation and antidepressants did not improve tamoxifen related side effects in our cohort.     

Surgeon level variation in outcome of repair of congenital diaphragmatic hernia with particular reference to the management of recurrence

IntroductionThe aim of this study is to investigate firstly, the rate of recurrence following primary repair of a congenital diaphragmatic hernia (CDH) and secondly, the rate of recurrence following revisional surgical repair. The primary outcome is rate of recurrence. Secondary outcomes are to establish whether recurrence is related to surgeon, surgeon volume, side of defect, the use of a patch, or a thoracopscopic approachMethodsAll repairs performed in an English regional center over 22 years were recorded. Possible explanatory variables were whether the repair was itself of a recurrence, the surgeon's identity, the surgeon's volume of prior repairs, the side of the defect, the use of a patch.Results198 repairs were performed; 170 primary repairs and 28 of recurrences. Failure occurred significantly more commonly among recurrences (32%) than primary repairs (11%), p = 0.005. Failure of the primary repair was significantly more common where a patch was used 8/34 (23%) rather than a sutured repair 10/136 (7%), p = 0.006, or where a thoracoscopic technique was used 4/13 (31%) rather than laparotomy 14/157 (9%) p = 0.01. Failure of the primary repair was unrelated to the identity of the surgeon (Χ² = 5, p = 0.9) or the volume of prior repairs (t = 0.3, p = 0.6). However, failure of repair of a recurrence was significantly related to the surgeon's volume of prior repairs (t = 2.3, p = 0.01) and the identity of the surgeon (Χ² = 17, p = 0.014), but not the use of a patch (Χ² = 1.6, p = 0.2).ConclusionsRepair of a recurrence of a CDH has a higher probability of failure than the original repair and is related to both the identity of the surgeon and the prior volume of experience. There is a volume outcome relationship for the repair of recurrence, but not the primary repair of CDH. Our study suggests the repair of recurrence of CDH should be restricted to surgeons with proven outcomes for this procedure.     

Role of FDG-PET/CT in evaluating surgical outcomes of operable breast cancer – Usefulness for malignant grade of triple-negative breast cancer

BackgroundThe aim of this study was to evaluate the significance of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for speculating the malignant level and prognostic value of operable breast cancers.MethodsOf 578 consecutive patients with primary invasive breast cancer who underwent curative surgery between 2005 and 2010, 311 patients (53.8%) who received FDG-PET/CT before initial therapy were examined.ResultsReceiver operating characteristics (ROC) curve analysis showed the cutoff value of the maximum standardized uptake value (SUV_max) to predict cancer recurrence was 3.8 in all patients and 8.6 in patients with the triple-negative subtype, respectively. In all patients, 3-year DFS rates were 98.8% for patients with a tumor of SUV_max ≤ 3.8 and 91.6% for patients with a tumor of SUV_max > 3.8 (p < 0.001). High value of SUV_max was significantly associated with large tumor size (p < 0.001), lymph node metastasis (p = 0.040), high nuclear grade (p < 0.001), lymphovascular invasion (p = 0.032), negative hormone receptor status (p < 0.001), and positive HER2 status (p = 0.014). Based on the results of multivariate Cox analysis in all patients, high SUV_max (p = 0.001) and negative hormone receptor status (p = 0.005) were significantly associated with poor prognosis. In patients with triple-negative subtype, 3-year DFS rates were 90.9% for patients with a tumor of SUV_max ≤ 8.6 and 42.9% for patients with a tumor of SUV_max > 8.6 (p = 0.002), and high SUV_max was the only significant independent prognostic factor (p = 0.047).ConclusionFDG-PET/CT is useful for predicting malignant behavior and prognosis in patients with operable breast cancer, especially the triple-negative subtype.     

Simple oncoplastic breast defect closure improves long-term cosmetic outcome of breast conserving surgery for breast cancer: A randomised controlled trial

IntroductionBreast conserving surgery (BCS) is associated with unsatisfactory cosmetic outcomes in up to 30% of patients, carrying psychological and quality-of-life implications. This study compares long-term cosmetic outcomes after BCS for breast cancer with v without simple oncoplastic defect closure.MethodsA randomised controlled trial was performed, recruiting patients who underwent BCS over four years and randomising to the “reshaping” group (closure of excision defect with mobilised breast tissue; n = 124) and to the “control” group (no attempt at defect closure; n = 109). The estimated excision volume (EEV) was <20% of breast volume (BV) in both groups. Photography and breast retraction assessment (BRA) were recorded preoperatively. Cosmetic outcomes were blindly assessed annually for five years by BRA, panel assessment of patients, and body image questionnaire (BIQ).ResultsThere were no significant differences between the reshaping and control groups in mean age (52.4 v 53.0; p = 0.63), body mass index (27.8 v 27.7; p = 0.80), margin re-excision (9 v 9; p = 0.78), mean BV (562.5 v 590.3 cc; p = 0.56), mean EEV (54.6 v 60.1 cc; p = 0.14), mean EEV/BV ratio (11.2 v 11.0; p = 0.84), or mean specimen weight (52.1 v 57.7 g; p = 0.24). Reshaping group patients had significantly better outcomes compared to control group patients in terms of mean BRA (0.9 v 2.8; p < 0.0001), achieving a score of “good” or “excellent” by panel assessment at 5 years (75.8% v 48%, p < 0.0001), body image questionnaire top score at 5 years (66.9% v 35.8%; p = 0.0001).ConclusionsSimple oncoplastic closure of defects after breast-conserving surgery improves long-term objective and subjective cosmetic outcomes.     

Patterns of metastatic spread in early breast cancer

AimsThe aim of this study was to prospectively investigate metastatic pathways of spread to lymph node versus bone marrow and identify biological characteristics that determine these patterns in early invasive breast cancer.Patients and methodsIn all, 177 patients with early invasive breast cancer underwent surgical extirpation of the primary tumour with sentinel lymph node biopsy (SLNB). Bone marrow (BM) aspiration was performed to screen for cytokeratin-positive cells by immunocytochemistry. Lymphatic spread was assessed by histopathological examination of lymph nodes (LN). A representative subset of 87 tumours was analysed by tissue microarray (TMA) to evaluate expression of markers that potentially influence haematogenous vs. lymphatic spread. Patients were followed up for a median of 54.7 months.ResultsOf the 177 patients, 114 (64%) were BM?/LN?, 38 (22%) BM?/LN+, 19 (11%) BM+/LN? and 6 (3%) BM+/LN+. Multivariate analysis of histopathological characteristics revealed that increasing tumour size was significantly associated with both LN positivity (p = 0.003) and BM positivity (p = 0.01), the presence of lymphovascular invasion significantly correlated with LN+ (p = 0.01), whereas lower histological grade was significantly associated with BM+ (p = 0.03). LN+ and BM+ were non-significantly negatively related to each other. Univariate analysis of the TMA data showed differential expression patterns for several factors; significant differences between effects on the two metastatic pathways (lymphatic vs. haematogenous) were found for expression of CD54 (p = 0.03), osteopontin (p = 0.04), bone sialoprotein (p = 0.04) and CXCR4 (p = 0.009). High expression of CD54, osteopontin and bone sialoprotein (BSP) was positively associated with BM + but was either not associated, or negatively associated, with LN+. High CXCR4 expression was positively associated with LN+ and negatively with BM+. High VEGF–C expression was associated with both LN+ and BM+, although this did not attain statistical significance. Due to the small number of clinical events during clinical follow-up, no associations were identified between metastatic spread patterns, recurrence and/or death.ConclusionThese findings suggest that distinct lymphatic and haematogenous metastatic pathways exist in early breast cancer and that these pathways are governed by specific biological markers.     

MarginProbe® – Final results of the German post-market study in breast conserving surgery of ductal carcinoma in situ

The goal in breast conserving surgery (BCS) of ductal carcinoma in situ (DCIS) is removal of the tumor with a clear surgical margin. However, re-excision rates are regrettably high. To date, there are no adequate procedures for intraoperative margin assessment of DCIS. A multicenter, single arm study was conducted to evaluate the benefit of a novel device (MarginProbe^®) in intraoperative margin assessment during BCS of DCIS, the associated reduction of re-excisions and the cosmetic outcome of the treated patients. We present results of 42 patients enrolled in 3 German institutions. The device was used as an adjunctive tool to standard of care. The device use was associated with a reduction in re-excision rates by 56%, from 39% to 17% (p = 0.018).     

Efficacy of clinical-grade human placental mesenchymal stromal cells in fetal ovine myelomeningocele repair

BackgroundWhile fetal repair of myelomeningocele (MMC) revolutionized management, many children are still unable to walk independently. Preclinical studies demonstrated that research-grade placental mesenchymal stromal cells (PMSCs) prevent paralysis in fetal ovine MMC, however this had not been replicated with clinical-grade cells that could be used in an upcoming human clinical trial. We tested clinical-grade PMSCs seeded on an extracellular matrix (PMSC-ECM) in the gold standard fetal ovine model of MMC.MethodsThirty-five ovine fetuses underwent MMC defect creation at a median of 76 days gestational age, and defect repair at 101 days gestational age with application of clinical-grade PMSC-ECM (3 × 10⁵ cells/cm², n = 12 fetuses), research-grade PMSC-ECM (3 × 10⁵ cells/cm², three cell lines with n = 6 (Group 1), n = 6 (Group 2), and n = 3 (Group 3) fetuses, respectively) or ECM without PMSCs (n = 8 fetuses). Three normal lambs underwent no surgical interventions. The primary outcome was motor function measured by the Sheep Locomotor Rating scale (SLR, range 0: complete paralysis to 15: normal ambulation) at 24 h of life. Correlation of lumbar spine large neuron density with SLR was evaluated.ResultsClinical-grade PMSC-ECM lambs had significantly better motor function than ECM-only lambs (SLR 14.5 vs. 6.5, p = 0.04) and were similar to normal lambs (14.5 vs. 15, p = 0.2) and research-grade PMSC-ECM lambs (Group 1: 14.5 vs. 15, p = 0.63; Group 2: 14.5 vs. 14.5, p = 0.86; Group 3: 14.5 vs. 15, p = 0.50). Lumbar spine large neuron density was strongly correlated with motor function (r = 0.753, p<0.001).ConclusionsClinical-grade placental mesenchymal stromal cells seeded on an extracellular matrix rescued ambulation in a fetal ovine myelomeningocele model. Lumbar spine large neuron density correlated with motor function, suggesting a neuroprotective effect of the PMSC-ECM in prevention of paralysis. A first-in-human clinical trial of PMSCs in human fetal myelomeningocele repair is underway.     

Breast reconstruction with the denervated latissimus dorsi musculocutaneous flap

ObjectiveTo analyze clinical implications of the thoracodorsal nerve division in the latissimus dorsi musculocutaneous flap breast reconstruction.Patients and methodsProspective cohort study was conducted on 29 patients. Breast reconstruction with latissimus dorsi musculocutaneous flap was performed unilaterally in 20 patients or bilaterally in 9 women (38 breasts). Thoracodorsal nerve was divided during reconstruction of 20 breasts (group 1) and was preserved for 18 breasts (group 2). Height, width, projection, area of the covering skin and volume of the reconstructed and healthy breasts were measured on the 3D images of the anterior chest wall, taken 6 weeks and 6 months postoperatively with the Di3D 3D camera. Data regarding tissue consistency, painfulness and animation of the reconstructed breast, symmetry of both breasts and overall satisfaction after the surgery were collected at 6 months.ResultsThe reconstructed and healthy breasts decreased in volume in group 1 (?45.85 cm³ ± 48.41 cm³, p = 0.0004; ?29.13 cm³ ± 14.98 cm³, p = 0.0009) and in group 2 (?31.5 cm³ ± 25.35 cm³, p = 0.0001; ?15.4 cm³ ± 21.96 cm³, p = 0.0537). There were no differences in decrease in volume between groups 1 and 2 (p > 0.05).Respondents in group 1 in comparison to group 2 showed similar satisfaction of the tissue consistency of the reconstructed breast (p > 0.05) and the level of symmetry between both breasts (p > 0.05), gave lower scores for painfulness (p < 0.0001), animation (p < 0.0001) and higher scores for the overall satisfaction about the reconstructed breast (p = 0.0001).ConclusionWe suggest that division of the thoracodorsal nerve during latissimus dorsi musculocutaneous flap breast reconstruction is a useful undertaking to minimize unnatural animation of the reconstructed breast.     

Primary and secondary distant metastatic breast cancer: Two sides of the same coin

ObjectivesThis study evaluated the differences between breast cancer (BC) patients who present with primary distant metastatic disease (PMD) and those who develop distant metastases during the course of their illness (secondary metastatic disease [SMD]) with regard to clinicopathological characteristics, patterns of metastatic sites, palliative therapy and survival.Patients & methodsBased on a cohort of patients with newly diagnosed BC (n = 1459), we analyzed all patients who had PMD (n = 92, 6.3%) and those who developed SMD (n = 277, 20.3%).ResultsThere were no significant differences with regard to the patient's age in which metastatic disease had been diagnosed (PMD/SMD: 64 years/66 years, p = 0.19). The SMD group had more often triple-negative carcinomas (25.5%/7.3%, p = 0.019); there were no significant differences with regard to grading (p = 0.61), HER2 status (p = 0.67) and hormonal receptor status (p = 1.00). The mean number of metastatic locations was similar (2.3/2.3, p = 0.91). While patients with PMD usually initiated systemic therapy, patients with SMD received systemic therapy after diagnosis of metastatic disease less often (16.4%/2.6%, p < 0.001). Both groups received palliative chemotherapy similarly often (PMD/SMD: 62.8%/63.3%, p = 1.00). The mean number of palliative therapy lines was similar (PMD/SMD: 2.8/3.2, p = 0.39). Compared to patients with SMD, patients who had PMD had a significantly improved metastatic disease survival (p < 0.001). The one-year, two-year and five-year survival rates were as follows: 76.9%/60.3%, 58.2%/43.0%, 23.1%/10.6%. The median survival times were 18.5 months and 32 months.ConclusionThe poorer prognosis of patients with SMD may be explained by differences in clinicopathological features of the tumor, metastatic patterns, the use palliative therapy and drug resistance of the tumor cells which occurs in therapy-naïve PMD patients at a later phase of the disease course.     

The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy

PurposeThe effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC.MethodsWe retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m² at baseline were considered obese, whereas those with a BMI <30 kg/m² were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure.ResultsAmong 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42–13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47–15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10⁻⁴–0.81; p = 0.025).ConclusionsObese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity.     

Improving medication adherence with adjuvant aromatase inhibitor in women with breast cancer: A randomised controlled trial to evaluate the effect of short message service (SMS) reminder

BackgroundMedication adherence is crucial for improving clinical outcomes in the treatment of patients. We evaluate the effect of short message service (SMS) reminder on medication adherence and serum hormones in patients with breast cancer on aromatase inhibitors.MethodsAn open-label, multi-centre, prospective randomised controlled trial of SMS versus Standard Care was conducted. Medication adherence was assessed via self-report using the Simplified Medication Adherence Questionnaire at baseline, 6 month, and 1 year. Androstenedione, estradiol, and estrone were measured at baseline and 1 year. The χ² test and mixed effects logistic regression was performed to compare medication adherence between groups. Difference in androstenedione and estrone levels were assessed using analysis of covariance, whereas χ² test and logistic regression was used for estradiol. Analysis was based on intention-to-treat.ResultsA total of 244 patients were randomised to receive weekly SMS reminder (n = 123) or Standard Care (n = 121) between May 2015 and December 2018. The odds of adherence was higher at 6-month in SMS (OR = 1.78, 95% CI 1.04–3.05, p = 0.034), and not significantly different at 1-year (OR = 1.15, 95% CI: 0.67–1.96 p = 0.617). Mixed effects logistic regression analysis showed higher odds of adherence in SMS over the 1-year period (OR = 2.35, 95% CI: 1.01–5.49, p = 0.048). There was no difference in serum hormone levels between groups.ConclusionSMS reminder improved medication adherence in the short-term but had no effect on serum hormones levels in the longer term. Future studies could investigate the use of tailored SMS intervention according to patient preference to improve its sustainability.     

Gender trends in applicants to general surgery residency programs in Canada

BackgroundSurgical disciplines lag behind non-surgical disciplines in attracting female trainees. Female representation of Canadian General Surgeons has not been evaluated in recent years in the literature. The objectives of this study were to assess gender trends in applicants to Canadian General Surgery residency programs and practicing general surgeons and subspecialists.MethodsThis retrospective cross-sectional study analyzed gender data for residency applicants ranking General Surgery as their first-choice discipline from publicly-available annual Canadian Residency Matching Service (CaRMS) R-1 match reports from 1998 to 2021. Aggregate gender data for practicing female physicians in General Surgery and related subspecialties, including Pediatric Surgery, obtained from annual Canadian Medical Association (CMA) census from 2000 to 2019 was also analysed.ResultsThere was a significant increase in the proportion of female applicants from 34% in 1998 to 67% in 2021 (p < 0.001) and of successfully matched candidates from 39% to 68% (p = 0.002) from 1998 to 2021. Success rates between male and female candidates were significantly different in 1998 (p < 0.001), but not in 2021 (p = 0.29). The proportion of practicing female General Surgeons also significantly increased from 10.1% in 2000 to 27.9% in 2019 (p = 0.0013), with variable trends in subspecialties.ConclusionGender inequality in General Surgery residency matches has normalized since 1998. Despite females representing more than 40% of applicants and successfully matched candidates to General Surgery since 2008, a gender gap still exists amongst practicing General Surgeons and subspecialists. This suggests the need for further cultural and systemic change to mitigate gender disparities.Type of studyOriginal research article, clinical research.Level of evidenceLevel III (Retrospective cross-sectional study).     

Impact of visceral fat on laparoscopy-assisted distal gastrectomy

BackgroundObesity is known to be a preoperative risk factor for gastric cancer surgery. However, the influence of obesity on laparoscopy-assisted distal gastrectomy (LADG) remains controversial. In the present study, we evaluated several obesity parameters and investigated the influence of obesity on the surgical outcomes of LADG for gastric cancer.Materials and methodsBetween January 2010 and July 2011, 84 patients who underwent LADG for gastric cancer were enrolled. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured in cross-sectional CT scan using SlimVision^® software. Patients were classified into two groups by the degree of BMI or VFA. Surgery time and blood loss were compared between each two groups. Predictive factors for perioperative complications were assessed by univariate and multivariate analyses.ResultsThere were no significant differences in surgery time or blood loss between patients with high and low BMIs. In contrast, high VFA patients had significantly longer surgery times (p = 0.0047) and higher estimated blood loss (p = 0.0034) than low VFA patients. By univariate and multivariate analyses, only a high VFA significantly predicted perioperative complications (p = 0.0162, p = 0.0288).ConclusionsWe suggest that VFA is more accurate than BMI in predicting surgery time, blood loss, and perioperative complications associated with LADG for gastric cancer. The visceral fat area could be efficiently assessed before laparoscopic surgery for gastric cancer in obese patients.