Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Reoperations after primary breast conserving surgery in women with invasive breast cancer in Catalonia, Spain: a retrospective study.

BACKGROUND: Although complete tumor resection is accepted as the best means to reduce recurrence, reoperations after lumpectomy are a common problem in breast cancer. The aim of this study was to assess the reoperation rates after primary breast conserving surgery in invasive breast cancer cases diagnosed in Catalonia, Spain, between 2005 and 2011 and to identify variations based on patient and tumour characteristics. METHODS: Women with invasive incident breast cancer identified from the Patient's Hospital Discharge Database [174.0-174.9 codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as the primary diagnosis] and receiving primary breast conserving surgery were included in the study and were followed up to 3 and 12 months by collecting information about repeat breast cancer surgery. RESULTS: Reoperation rates after primary breast conserving surgery decreased from 13.0 % in 2005 to 11.7 % in 2011 at 3 months and from 14.2 % in 2005 to 12.9 % in 2011 at 12 months' follow-up. While breast conservation reoperations saw a slight, non-significant increase in the same period (from 5.7 to 7.3 % at 3 months, and from 6.0 to 7.5 % at 12 months), there was a significant decrease in radical reoperation (from 7.3 to 4.4 % at 3 months and from 8.2 to 5.4 % at 12 months). Overall, additional breast surgeries decreased among younger women. CONCLUSIONS: Despite the rise of breast conserving surgery, reoperation rates following initial lumpectomy in Catalonia decreased by 10 % at 3 and 12 months' follow-up, remaining low and almost unchanged. Ultimately, there was also a significant decrease in mastectomies.

[Lymphoscintigraphy and sentinel node biopsy in non-palpable breast cancer]. / Linfogammagrafía y biopsia del ganglio centinela en el carcinoma no palpable de mama.

OBJECTIVE: The aim of the study was to evaluate the efficacy of lymphatic mapping and sentinel node biopsy in non-palpable breast cancer (NPBC) patients in comparison with palpable breast cancer (PBC) patients. MATERIAL AND METHODS: 199 breast cancer patients were studied. Patients were classified into two groups: NPBC and PBC. Following sentinel node biopsy all patients underwent axillary lymphadenectomy. Surgery was performed at 4-24 h after peritumoral injection of 111MBq 99mTc-nanocolloid. Histological sentinel node analysis was performed by cytological imprinting and delayed study. The following parameters were analyzed in both groups: scintigraphic and surgical detection rates, true positives (TP), true negatives (TN), sensitivity (S), predictive negative value (PNV), false negative rate (FNR) and global precision (GP) of the technique. RESULTS: No significant differences were observed (p > 0.05) in either the lymphoscintigraphy or surgical sentinel node detection, or drainage to internal mammary chain (p = 0.211) in both groups. Metastatic axillary prevalence was lower in NPBC group (p = 0.019). Similar S, NPV and GP values (>90 %) and FNR (< or = 6 %) were found in both groups. CONCLUSIONS: The reliability of the technique is similar in both groups. Drainage is predominantly axilar. Drainage to internal mammary chain was more frequently seen in medial tumours and in NPBC. Metastatic axillary prevalence was lower in the NPBC group.

[Influence of tumor location in patients with breast cancer on the sentinel node detection]. / Influencia de la localización del cáncer de mama en la detección del ganglio centinela.

OBJECTIVE: To evaluate the influence of tumour quadrant localization on the sentinel node (SN) detection and the visualisation of internal mammary chain (IM) drainage by radioisotopic techniques. 316 patients with breast cancer were studied. Mean age 57 years (range 29-88). All patients received 37-74 MBq of 99mTc-albumin nanocolloid in 2 ml by peritumoral injection. The breast cancer was located in the upper outer quadrant in 189 patients, in the upper inner in 57, in the lower outer in 57, in the lower inner in 55 and in the subareolar area in 18 patients. At two hours p.i., anterior and lateral chest lymphographies were obtained. The SN location was marked on the patient skin with permanent ink. SN was identified intraoperatively by the gamma probe. Histopatological analysis included imprints, delayed hematoxilin-eosin, inmunohistochemistry CAM 19-2 and PCR. RESULTS: The scintigraphy and surgical detection was in the upper outer quadrant of 90 % and 93 % respectively; in the lower outer quadrant of 91 % and 95 %, in the upper inner quadrant of 93 % and 95 %, in the lower inner quadrant 87 % and 95 % and in the subareolar area in 94 % and 83 %. The IM chain drainage was of 6 % in the UO, in the LO of 5 %, in the UI of 12 %, in the LI of 20 % and none in subareolar. CONCLUSIONS: Our data suggest that sentinel node location (quadrant) is not a influential factor in the scintigraphy and surgical detection. Tumours localised in internal quadrant show a higher rate of IM chain drainage.

Subdermal re-injection: a method to increase surgical detection of the sentinel node in breast cancer without increasing the false-negative rate.

PURPOSE: The aim of this study was to evaluate in breast cancer whether subdermal (SB) re-injection improves surgical detection (SD) of the sentinel node (SN) in patients with negative lymphoscintigraphy on peritumoral (PT) injection, without increasing the false-negative (FN) rate. METHODS: Group I comprised 261 patients with invasive breast cancer >3 cm and clinically negative axilla treated with primary chemotherapy. Axillary lymphadenectomy was performed in all of these patients. Group IA comprised 201 patients with PT injection, while group IB comprised 60 patients with SB injection in the tumour quadrant. Group II comprised 652 patients with breast cancer <3 cm; in 73 of these patients with negative lymphoscintigraphy, SB re-injection was performed. For lymphoscintigraphy, 37-55 MBq (99m)Tc-albumin nanocolloid in 1 ml was used for PT injection, and 18 MBq in 0.2 ml for SB injection. Five-minute images were obtained 2 h p.i. for PT injection and 20-30 min p.i. for SB injection. SD was performed 4 or 24 h p.i. Lymphoscintigraphic (LD), surgical and internal mammary (IM) detection rates were calculated. In group I, FN, negative predictive value (NPV) and accuracy (A) were calculated. Statistical analysis was performed using the chi-square test. RESULTS: In percentages, results were as follows: Group IA: SD: 84.1, FN: 13.6, NPV: 88.9, A: 78.6, IM: 14.5*. Group IB: SD: 90, FN: 0, NPV: 100, A: 90, IM: 1.7* (*p<0.025). Group II: PT injection only: LD: 82.4, SD: 94; PT injection+SB re-injection: LD: 90, SD: 98.5. SD was 97.8** in patients with positive lymphoscintigraphy and 58.5** when lymphoscintigraphy was negative (**p<0.001). CONCLUSION: For correct staging, including extra-axillary drainage, peritumoural injection should first be performed. When the SN is not visualised, and only in those cases, SB re-injection should be performed, which increases the SD rate without increasing the FN rate.