Clinical feasibility and oncological safety of non-radioactive targeted axillary dissection after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: a prospective diagnostic and prognostic study.

BACKGROUND: Targeted axillary dissection (TAD) includes biopsy of clipped lymph node and sentinel lymph nodes. However, clinical evidence regarding clinical feasibility and oncological safety of non-radioactive TAD in a real-world cohort remains limited. METHODS: In this prospective registry study, patients routinely underwent clip insertion into biopsy-confirmed lymph node. Eligible patients received neoadjuvant chemotherapy followed by axillary surgery. Main endpoints included the false-negative rate (FNR) of TAD and nodal recurrence rate. RESULTS: Data from 353 eligible patients were analyzed. After completion of neoadjuvant chemotherapy, 85 patients directly proceeded to axillary lymph node dissection (ALND), furthermore, TAD with or without ALND was performed in 152 and 85 patients, respectively. Overall detection rate of clipped node was 94.9% (95% CI, 91.3-97.4%) and FNR of TAD was 12.2% (95% CI, 6.0-21.3%) in our study, with FNR decreasing to 6.0% (95% CI, 1.7-14.6%) in initially cN1 patients. During a median follow-up of 36.6 months, 3 nodal recurrences occurred (3/237 with ALND; 0/85 with TAD alone), with a 3-year freedom-from-nodal-recurrence rate of 100.0% among the TAD-only patients and 98.7% among the ALND patients with axillary pathologic complete response ( P =0.29). CONCLUSIONS: TAD is feasible in initially cN1 breast cancer patients with biopsy-confirmed nodal metastases. ALND can safely be foregone in patients with negativity or a low volume of nodal positivity on TAD, with a low nodal failure rate and no compromise of 3-year recurrence-free survival.

Trends and clinicopathological predictors of axillary evaluation in ductal carcinoma in situ patients treated with breast-conserving therapy.

The aim of this study was to investigate the trends of axillary lymph node evaluation in ductal carcinoma in situ (DCIS) patients treated with breast-conserving therapy (BCT) and to identify the clinicopathological predictors of axillary evaluation. DCIS patients treated with BCT in 2006-2015 at our institute were retrospectively included in the analysis. Patients were categorized into three groups: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), and non-evaluation. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted axillary evaluation. A total of 315 patients were identified, among whom 135 underwent SLNB, and 15 underwent ALND. The proportion of patients who underwent axillary evaluation increased from 33.0% in 2006-2010 to 53.8% in 2011-2015 (P < 0.001), however, no patients had lymph node metastasis based on final pathology. In multivariate analysis, high-grade tumor favored axillary evaluation (OR = 4.376, 95% CI:1.410-13.586, P = 0.011); while excision biopsy favored no axillary evaluation compared with other biopsy methods (OR = 0.418, 95% CI: 0.192-0.909, P = 0.028). Subgroup analysis of patients treated in 2011-2015 revealed that high-grade tumor (OR = 5.898, 95% CI: 1.626-21.390, P = 0.007) and palpable breast lump (OR = 2.497, 95% CI: 1.037-6.011, P = 0.041) were independent predictors of axillary lymph node evaluation. Despite the significant decrease in ALND and a concerning overuse of SLNB, we identified no axillary lymph node metastasis, which justified omitting axillary evaluation in these patients. High-grade tumor, palpable lump, and biopsy method were independent predictors of axillary evaluations. Excision biopsy of suspicious DCIS lesions may potentially preclude the invasive component of the disease and help to avoid axillary surgery.

A prospective study of breast anthropomorphic measurements, volume and ptosis in 605 Asian patients with breast cancer or benign breast disease.

OBJECTIVES: The current study aims to summarize breast anthropomorphic measurement features in Chinese patients with breast diseases and to investigate their potential correlations with demographic factors. MATERIALS AND METHODS: Fifteen breast anthropomorphic parameters of 605 Chinese female patients were collected prospectively. Breast ptosis status was scaled by two methods and breast volume was calculated according to a modified formula of BREAST-V. RESULTS: Among 1210 breasts, the average breast volume was 340.0±109.1 ml (91.8-919.2 ml). The distance from the nipple to the inframammary fold was 7.5±1.6 cm in the standing position. The width of the breast base was 14.3±1.4 cm (8.5-23.5 cm). The incidence of breast ptosis was 22.8% (274/1204), of which 37 (23.5%) and 79 (31.7%) women had severe ptosis assessed by different criteria. Increased height (OR[odds ratio] = 1.500, P<0.001), post-menopausal status (OR = 1.463, P = 0.02), increased BMI, breastfeeding for 7-12 months (OR = 1.882, P = 0.008) and more than one year (OR = 2.367, P = 0.001) were risk factors for an increased breast volume. Post-menopausal status (OR = 2.390, P<0.001 and OR = 2.621, P<0.001 for different scales), BMI≥24.7 kg/m2 (OR = 3.149, P<0.001 and OR = 2.495, P = 0.002), breastfeeding for 7-12 months (OR = 4.136, P = 0.004 and OR = 4.010, P = 0.002), and breastfeeding for more than one year (OR = 6.934, P<0.001 and OR = 6.707, P<0.001) were independent risk factors for breast ptosis. CONCLUSIONS: The current study provides anthropomorphic measurements data of Chinese women with breast diseases, which are useful for cosmetic and reconstructive breast surgery decisions. Post-menopausal status, increased BMI, and breastfeeding for more than six months were independent risk factors for both increased breast volume and breast ptosis.

Surgical management of breast cancer in China: A 15-year single-center retrospective study of 18,502 patients.

The aim of the study was to review the surgical trends in breast cancer treatment in China over the past 15 years and to explore the possible factors related to the choice of surgical modality.The medical records of 18,502 patients with unilateral early stage breast cancer who underwent surgery from January 1999 to December 2013 at our institute were retrospectively reviewed. The utilization of different surgical modalities and the associated clinicopathological factors were analyzed. Furthermore, the prognostic role of surgical modality was also evaluated.The median patient age was 50.0 years. According to the pTNM staging system, 12.5% of the patients were classified as stage 0; 30.2% as stage I; 40.0% as stage II; and 17.3% as stage III. In total, 9.3% of the patients could not be staged. Overall, 67.1% of the breast cancer cases were estrogen receptor (ER) positive. The pattern of breast cancer surgery has changed tremendously over the past 15 years (P < 0.001). The pattern of mastectomy has shifted from radical mastectomy to modified radical mastectomy and simple mastectomy + sentinel lymph node biopsy. A total of 81.7% of the patients underwent mastectomy without immediate reconstruction, 15.2% underwent breast-conserving surgery (BCS), and 3.7% received immediate breast reconstruction after mastectomy. Age, TNM staging, and pathological characteristics greatly affected the choice of surgical modality. The 5-year recurrence-free survival (RFS) rates for the mastectomy, BCS, and reconstruction groups were 87.6%, 93.2%, and 91.7%, respectively (P < 0.001); the RFS rate was likely affected by distant recurrence instead of loco-regional recurrence. We also identified improved RFS over time, stratified by surgical modality and tumor stage. Multivariate Cox-regression analysis revealed that time of treatment, tumor stage, tumor grade, LVI status, and ER status were independent prognostic factors for RFS in our cohort, whereas surgical modality was not.Mastectomy remains the most prevalent surgical modality used to manage early stage breast cancer in China, although the utilization of BCS has increased in the past decade. However, surgical management was not a prognostic factor for RFS. The selection of appropriate patients depended on the assessment of multiple clinicopathological factors, which is essential for making surgical decisions.

Current status of breast reconstruction in China: an experience of 951 breast reconstructions from a single institute.

BACKGROUND: Since mastectomy remained the primary strategy for treating breast cancer in China, post-mastectomy reconstruction is of great importance in the Chinese population. The current study aimed to assess the current status of breast reconstruction in China. METHODS: We reviewed all patients who received breast reconstruction from August 2000 to July 2015 in the Department of Breast Surgery in our institute. Patients' baseline characteristics, reconstruction strategy, final pathology and loco-regional recurrence (LRR) information were collected. RESULTS: A total of 951 breast reconstructions were conducted during the past 15 years, among which 247 (27.0%) were abdominal flap reconstruction; 471 (51.5%) were latissimus dorsi myocutaneous ± implant; and 233 (25.5%) were prosthesis-based reconstruction. The majority of cases (78.1%) were invasive breast cancer and up to 894 cases (94.0%) were immediate reconstruction. Prosthesis-based reconstruction rapidly increased in recent years, and was associated with bilateral reconstruction, contralateral augmentation and higher complications. 18 patients (2.0%) developed local-regional recurrence at the median follow-up time of 26.6 months (range, 3.7-62.0 months). A total of 66 nipple-areolar complex-sparing mastectomies (NSMs) (6.9%) were performed, none of which developed recurrence. CONCLUSIONS: Breast reconstruction cases increased over the 15 years with the change of paradigm. Most strikingly, prosthesis-based reconstruction rapidly gained its prevalence and became the most common strategy. NSM was only performed for highly selected patients. Patients with breast reconstruction were able to achieve satisfactory loco-regional control in our cohort.

Predicting sentinel lymph node metastasis in a Chinese breast cancer population: assessment of an existing nomogram and a new predictive nomogram.

We assessed the MSKCC nomogram performance in predicting SLN metastases in a Chinese breast cancer population. A new model (the SCH nomogram) was developed with clinically relevant variables and possible advantages. Data were collected from 1,545 patients who had a successful SLN biopsy between March 2005 and November 2011. We validated the MSKCC nomogram in the modeling and validation group. Clinical and pathologic features of SLN biopsy in modeling group of 1,000 patients were assessed with multivariable logistic regression to predict the presence of SLN metastasis in breast cancer. The SCH nomogram was created from the logistic regression model and subsequently applied to 545 consecutive SLN biopsies. By multivariate analysis, age, tumor size, tumor location, tumor type, and lymphovascular invasion were identified as independent predictors of SLN metastasis. The SCH nomogram was then developed using the five variables. The new model was accurate and discriminating (with an AUC of 0.7649 in the modeling group) compared to the MSKCC nomogram (with an AUC of 0.7105 in the modeling group). The area under the ROC curve for the SCH nomogram in the validation population is 0.7587. The actual probability trends for the various deciles were comparable to the predicted probabilities. The false-negative rates of the SCH nomogram were 1.67, 3.54, and 8.20 % for the predicted probability cut-off points of 5, 10, and 15 %, respectively. Compared with the MSKCC nomogram, the SCH nomogram has a better AUC with fewer variables and has lower false-negative rates for the low-probability subgroups. The SCH nomogram could serve as a more acceptable clinical tool in preoperative discussions with patients, especially very-low-risk patients. When applied to these patients, the SCH nomogram could be used to safely avoid a SLN procedure. The nomogram should be validated in various patient populations to demonstrate its reproducibility.

A prospective comparison of molecular assay and touch imprint cytology for intraoperative evaluation of sentinel lymph nodes.

BACKGROUND: Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastases enables the selection of patients for axillary lymph node dissections during the same operation, reducing the need for a second operation. The present study aimed to prospectively compare the GeneSearch(TM) Breast Lymph Node (BLN) Assay with touch imprint cytology (TIC) for intraoperative evaluation of SLNs. METHODS: SLNs were sectioned in 1.5 - 3.0 mm pieces. TIC was performed on all pieces and the BLN Assay and postoperative histology evaluations were performed on different alternating node pieces. Overall performance of the BLN Assay was compared with that of TIC relative to the postoperative histology results. RESULTS: A total of 90 patients enrolled in the study. Complete intraoperative data for both the BLN Assay and TIC were collected in 86 patients. The sensitivity, specificity, and overall accuracy of the BLN Assay were 82%, 97%, and 92%, respectively on a per patient basis compared with those of TIC which were 67%, 100%, and 90%. CONCLUSIONS: Performance of the BLN Assay was superior to that of TIC and the additional application of TIC did not help improve the total sensitivity and accuracy of the intraoperative assessment. The existence of ectopic breast tissue might be a possible cause of false positive for the BLN assay. In addition, the BLN Assay complements histopathology assessment and can minimize sampling error without increasing pathologists' workload.

The evaluation and optimization of intraoperative touch imprint cytology for sentinel lymph nodes in early-stage breast cancer in China.

BACKGROUND: Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastasis reduces the need for additional surgery in patients with involved nodes. The present study evaluates the clinical value of multiple cross-sectional touch imprint cytology (TIC) as an intraoperative assessment for the diagnosis of SLN metastasis. METHODS: This study consisted of 366 patients with surgically harvested SLNs that were sliced along their long axis at 2.0-3.0-mm intervals and 122 patients with SLNs that were sliced along their short axis at 1.5-mm intervals using a cutting apparatus designed by our group. The first group of patients was enrolled in this study between February 2005 and February 2008, while the second group was enrolled between March 2008 and January 2009. Serial sectioning of the SLNs at 100-microm intervals with hematoxylin-eosin (H&E) staining was used as the gold standard for pathological diagnosis. RESULTS: Multiple cross-sectional TIC has a sensitivity, specificity, and overall accuracy rate of 92.0, 99.0, and 97.5%, respectively, on a per-patient basis, and it is superior to the standard imprint preparation protocol. Furthermore, the multiple cross-sectional TIC technique developed in this study was observed to detect more accurately macrometastases on a per-patient basis in comparison to the typical protocol (P = 0.023). Of the patients included in this study, 97.7% had a positive SLN within their first three harvested SLNs. CONCLUSIONS: Multiple cross-sectional TIC is superior to the standard protocol, especially due to its ability to locate macrometastasis. Limiting intraoperative TIC to the first three harvested SLNs in the diagnosis of SLN metastasis may make this diagnostic procedure significantly cheaper and easier for pathologists to perform.

[Evaluation of intraoperative molecular assay in sentinel lymph node biopsy from breast cancer patients].

OBJECTIVE: to evaluate the application of GeneSearch(TM) breast lymph node assay in intraoperative detection of metastases in sentinel lymph node (SLN) from breast cancer patients. METHODS: a total of 225 SLN from 88 patients was prospectively studied. Each SLN was cut into 2 mm slabs which were examined by intraoperative imprint cytology (IIC) first, followed by GeneSearch assay and post-operative serial sectioning. GeneSearch used real-time fluorescence quantitative RT-PCR technology to detect the expression of CK19 and mammaglobin in SLN. The results of GeneSearch assay were correlated with those of IIC and post-operative serial sectioning. RESULTS: amongst the 88 cases studied, 225 SLNs were found, and obvious metastatic carcinoma cells were identified in 27 SLNs and micrometastasis in 9 SLNs. One hundred and eight-nine SLNs were considered as "negative" (with "isolated tumor cells" present in 5 SLNs). The turn-around time of intraoperative GeneSearch assay ranged from 35 to 45 minutes (mean = 40 minutes). The concordance rate between GeneSearch assay and post-operative serial sectioning was 95.6% (215/225), with a sensitivity of 86.1% (31/36), compared with 94.7% (213/225) and 72.2% (26/36) respectively for IIC. The size of metastatic foci correlated with the Ct value of CK19 and mammaglobin (P < 0.01). CONCLUSIONS: GeneSearch assay for intraoperative detection of metastase in SLN has a satisfactory performance and demonstrates a relatively higher sensitivity than IIC. The potential clinical application still requires further evaluation of larger number of cases.