Do we need reshape rTNM staging system for ipsilateral breast tumor recurrence of breast cancer? A population-based, propensity score matched cohort study.

BACKGROUND: The aim of the study was to explore the role of recurrent TNM (rTNM) staging in predicting prognosis for ipsilateral breast tumor recurrence (IBTR) and determine the optimal treatment strategy for IBTR. METHOD: IBTR cases were identified from the Surveillance, Epidemiology, and End Results (SEER) database spanning the years 2000-2018. Cox proportional hazards analysis was performed to examine factors associated with overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) was employed to match IBTR with primary early breast cancer (EBC) based on clinicopathological characteristics. Investigations into the impact of different therapies were also included. RESULTS: Of the 4375 IBTR cases included in the study, the 5-year OS was 87.1%, 71.6% and 58.7% in rTNM stages I, II and III, respectively. After PSM, while IBTR patients had worse survival to primary EBC patients, prognosis of IBTR for different rTNM stage always closely aligned with the corresponding stage of primary EBC. Repeat breast-conserving surgery (BCS) with radiation therapy was equivalent to mastectomy with respect to OS and BCSS. Chemotherapy was favorable for OS and BCSS in estrogen receptor (ER)-negative IBTR or IBTR occurring within a 60-month interval. CONCLUSIONS: rTNM staging system has an outstanding prognostic value for survival outcome of patients with IBTR, and IBTR and primary EBC may have potentially analogous features in the context of TNM staging. BCS plus radiation therapy may be an alternative. IBTR cases who have experienced recurrence with short intervals and with ER-negative tumors might benefit from chemotherapy.

Potential rapid intraoperative cancer diagnosis using dynamic full-field optical coherence tomography and deep learning: A prospective cohort study in breast cancer patients.

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin (H&E) histology, such as frozen section, are time-, resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography (D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group (n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma (IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ (DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests (n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%; only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow (approximately 3 min) was significantly shorter than that required for traditional procedures (approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.

Neoadjuvant docetaxel and capecitabine (TX) versus docetaxel and epirubicin (TE) for locally advanced or early her2-negative breast cancer: an open-label, randomized, multi-center, phase II Trial.

PURPOSE: The combination of taxanes and anthracyclines is still the mainstay of chemotherapy for early breast cancer. Capecitabine is an active drug with a favorable toxicity profile, showing strong anti-tumor activity against metastatic breast cancer. This trial assessed the efficacy and safety of the TX regimen (docetaxel and capecitabine) and compared it with the TE (docetaxel and epirubicin) regimen in locally advanced or high risk early HER2-negative breast cancer. PATIENTS AND METHODS: This randomized clinical trial was conducted at five academic centers in China. Eligible female patients were randomly assigned (1:1) to the TX (docetaxel 75 mg/m2 d1 plus capecitabine 1000 mg/m2 twice d1-14, q3w) or TE (docetaxel 75 mg/m2 d1 plus epirubicin 75 mg/m2 d1, q3w) groups for four cycles. The primary endpoint was a pathological complete response in the breast (pCR). Secondary endpoints included pCR in the breast and axilla, invasive disease-free survival (iDFS), overall survival (OS), and safety. RESULTS: Between September 1, 2012, and December 31, 2018, 113 HER2-negative patients were randomly assigned to the study groups (TX: n = 54; TE: n = 59). In the primary endpoint analysis, 14 patients in the TX group achieved a pCR, and nine patients in the TE group achieved a pCR (25.9% vs. 15.3%), with a not significant difference of 10.6% (95% CI -6.0-27.3%; P = 0.241). In a subgroup with high Ki-67 score, TX increased the pCR rate by 24.2% (95% CI 2.2-46.1%; P = 0.029). At the end of the 69-month median follow-up period, both groups had equivalent iDFS and OS rates. TX was associated with a higher incidence of hand-foot syndrome and less alopecia, with a manageable toxicity profile. CONCLUSION: The anthracycline-free TX regimen yielded comparable pCR and long-term survival rates to the TE regimen. Thus, this anthracycline-free regimen could be considered in selected patients. TRIAL REGISTRATION: ACTRN12613000206729 on 21/02/2013, retrospectively registered.

Breast cancer early detection by using Fourier-transform infrared spectroscopy combined with different classification algorithms.

Early detection of breast cancer is of great value in improving the prognosis. The current detection methods of breast cancer have their own limitations. In this study, we investigated the feasibility of Fourier Transform Infrared (FT-IR) spectroscopy combined with different classification algorithms for the early detection of breast cancer in a large sample of 526 patients, including 308 invasive breast cancer, 101 ductal carcinoma in situ, and 117 healthy controls. The serum was measured with FT-IR spectroscopy. Kennard-Stone (KS) algorithm was used to divide the data into the training set and testing set. Support vector machine (SVM) model and back propagation neural network (BPNN) model were used to distinguish ductal carcinoma in situ, invasive breast cancer from healthy controls. The accuracies of the SVM model and BPNN model were 92.9% and 94.2%. To determine the effect of different material absorption bands on early detection, the band was divided into four parts including 900-1425 cm-1, 1475-1710 cm-1, 2800-3000 cm-1, and 3090-3700 cm-1, to be modeled and detected respectively. The final results showed that the ranges 900-1425 cm-1 and 1475-1710 cm-1 had superior classification accuracies. The region 900-1425 cm-1 corresponded to the lipids, proteins, sugar, and nucleic acids, and the region 1475-1710 cm-1 corresponded to the proteins. The biochemical substances in other bands also contributed some unique potential to the classification, so the classification accuracy was the best in the full band. The study indicates that serum FT-IR spectroscopy combined with SVM and BPNN models is an effective tool for the early detection of breast cancer.

Physicians' Perception of the Evidence in Relation to Primary Endpoints of Clinical Trials on Breast Cancer.

Objective: To investigate physicians' perception of the evidence of clinical trials on breast cancer. Methods: A survey was conducted by the Chinese Society of Breast Surgeons. We investigated the physicians' perception of meaningful endpoints, appropriate follow-up duration, and clinically acceptable benefit through online questionnaires. Results: Among 278 validated questionnaires, the majority of the questions had no consistent answer. For local treatment, 30.6, 28.8, and 28.4% of participants regarded locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) as the most meaningful endpoint, respectively, 47.5% believed that 5-year follow-up can alter clinical practice, and 34.5% thought it should be >10 years. In the adjuvant setting, 45.7, 38.5, and 12.9% regarded DFS, OS, and LRR as the most meaningful endpoint, respectively, 52.5% thought that 10-year follow-up was solid, while 37.4% thought that 5-year follow-up was enough. In the advanced setting, 49.6, 24.1, and 23.7% considered progression-free survival, quality of life, and OS the most meaningful endpoint, respectively, and 39.6 and 28.8% considered that a follow-up of 1 year and 3 years, respectively, was meaningful. Similarly, the clinically acceptable absolute difference was inconsistent. Conclusion: Most Chinese oncologists advocated that surrogate endpoints could be used in certain circumstances, though OS was the most reliable one in breast cancer studies. Doctors' perceptions of follow-up time and magnitude of benefit vary widely, reflecting the fact that there are many unanswered questions about supporting the use of new cancer treatments; a common understanding needs to be reached, such as a very consensual surrogate endpoint and a meaningful sufficiently large therapeutic benefit.

Detection of Structural Variations and Fusion Genes in Breast Cancer Samples Using Third-Generation Sequencing.

Background: Structural variations (SVs) are common genetic alterations in the human genome that could cause different phenotypes and diseases, including cancer. However, the detection of structural variations using the second-generation sequencing was limited by its short read length, which restrained our understanding of structural variations. Methods: In this study, we developed a 28-gene panel for long-read sequencing and employed it to Oxford Nanopore Technologies and Pacific Biosciences platforms. We analyzed structural variations in the 28 breast cancer-related genes through long-read genomic and transcriptomic sequencing of tumor, para-tumor, and blood samples in 19 breast cancer patients. Results: Our results showed that some somatic SVs were recurring among the selected genes, though the majority of them occurred in the non-exonic region. We found evidence supporting the existence of hotspot regions for SVs, which extended our previous understanding that they exist only for single nucleotide variations. Conclusion: In conclusion, we employed long-read genomic and transcriptomic sequencing to identify SVs from breast cancer patients and proved that this approach holds great potential in clinical application.

The Impact of Reproductive Factors on the Risk of Breast Cancer by ER/PR and HER2: A Multicenter Case-Control Study in Northern and Eastern China.

BACKGROUND: Previous studies have suggested that reproductive factors are associated with breast cancer risk. Breast cancer subtypes have distinct natural characteristics and may also have unique risk profiles. The purpose of this study was to determine whether reproductive factors affect the risk of breast cancer by estrogen receptor (ER)/progesterone receptor (PR) and HER2 status. METHODS: A multicenter, case-control study was conducted. There were 1170 breast cancer patients and 1170 age- and hospital-matched females included in the analysis. Self-reported data were collected about lifestyle behaviors, including reproductive factors. Breast cancer cases were categorized subtypes according to ER, PR, and HER2 expression as HR- positive, HER2-enriched, and triple negative breast cancer (TNBC). Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Having ≤1 child increased risk of HR-positive breast cancer (OR 1.882; 95%CI 1.29-2.74), especially in the premenopausal group (OR 2.212; 95%CI 1.23-3.99). Compared with women who first gave birth after age 30 years, earlier age at first birth decreased the risk of HR-positive breast cancer (≤23 years: OR 0.209; 95%CI 0.14-0.30; 24-29 years: OR 0.256; 95%CI 0.18-0.36; P < .001). Compared with those who had an average breastfed/birth period of more than 2 years, those with an average period less than 6 months had an elevated risk of all subtypes (HR positive: OR 2.690; 95%CI 1.71-4.16, P < .001; HER2-enriched: OR 3.779; 95%CI, 1.62-8.79, P = .001; TNBC: OR 2.564; 95%CI 1.11-5.94, P = .022). For postmenopausal patients, shorter period of lifetime menstrual cycles (≤30 years) had an obviously decreased risk in HR-positive cases (OR 0.397; 95%CI 0.22-0.71), while there was no similar appearance in other molecular subtypes. CONCLUSION: The results suggest that reproductive behaviors affect risk of breast cancer differently according to ER/PR and HER2 status.

Determination of Bioelectrical Impedance Thresholds for Early Detection of Breast Cancer-related Lymphedema.

Background: Bioelectrical impedance technology is a common technique used for the early detection of breast cancer-related lymphedema (BCRL). However, studies on the threshold value established by Inbody 720 device (Biospace, Korea) have been extremely limited. We aimed to determine its reference range and cutoff values. Methods: All patients were recruited from October 2017 to October 2019 at the Peking University People's Hospital Breast Center. In total, 82 patients with unilateral BCRL and 1305 healthy subjects were recruited in this study. We measured the extracellular fluid (ECF) ratio, extracellular water (ECW) ratio, as well as the single-frequency bioimpedance analysis (SFBIA) ratios at 1 and 5 kHz with the Inbody 720 device. The Youden index-based cutoff points, mean + 2SD and mean + 3SD values of these four indicators for both dominant and nondominant arms were also calculated. Results: Data were collected from 1387 women, including healthy subjects and patients with lymphedema. All statistical analyses were performed with SPSS. Significant differences were found between the two groups in the ECW, ECF, and SFBIA ratios. For the dominant affected arms, the Youden index-based cutoff points for the ECF, ECW, as well as SFBIA ratios at 1 and 5 kHz were 1.009, 1.008, 1.068, and 1.068, respectively. For the nondominant affected arms, the Youden index-based cutoff points were 1.014, 1.013, 1.047, and 1.048, respectively. The mean + 2 standard deviations (SD) and mean + 3SD values were also calculated. Conclusions: We determined the Youden index-based cutoff points, mean + 2SD and mean + 3SD values of the ECF, ECW, as well as SFBIA ratios at 1 and 5 kHz for both dominant and nondominant arms with data from 1305 healthy subjects. Next, the Youden index-based cutoff points, the mean + 2SD and mean + 3SD values were used to recognize patients with lymphedema. We found that the Youden index-based cutoff points and the mean + 2SD showed similar identification capacity on lymphedema, and they seemed to distinguish more patients with lymphedema than mean + 3SD values.

Application of the ACOSOG Z0011 criteria to Chinese patients with breast cancer: a prospective study.

BACKGROUND: Although the ACOSOG Z0011 study showed that axillary lymph node dissection (ALND) could be avoided in a specific population of sentinel lymph node-positive patients, it is not widely accepted by Chinese surgeons. We conducted a prospective single-arm study to confirm whether or not the results of Z0011 are applicable to Chinese patients. METHODS: Patients conforming to the Z0011 criteria were prospectively enrolled at the Peking University People's Hospital Breast Center from November 2014 to June 2019. The clinicopathological features of the study group were compared with those of the Z0011 study group. Lymphedema after surgery, the incidence of local-regional recurrence, and survival were analyzed. RESULTS: One hundred forty-two patients who met the Z0011 eligibility criteria were enrolled in this study; 115 underwent sentinel lymph node biopsy (SLNB) alone. Compared with the Z0011 trial, younger patients were included (median age, 52 [26-82] years vs 54 [25-90] years; P = 0.03). For clinical T stage, tumor histology, hormone status, lymphovascular invasion, and the number of positive sentinel lymph nodes (SLNs), no statistically significant differences were observed. More patients received adjuvant chemotherapy and endocrine therapy in this study (90.85% vs 58.0% and 80.99% vs 46.6% respectively, P <0.001). A similar percentage of patients received radiotherapy, but more nodal radiotherapy procedures were carried out in our study (54.5% vs 16.9%). After a median follow-up of 29 months, only 1 patient (0.9%) had ipsilateral breast tumor recurrence, and no regional recurrence occurred. CONCLUSION: Our study showed that it is achievable to avoid ALND in patients eligible for Z0011 in China. TRIAL REGISTRATION: ClinicalTrials.gov. Registration number NCT03606616 . Retrospectively registered on 31 July 2018.

Evaluating and Balancing the Risk of Breast Cancer-Specific Death and Other Cause-Specific Death in Elderly Breast Cancer Patients.

Purpose: The dilemma of undertreatment and overtreatment of elderly breast cancer patients is common. This study aimed to investigate clinicopathological features, treatment modalities, and survival in women diagnosed with breast cancer at age 70 years or over, and to assist clinicians in developing individualized treatment plans by balancing the risks of breast cancer-specific death (BCSD) and other cause-specific death (OCSD). Methods: This retrospective study included 420 women who were diagnosed with pathologically confirmed invasive breast cancer at age 70 years or older from January 2008 to December 2015 at Peking University People's Hospital (PKUPH). We collected baseline health status, tumor characteristics, treatment choices, and outcomes and created nomograms for clinicians to estimate individualized BCSD and OCSD risk directly. Results: During a median follow-up of 71.5 months (range 2 to 144 months) in patients with stage I-III tumors, breast cancer specific survival (BCSS) was 92.4% (376/407) and overall survival (OS) was 78.1% (318/407). There were 89 deaths, and 65.2% (58/89) were non-breast cancer related. Upon multivariate analysis by Cox regression model, tumor size, positive lymph nodes, Ki-67, and surgery were independent predictors of BCSS, and comorbidities, positive lymph nodes, Ki-67, surgery, and endocrine therapy were independent predictors of OS. Propensity score weighted (PSW) was applied to analyze therapeutic efficacy, and there was BCSS and OS benefit with surgery (both p < 0.001), BCSS benefit with chemotherapy (p = 0.029), BCSS and OS benefit with endocrine therapy (p = 0.006 and 0.004), and neither BCSS nor OS benefit with radiotherapy (RT) (p = 0.348 and 0.289). Competing-risk nomograms were developed to estimate cumulative mortality probabilities for BCSD and OCSD for individual patients according to clinicopathologic characteristics and treatments. The calibration curves displayed exceptionally, with C-indexes 0.714 for BCSD and 0.717 for OCSD. Conclusions: Older patients had greater risk of dying from non-breast cancer causes. Surgery, chemotherapy, and endocrine therapy were associated with improved survival. Competing risk nomograms allowed individual assessment of BCSD and OCSD, based on clinicopathological characteristics and treatment options, and can be used as a tool to help in choosing appropriate treatment strategies. This study was approved by the Peking University People's Hospital Research Ethics Board on September 4, 2018.

Long-term follow-up results of fluorescence and blue dye guided sentinel lymph node biopsy in early breast cancer.

PURPOSE: This study aimed to assess the efficacy of the combination of indocyanine green (ICG) and methylene blue (MB) dye in early breast cancer patients undergoing sentinel lymph node biopsy (SLNB). METHODS: Between January 2011 and December 2015, 1061 early breast cancer patients underwent SLNB were included. SLNB was performed for enrolled patients by injection of both ICG and MB. Detection rate, positivity, and number of sentinel lymph nodes (SLNs) by ICG and MB were analysed. Axillary recurrence and arm lymphedema at 5.6-year follow-up were reported. RESULTS: The combination of ICG and MB resulted in a very high detection rate of 99.6%, the median number of sentinel lymph nodes was 3. A total of 374 histologically confirmed positive SLNs were detected in 237 patients, 96.6% of the positive patients and 94.1% of the positive nodes could be identified by the combination of ICG and MB. After a median follow-up of 5.6 (2-9.3) years, 0.64% of patients with negative SLNs had ipsilateral axillary recurrence, and the incidence of arm lymphedema was 2.1%. CONCLUSIONS: Although the missing isotope control weakens the interpretation of the findings, the dual tracing modality of ICG and MB, without involvement of radioactive isotopes, was an effective method for SLNB in patients with early breast cancer. TRIAL REGISTRATION: ACTRN12612000109808. Registered on 23 January 2012.

Use of high-resolution full-field optical coherence tomography and dynamic cell imaging for rapid intraoperative diagnosis during breast cancer surgery.

BACKGROUND: Although traditional intraoperative assessments (ie, frozen sections) may lower reoperation rates in patients with breast cancer, time/tissue limitations and accuracy concerns have discouraged their routine clinical use. Full-field optical coherence tomography (FFOCT) and dynamic cell imaging (DCI) are novel optical imaging techniques offering rapid histologic approximations that are unfettered by requisite handling steps. This study was conducted to determine the feasibility and diagnostic utility of FFOCT and DCI in examining breast and lymph node specimens during breast cancer surgery. METHODS: FFOCT and DCI were applied to normal and cancerous breast tissue, benign breast lesions, and resected axillary lymph nodes. The tissues were then subjected to conventional processing and staining (hematoxylin-eosin) for purposes of comparison. RESULTS: A total of 314 specimens, including 173 breast biopsies (malignant, 132; benign/normal, 41) and 141 resected lymph nodes (tumor-positive, 48; tumor-negative, 93), were obtained from 158 patients during breast surgery for prospective imaging evaluations. In breast cancer diagnosis, the minimum sensitivities (FFOCT, 85.6%; DCI, 88.6%) and specificities of optical imaging (FFOCT, 85.4%; DCI, 95.1%) were high, although they diverged somewhat in nodal assessments (FFOCT sensitivity, 66.7%; FFOCT specificity, 79.6%; DCI sensitivity, 83.3%; DCI specificity, 98.9%). CONCLUSIONS: These timely and tissue-sparing optical imaging techniques proved highly accurate in diagnosing breast cancer and nodal metastasis. They compare favorably with routine histologic sections and demonstrate their promise in this setting.

Using the axillary reverse mapping technique to screen breast cancer patients with a high risk of lymphedema.

BACKGROUND: Preventing breast cancer-related lymphedema (BCRL) by preserving upper lymphatic drainage is still controversial. Our study aimed to use the axillary reverse mapping (ARM) technique in patients who underwent axillary surgery to analyse the correlation between postoperative residual ARM nodes and the occurrence of lymphedema, select candidates at high risk of developing lymphedema, and analyse the oncologic safety of ARM nodes. METHODS: Patients undergoing sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) from October 2015 to February 2016 at the Peking University People's Hospital Breast Center were prospectively recruited for the study. ARM was performed in all patients before surgery. ARM nodes were separated from SLNB and ALND specimens. Data were collected on the identification of ARM nodes before surgery, number of residual ARM nodes after surgery, nodal status, crossover rate, and correlation between residual ARM nodes and the occurrence of lymphedema. RESULTS: The analysis included 78 patients. Of the 53 patients who underwent SLNB, crossover between ARM nodes and breast sentinel lymph nodes (SLNs) was seen in 22 specimens. The incidence of ARM node metastasis was 1.89% (1/53) and 25% (9/36) in the SLNB and ALND groups, respectively. The number of positive axillary lymph nodes was associated with the involvement of ARM nodes (P = 0.036). The incidence of residual ARM nodes was significantly higher in the SLNB group than in the ALND group (67.6% vs. 37.9%, P = 0.016). The incidence of lymphedema was significantly higher in the ALND group than in the SLNB group (33.3% vs. 5.4%, P = 0.003). CONCLUSIONS: For SLNB, the ARM technique can help to resect SLNs more accurately. However, we do not recommend using the ARM technique to preserve ARM nodes in patients undergoing ALND due to oncologic safety issues. Nevertheless, we can predict patients undergoing axillary surgery who are more likely to have a high risk of lymphedema by assessing residual ARM nodes. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov in February 2016. The clinical trial registration number is NCT02691624.

Lymph Node Predictive Model with in Vitro Ultrasound Features for Breast Cancer Lymph Node Metastasis.

Ultrasound diagnosis of axillary lymph nodes has the advantages of ease, convenience and low cost; however, most previous studies evaluated lymph node metastasis of the entire axilla rather than the association between the ultrasound features of a single lymph node and its pathology. This prospective study was performed to explore the ultrasound features of lymph nodes observed in bionic medium in vitro and to develop a lymph node-specific model for prediction of metastasis based on analysis of the association between the ultrasound features and pathology of each lymph node. From November 1, 2017 to December 19, 2017, 373 nodes (54 patients) were enrolled into the modeling group; from December 20, 2017 to January 12, 2018, 139 lymph nodes (22 patients) were enrolled into the validation group. Lymph nodes from sentinel lymph node biopsy or axillary lymph node dissection were enrolled. Individual lymph nodes were placed in bionic medium and observed separately using ultrasound. Traditional ultrasound features of metastatic nodes (long axis, short axis, cortical thickness and hilum loss) were recorded, and the longitudinal-to-transverse axis ratio (L/T) and cortical proportion were calculated. Pathologic results specific to each lymph node were recorded. On the basis of two-level binary logistic regression, independent predictors of lymph node metastasis in the modeling group were lymph node long axis (p = 0.004), short axis (p < 0.001), L/T (p = 0.006), cortical thickness (p = 0.001) and hilum loss (p < 0.001). When analysis was done at the node level, the areas under the curve of the modeling and validation groups were 0.97 and 0.75, respectively. When validation was done at the patient level, the areas under the curve of the modeling and validation groups were 0.96 and 0.93, respectively. The model for prediction of metastasis based on the ultrasound features and pathology of each lymph node is of good predictive value for lymph node metastasis.

Could axillary clearance be avoided in clinically node-negative breast cancer patients with positive nodes diagnosed by ultrasound guided biopsy in the post-ACOSOG Z0011 era?

BACKGROUND AND OBJECTIVES: The role of ultrasound (US) guided biopsy in selecting patients for an upfront lymph node dissection (ALND) has been controversial following the publication of the American College of Surgeons (ACOSOG) Z0011 data. The purpose of this study was to investigate if patients with positive axillary lymph nodes (LNs) proven by US guided biopsy should be recommended for ALND and to analyze the utility of preoperative US and US guided biopsy in planning axillary surgery to avoid both unnecessary ALND and unnecessary SLNB. METHODS: Patients with a positive preoperative LN biopsy were identified and evaluated to determine their suitability for inclusion according to the criteria proposed in the Z0011 data. The correlation of the number of suspicious nodes found using US with the number of positive nodes on ALND was studied. RESULTS: A total of 261 breast cancer patients who had a positive preoperative LN needle biopsy were identified, among them, 79 patients with cT1-2N0 breast cancer and ALND were enrolled in the study. Thirty-one patients (39.2%) had ≤2 positive nodes identified in pathology and 10 patients (12.7%) met all of the Z0011 criteria and might have been spared ALND. A significantly greater proportion of women with ≥3 positive nodes during ALND had >1 abnormal LN identified using US compared to women with ≤2 positive LNs found using ALND (66.7% vs. 6.5%, p<0.0001). CONCLUSION: US with needle biopsy is valuable to patients with multiple suspicious nodes found using US while SLND without US guided needle biopsy is suggested if only one abnormal LN is detected on US in the post-Z0011 era.

Three inflammation-related genes could predict risk in prognosis and metastasis of patients with breast cancer.

BACKGROUND: Current predictive model is not developed by inflammation-related genes to evaluate clinical outcome of breast cancer patients. METHODS: With mRNA expression profiling, we identified 3 mRNAs with significant expression between 15 normal samples and 669 breast cancer patients. Using 7 cell lines and 150 paraffin-embedded specimens, we verified the expression pattern by bio-experiments. Then, we constructed a three-mRNA model by Cox regression method and approved its predictive accuracy in both training set (n = 1095) and 4 testing sets (n = 703). RESULTS: We developed a three-mRNA (TBX21, TGIF2, and CYCS) model to stratify patients into high- and low-risk subgroup with significantly different prognosis. In training set, 5-year OS rate was 84.5% (78.8%-90.5%) vs 73.1% (65.9%-81.2%) for the low- and high-risk group (HR = 1.573 (1.090-2.271); P = 0.016). The predictive value was similar in four independent testing sets (HR>1.600; P < 0.05). This model could assess survival independently with better predictive power compared with single clinicopathological risk factors and any of the three mRNAs. Patients with both low-risk values and any poor prognostic factors had more favorable survival from nonmetastatic status (HR = 1.740 (1.028-2.945), P = 0.039). We established two nomograms for clinical application that integrated this model and another three significant risk factors to forecast survival rates precisely in patients with or without metastasis. CONCLUSIONS: This model is a dependable tool to predict the disease recurrence precisely and could improve the predictive accuracy of survival probability for breast cancer patients with or without metastasis.

Retrospective analysis of concurrent docetaxel and epirubicin neoadjuvant versus adjuvant chemotherapy: Which leads to better outcomes for different subtype breast cancer patients?

Different biological subtype breast cancers respond differently to neoadjuvant chemotherapy, but it is unknown whether neoadjuvant or adjuvant chemotherapy leads to different long-term survival in each specific subtype although equal outcomes have been reported in general population. This study sought to clarify whether the selection of either neoadjuvant or adjuvant chemotherapy was linked to a differential survival benefit based on breast cancer subtypes.A prospectively maintained breast cancer database was queried from 2000 to 2008. All patients with a diagnosis of stage II and III breast cancer who received neoadjuvant or adjuvant chemotherapy were identified, only patients receiving docetaxel and epirubicin (TA) regimen were included. Patients were divided according to the administration of neoadjuvant or adjuvant chemotherapy. The biological subtypes were determined by immunohistochemical tests. The outcomes between neoadjuvant and adjuvant chemotherapy were compared in each different subtype. Kaplan-Meier curves were generated, and the Cox model was used to estimate the association between death risk and chemotherapy timing while adjusting for potentially confounding factors. P values < .05 were considered statistically significant.Of the 406 patients included, 201 (49.5%) received neoadjuvant chemotherapy, and 205 (50.5%) received an adjuvant TA regimen. Patients with the HER2+ and TNBC subtypes showed significantly higher pCR rates than patients with luminal types (P < .05). In general population, the neoadjuvant and adjuvant chemotherapy groups showed little survival variance (HR=1.15, 95% confidence interval (CI) .69-1.91, P=.60). In luminal B-like patients, neoadjuvant chemotherapy led to worse overall survival (OS) than adjuvant therapy (HR=2.92, 95%CI 1.20 to 8.31, P = .02). In patients with the HER2+ subtype, neoadjuvant treatment corresponded to better OS (HR = .10, 95%CI .02-.58, P = .01). In contrast, patients with luminal A-like (HR = 1.14, 95%CI .53-2.43, P = .74) and TNBC disease (HR = 1.00, 95%CI .27-3.73, P = >.99) who underwent neoadjuvant chemotherapy showed equivalent OS when compared to patients undergoing adjuvant therapy.Neoadjuvant versus adjuvant chemotherapy results in a disparate impact on overall survival among patients with variant subtype breast cancer. When neoadjuvant chemotherapy was given, luminal B-like patients showed worse outcome, while patients with HER2+ disease had better OS. Prospective studies are necessary to determine and optimize the timing of chemotherapy for breast cancers with different molecular backgrounds.

Comparison of sentinel lymph node biopsy guided by indocyanine green, blue dye, and their combination in breast cancer patients: a prospective cohort study.

BACKGROUND: Recent studies show that near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the performance of sentinel lymph node (SLN) mapping. The current cohort study was designed to assess the value of the combination of ICG and methylene blue (MB) dye in patients undergoing SLN biopsy. METHODS: A prospective self-controlled trial was designed to detect the difference in the detection efficacies of ICG, MB, and combined ICG and MB (ICG + MB) navigation methods. Between 2010 and 2013, 198 consecutive early breast cancer patients eligible for sentinel lymph node biopsy were enrolled and 200 biopsy procedures were performed by injection of both ICG and MB. SLNs were searched and removed under the guidance of fluorescence and/or blue dye. The mapping characteristics, the detection rate of SLNs and positive SLNs, and the number of SLNs of ICG, MB, and ICG + MB were compared. Injection safety of ICG and MB was evaluated. RESULTS: Fluorescence imaging of lymphatic flow, which is helpful to locate the incision site, could be seen in 184 of 200 procedures. The nodal detection rate of ICG, MB, and ICG + MB samples was 97, 89, and 99.5% (χ 2 = 26.2, p < 0.001), respectively, with the combination method yielding a superior identification result. The addition of ICG to the MB method resulted in the identification of more lymph nodes (median 3 versus 2) and more positive axillas (22.7% involved axillas were discovered by fluorescence only) than either method alone. No acute or chronic allergic reaction was observed in this study. However, 23 patients (23/82) who received breast-conserving therapy reported temporary skin staining, and 5 patients had permanent tattooing. Palpable subcutaneous nodules at the injection sites were reported in nine patients. There were no reports of skin necrosis. CONCLUSIONS: The lymphatic navigation by ICG fluorescence detects SLNs at a high detection rate and improves the mapping performance when added to the MB method. The novel ICG + MB dual tracing modality, without involvement of radioactive isotopes, exhibits great potential as an alternative to traditional standard mapping methods. TRIAL REGISTRATION: ACTRN12612000109808 . Retrospectively registered on 23 January 2012.

Mammary ductoscopy and follow-up avoid unnecessary duct excision in patients with pathologic nipple discharge.

BACKGROUND AND OBJECTIVES: The goal of this study was to evaluate the efficacy of ductoscopy and follow-up for the diagnoses of intraductal lesions and the concomitant advantages of avoiding surgery for patients with pathologic nipple discharge (PND). METHODS: Two hundred and sixty-six ductoscopies were performed for 238 women. Patients with positive ductoscopies underwent surgery. If no positive lesions were present upon ductoscopy, the women were followed. RESULTS: Of 266 ductoscopic examinations, 168 (63.2%, 168/266) breasts from 165 patients were found to have positive images. The final histopathological results revealed that 93 patients with intraductal papilloma, 42 with intraductal papillomatosis, 15 with ADH lesions, DCIS in 9 patients, 1 case with invasive ductal carcinoma (IDC), 6 cases with duct ectasia, and 2 cases with inflammation. Seventy-three patients with negative results upon ductoscopy were followed with a median time of 48 months. Twelve patients had PND recurrence and were diagnosed as papilloma or papillomatosis based on pathology after surgery. PND disappeared for 51 patients after ductoscopy, and no recurrence or disease evolvement was founded for them. CONCLUSION: Ductoscopy and follow-up were advantageous for selecting patients to undergo surgery or surveillance. The recurrence of PND after ductoscopy might be a strong predictor for having intraductal disease.

A logistic regression model for predicting axillary lymph node metastases in early breast carcinoma patients.

Nodal staging in breast cancer is a key predictor of prognosis. This paper presents the results of potential clinicopathological predictors of axillary lymph node involvement and develops an efficient prediction model to assist in predicting axillary lymph node metastases. Seventy patients with primary early breast cancer who underwent axillary dissection were evaluated. Univariate and multivariate logistic regression were performed to evaluate the association between clinicopathological factors and lymph node metastatic status. A logistic regression predictive model was built from 50 randomly selected patients; the model was also applied to the remaining 20 patients to assess its validity. Univariate analysis showed a significant relationship between lymph node involvement and absence of nm-23 (p = 0.010) and Kiss-1 (p = 0.001) expression. Absence of Kiss-1 remained significantly associated with positive axillary node status in the multivariate analysis (p = 0.018). Seven clinicopathological factors were involved in the multivariate logistic regression model: menopausal status, tumor size, ER, PR, HER2, nm-23 and Kiss-1. The model was accurate and discriminating, with an area under the receiver operating characteristic curve of 0.702 when applied to the validation group. Moreover, there is a need discover more specific candidate proteins and molecular biology tools to select more variables which should improve predictive accuracy.