Homologous recombination deficiency reflects the heterogeneity and monitoring treatment response for patients with breast cancer.

BACKGROUND: In breast cancer (BC), homologous recombination defect (HRD) is a common carcinogenic mechanism. It is meaningful to classify BC according to HRD biomarkers and to develop a platform for identifying BC molecular features, pathological features and therapeutic responses. METHODS: In total, 109 HRD genes were collected and screened by univariate Cox regression analysis to determine the prognostic genes, which were used to construct a consensus matrix to identify BC subtype. Differentially expressed genes (DEGs) were filtered by the Limma package and screened by random forest analysis to build a model to analyze the immunotherapy response and sensitivity and prognosis of patients suffering from BC to different drugs. RESULTS: Thirteen out of 109 HRD genes were prognostic genes of BC, and BC was classified into two subgroups based on their expression. Cluster 1 had a significantly backward survival outcome and a significantly higher adaptive immunity score relative to cluster 2. Six genes were identified by random forest analysis as factors for developing the model. The model provided a prediction called risk score, which showed a significant stratification effect on BC prognosis, immunotherapy response and IC50 values of 62 drugs. CONCLUSIONS: In the present study, two HRD subtypes of BC were successfully identified, for which mutation and immunological features were determined. A model based on differential genes of HRD subtypes was established, which was a potential predictor of prognosis, immunotherapy response and drug sensitivity of BC.

Analysis and prediction of second primary malignancy in patients with breast cancer.

Second primary malignancy (SPM) is common in breast cancer (BC). The present study aimed to profile the characteristics of BC with SPM and to identify patients at high risk of SPM. Clinical and outcome data of BC cases were retrieved from the SEER database. Principal component analysis and a random forest model were utilized to create a model for predicting the occurrence of SPMs. Of the 286,047 BC cases analyzed, 9.32% developed SPMs. Approximately 70% of BCs that developed SPMs were ductal carcinoma and 71% of BCs that developed SPMs were human epidermal growth factor receptor 2 (HER2)-/hormone receptor (HR)+. The overall survival (OS) of the SPM cohort was significantly worse (hazard ratio: 1.49; 95% CI: 1.44-1.53; log-rank P<0.001). After adjusting for metastasis status, SPM was still a poor prognostic factor (hazard ratio: 1.71; 95% CI: 1.70-1.82; log-rank P<0.001). Of note, 50.5% of the SPMs occurred in the breast and the OS of the breast SPM group was significantly better than that of the other single-organ SPM group (hazard ratio: 0.46; 95% CI: 0.45-0.49; log-rank P<0.001) and the multiple-organ SPM group (hazard ratio: 0.44; 95% CI: 0.39-0.50; log-rank P<0.001). A random forest model created from clinical features predicted SPM with a positive predictive value of 32.3% and negative predictive value of 90.7% in the testing set. Thus, SPM occurs in nearly 1/10 of BC survivors and its existence and occurrence site significantly influence OS. SPM may be partly predicted from clinical features. In addition, it was indicated that postmenopausal elderly patients with a HER2-/HR+ molecular subtype should be more watchful and undergo screenings for SPMs.

Oral adverse effects of CDK4/6 inhibitors among breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Cyclin-dependent kinase (CDK) inhibitors are widely used to treat hormone receptor-positive (HR+) breast cancer due to their efficient performance in improving survival outcomes. Although the side effects of these agents on the hematological and gastrointestinal systems have attracted significant attention, the adverse effects that have direct impacts on patients' quality of life, such as stomatitis, have not been well explored to date. METHODS: A systematic literature search was conducted in the PubMed, Google Scholar, European Society of Medical Oncology (ESMO), and American Society of Clinical Oncology databases. Phase 2 and 3 randomized trials on CDK4/6 inhibitors (CDK4/6Is) were identified and used in the meta-analysis based on the completeness of their safety data. RESULTS: Of the 904 records screened, 40 studies were considered relevant. Six studies were used in the meta-analysis, with a total of 2,980 patients in the safety population. The pooled relative risk (RR) and risk difference (RD) for any-grade stomatitis were 2.02 (95% CI: 1.65-2.48) and 0.10 (95% CI: 0.05-0.15), respectively. In the subgroup analysis, higher RRs were observed among patients receiving letrozole as basic endocrine therapy (ET) (8.50, 95% CI: 2.22-32.57) or palbociclib-containing regimens (2.44, 95% CI: 1.88-3.18), whereas the RDs showed no significant difference. DISCUSSION: All CDK4/6Is, especially palbociclib, could increase the risk of developing stomatitis among patients with breast cancer. Prevention and management of CDK4/6Is-related stomatitis may effectively reduce its secondary impacts. Due to the lack of individual-level data, some important personal confounding variables could not be controlled. Besides, the explanations of the secondary effects of stomatitis in this study were only based on the literature and professional knowledge. The specific quantitative impacts on patient quality of life and compliance require further questionnaire investigation. More in-depth individual-level data are needed to quantify the effect of stomatitis on patients' quality of life and treatment compliance.

Pruritic breast mass with palpable lymph nodes in a male patient: a case report.

This paper presents a case study of a 78-year-old male patient who presented with exacerbated skin redness and edema on the left chest wall, especially on the left breast, and who had been suffering from associated pruritus for 6 months. The patient also presented with enlarged ipsilateral axillary lymph nodes that were suspected to be carcinomas after a preliminary ultrasound and enhanced computerized tomography (CT) examination were performed. To examine these symptoms, an ultrasound-guided core biopsy and a chronic inflammatory test were also performed. The results of the excision biopsy and the immunohistochemistry test of the left breast and ipsilateral lymph node revealed no signs of cancer in this patient. Finally, combined with his medical history, the laboratory tests and pathology results, the patient was diagnosed with plasma cell mastitis (PCM) after another suspicious lesion (e.g., inflammatory breast cancer, etc.) was excluded. PCM is a kind of benign lesion of the breast with an unclear etiology. It usually affects non-pregnant and non-lactational females, who display clinical symptoms that are often similar to those of inflammatory breast cancer (IBC), the main manifestations were erythema and edema on the chest wall. To date, there is no standardized clinical treatment strategy or management approach for PCM.

Analysis of factors influencing postoperative drainage time in breast cancer.

BACKGROUND: To investigate the related factors affecting the postoperative indwelling time of drainage tubes (hereinafter referred to as drainage time) in breast cancer (BC) and evaluate the effect of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) preparation on reducing postoperative drainage time. METHODS: The clinical data of 165 BC patients in our hospital, including the postoperative drainage time and occurrence of seroma and related complications (such as fever, incision infection, and flap necrosis) after extubation, were retrospectively analyzed. Univariate, multivariate, and stratified analyses were used to determine the correlations between 15 factors including age, body weight, body mass index (BMI), and PA-MSHA preparation, and the postoperative total drainage volume and drainage time. RESULTS: Age, BMI, and PA-MSHA preparation were independent factors affecting the postoperative drainage volume and drainage time of BC patients. Age and BMI were positively correlated with postoperative drainage volume and drainage time (P≤0.004, P≤0.037). PA-MSHA preparation significantly reduced the postoperative total drainage volume and drainage time (P<0.001), decreased the incidence of seroma after extubation (P=0.024), and did not increase complications (P>0.05). CONCLUSIONS: Obese and elderly patients were at a significantly high risk of a high drainage volume and long drainage time. Local treatment with PA-MSHA preparation had the advantages of reducing postoperative drainage volume, reducing drainage time, preventing seroma, and not increasing complications, and was a safe and effective treatment. For BC patients aged over 60 years and with a BMI ≥25, the intraoperative local spraying of wounds with PA-MSHA preparation to reduce postoperative drainage times is a valuable option.

Redefining Criteria to Ensure Adequate Sentinel Lymph Node Biopsy With Dual Tracer for Breast Cancer.

BACKGROUND: For sentinel lymph node biopsy (SLNB) in patients with breast cancer, the dual tracer of blue dye and radioisotope with the 10% rule that all nodes with radioactive count of 10% or more of the hottest node ex vivo should be removed is widely accepted. However, the cut-off point of radioactivity is being questioned for possibly excessive removal of negative nodes. METHODS: To compare different percentile rules and optimize the criteria for identifying SLNs, we established a database which prospectively collected the radioactivity, status of blue dye and the pathological results of each SLN in breast cancer patients who successfully underwent SLNB with a combination of methylene blue and radioisotope. RESULTS: A total of 2,529 SLNs from 1,039 patients were identified from August 2010 to August 2019. 16.4% (414/2,529) positive nodes were removed at a cost of 83.6% (2115/2,529) negative nodes removed excessively. Up to 17.9% (375/2,115) negative nodes were removed as radioactively hot nodes without blue staining. By gradually increasing the threshold by each 10%, the number of negative nodes identified reduced by 18.2% (385/2,115) with only three node-positive patients (1.0%) missed to be identified using the "40% + blue" rule. In patients with ≥ 2 SLNs removed, 12.3% (238/1,942) negative nodes avoided unnecessary removal with only 0.8% (2/239) positive patients missed with the "hottest two + blue" rule. CONCLUSIONS: Our data indicated that the "40% + blue" rule or the "hottest two + blue" rule for SLNB with the dual tracer of blue dye and radioisotope may be considered as a potential alternative rule to minimize extra nodes resected. Nonetheless, it should be validated by prospective trials with long-term follow-up.

Overexpression of lncRNA TATDN1 Promotes Cancer Cell Proliferation in Triple Negative Breast Cancer by Regulating miR-26b Methylation.

BACKGROUND: Long non-coding RNA (lncRNA) TatD DNase Domain Containing 1 (TATDN1) is a recently characterized oncogenic lncRNA in several types of cancer including breast cancer. Our preliminary microarray analysis revealed its upregulation in triple negative breast cancer (TNBC) and its inverse correlation with microRNA-26b (miR-26b), which is a tumor suppressive miRNA in breast cancer. This study was therefore carried out to investigate the interaction between TATDN1 and miR-26b in TNBC. METHODS: A total of 66 pairs of TNBC and non-tumor tissues were collected from 66 patients (45.8 ± 10.5 years old) with TNBC through biopsy under the guidance of MRI before initiation of any therapies. Quantitative reverse transcription PCR (RT-qPCR), transient cell transfection, methylation specific PCR (MSP) and cell proliferation assay were carried out in this study. RESULTS: We found that TATDN1 was upregulated and miR-26b was downregulated in TNBC. Correlation analysis showed that the expression of TATDN1 and miR-26b was inversely correlated. In TNBC cells, overexpression of TATDN1 mediated the downregulation of miR-26b. Knockdown of TATDN1 led to the upregulation of miR-26b. Methylation-specific PCR showed that TATDN1 positively regulated the methylation of miR-26b gene. Cell proliferation analysis showed that TATDN1 positively regulated the proliferation of TNBC cells. Overexpression of miR-26b attenuated the effects of TATDN1 overexpression on cell proliferation. CONCLUSION: Therefore, overexpression of TATDN1 promotes cancer cell proliferation in TNBC by regulating the methylation of miR-26b gene.

Accuracy of Sentinel Lymph Node Biopsy in Breast Cancer: Pitfalls in the Application of Single Tracers.

BACKGROUND: Radioisotopes and blue dyes are used as dual tracers in the current gold standard procedure of sentinel lymph node (SLN) biopsy (SLNB) performed for breast cancer. However, the blue dye or the radioisotope as a single tracer is also being applied in some institutes. We aimed to explore the risk factors for the miss-detection of SLNs with the radioisotope and the blue dye and to describe the distribution of SLNs missed by each tracer. PATIENTS AND METHODS: Patients undergoing SLNB with radioisotope and blue dye as dual mapping agents were enrolled between August 2010 and August 2018. Radioactivity count, blue dye staining status, and size and location of each SLN were prospectively documented. RESULTS: In total, 2382 SLNs from 1010 patients were included for statistical analyses. The sentinel node identification rate was 100% for dual tracers, 99.4% for radioisotope, and 89.1% for blue dye. SLN identification using the blue dye was more likely to fail in patients undergoing breast-conserving surgery (p < 0.001) and mastectomy with reconstruction (p = 0.005). Furthermore, miss-detection was significantly more frequent in smaller and uninvolved nodes. Among all SLNs, 8.2% were located in level II and one was in level III. Notably, single tracer of blue dye tended to fail in the detection of lymph nodes in higher levels (p < 0.001). CONCLUSION: This study explored the association between features and the incidence of the failure to detect SLNs using radioisotope and blue dye. The locations of the miss-detected SLNs are demonstrated to provide a reference for SLNBs conducted using blue dye or radioisotope as a single tracer.

The effect of subcutaneous local spraying of Pseudomonas aeruginosa preparation to reduce postoperative drainage time in patients with breast cancer.

BACKGROUND: To evaluate the efficacy of subcutaneous local spraying of Pseudomonas aeruginosa (P. aeruginosa) preparation (PAP) to reduce the postoperative drainage time in patients with breast cancer (BC). METHODS: The PAP was prepared from an inactivated P. aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) strain, a genetically engineered heat-inactivated PA strain with, mannose-sensitive binding activity, which can induce tumor cell apoptosis. This study is its retrospective nature, a total of 65 BC patients (PAP group) who underwent subcutaneous local spraying of PAP in the operation area at West China Hospital of Sichuan University between June 2019 and October 2019, and 32 BC patients without treatment (non-PAP group, without intraoperative subcutaneous local spraying of PAP in the operation area) were enrolled. Daily drainage volume, drainage time, presence of seroma after extubation, and treatment complications (such as fever, incision infection, and flap necrosis) were recorded. RESULTS: No significant differences in age, height, weight, age of initial menstruation, menopause, body mass index (BMI), tumor size, lymph node metastasis, or treatment complications were found between the two groups (P>0.05). Drainage volume and drainage time in the PAP group were significantly lower than those in the non-PAP group (P<0.001). Additionally, the incidence of seroma after extubation was significantly lower in the PAP group compared to the non-PAP group (P=0.009). CONCLUSIONS: Subcutaneous local spraying of PAP on the operation area may be helpful to reduce drainage volume, shorten drainage time, and prevent the occurrence of seroma after BC surgery.

Retrospective observational study of breast reconstruction with extended latissimus dorsi flap following skin-sparing mastectomy.

The study was aimed to evaluate oncological safety and patient satisfaction in relatively late stage breast cancer patients who was treated with skin-sparing mastectomy (SSM) followed by breast reconstruction with an extended latissimus dorsi (LD) flap. Oncological safety, postoperative complications, and cosmetic results were retrospectively analyzed in patients who underwent extended LD flap breast reconstruction following SSM between October 2011 and August 2014. A total of 62 patients who underwent 63 breast reconstructions were enrolled in the study. Local recurrence rate was 1.6% over a median follow-up of 63 months. On final aesthetic assessment, 37 reconstructions were rated excellent, 19 good, 5 fair, and 2 poor. Reconstruction-related complications occurred in 22 patients (34.9%); these patients' satisfaction scores were significantly lower than those of patients without complications (P < .05). Five patients developed shoulder movement limitation, and 2 had minor twitching and pain in the reconstructed breast. However, these patients did not find their problems disabling and were able to live normally. SSM followed by breast reconstruction with extended LD flap can improve patients' postoperative quality of life and is as oncologically safe as total mastectomy even in patients with tumors of relatively late stage.

The value of positive lymph nodes ratio combined with negative lymph node count in prediction of breast cancer survival.

BACKGROUND: Positive lymph node ratio (LNR), defined as ratio of positive lymph nodes to all lymph nodes removed, is a powerful prognostic factor in invasive breast cancer. Here we focused on the impact of negative lymph node (NLN) count on the prediction of value of LNR in breast cancer survival. METHODS: Of 929 invasive breast cancer patients were enrolled in our retrospective study. We use Kaplan-Meier to calculate the 5-year overall survival (OS) according to different clinicopathologic parameters. The prediction value of NLN count and LNR in OS was examined. RESULTS: The optimal cutoff of NLN count was designated as 9. Five-year OS was 77.0% and 95.0% in patients with NLN of 0-9 and ≥10, respectively (P<0.001). Among 204 patients who had 0-9 NLN, 25 patients with LNR 0-20.0% had 5-year OS of 95.7%, 104 patients with LNR 20.1-65.0% had 5-year OS of 83.4%, and 75 patients with LNR 65.1-100.0% had 5-year OS of 61.7% (P<0.001); Among 725 patients who had NLN ≥10, 650 patients with LNR 0-20.0% had 5-year OS of 96.1%, 68 patients with LNR 20.1-65.0% had 5-year OS of 86.8%, and 7 patients with LNR 65.1-100% had 5-year OS of 71.4% (P<0.001). CONCLUSIONS: High NLN count is associated with improved survival in invasive breast cancer patients. Combining NLN count with LNR could be considered as an alternative to LNR alone in prediction of postoperative breast cancer survival.

Criteria derived from serum markers can precisely evaluate axillary status in breast cancer patients.

BACKGROUND: A noninvasive method to confirm the presence of lymph node metastases (LNM) in breast cancer patients is lacking. This study aimed to identify markers from peripheral blood that have diagnostic value in evaluating axillary LNM. METHODS: We tested 26 factors in serum from 57 patients with resectable breast cancer by the Luminex assay. Differences between node-negative and node-positive patients were assessed. The diagnostic value of the factors was determined by further analyses and a validation test. RESULTS: Matrix metalloproteinase-1, hepatocyte growth factor, and chemokine ligand 5 were independent risk factors for LNM. However, receiver operating characteristic analysis showed that these factors alone were not ideal predictors. The LNM score (LNMS), derived from combining these markers, correlated significantly with numbers of positive lymph nodes. Patients with LNMS of 0 had few LNM, axillary lymph node dissection (ALND) could be avoided, and sentinel lymph node biopsy (SLNB) was unnecessary. Very high accuracy was achieved for patients with LNMS of 1 with SLNB using only methylene blue, patients with LNMS of 3 required ALND, and patients with LNMS of 2 needed SLNB using both a radioactive isotope and methylene blue, and ALND. CONCLUSIONS: The LNMS derived from matrix metalloproteinase-1, hepatocyte growth factor, and chemokine ligand 5 serum levels identified the axillary lymph node status with high accuracy. Patients with higher LNMS had a greater probability of LNM.