PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

BACKGROUND: Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. METHODS: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored. RESULTS: Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment (Padjusted = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827-0.997) was achieved in the integrated model. CONCLUSIONS: Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy.

Safety and Feasibility of Minimally Invasive (Laparoscopic/Robotic-Assisted) Nipple-Sparing Mastectomy Combined with Prosthesis Breast Reconstruction in Breast Cancer: A Single-Center Retrospective Study.

BACKGROUND: Minimally invasive (robotic or laparoscopic-assisted) nipple-sparing mastectomy combined with prosthesis breast reconstruction (NSM-PBR) is associated with smaller scars and greater patient satisfaction. However, the oncological safety of minimally invasive NSM-PBR remains controversial. PATIENTS AND METHODS: This was a retrospective study of patients with breast cancer who underwent breast reconstruction between 1 January 2006 and 20 February 2021. Demographic and clinicopathological characteristics, operation information, postoperative complications, and survival outcomes were analyzed. RESULTS: In all, 292 patients underwent minimally invasive NSM-PBR and 205 underwent open NSM-PBR for breast cancer. In the minimally invasive NSM-PBR group, 268 (91.8%) patients underwent laparoscopy and 24 (8.2%) patients underwent robot-assisted NSM-PBR. Mean operation time in the minimally invasive NSM-PBR group was significantly longer than that in the open NSM-PBR group (P = 0.023). Mean intraoperative blood loss was significantly less in the minimally invasive NSM-PBR group (P < 0.05). There was no significant between-group difference in total complications. Similarly, there were no significant between-group differences in overall survival, recurrence-free survival, and local recurrence rate (P = 0.450, P = 0.613, and P = 0.679, respectively). CONCLUSIONS: The complication, recurrence, and mortality rates in minimally invasive NSM-PBR group were comparable to those in open NSM-PBR group. Our preliminary results are encouraging and suggest that minimally invasive NSM-PBR affords good cosmetic results and its oncological safety is comparable to that of open surgery.

Neoadjuvant Pyrotinib plus Trastuzumab and Chemotherapy for Stage I-III HER2-Positive Breast Cancer: A Phase II Clinical Trial.

LESSONS LEARNED: This is the first trial to explore the neoadjuvant therapy of pyrotinib in HER2-positive operable and locally advanced breast cancer, in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab. Results primarily showed that pyrotinib in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab was effective and safe in HER2-positive operable and locally advanced breast cancer. A subsequent randomized controlled trial is still warranted to confirm these results. BACKGROUND: The efficacy and safety of neoadjuvant therapy of pyrotinib, a new irreversible tyrosine kinase inhibitor (TKI), was first estimated in patients with HER2-positive breast cancer in this phase II study, in combination with trastuzumab and chemotherapy. METHODS: Between February 19, 2019, and November 20, 2019, 20 female Chinese patients with stage I-III HER2-positive breast cancer were assigned to receive eight cycles of neoadjuvant pyrotinib (P) in combination with four cycles of epirubicin (E) and cyclophosphamide (C) followed by four cycles of docetaxel (T) and trastuzumab (H), once every 3 weeks, referred to as P + EC-TH. RESULTS: A total of 19 patients completed the therapy and final surgery. The total pathological complete response (tpCR) rate was 73.7% (95% confidence interval [CI], 48.8-90.9), and no recurrence or metastasis occurred during the short-term follow-up period. The objective response rate (ORR) was 100% (95% CI, 82.4-100). The most common adverse events (AEs) were diarrhea and leukopenia in 18 of 20 patients (90%), but no grade 5 AEs were reported. CONCLUSION: This study showed that in HER2-positive operable or locally advanced breast cancer, the tpCR rate of P + EC-TH neoadjuvant therapy was about twice as high as that of EC-TH neoadjuvant therapy reported in other trials, with tolerable side effects.

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Less micrometastatic risk related to circulating tumor cells after endoscopic breast cancer surgery compared to open surgery.

BACKGROUND: Increase of circulating tumor cells (CTCs) has been found after surgery for various carcinomas but not confirmed for breast cancer, and whether endoscopic surgery confers identical effect to CTCs as open surgery did is not clear. The present study aimed to investigate whether CTCs increase after surgery and whether there is a difference between open surgery and endoscopic surgery. METHODS: Pre- and postoperative peripheral blood (5 mL) obtained from 110 female patients with operable breast cancer (53 underwent endoscopic surgery, 57 underwent open radical mastectomy). Quantitative real-time reverse transcription-PCR was done to detect cytokeratin 19 mRNA-positive CTC. CTC detection rate, cell number and the increase after surgery (named micrometastasis) were compared between the two groups. RESULTS: In the open group, CTC positive rate before and after surgery were 22.81 and 33.33%; median CTC number before and after surgery were 0.21 and 0.43 and 17 patients (29.82%) had increased micrometastatic risk. In the endoscopic group, CTC positive rate before and after surgery were 24.53 and 28.30%; median CTC number before and after surgery were 0.27 and 0.36, and 8 patients (15.09%) had increased micrometastatic risk. There was a suggestive higher postoperative CTC detection rate and CTC number and a significant increased postoperation micrometastatic risk was observed in the open group compared to the endoscopic group (OR = 3.19, 95%CI: 1.05-9.65) after adjustment for clinicopathologic characteristics. DISCUSSION: CTC tends to increase in breast cancer patients after surgery, and the micrometastatic risk was higher for open surgery compared to endoscopic surgery. TRIAL REGISTRATION: This study was prospectively registered at Chinese Clinical Trial Register (ChiCTR-OCH-10000859, 24 April 2010).

Evaluation of the tracing effect of carbon nanoparticle and carbon nanoparticle-epirubicin suspension in axillary lymph node dissection for breast cancer treatment.

BACKGROUND: Carbon nanoparticle suspension, using smooth carbon particles at a diameter of 21 nm added with suspending agents, is a stable suspension of carbon pellets of 150 nm in diameter. It is obviously inclined to the lymphatic system. There were some studies reporting that carbon nanoparticles are considered as superior tracers for sentinel lymph nodes because of their stability and operational feasibility. However, there were few study concerns about the potential treatment effect including tracing and local chemotherapeutic effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. METHODS: In the current study, a randomized controlled analysis was performed to investigate the potential treatment effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. A total of 90 breast cancer patients were randomly divided into three equal groups: control, tracer, and drug-load groups. The control group patients did not receive any lymphatic tracers, the tracer group patients were subcutaneously injected with 1 ml carbon nanoparticle suspension, and the drug-load group patients were injected with 3 ml carbon nanoparticle-epirubicin suspension at four separate sites around the areola 24 h before surgery. Modified radical mastectomy, endoscopic subcutaneous mammary resection plus axillary lymph node dissection, and immediate reconstruction with implants or breast-conserving surgery were performed. RESULTS: The mean number of the dissected lymph nodes per patient was significantly higher in the tracer (21.3 ± 6.1) and drug-load (19.5 ± 3.7) groups than in the control group (16.7 ± 3.4) (P < 0.05). Most lymph nodes in the former two groups were stained black (75.7 and 73.3 %, respectively), but with no significant difference between the groups. Most metastatic lymph nodes were also stained black in the tracer group (68.6 %) and drug-load group (78.1 %) and with no significant difference between the groups (P = 0.198). Microscopic examination revealed that the carbon nanoparticles were localized around or among the cancer cell masses and residues of necrotized cancer cells surrounded by fibroblastic proliferation could be found within the stained lymph nodes in the drug-load group. CONCLUSIONS: The majority of axillary lymph nodes were stained black by the suspension of carbon nanoparticles, which helped identify the lymph nodes from the surrounding tissues and avoided aggressive axillary treatment. Thus, a combination therapy of carbon nanoparticles with epirubicin could play an important role in lymphatic chemotherapy without affecting tracing. TRIAL REGISTRATION: ChiCTRTRC13003419.

Mammotome-assisted endoscopic breast-conserving surgery: a novel technique for early-stage breast cancer.

BACKGROUND: Because of its minimally invasive and highly accurate nature, the use of Mammotome, a vacuum-assisted breast biopsy device has proven beneficial to the treatment of benign breast lesions. Taking advantage of endoscopic and Mammotome techniques together, we utilized the Mammotome device for therapeutic excision of malignant lesions in breast-conserving surgery (BCS). METHODS: Between December 2009 and January 2010, two patients with early breast cancer received Mammotome-assisted endoscopic BCSs. Under ultrasound monitoring, the Mammotome system dissected the surrounding tissue and freed the tumor en bloc leaving negative margins; endoscopic axillary lymph node dissection then followed. RESULTS: The operation time was less than 180 minutes and the mean blood loss was 60 ml. The post-operative pathology report confirmed two patients to have invasive ductal carcinoma, one without axillary lymph nodes metastasis (0/11) and the other with one lymph node metastasis (1/21). No adverse events were noted. During a mean follow-up of 26.5 months, no evidence of recurrence or metastasis was found. The patients were satisfied with the cosmetic results. CONCLUSIONS: Mammotome-assisted endoscopic surgery appears to be a valuable option for early breast cancer. The long-term therapeutic effect remains to be confirmed.

Dynamic and quantitative method of analyzing service consistency evolution based on extended hierarchical finite state automata.

This paper is concerned with the dynamic evolution analysis and quantitative measurement of primary factors that cause service inconsistency in service-oriented distributed simulation applications (SODSA). Traditional methods are mostly qualitative and empirical, and they do not consider the dynamic disturbances among factors in service's evolution behaviors such as producing, publishing, calling, and maintenance. Moreover, SODSA are rapidly evolving in terms of large-scale, reusable, compositional, pervasive, and flexible features, which presents difficulties in the usage of traditional analysis methods. To resolve these problems, a novel dynamic evolution model extended hierarchical service-finite state automata (EHS-FSA) is constructed based on finite state automata (FSA), which formally depict overall changing processes of service consistency states. And also the service consistency evolution algorithms (SCEAs) based on EHS-FSA are developed to quantitatively assess these impact factors. Experimental results show that the bad reusability (17.93% on average) is the biggest influential factor, the noncomposition of atomic services (13.12%) is the second biggest one, and the service version's confusion (1.2%) is the smallest one. Compared with previous qualitative analysis, SCEAs present good effectiveness and feasibility. This research can guide the engineers of service consistency technologies toward obtaining a higher level of consistency in SODSA.

Anomaly monitoring method for key components of satellite.

This paper presented a fault diagnosis method for key components of satellite, called Anomaly Monitoring Method (AMM), which is made up of state estimation based on Multivariate State Estimation Techniques (MSET) and anomaly detection based on Sequential Probability Ratio Test (SPRT). On the basis of analysis failure of lithium-ion batteries (LIBs), we divided the failure of LIBs into internal failure, external failure, and thermal runaway and selected electrolyte resistance (R(e)) and the charge transfer resistance (R(ct)) as the key parameters of state estimation. Then, through the actual in-orbit telemetry data of the key parameters of LIBs, we obtained the actual residual value (R(X)) and healthy residual value (R(L)) of LIBs based on the state estimation of MSET, and then, through the residual values (R(X) and R(L)) of LIBs, we detected the anomaly states based on the anomaly detection of SPRT. Lastly, we conducted an example of AMM for LIBs, and, according to the results of AMM, we validated the feasibility and effectiveness of AMM by comparing it with the results of threshold detective method (TDM).

Observational cohort study on safety and efficacy of robotic thyroidectomy with super-meticulous capsular dissection versus open surgery for thyroid cancer: Postoperative dynamic risk assessment of radioactive iodine therapy.

OBJECTIVE: To assess the efficacy and safety of robotic thyroidectomy (RT) with super-meticulous capsular dissection (SMCD) versus open thyroidectomy (OT) we used a dynamic risk assessment system incorporating 131I-WBS along with radioactive iodine (RAI) efficacy evaluation. BACKGROUND: Currently, the therapeutic efficacy of robotic surgery remains controversial. The 131I whole-body scan (131I-WBS) dynamic risk assessment system can detect small residual thyroid tissues and lesions, which may be used as indicators for the surgical efficacy of RT or OT thyroidectomy in differentiated thyroid cancer (DTC). METHODS: This retrospective cohort study included 2,349 patients who underwent total thyroidectomy followed by RAI therapy in our department between August 2017 and June 2023. Propensity score matching was performed at a ratio of 1:3 based on surgical type and mean follow-up duration to minimize selection bias after excluding those lost to follow-up. The primary outcome was surgical completeness, assessed using a dynamic risk system incorporating 131I-WBS along with RAI efficacy evaluation. RESULTS: There was no significant difference in the number of metastatic lymph nodes removed between the two groups (P=0.45). The incidence rate of parathyroid gland transplantation was 395 (68.7%) in the OT group and 8 (3.8%) in the RT group (P<0.001). There were no differences in the thyroidectomy completeness based on the 3-hour iodine uptake rate and 99mTcO4- thyroid imaging between the two groups. The dynamic risk assessment with and without 131I-WBS showed significant differences (P<0.001). The postoperative and post-RAI dynamic risk scores, evaluated at the time of RAI and 6 months after RAI, did not differ significantly between the two groups (P>0.05). The rates of transient and permanent hypoparathyroidism were higher in the OT group than in the RT group (P<0.05). The local recurrence rates showed no significant difference between the groups. CONCLUSIONS: This study demonstrates that RT with SMCD can achieve outcomes equivalent to those of traditional open surgery when integrating the 131I-WBS dynamic evaluation system and the therapeutic effects of RAI. Additionally, robot surgery demonstrated a notable advantage in protecting parathyroid function.

Patient-reported outcomes of mesh in minimally invasive (laparoscopic/robot-assisted) immediate subpectoral prosthesis breast reconstruction: a retrospective study.

BACKGROUND: Although there is increasing interest in minimally invasive prosthesis breast reconstruction (PBR), whether meshes application in minimally invasive PBR can improve complications and cosmetic effects remains controversial. The author retrospectively analyzed postoperative complications and evaluated patient-reported quality-of-life outcomes in minimally invasive PBR with and without mesh. METHODS: This study enrolled patients who underwent minimally invasive nipple-sparing mastectomy (NSM) followed by PBR. We used the TiLOOP bra for the mesh-assisted procedure. Patient demographics and postoperative complications data were compared between the procedures. Patient-reported outcomes were evaluated with the Breast-Q. RESULTS: A total of 158 patients underwent 160 minimally invasive NSM-PBR (with mesh, n = 64; without, n = 94). Postoperative complications were comparable in the mesh-assisted (5 [7.7%]) and non-mesh-assisted (5 [5.3%]) groups (p = 0.533). The most common complication in non-mesh-assisted group was infection, with four (4.2%) cases. In mesh-assisted group, implant exposure occurred in two (3.1%) patients. Removal of prosthesis was uncommon, with two (3.1%) and three (3.2%) cases in the mesh-assisted and non-mesh groups, respectively (p = 0.977). The BREAST-Q questionnaire was completed by 52 (81.3%) patients in the mesh-assisted group and 68 (72.3%) in the non-mesh-assisted group. Comparing the non-mesh group, patients in mesh-assisted group had improved scores on the BREAST-Q Satisfaction with breast (66.0) (p < 0.05), Physical Well-being (80.0), and Sexual Well-being (56.0). CONCLUSIONS: Mesh-assisted minimally invasive NSM-PBR has good aesthetic outcomes and high patient satisfaction. There were no significant differences in complication rates between the mesh-assisted and non-mesh-assisted groups.

Safety and efficacy of anlotinib combined with taxane and lobaplatin in neoadjuvant treatment of clinical stage II/III triple-negative breast cancer in China (the neoALTAL trial): a single-arm, phase 2 trial.

Background: Anlotinib is a new type of tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1/2/3, platelet-derived growth factor receptors α/ß, and fibroblast growth factor receptors 1-4 and c-Kit, with a broad spectrum of inhibitory effects on tumor angiogenesis and growth. It has been proven effective in HER2-negative metastatic breast cancer, but its efficacy in early-stage triple-negative breast cancer (TNBC) is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients with TNBC. Methods: Patients with clinical stage II/III TNBC were treated with 5 cycles of anlotinib (12 mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 ,d1, q3w or nab-paclitaxel 125 mg/m2, d1 and d8, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0) and the secondary endpoints include breast pCR (bpCR), axillary pCR (apCR), residual cancer burden (RCB), objective response rate (ORR), survival, and safety. Exploratory endpoints were efficacy biomarkers based on Fudan University Shanghai Cancer Center Immunohistochemical (FUSCC IHC) classification for TNBC and next-generation sequencing (NGS) of DNA from tumor tissue and blood samples of patients with 425-gene panel. This trial is registered with www.chictr.org.cn (ChiCTR2100043027). Findings: From Jan 2021 to Aug 2022, 48 patients were assessed and 45 were enrolled. All patients received at least one dose of study treatment and underwent surgery. The median age was 48.5 years (SD: 8.7), 71% were nodal involved, and 20% had stage III. In the intention-to-treat population, 26 out of 45 patients achieved pCR (57.8%; 90% CI, 44.5%-70.3%), and 39 achieved residual cancer burden class 0-I (86.7%; 95% CI, 73.2%-94.9%). The bpCR and apCR rate were 64.4% (29/45) and 71.9% (23/32), respectively. No recurrence or metastasis occurred during the short-term follow-up. Based on the FUSCC IHC-based subtypes, the pCR rates were 68.8% (11/16) for immunomodulatory subtype, 58.3% (7/12) for basal-like immune-suppressed subtype and 33.3% (4/12) for luminal androgen receptor subtype, respectively. NGS revealed that the pCR were 77% (10/13) and 50% (14/28) in MYC-amplified and wild-type patients, respectively, and 78% (7/9) and 53% (17/32) in gBRCA1/2-mutated and wild-type patients, respectively. The median follow-up time of the study was 14.9 months (95% CI: 13.5-16.3 months). There was no disease progression or death during neoadjuvant therapy. No deaths occurred during postoperative follow-up. In the safety population (N = 45), Grade 3 or 4 treatment emergent adverse events occurred in 29 patients (64%), and the most common events were neutropenia (38%), leukopenia (27%), thrombocytopenia (25%), anemia (13%), and hypertension (13%), respectively. Interpretation: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and encouraging antitumor activity for patients with clinical stage II/III TNBC. Funding: Chongqing Talents Project, Chongqing Key Project of Technology Innovation and Application Development and Chongqing Outstanding Youth Natural Science Foundation.

Shrink pattern of breast cancer after neoadjuvant chemotherapy and its correlation with clinical pathological factors.

BACKGROUND: Breast conservation therapy (BCS) after neoadjuvant chemotherapy (NCT) can improve patients' quality of life. Currently used intraoperative examination for negative margins may not be sufficient to detect microresidual foci, which are a risk factor for local recurrence. This study was conducted to investigate the shrinking pattern of breast cancer and residual tumors as a risk factor for BCS after NCT. METHODS: Ninety women with stage II or III invasive ductal carcinoma who achieved partial response after NCT with paclitaxel and epirubicin were enrolled. All patients had undergone modified radical mastectomy. One-half of the surgical specimens were subjected to subserial sectioning. Pathological changes of tumor bed and pericancerous tissues were examined with an optical microscope. The levels of estrogen receptors, progesterone receptors and HER2 were analyzed by immnohistochemical staining. RESULTS: The residual tumors were classified into three types according to their microscopic morphology: solitary lesion, multifocal and patchlike lesions, and main residual tumor with satellite lesions. Type I residual tumors were found in 55 patients (61%), type II in 30 patients (33%) and type III in 5 patients (6%). Types II and III were often associated with larger primary tumors. The types of residual tumors were not correlated with the status of hormone receptors or HER2. CONCLUSION: Three types of residual tumors were observed after NCT. The solitary residual tumor is most common, but main residual tumors with satellite lesions are most likely to cause local recurrence after BCS. Subserial sectioning would improve the identification of microfoci and patient survival after BCS.

Prospective cohort study of parathyroid function and quality of life after total thyroidectomy for thyroid cancer: robotic surgery vs. open surgery.

OBJECTIVE: To compare robot-assisted thyroidectomy (RT) and open thyroidectomy (OT) through a prospective cohort study focusing on the rate of postoperative hypoparathyroidism, efficacy, and quality of life (QoL). SUMMARY BACKGROUND DATA: Hypoparathyroidism is a frequent complication after thyroidectomy. Reducing the risk of hypoparathyroidism after total thyroidectomy is a crucial and difficult task for thyroid surgeons. METHODS: We prospectively enroled 306 patients with papillary thyroid carcinoma into an RT group and OT group. The former used "super-meticulous" capsular dissection) and the latter used traditional meticulous capsular dissection. Patients were evaluated by scales [Short Form (SF)-36, Visual Impairment Scale (VIS), Swallowing Impairment Scale (SIS), Neck Impairment Scale (NIS), Scar questionnaire (SCAR-Q)]. RESULTS: The rates of transient hypoparathyroidism, permanent hypoparathyroidism, and transient hypocalcemia after surgery in the OT group and RT group were significantly different ( P <0.001). SIS and VIS scores in the two groups were significantly different ( P <0.001). SF-36 showed significant differences ( P <0.001) in the subsections of "physiological function", "body pain", "general health", "vitality", "social function", "role emotional", and "mental health" between the two groups. SCAR-Q showed that the length and appearance of scars showed significant differences between the two groups. CONCLUSIONS: RT with Super-meticulous capsular dissection can protect parathyroid function and improve postoperative QoL, and could be a new option for robot-assisted surgery against thyroid cancer.

A multicenter single-arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

The objective of this multicenter, single-arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy-THPy) in the treatment of patients with stage II-III HER2-positive breast cancer. The present study enrolled patients with stage II-III HER2-positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21-day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention-to-treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7-75.8%), while the objective response rate was 89.1%. In the post-hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy-THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II-III HER2-positive breast cancer.

Assessment accuracy of core needle biopsy for hormone receptors in breast cancer: a meta-analysis.

The concordance of hormone receptors (HR) status identified by core needle biopsy (CNB) compared with excisional biopsy (EB) has been widely reported, but results were extremely variable and underpowered. To derive a more precise estimation of assessment accuracy of CNB for HR in breast cancer, we conducted a meta-analysis of all eligible studies comparing concordance or disconcordance between CNB and EB for HR status. Eligible articles were identified by search of databases including PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database for the period up to November 2011, and the reference lists of identified studies, relevant reviews, meta-analyses, and abstracts from recent conference proceedings were reviewed as a augmented searching. Finally, a total of 21 articles involving 2,450 patients for estrogen receptor (ER) and 2,448 patients for progesterone receptor (PR) were included and analyzed in this analysis. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies checklist. The overall aggrement between CNB and EB were 92.8 % for ER (κ = 0.78) and 85.2 % for PR (κ = 0.66), indicating a good agreement in PR and a better result in ER. The pooled sensitivity and specificity were 97.3 % (95 % CI 96.0-98.2) and 82.0 % (95 % CI 68.2-90.6) for ER, and the corresponding values for PR were 92.3 % (95 % CI 88.2-95.1) and 76.5 % (95 % CI 64.6-85.3), respectively. The pooled positive likelihood ratios was 5.39 % (95 % CI 2.92-9.97) and the negative likelihood ratios was 0.03 % (95 % CI 0.02-0.05) for ER, the corresponding values for PR were 3.93 % (95 % CI 2.53-6.11) and 0.10 % (95 % CI 0.07-0.16), respectively. In summary, although a good agreement was observed between CNB and EB for both ER and PR, we still suggest that negative HR testing results should be interpreted with caution or repeated on EB.

Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy.

BACKGROUND: Biological molecular markers such as proto-oncogene erbB-2 (HER-2/neu, c-erbB-2), the CXC chemokine receptor 4 (CXCR4), estrogen receptor (ER), Proliferating Cell Nuclear Antigen (PCNA), DNA topoisomerase II (topo II), P-glycoprotein (P-gp) and glutathione S-transferase (GST) were observed for changes after administration of neochemotherapy and whether these protein expression changes were correlated with response to chemotherapy. METHODS: Sixty-four patients with primary breast cancer who had undergone neo-adjuvant chemotherapy were enrolled in the present study. The expressions of C-erbB-2, CXCR4 and ER-α were measured by immunohistochemistry (IHC) on full tissue sections and on tissue microarrays (TMAs). PCNA, TopoII, P-gp and GST were measured by IHC on TMAs. On the other hand, CXCR4, C-erbB-2 and ER-α expressions were detected using western blot analysis to 16 pairs of fresh preoperative core biopsies. The final surgical specimens were obtained from patients with breast carcinoma who received neo-adjuvant chemotherapy and obtained a partial response (PR). RESULTS: Our data demonstrated that the levels of C-erbB-2, CXCR4 and ER-α in patients decreased after they received neo-adjuvant chemotherapy on full tissue sections and on TMAs. The PCNA level was down-regulated after receiving neo-adjuvant chemotherapy, and no significant change was observed for TopoII, P-gp and GST. The levels of C-erbB-2, CXCR4 and ER-α were also down-regulated after neo-adjuvant chemotherapy was administered, as detected by western blot. In addition, the change expressions of C-erbB-2 and CXCR4 in specimens tended to be correlated with pathological change to neo-adjuvant chemotherapy on full tissue sections and on TMAs in a Pearson chi-square analysis. CONCLUSIONS: As demonstrated in our study, after breast cancer patients were treated with neo-adjuvant systemic therapy, decreased expressions of C-erbB2, ER-α and CXCR4 were observed. Down-regulated expressions of c-erbB-2 and CXCR4 may be a novel mechanism of chemotherapy; the changes of these objective markers may be useful in evaluating the clinical response of neo-adjuvant chemotherapy in breast cancer.

A Prospective Self-Controlled Study of Indocyanine Green, Radioisotope, and Methylene Blue for Combined Imaging of Axillary Sentinel Lymph Nodes in Breast Cancer.

PURPOSE: This self-controlled study aimed to clarify whether indocyanine green (ICG) could be an alternative tracer in the absence of radioisotope (RI) for combined imaging of axillary sentinel lymph node (SLN) in breast cancer. METHODS: Primary breast cancer, clinically axillary node-negative patients (n = 182) were prospectively enrolled from March 2015 to November 2020. ICG, methylene blue (MB), and RI were used to perform axillary sentinel lymph node biopsy (SLNB). The main observation index was the positivity of ICG + MB vs. RI + MB in axillary SLNB; the secondary observation indicators were the axillary SLN detection rate, mean number of axillary SLNs detected, mean number of metastatic axillary SLNs detected, and safety. RESULTS: All 182 patients had axillary SLNs; a total of 925 axillary SLNs were detected. Pathological examination confirmed metastatic axillary SLN in 42 patients (total of 79 metastatic SLNs). Positivity, detection rate of SLNs, detection rate of metastatic SLNs, and the number of metastatic SLNs detected were comparable with RI+MB and ICG+MB (p > 0.05). The mean number of axillary SLNs detected was significantly higher with ICG+MB than with RI+MB (4.99 ± 2.42 vs. 4.02 ± 2.33, p < 0.001). No tracer-related adverse events occurred. CONCLUSIONS: ICG appears to be a safe and effective axillary SLN tracer, and a feasible alternative to RI in combined imaging for axillary SLN of breast cancer.

Association of Long-term Oncologic Prognosis With Minimal Access Breast Surgery vs Conventional Breast Surgery.

Importance: Minimal access breast surgery (MABS) has been used in breast cancer management. However, long-term prognostic data associated with MABS vs conventional breast surgery (CBS) are lacking. Objective: To investigate long-term therapeutic outcomes associated with MABS vs CBS for breast cancer management. Design, Setting, and Participants: In this single-center retrospective cohort study, 9184 individuals were assessed for inclusion. After exclusions, 2412 adult female individuals were included who were diagnosed with stage 0 to III breast cancer, underwent unilateral breast surgery between January 2004 and December 2017, and had no distant metastasis or history of severe underlying disease. Propensity score matching was performed to minimize selection bias. Data were analyzed from January 1, 2004, to December 31, 2019. Exposures: MABS or CBS. Main Outcomes and Measures: Data on demographic and tumor characteristics and long-term outcomes were collected and analyzed. Results: This study included 2412 patients (100% female; median [IQR] age, 44 [40-49] years). Of these, 603 patients underwent MABS (endoscopic, endoscopy-assisted, or robot-assisted procedures in 289, 302, and 12 patients, respectively) and 1809 patients underwent CBS. The median follow-up time was 84 months (93 in the MABS group and 80 months in the CBS group). Intergroup differences were not significant for the following parameters: 10-year local recurrence-free survival (93.3% vs 96.3%; hazard ratio [HR], 1.39; 95% CI, 0.86-2.27; P = .18), regional recurrence-free survival (95.5% vs 96.7%; HR, 1.38; 95% CI, 0.81-2.36; P = .23), and distant metastasis-free survival (81.0% vs 82.0%; HR, 0.95; 95% CI, 0.74-1.23; P = .72). The 5-, 10-, and 15-year disease-free survival rates in the MABS group were 85.9%, 72.6%, and 69.1%, respectively. The corresponding rates in the CBS group were 85.0%, 76.6%, and 70.7%. The intergroup differences were not significant (HR, 1.07; 95% CI, 0.86-1.31; P = .55). The 5-, 10-, and 15-year overall survival rates in the MABS group were 92.0%, 83.7%, and 83.0%, respectively. The corresponding rates in the CBS group were 93.6%, 88.7%, and 81.0%. The intergroup differences were not significant (HR, 1.29; 95% CI, 0.97-1.72; P = .09). Post hoc subgroup analysis showed no significant intergroup differences in disease-free survival. Conclusions and Relevance: In this cohort study, long-term outcomes following MABS were not significantly different from those following CBS in patients with early-stage breast cancer. MABS may be a safe and feasible alternative in this patient population.

Breast cancer and Poland's syndrome: a case report and literature review.

Poland's syndrome is a rare congenital development malformation characterized by unilateral chest wall hypoplasia and ipsilateral hand abnormalities. It is also known to be associated with some malignant diseases. We herein report a case of Poland's syndrome associated with invasive ductal carcinoma of breast, and review the literatures to investigate the clinical characteristics of breast cancer with Poland's syndrome.