Label-free detection of invasive micropapillary carcinoma of the breast using multiphoton microscopy

Invasive micropapillary carcinoma of the breast (IMPC) is a rare form of breast cancer with unique histological features, and is associated with high axillary lymph node metastasis and poor clinical prognosis. Thus, IMPC should be diagnosed in time to improve the treatment and management of patients. In this study, multiphoton microscopy (MPM) is used to label-free visualize the morphological features of IMPC. Our results demonstrate that MPM images are well in agreement with hematoxylin and eosin staining and epithelial membrane antigen staining, indicating MPM is comparable to traditional histological analysis in identifying the tissue structure and cell morphology. Statistical analysis shows significant differences in the circumference and area of the glandular lumen and cancer nest between the different IMPC cell clusters with complete glandular lumen morphology, and also shows difference in collagen length, width, and orientation, indicating the invasive ability of different morphologies of IMPC may be different.     

Predicting the response of localised oesophageal cancer to neo-adjuvant chemoradiation

Background

One of the most exciting and talked about new surgical techniques in breast cancer surgery is the sentinel lymph node biopsy. It is an alternative procedure to standard axillary lymph node dissection, which makes possible less invasive surgery and side effects for patients with early breast cancer that wouldn't benefit further from axillary lymph node clearance. Sentinel lymph node biopsy helps to accurately evaluate the status of the axilla and the extent of disease, but also determines appropriate adjuvant treatment and long-term follow-up. However, like all surgical procedures, the sentinel lymph node biopsy is not appropriate for each and every patient.

Methods

In this article we review the absolute and relative contraindications of the procedure in respect to clinically positive axilla, neoadjuvant therapy, tumor size, multicentric and multifocal disease, in situ carcinoma, pregnancy, age, body-mass index, allergies to dye and/or radio colloid and prior breast and/or axillary surgery.

Results

Certain conditions involving host factors and tumor biologic characteristics may have a negative impact on the success rate and accuracy of the procedure. The overall fraction of patients unsuitable or with multiple risk factors that may compromise the success of the sentinel lymph node biopsy, is very small. Nevertheless, these patients need to be successfully identified, appropriately advised and cautioned, and so do the surgeons that perform the procedure.

Conclusion

When performed by an experienced multi-disciplinary team, the SLNB is a highly effective and accurate alternative to standard level I and II axillary clearance in the vast majority of patients with early breast cancer.     

Comparison of Clinicopathological Features and Treatments between Young (≤40 Years) and Older (>40 Years) Female Breast Cancer Patients in West China: A Retrospective,Epidemiological, Multicenter,Case Only Study

The incidence of young cases of breast cancer is higher in China compared to the western world. We aimed to explore differences in risk factors, clinicopathological features and treatment modes of young female breast cancer compared to older patients in West China. We collected clinical information from 12,209 female breast cancer patients in West China, including risk factors, clinicopathological features and treatment modes, from January 2010 to December 2012. Chi-square tests and the multivariate logistic regression analysis were applied for statistical analysis. There were 2,682 young (≤40 years) cases and 9,527 older cases at the time of breast cancer diagnosis. Young patients had a greater tumor diameter at diagnosis, and a higher probability of axillary lymph node and distant metastasis (P < 0.05). The progesterone receptor positive expression rate, estrogen receptor/progesterone receptor double positive expression rate, and human epidermal growth factor receptor 2 (HER2) negative expression rate was higher in young patients compared to older patients (P < 0.05). For young patients, the age at menarche was earlier, they had lower marriage rates, fewer pregnancies and births, and a lower breastfeeding rate (P < 0.05). A higher proportion of young patients underwent advanced operations, neoadjuvant and adjuvant chemotherapy, radiotherapy, and endocrine therapy compared to older patients (P < 0.05). We found significant differences in the clinicopathological features, risk factors and treatment modes between young (≤40 years) and older (>40 years) female breast cancer patients in West China. As some of these results differ from those found in the western female population, it is likely that the mechanism of tumorigenesis of young female breast cancer patients in West China may differ from that in western developed countries. Further investigation into the regional differences in breast cancer tumorigenesis is warranted.     

Letrozole versus tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy

Letrozole, a third generation aromatase inhibitor, has been compared with tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy. In a first-line trial in advanced disease, 939 post menopausal women were randomised double blind to receive treatment with letrozole 2.5 mg daily or tamoxifen 20 mg daily. Letrozole was significantly superior in terms of median time to progression (9.4 months versus 6.1 months, P = 0.0001), objective response (30% versus 20%, P = 0.0006), and clinical benefit (49% versus 38%, P = 0.0001). Superiority of letrozole was independent of disease site, receptor status, or prior adjuvant anti-oestrogen therapy. In an extended phase of this trial, 200 patients were crossed over to tamoxifen after letrozole, compared with 197 crossed over to letrozole after tamoxifen. Median overall survival was 34 months for letrozole versus 30 months for tamoxifen (not significant).

In a similar randomised double-blind neoadjuvant trial, 337 post menopausal patients with large ER/or PgR positive T2–T4 cancers, either requiring mastectomy or locally advanced, were randomised to preoperative letrozole or tamoxifen for 4 months prior to surgery. Overall response was 55% for letrozole versus 36% for tamoxifen (P < 0.001). Conservative surgery was possible in 45% of patients treated with letrozole versus 35% with tamoxifen (P = 0.022).

In both trials, both treatments were well tolerated with no significant differences in side effects.

These results indicate that letrozole is more active than tamoxifen both as neoadjuvant therapy and as first-line treatment in advanced disease. They support the importance of current adjuvant trials comparing the two treatments.     

Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer

The indication of neoadjuvant chemotherapy has been recently extended; it is now applied not only in locally advanced breast cancer but in primarily resecable tumours as well, in order to promote breast conservation. Based on recent clinical results, the reconsideration of traditional lymph node dissection in axillary staging is timely in patients receiving neoadjuvant chemotherapy. Precise axillary staging needs surgical removal of lymph nodes. Based on prospective randomised trials, sentinel lymph node biopsy appears to be appropriate for axillary staging even in tumours requiring neoadjuvant treatment. The extended indication of sentinel lymph node biopsy raises several questions and problems. In the present paper the authors review the results and possible limitations of sentinel lymph node biopsy in relation to neoadjuvant chemotherapy.     

初诊腋窝淋巴结阳性乳腺癌新辅助化疗后对腋窝淋巴结转阴性前哨活检的影响分析

摘要 目的：探究对初诊腋窝淋巴结阳性乳腺癌行新辅助化疗患者开展腋窝前哨淋巴结活检的临床意义。方法：选择2017年1月至2020年10月于我院接受改良根治术或保乳术治疗的100例初诊腋窝淋巴结阳性乳腺癌患者,将其中50例病理检测II B、III期行4~8个疗程新辅助化疗后实施前哨淋巴结活检患者设为研究组,将50例I、II A期直接行前哨淋巴结活检患者设为对照组,对比两组患者前哨淋巴结检出率、准确率、假阴性率和灵敏度,同时就患者病理特征与前哨淋巴结检出率的相关性开展分析。结果：（1）比较显示研究组患者与对照组患者在前哨淋巴结检出数、前哨淋巴结检出率以及前哨淋巴结假阴性率方面组间差异不大（P>0.05）;（2）病理学特征分析显示肿瘤直径以及临床N分期同新辅助化疗后患者前哨淋巴结检出阳性率密切相关（P<0.05）。结论：对初诊腋窝淋巴结阳性行新辅助化疗乳腺癌患者实施前哨淋巴结活检具有较显示的临床意义,能够较好的预测患者腋窝淋巴结状况,同时化疗前肿瘤直径、临床N分期是影响前哨淋巴结检出率的重要影响因素。     

Patterns of post-operative irradiation in breast cancer patients submitted to neoadjuvant chemotherapy

Background/AimPost-operative radiation therapy (PORT) is associated with improvement in loco-regional control and survival rates in early breast cancer. However, the evidence of benefit in patients after treatment with neoadjuvant chemotherapy (NAC) is poor. We aimed to assess the impact of the type of surgery in the PORT plan and the role of the PORT fields in clinical outcomes in breast cancer patients who had undergone NAC followed by surgery.Materials and methodsWe performed a retrospective analysis of all non-metastatic breast cancer patients treated between 2008 and 2014 at our institution who had received NAC and PORT.ResultsA total of 528 women were included of whom 396 were submitted to mastectomy or nipple-sparing/skin-sparing mastectomy. Most (92.8%) of the patients had locally advanced disease (clinical stage IIB to IIIC). All patients underwent irradiation for breast or chest wall. Most patients received PORT to the supraclavicular and axillary (levels II and III) nodes (87.1% and 86.4% for breast-conserving surgery and 95.1% and 93.8% for mastectomy and nipple-sparing/skin-sparing mastectomy, respectively). Irradiation of level I axillary and internal mammary nodes was uncommon. The disease-free survival and overall survival rates at 3 years were 72% and 85%, respectively. There were no statistically significant differences in clinical outcomes according to the use of nodal irradiation.ConclusionsAfter NAC, most patients received irradiation of the breast/chest wall and axillary and supraclavicular nodes. In this setting, PORT to breast/chest wall with or without regional nodal irradiation was safe and effective, with acceptable disease-free and overall survival rates reported in this high-risk population.     

Clinical management of secondary angiosarcoma after breast conservation therapy

Aim

The aim of this paper is to summarize the treatment outputs of secondary angiosarcoma after breast conservation therapy at St. Eizabeth Cancer Centre, Slovakia.

Background

Angiosarcoma of the breast is a rare but very aggressive malignant tumor of the vascular endothelium, characterized by rapidly proliferating and extensively infiltrating growth. Breast angiosarcoma may occur de novo, or as a complication of radiation therapy, or chronic lymphedema secondary to axillary lymph node dissection for mammary carcinoma. Radiotherapy in the treatment of breast cancer is associated with an increased risk of subsequent sarcoma.

Materials and methods

Retrospective study of medical records from the cancer databases was done in order to analyze the secondary breast angiosarcoma. This disease is an iatrogenic condition that warrants close follow-up and judicial use of radiotherapy in breast conserving therapy. Therefore, it is more prevalent in cases treated with radiotherapy, occurring especially in or adjacent to the radiation field. Clinical histories and follow-up data of identified patients after breast conservation therapy of invasive breast cancer were reviewed. In addition, a comprehensive literature review on diagnosis and treatment procedures was done in order to summarize state-of-the-art clinical approach.

Results and discussions

Three cases of secondary angiosarcoma after breast conservation therapy (BCT) were identified among 4600 patients treated at St. Elizabeth Cancer Institute during previous 16 years (1995–2011). Secondary breast angiosarcoma was diagnosed in a median period of 11 years following primary radiotherapy, median age at the time of diagnosis was 75 years. Surgical treatment consisted of radical mastectomy. The first patient, a 56-year-old woman received neoadjuvant chemotherapy (docetaxel + gemcitabin), second one (75 year) was treated by radiotherapy (TD 26 Gy, 2 Gy per fraction), since chemotherapy was not indicated. The last patient (80 year) got adjuvant chemotherapy (paclitaxel). Average follow up of the patients was 31 months. As of 31 July 2012, our patients were doing well without evidence of recurrent disease after treatment.

Conclusions

Angiosarcoma remains a difficult management problem with poor loco-regional and distal control. In our study, an overall incidence rate of secondary breast angiosarcoma is 0.065%. Although the prognosis for this disease is poor (typical survival period is 14.5–34 months with a 5-year survival rate of approximately 15%), all the three patients treated at our institute are alive and disease-free at the end of reported period. Finally, it is assumed that the use of breast conserving therapy will increase the incidence of post-irradiation angiosarcoma but the small difference in risk of subsequent sarcoma of the breast cancer patients receiving radiotherapy does not suppress its benefit.     

Beyond Axillary Lymph Node Metastasis,BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy

BackgroundTriple-negative breast cancers (TNBC) are a specific subtype of breast cancers with a particularly poor prognosis. However, it is a very heterogeneous subgroup in terms of clinical behavior and sensitivity to systemic treatments. Thus, the identification of risk factors specifically associated with those tumors still represents a major challenge. A therapeutic strategy increasingly used for TNBC patients is neoadjuvant chemotherapy (NAC). Only a subset of patients achieves a pathologic complete response (pCR) after NAC and have a better outcome than patients with residual disease.PurposeThe aim of this study is to identify clinical factors associated with the metastatic-free survival in TNBC patients who received NAC.MethodsWe analyzed 326 cT1-3N1-3M0 patients with ductal infiltrating TNBC treated by NAC. The survival analysis was performed using a Cox proportional hazard model to determine clinical features associated with prognosis on the whole TNBC dataset. In addition, we built a recursive partitioning tree in order to identify additional clinical features associated with prognosis in specific subgroups of TNBC patients.ResultsWe identified the lymph node involvement after NAC as the only clinical feature significantly associated with a poor prognosis using a Cox multivariate model (HR = 3.89 [2.42–6.25], p<0.0001). Using our recursive partitioning tree, we were able to distinguish 5 subgroups of TNBC patients with different prognosis. For patients without lymph node involvement after NAC, obesity was significantly associated with a poor prognosis (HR = 2.64 [1.28–5.55]). As for patients with lymph node involvement after NAC, the pre-menopausal status in grade III tumors was associated with poor prognosis (HR = 9.68 [5.71–18.31]).ConclusionThis study demonstrates that axillary lymph node status after NAC is the major prognostic factor for triple-negative breast cancers. Moreover, we identified body mass index and menopausal status as two other promising prognostic factors in this breast cancer subgroup. Using these clinical factors, we were able to classify TNBC patients in 5 subgroups, for which pre-menopausal patients with grade III tumors and lymph node involvement after NAC have the worse prognosis.     

乳腺癌患者的临床特征及其辅助治疗的影响因素分析

目的:探讨乳腺癌患者的临床病理特点及其辅助治疗的影响因素。方法:选取2009年1月~2012年2月我院收治的114例60岁以上的乳腺癌患者,按照年龄将其分为60~69岁组以及70岁以上组,对两组患者的临床特点、病例特点以及辅助治疗的模式进行对比分析。结果:两组患者在合并疾病、癌肿大小、病理学类型、受累淋巴结、以及雌孕激素受体阳性率、表皮生长因子2过度表达、肿瘤抑制基因P53阳性率以及Ki-67增殖指数等方面相比较,差异均无统计学意义(P0.05)。两组患者的手术治疗方式以及术后辅助化疗情况相比较,差异有统计学意义(P0.05)。多因素Logistic回归分析发现,年龄、淋巴结受累情况以及雌激素受体是否阳性成为术后辅助化疗主要考虑的因素。随诊2年,60~69岁组与70岁以上组患者的2年无复发生存率分别为88.89%(64/72)、92.86%(39/42),两组相比较,差异无统计学意义(P0.05)。结论:70岁以上的乳腺癌患者的临床特点与60~69岁的患者相比较无明显差异,目前,临床治疗采取的方法有所不同,但均能够达到较好的效果。年龄、淋巴结受累情况以及雌激素受体是否阳性成为医生考虑术后辅助化疗方案的主要因素。     

Modulation of Mutational Landscape in HER2-Positive Breast Cancer after Neoadjuvant Chemotherapy

IntroductionIn early-stage HER2 positive breast cancer (BC) patients, tumor response to neoadjuvant chemotherapy (NACT) predict survival outcomes. Patients achieving less than pathological complete response (pCR) have a worse prognosis, however, this group is heterogeneous. Nowadays limited data on predictive/prognostic biomarkers in patients with residual cancer disease are available.MethodsUsing next-generation sequencing technology, we evaluated a panel of 21 cancer genes in a group of HER2 positive BC patients with residual disease after NACT. A control group of patients who achieved the pCR was selected too. The BC mutational profile was analyzed on both the tumor diagnostic biopsy and matched residual disease.ResultsOverall, the detection rate of mutations was 79% in the No-pCR group versus 90% in the pCR cohort and 98% in the residual BC. The most mutated genes were TP53 and PIK3CA. No correlations between single gene mutations and survival outcomes were found. In no-pCR cohort, 52% of patients had different mutational profile after NACT, 69% of them had an increased in the number of mutated genes. Mutational profile changes from diagnostic biopsy to residual BC were a negative prognostic factor in term of relapse free survival: recurrence probability in different gene profile sub-group was 42% vs 0% in the same profile one (P = .019).ConclusionsTreatment selective pressure on tumor cells due to NACT changed the gene mutational profile in more than half of BC patient with residual tumor disease. Treatment-induced gene mutations significantly increase the risk of relapse. Profiling primary and residual BC is a major step in order to further personalized adjuvant treatment strategy.     

Clinicopathologic Factors Related to the Histological Tumor Grade of Breast Cancer in Western China: An Epidemiological Multicenter Study of 8619 Female Patients

BACKGROUND AND PURPOSE: Breast cancer is now recognized as a clinically heterogeneous disease with a wide spectrum of epidemiological and clinicopathologic features. We aimed to evaluate whether epidemiological and clinicopathologic features are associated with the histological tumor grade of breast carcinomas in Western China. METHODS: We retrospectively collected data from the Western China Clinical Cooperation Group and assessed associations between clinicopathologic factors and histological tumor grade in 8619 female breast cancer patients. Patients were divided into two groups: Group I (tumor grade I/II) and Group II (tumor grade III). Univariable analysis and multivariable logistic regression models were used to analyze the relationships between clinicopathologic factors and tumor grade. RESULTS: Patients presenting with positive axillary lymph nodes, large tumor size (>2?cm), lymphovascular invasion, hormone receptor negativity, human epidermal growth factor receptor 2 (HER-2) positivity, and triple negativity tended to have an increased risk of a high tumor grade. However, the number of pregnancies or births was inversely correlated with the risk of a high tumor grade. In addition, patients presenting with grade III tumors were more likely to receive aggressive treatment, such as adjuvant chemotherapy, anti–HER-2 therapy, and level III axillary lymph node dissection. CONCLUSIONS: Our results suggested that several clinicopathologic factors were associated with high tumor grade of breast cancer patients in Western China.     

Multiphoton tomography in differentiation of morphological and molecular subtypes of breast cancer: A quantitative analysis

In this study multiphoton tomography, based on second harmonic generation (SHG), and two-photon-excited fluorescence (TPEF) was used to visualize both the extracellular matrix and tumor cells in different morphological and molecular subtypes of human breast cancer. It was shown, that quantified assessment of the SHG based imaging data has great potential to reveal differences of collagen quantity, organization and uniformity in both low- and highly- aggressive invasive breast cancers. The values of quantity and uniformity of the collagen fibers distribution were significantly higher in low-aggressive breast cancer compared to the highly-aggressive subtypes, while the value representing collagen organization was lower in the former type. Additionally, it was shown, that TPEF detection of elastin fibers and amyloid protein may be used as a biomarker of detection the low-aggressive breast cancer subtype. Thus, TPEF/SHG imaging offers the possibility of becoming a useful tool for the rapid diagnosis of various subtypes of breast cancer during biopsy as well as for the intraoperative determinination of tumor-positive resection margins.     

新辅助化疗后腋窝病理完全缓解乳腺癌的预后分析

摘要 目的：研究乳腺癌患者新辅助化疗（NAC）后达到腋窝淋巴结病理完全缓解（pathologic complete response of axillary,apCR）的远期生存以及影响远期生存的相关因素分析。方法：回顾性分析哈尔滨医科大学附属肿瘤医院乳腺外科624例乳腺癌患者的住院资料,采用Kaplan-Meier生存分析以及COX回归分析的统计学分析方法,分析乳腺癌患者新辅助化疗后腋窝状态与无病生存（DFS）和总生存（OS）的关系及影响apCR预后的因素。结果：apCR与非apCR患者比较DFS（P=0.013）和OS（P=0.037）差异具有统计学意义,apCR患者的预后与年龄、肿瘤大小、肿瘤受体状态、HER-2、ki67状态、分子分型等因素无相关性。结论：与非apCR患者相比,乳腺癌患者新辅助化疗后apCR患者预后更好,但apCR患者预后良好的因素仍需进一步临床试验分析。     

Urinary pS2/TFF1 levels in the management of hormonodependent breast carcinomas

pS2/TFF1 overexpression in breast carcinomas correlates with response to hormonotherapy. We evaluated the clinical relevance of urinary pS2/TFF1 in breast cancer patients. In healthy controls (100 cases), it represents an individual and relatively stable parameter. Although 24 out 83 pre-operative breast cancer patients showed elevated levels, both the sensitivity and specificity of the test were too low for breast cancer screening. However, neoadjuvant hormonotherapy decreased pS2/TFF1 levels in nine out of 20 patients. Furthermore, among 22 patients receiving long-term adjuvant hormonotherapy, four exhibited elevated levels, two of them at the time of relapse. Thus, urinary pS2/TFF1 quantification might be suitable as an in vivo diagnosis for tumor hormonodependency, and disease follow-up during hormonotherapy.     

乳腺化生性癌的病理特征、复发和生存情况分析

目的:探讨乳腺化生性癌的病理特征、复发和生存情况。方法:选取我院于2002年1月至2015年12月期间收治的7例乳腺化生性癌患者临床病历资料进行回顾性分析,讨论乳腺化生性癌的病理特点和鉴别诊断、组织起源以及治疗预后等。结果:7例乳腺化生性癌PR、ER和HER-2均显示为阴性,广谱CK则显示为阳性;所有入选患者均显示EGFR阳性,其中有3例患者显示p53阳性,4例患者显示CK5/6阳性。此外,3例患者经腋窝淋巴结清扫后显示有2例患者出现腋窝淋巴结转移,4例患者经前哨淋巴结活检后结果:显示无癌转移。结论:乳腺化生性癌在临床上属于乳腺癌中较为罕见的亚型,其生物学行为和生存预后均不佳,HER-2和PR、ER等多显示为阴性,容易复发,目前主要治疗方法:为在手术治疗的基础上加以放射治疗。     

Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population

In the Kingdom of Saudi Arabia (KSA), breast cancer constitutes 18% of all cancers in Saudi women. Whilst locally advanced breast cancer disease is unusual in Western countries, it constitutes more than 40% of all non-metastatic breast cancer in KSA. The relative frequency of locally advanced disease among our breast cancer population and the lack of a uniform consensus in the literature about its optimal management have prompted this retrospective analysis of the medical records of patients with Stage III breast cancer patients seen at King Faisal Specialist Hospital and Research Center between 1981 and 1991. In all, 315 patients were identified. Their median age ±SD was 46±11.6 years which is distinctly different from the 60–65 years median age in industrial Western nations. Most patients were younger than 50 years (64%) and premenopausal (62%). Patients were approximately equally divided between Stage III A and Stage III B Patients received multimodality treatment, including surgery., adjuvant chemotherapy, tamoxifen, and adjuvant radiotherapy. Sixty-one patients were excluded from survival analysis as they were considered lost to follow-up. Of the remaining 254 patients, 73 (29%) were alive and disease free, and 18 patients (7%) were alive but, with evidence of the disease. The remaining 163 (64%) had died from breast cancer or its related complications. Their median overall survival (OS) was 54 months, (95%, Cl, 27 to 121 months) and the median progression-free survival (PFS) was 28.8 months (95% Cl, 14.2 to 113 months). Cox proportional hazard, model identified Stage III B and the number of positive axillary lymph nodes as poor predictors of OS and PFS. Radiotherapy was the only adjuvant modality that affected survival favourably. The prognosis of patients with Stage III disease remains poor despite the use of a multimodality approach. The overall young age of our patients may have contributed to the poor outcome. Moreover, the adverse effect of Stage III B disease (as compared with Stage III A) and axillary nodal status was evident. Whilst the favourable effect of radiotherapy on survival was demonstrated, the lack of independent efficacy of other modalities (adjuvant chemotherapy and tamoxifen) or the apparent deleterious effect of neoadjuvant chemotherapy should be addressed with discretion in such retrospective analysis. Optimal management of patients with locally advanced breast cancer disease should be appraised in well designed, prospective, randomised studies.     

乳腺癌腋窝淋巴结转移患者应用多普勒超声与CT的诊断价值比较

摘要 目的：探讨乳腺癌腋窝淋巴结转移患者应用多普勒超声与CT的诊断价值比较。方法：回顾性分析2017年3月至2019年3月我院接诊的60例经过手术病理证实的乳腺癌患者。比较多普勒超声与128排螺旋CT在乳腺癌腋窝淋巴结转移中的检出率、声像特征比较及两组灵敏度、特异度、准确度。结果：在术后经过病理证实的60例乳腺癌手术患者中,有38例为腋窝淋巴结转移,有22例未腋窝淋巴结转移,在多普勒超声诊断结果对乳腺癌腋窝淋巴结转移诊断中,36例得到确诊,在128排螺旋CT诊断中,30例得到确诊;多普勒超声皮质向心性生长、淋巴结内钙化灶、淋巴结横直径比值及淋巴结边界模糊检出率均显著高于128排螺旋CT检出率,差异显著（P＜0.05）;将病理结果作为金标准。多普勒超声灵敏度、特异度、准确度均比128排螺旋CT结果高,两组方式比较具有显著差异（P＜0.05）。结论：多普勒超声在乳腺癌腋窝淋巴结转移中诊断价值高,可帮助临床提供正确诊断,以选择合适的治疗方案。     

Distinguishing metastatic triple‐negative breast cancer from nonmetastatic breast cancer using second harmonic generation imaging and resonance Raman spectroscopy

Triple‐negative breast cancer (TNBC) is an aggressive subset of breast cancer that is more common in African‐American and Hispanic women. Early detection followed by intensive treatment is critical to improving poor survival rates. The current standard to diagnose TNBC from histopathology of biopsy samples is invasive and time‐consuming. Imaging methods such as mammography and magnetic resonance (MR) imaging, while covering the entire breast, lack the spatial resolution and specificity to capture the molecular features that identify TNBC. Two nonlinear optical modalities of second harmonic generation (SHG) imaging of collagen, and resonance Raman spectroscopy (RRS) potentially offer novel rapid, label‐free detection of molecular and morphological features that characterize cancerous breast tissue at subcellular resolution. In this study, we first applied MR methods to measure the whole‐tumor characteristics of metastatic TNBC (4T1) and nonmetastatic estrogen receptor positive breast cancer (67NR) models, including tumor lactate concentration and vascularity. Subsequently, we employed for the first time in vivo SHG imaging of collagen and ex vivo RRS of biomolecules to detect different microenvironmental features of these two tumor models. We achieved high sensitivity and accuracy for discrimination between these two cancer types by quantitative morphometric analysis and nonnegative matrix factorization along with support vector machine. Our study proposes a new method to combine SHG and RRS together as a promising novel photonic and optical method for early detection of TNBC.     

Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study

BackgroundIn patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study.Methods and findingsWe prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient’s tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients’ tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/− adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing.ConclusionsWe confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM.Trial registrationACTRN12612000345886.