Primary Systemic Treatment Research Articles

Abstract P3-12-08: The role of neo-bioscore staging system in guiding the optimal strategies for regional nodes irradiation following primary systemic treatment in breast cancer patients with cN1 and ypN0-1

Abstract Purpose: Following primary systemic treatment (PST), the optimal strategies for regional nodal irradiation (RNI) are currently under active investigation, especially in patients with pretreatment cN1 and posttreatment ypN0-1. The Neo-Bioscore staging system has showed promising prospect in assessing prognosis after PST. In this analysis, we evaluate the role of Neo-Bioscore staging system in guiding RNI following PST in patients with cN1 and ypN0-1. Methods and Materials: Continuous women with cN1 pretreatment and who received PST with ypN0 or ypN1 posttreatment between 2009 and 2014 were retrospectively reviewed. According to the report by Mittendorf et al, the Neo-Bioscore staging system is on the basis of pretreatment clinical stage, posttreatment pathologic stage, estrogen receptor (ER) status, HER2 status and grade stage, and assigned and summed points for each factor as shown in. A pathologic complete response (pCR) was defined as no invasive disease in the breast or regional lymph nodes after surgery. The curves for survival were generated using the Kaplan-Meier method and compared using the Log-rank test. Point Assignments for the Neo-Bioscore Staging SystemsFactorsPointsClinical stage I0IIA0IIB1IIIA1IIIB2IIIC2Pathologic stage 00I0IIA1IIB1IIIA1IIIB1IIIC2Tumor Biomarker ER negative1HER2 negative1Grade 31 Results: One hundred and sixty-three patients were enrolled in this study, of them 18 patients received breast conserving surgery. Of the 163 patients, 119 (73%) received RNI. At surgery, 36 patients (22.1%) achieved pCR, while 89 patients (54.6%) achieved ypN0. The median follow-up was 59.4 months (rang: 16-106). In the whole cohort, RNI was associated with non-significant improved outcomes, with a 5-year locoregional recurrence free survival (LRRFS) rate of 98.6% vs. 95.7% (P=0.393), a regional recurrence free survival (RRFS) rate of 98% vs. 97.7% (P=0.865), a 5-year distant metastasis free survival (DMFS) rate of 91.6% vs. 83.4% (P=0.052), a 5-year any first recurrence free survival (RFS) rate of 90.9% vs. 87.4% (P=0.43), and a 5-year overall survival (OS) rate of 98% vs. 91.9% (P=0.097) in the RNI and non-RNI group, respectively. In the subgroup of patients with Neo-Bioscore score of 1 to 3, RNI significantly increased the 5-year DMFS rate of 97% vs. 76.9% (P=0.002), 5-year RFS rate of 95.5% vs. 76.9% (P=0.007) and 5-year OS rate of 100% vs. 89.2% (P=0.005). However, no significant difference in outcomes was found between RNI and non-RNI group in patients with Neo-Bioscore score of 4 to 6. Among patients who not achieved pCR and those with ypN1, RNI significantly increased DMFS (both P<0.05). Conclusions: Not all patients with cN1 and ypN0-1 could significantly benefit from RNI following PST, those with low Neo-Bioscore score were likely to benefit more. Citation Format: Cao L, Chen J-Y. The role of neo-bioscore staging system in guiding the optimal strategies for regional nodes irradiation following primary systemic treatment in breast cancer patients with cN1 and ypN0-1 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-08.

Abstract P6-02-16: The efficacy of preoperative pathological features to improve diagnosis accuracy in lymph node metastasis by axillary ultrasound

Abstract Purpose Recently a sentinel lymph node biopsy has been a part of standard surgical procedure instead of an axillary dissection with a mastectomy for breast cancers. It is necessary to make an accurate diagnosis of lymph node metastasis for deciding surgical procedure either a sentinel lymph node biopsy or an axillary dissection. Preoperative ultrasound is one of widely used tools to make a diagnosis of sentinel lymph node. This study presents results regarding preoperative pathological features to improve diagnosis accuracy of sentinel lymph node by preoperative axillary ultrasound. Materials and methods One doctor performed preoperative ultrasound. He used HITACHI HI VISION Ascendus. Axillary lymph node metastasis was suspected when these findings were observed such as partial thickening of lymph node cortex, loss of lymph nodes' hilum, circular swelling shape change and difference compared to a contralateral axillary lymph node. When we suspected axillary lymph node metastasis, we performed fine needle aspiration cytology except other findings such as CT, MRI or physical appearance showed obvious axillary lymph node metastasis. Preoperative core needle biopsies were performed to determine pathologic types and hormone characters. Clinical cases such that ductal carcinoma in situ, lobular carcinoma and ones with primary systemic treatment (neoadjuvant therapy) were excluded from statistical analysis. Results During a study period between April 2015 and December 2017, altogether 662 patients were participated in this study. 304 cases were analyzed by statistical analysis. 268 cases were diagnosed as negative and 36 case as positive in axillary lymph node metastasis by preoperative ultrasound. In the 268 cases 225 cases were diagnosed as negative by sentinel lymph node biopsy during operations (84.0%) but 43 cases were diagnosed as positive (16.0%). 23% cases included less than 20mm micro metastasis (10/43). To investigate correlation between false negative ratio of axillary lymph node metastasis diagnosed by an ultrasound and preoperative pathological features such as hormone receptor, HER2, Ki-67, nuclear grade and subtypes (Luminal, Her2 and triple negative). The false negative ratio was 17.0% vs 11.1% in hormone receptor (positive vs negative, p = 0.434), 14.5% vs 16.0% in HER2 (positive vs negative, p = 0.887), 15.4% vs 19.1% in Ki-67 (<20% vs ≥20%, p = 0.441), 18.4% vs 9.38% in nuclear grade (1 vs 2 and 3, p = 0.997), 11.3% vs 23.8% vs 16.7% vs 16.7% (Luminal A vs Luminal B vs Her2 vs triple negative, p>0.05). Conclusion There were no statistical significant difference between the axillary lymph node metastasis diagnosed by an ultrasound and the preoperative pathological features. However cases categorized in Luminal B by preoperative pathology had relatively high false negative ratio of axillary lymph node metastasis diagnosed by an ultrasound. It is necessary to investigate a way to improve diagnosis accuracy of sentinel lymph node by a preoperative axillary ultrasound. Citation Format: Koike R, Fujita T, Sata N, Shiozawa M, Miyazaki C, Sakuragi M, Shiba S, Tanaka Y. The efficacy of preoperative pathological features to improve diagnosis accuracy in lymph node metastasis by axillary ultrasound [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-16.

Abstract ES9-3: Triple negative breast cancer: Current and future directions in metastatic patients

Abstract Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) with both early and metastatic disease. The poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets and other approaches to treat these patients. Massively parallel sequencing and other 'omics' technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 'BRCAness', as well as a subgroup with a high degree of tumor-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. Additional data from trials with antibody drug conjugates have yielded promising results. We discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities. Citation Format: Chang J. Triple negative breast cancer: Current and future directions in metastatic patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES9-3.

Stereotactic Radiosurgery for Multiple Brain Metastases.

To give an overview on the current evidence for stereotactic radiosurgery of brain metastases with a special focus on multiple brain metastases. While the use of stereotactic radiosurgery in patients with limited brain metastases has been clearly defined, its role in patients with multiple lesions (> 4) is still a matter of controversy. Whole-brain radiation therapy (WBRT) has been the standard treatment approach for patients with multiple brain lesions and is still the most commonly used treatment approach worldwide. Although distant brain failure is improved by WBRT, the overall survival is not readily impacted. As WBRT is associated with significant neurocognitive decline compared to stereotactic radiosurgery (SRS), SRS has been explored and increasingly utilized for selected patients with multiple brain metastases. Recent clinical data indicated the feasibility of stereotactic radiosurgery to multiple brain metastases with a similar survival in patients with more than 4 brain metastases versus patients with a maximum of 4 brain metastases. Also, neurocognitive function and quality of life was maintained after stereotactic radiosurgery which is essential in a palliative setting. The application of stereotactic radiosurgery with Gamma Knife, Cyberknife, or LINAC-based equipment has emerged as an effective and widely available treatment option for patients with limited brain metastases. Although not formally proven in prospective studies, SRS may also be considered as a safe and effective treatment option in selected patients with multiple brain metastases. Especially in patients with a favorable prognosis, survival over several years is observed also in the setting of multiple BM. For these patients, avoidance of the neurocognitive damage of WBRT is desirable, and SRS is often a more appropriate treatment in the current multimodality treatment of BM in which systemic treatment is often the cornerstone of the treatment. For patients with an intermediate (3-12months) and poor prognosis (< 3months), the application of WBRT becomes more and more controversial, because of its acute side effects, such as hair loss and fatigue and, thereby, detrimental effect on quality of life. For these patients, best supportive care, primary systemic treatment, and even SRS may be preferred over WBRT on an individualized patient basis.

Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote chemoresistance by activating the NF-\u03baB pathway in breast cancer cells

BackgroundChemotherapy is the primary established systemic treatment for patients with breast cancer, especially those with the triple-negative subtype. Simultaneously, the resistance of triple-negative breast cancer (TNBC) to chemotherapy remains a major clinical problem. Our previous study demonstrated that the expression levels of PTN and its receptor PTPRZ1 were upregulated in recurrent TNBC tissue after chemotherapy, and this increase was closely related to poor prognosis in those patients. However, the mechanism and function of chemotherapy-driven increases in PTN/PTPRZ1 expression are still unclear.MethodsWe compared the expression of PTN and PTPRZ1 between normal breast and cancer tissues as well as before and after chemotherapy in cancer tissue using the microarray analysis data from the GEPIA database and GEO database. The role of chemotherapy-driven increases in PTN/PTPRZ1 expression was examined with a CCK-8 assay, colony formation efficiency assay and apoptosis analysis with TNBC cells. The potential upstream pathways involved in the chemotherapy-driven increases in PTN/PTPRZ1 expression in TNBC cells were explored using microarray analysis, and the downstream mechanism was dissected with siRNA.ResultsWe demonstrated that the expression of PTN and PTPRZ1 was upregulated by chemotherapy, and this change in expression decreased chemosensitivity by promoting tumour proliferation and inhibiting apoptosis. CDKN1A was the critical switch that regulated the expression of PTN/PTPRZ1 in TNBC cells receiving chemotherapy. We further demonstrated that the mechanism of chemoresistance by chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis depended on the NF-κB pathway.ConclusionsOur studies indicated that chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis play a critical role in chemoresistance, which suggests a novel strategy to enhance chemosensitivity in breast cancer cells, especially in those of the triple-negative subtype.

Patterns of Regression in Breast Cancer after Primary Systemic Treatment.

Despite national guidelines, the evaluation of effects of primary systemic treatment (PST) in breast cancer is a complex challenge. Our aims were to evaluate the response patterns focusing on correlations of radiological and pathological tumor size, regression heterogeneity in different molecular subtypes, cellularity changes and the incidence of enlarged, multinucleated neoplastic cells related to therapy. Slides of pretreatment biopsies and resection specimens of consecutive cases were reevaluated focusing on heterogeneity of regression per whole slide, and 40x or 100x magnification fields. Alteration in cellularity and the presence of multinucleated tumor giant cells were noted. The correlation of pathological and radiological sizes and their alterations were analyzed by Spearman rank correlation. The present study included 106 tumors. A decrease in size (84.9%) and cellularity (76.4%) was noted in all molecular subtypes. Inhomogeneous regression was found in 45.3%, with minor inhomogeneity in the majority. Scatter pattern regression was seen only in 8 cases (7.5%). Significant correlations were found between the pathological and radiological sizes (p = 0.02), and between the alterations of cellularity and pathological and radiological size (p = 0.04; p = 0.03, respectively). Multinucleated tumor giant cells were noted in 17.9% (n = 19), nearly exclusively in cases treated with PST including taxanes. Regression inhomogeneity following PST is present in about half of the cases, and is not related to molecular subtypes. The evaluation of the maximum area of the tumor bed is recommended for the proper evaluation of regression. Multinucleated tumor giant cells are related to PST including taxane derivate, and may cause upgrading.

Should CARMENA Really Change our Attitude Towards Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma? A Systematic Review and Meta-Analysis Evaluating Cytoreductive Nephrectomy in the Era of Targeted Therapy.

Cytoreductive nephrectomy in metastatic renal cell carcinoma (mRCC) patients has been common clinical practice due to evidence that resection of the primary tumor results in a survival benefit regardless of systemic treatment. Recently, the first large phase III randomized, non-inferiority prospective clinical trial evaluating this surgical approach demonstrated that systemic treatment alone was not inferior to primary surgery plus systemic treatment. Our aim was to evaluate if cytoreductive nephrectomy results in a survival benefit over systemic treatment alone in patients with mRCC and in specific subgroups, including patients with brain metastases, poor performance status, poor prognosis according to IMDC or MSKCC criteria, and clear cell and non-clear cell histologies. We identified 16 published studies providing complete data for the comparison between cytoreductive nephrectomy + systemic treatment versus systemic treatment alone, and selected 9 for subgroup analysis. The inverse variance technique was applied for the meta-analysis of hazard ratios (HR), and, due to the intrinsic heterogeneity of the data, we adopted a random effects model. Risk of bias among the studies was estimated by the Newcastle-Ottawa Scale (NOS). Our analysis suggested a survival benefit for patients receiving cytoreductive nephrectomy (pooled HR of 0.48, 95% confidence interval of 0.42-0.56) in the overall population. Survival advantages were also observed in patients with clear cell and non-clear renal cell carcinoma, while no benefit was evident in patients with brain metastasis, poor performance status, and poor risk. Cytoreductive nephrectomy seems to result in a survival benefit in both clear cell and non-clear cell histology, while no survival advantage was found in patients with specific clinical features. Despite a high level of heterogeneity, our results highlight the importance of a good selection of patients to whom a primary surgical approach could be proposed.

Radioactive Iodine-Refractory Differentiated Thyroid Cancer in the Elderly.

Current treatment approach for DTC includes surgery, thyroid-stimulating hormone (TSH) suppression, radioactive iodine, external beam radiotherapy, or systemic treatments such as kinase inhibitors. Radioactive iodine therapy (RAI) is the primary first-line systemic treatment for advanced DTC. However, during the course of treatment, the tumor may become refractory to RAI. Elderly patients are more likely to be diagnosed with advanced disease that can be refractory to RAI. The advent of TKIs (tyrosine kinase inhibitors) and their usage in RAI refractory disease has shown improved progression-free survival. These agents are, however, associated with increased toxicity. The variable nature of disease and toxicity associated with the systemic therapy makes it important to have an individualized approach to management, especially in the elderly population who can be more susceptible to toxicities.

CD73: a new biomarker in triple-negative breast cancer

Triple-negative breast cancer (TNBC) constitute 10–20% of all breast cancers and are characterized by the lack of hormone receptors (estrogen and progesterone receptors) and HER2/neu expression (1). TNBC are not eligible to hormonotherapy and Herceptin/trastuzumab targeted therapy and are generally associated with poor clinical outcome (2). Anthracycline/taxane-based neoadjuvant chemotherapy is the primary systemic treatment but resistance to this treatment is common and the identification of new potential therapeutic molecules is required to improve the outcome of TNBC patients.

Evaluation at 3 years of concurrent bevacizumab and radiotherapy for breast cancer: Results of a prospective study

PurposeTo determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy. Material and methodsThis is a single-arm, multicentre, prospective study, of the toxicity of adjuvant concomitant association of bevacizumab and radiotherapy in patients with breast cancer. Toxicity was assessed by the Common Terminology Criteria for Adverse Events version 3.0 during the radiotherapy and follow-up clinics at 12 and 36 months after its completion. The study was designed to evaluate the toxicity at one year, 3 years and 5 years. ResultsSixty-four patients were included from October 2007 to August 2010. All of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases after primary systemic treatment). All patients received non-fractionated radiotherapy to breast or chest wall with or without irradiation of regional lymph nodes. Early toxicity has been previously reported. Median follow-up was 46.4 months (range: 18–77 months). Median age was 53 years old (range: 23–68 years). The 3-years overall survival was 93% (range: 87–100%). Evaluation of the toxicity at 3 years was available for 67% of the patients. There was a low rate of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2% grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4 toxicity was observed. No patient had a left ventricular ejection fraction below 50% at 3 years. ConclusionsConcurrent bevacizumab with locoregional radiotherapy is associated with acceptable 3-years toxicity in patients with breast cancer.

Outcome of postmastectomy radiotherapy after primary systemic treatment in patients with clinical T1-2N1 breast cancer

PurposeThe role of postmastectomy radiotherapy following primary systemic treatment in patients with clinical T1-2N1 breast cancer remains a controversial issue. The purpose of this study was to evaluate the benefit of postmastectomy radiotherapy following primary systemic treatment. Patients and methodsBetween 2005 and 2012, in two independent institutions, female patients with T1-2N1 breast cancer receiving primary systemic treatment followed by mastectomy and lymph node dissection because bad response, then treated with or without chest wall and regional lymph node irradiation have been studied retrospectively. The patients received normofractionated radiotherapy using 3D conformal photons or electron techniques. Locoregional recurrence-free survival, distant metastasis-free survival and disease-free survival were calculated using Kaplan-Meier method. Univariate analysis of potential prognostic factors was performed using log-rank test. ResultsEighty-eight patients have been studied. Of them, 75 patients received postmastectomy radiotherapy. At surgery, 53 patients achieved ypN0. Median follow-up was 67 months. Postmastectomy radiotherapy significantly improved locoregional recurrence-free survival, with a 5-year rate of 96.9% versus 78.6% in the group that did not have postmastectomy radiotherapy. In the subgroup of 53 patients achieving ypN0, postmastectomy radiotherapy improved locoregional recurrence-free survival (a 5-year rate of 94.7% vs. 72.9%), distant metastasis-free survival (a 5-year rate of 92.8% vs. 75%) and disease-free survival (a 5-year rate of 92.9% vs. 62.5%). By univariate analysis, postmastectomy radiotherapy was the only significant prognostic factor affecting locoregional recurrence-free survival. ConclusionsFor patients with clinical T1-2N1 disease, postmastectomy radiotherapy could significantly improve locoregional recurrence-free survival after primary systemic treatment and be even more therapeutic in the subgroup of patients with good response for primary systemic treatment by improving locoregional recurrence-free, distant metastasis-free and disease-free survival. Larger prospective studies are needed to confirm our findings.

Response to primary systemic treatment and its influence on the extent of subsequent axillary surgery – Single center experience

Introduction: Primary systemic treatment (PST) in selected breast cancer (BC) patients has become more common in the last decade. We evaluated the influence of PST on the extent of subsequent axillary surgery.

Response to primary systemic treatment by tumor type and its effect on the extent of the subsequent breast surgery – Single center experience

Introduction: Primary systemic treatment (PST) in selected breast cancer (BC) patients has become more common in the last decade. We evaluated the effect of PST on the extent of subsequent breast surgery.

Psychological Stress and Coping Resources during Primary Systemic Therapy for Breast Cancer. Results of a Prospective Study.

Introduction This prospective study reports on the impact of psychological factors on women with primary breast cancer undergoing neoadjuvant chemotherapy. These women are in a special situation, where they not only have to deal with the shock of the cancer diagnosis but also with the fact that the malignant tumor will not be removed immediately but only after completing chemotherapy. A situation like this is stressful and requires a personal strength which not every woman may have. Methods In a prospective study 53 patients were assessed using various psychological and psycho-oncological questionnaires which aimed to evaluate their psychological stress and their coping resources. The women were evaluated before starting systemic treatment (t-1) and again immediately after completing chemotherapy but prior to surgery (t-2). The patients were also asked about their coping strategies at t-1 and t-2. Using the Ulm Coping Manual (UCM) the interviews were rated by independent assessors blinded to the respective patient's medical data. Patients were followed up for 3.7-5.5 years after completing chemotherapy. Results Patients with poor psychosocial adjustment to the situation were identified prior to starting treatment (at t-1). The social coping strategies of these women were found to be inadequate. Their coping behavior was characterized by resignation and they did not attempt to seek social support. This was found to increase their overall risk of recurrence or of developing another type of malignancy during the follow-up period. The study also identified patients who coped significantly better with primary systemic treatment by strengthening their coping strategies. Conclusion Careful psychological screening of women's vulnerabilities or strengths immediately after the diagnosis and prior to any oncological treatment is strongly recommended. This would help to identify those patients early on who will require additional psycho-oncological support due to their psychological vulnerability.

Abstract P2-01-07: Selective elimination of axillary surgery after primary systemic treatment in clinically node-positive breast cancer patients by combining PET/CT and the MARI procedure (marking the axilla with radioactive iodine seeds)

Abstract Background The increasing use of primary systemic treatment (PST) for patients with breast cancer enables more breast conserving surgery. In addition, PST converts node-positive into node-negative disease in 20-40% of patients. However, the current guidelines still recommend axillary lymph node dissection (ALND) for clinical node-positive disease (cN+), even if it became node-negative after PST, since false-negative rates of sentinel lymph node biopsy after PST range from 5-30%. Recently, an alternative technique has been introduced to stage the axilla after PST: the MARI-procedure (sensitivity 97%; FNR 7%), in which a tumour-positive lymph node is marked with a radioactive iodine seed before the start of PST and selectively removed after PST. In the present study, we propose a new strategy for treatment of the axilla in cN+ patients by combining results of the pre-PST PET/CT with the post-PST MARI-procedure. Material and methods All patients who received a MARI-procedure from July 2014 until May 2016 were included. Before the start of PST a PET/CT was performed for axillary staging and the detection of distant metastasis. A radioactive iodine seed was placed in a proven tumour-positive axillary lymph node (MARI-node), after which PST was given according to Dutch national guidelines. At our institute, we have implemented a protocol in which results of the pre-PST PET/CT and the post-PST MARI-procedure determine the type of axillary treatment. Patients with 1-3 positive axillary lymph nodes (ALNs) on PET/CT and a tumour-negative MARI-node receive no further axillary treatment. Patients with ≤3 positive ALNs on PET/CT and a tumour-positive MARI-node receive axillary radiotherapy, as well as patients with &amp;gt;3 positive ALNs on PET/CT and a tumour-negative MARI-node. An ALND is only performed in patients with &amp;gt;3 positive ALNs on PET/CT and a tumour-positive MARI-node. Results In total 168 patients received a PET/CT and a MARI procedure, of whom 43% were hormone receptor positive, 28% triple negative and 29% Her2-positive. One hundred and eight patients (64%) showed ≤ 3 and 60 patients (36%) &amp;gt;3 suspected ALNs on PET/CT before the start of PST. The axillary pathologic complete response was 39%. In 134 patients (80%) an ALND was omitted; of these patients 94 (56%) were treated with axillary radiotherapy and 40 patients (24%) received no further axillary treatment. In 34 patients (20%) an ALND was performed (Table 1). The median number of positive additional nodes at ALND was 5 (range 0-16). During a median follow-up of 6 months there were no local recurrences. Axillary treatmentSuspective ALNs on PET/CTOutcome MARIAxillary Treatment NoneRadiotherapyALND + Radiotherapy≤3Negative40-- Positive-68-&amp;gt;3Negative-26- Positive--34Total409434ALN: axillary lymph nodes; ALND: axillary lymph node dissection; MARI: Marking the Axilla with Radioactive Iodine Seeds Conclusion Combining pre-PST axillary staging with PET/CT and post-PST staging with use of the MARI-procedure results in a reduction of 80% of axillary lymph node dissections in breast cancer patients with clinical node-positive disease. Citation Format: van der Noordaa MEM, Straver M, van Duijnhoven FH, Groen E, Stokkel M, Vrancken Peeters M-JTFD. Selective elimination of axillary surgery after primary systemic treatment in clinically node-positive breast cancer patients by combining PET/CT and the MARI procedure (marking the axilla with radioactive iodine seeds) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-07.

37. Selective elimination of axillary surgery after primary systemic treatment in clinically node-positive breast cancer patients by combining PET/CT and the MARI procedure (Marking the Axilla with Radioactive Iodine Seeds)

37. Selective elimination of axillary surgery after primary systemic treatment in clinically node-positive breast cancer patients by combining PET/CT and the MARI procedure (Marking the Axilla with Radioactive Iodine Seeds)

250. Towards omitting breast cancer surgery in selective patient groups: Assessment of pathologic complete response after primary systemic treatment using multiple biopsies ‘The MICRA trial’

250. Towards omitting breast cancer surgery in selective patient groups: Assessment of pathologic complete response after primary systemic treatment using multiple biopsies ‘The MICRA trial’

Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with T2 to T4, N0 and N1 breast cancer

BackgroundHistological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. MethodsIn this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. ResultsThe SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0–96.3%) and a false-negative rate of 14.0% (95% CI = 6.3–25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2–93.7%), an accuracy of 94.9% (95% CI = 90.3–97.8%) and a negative predictive value of 92.7% (95% CI = 86.1–96.8%). ConclusionIdentification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered.

Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.

Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) in both the early and advanced-stages of the disease. The lack of targeted therapies and the poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets to treat patients with these tumours. Massively parallel sequencing and other 'omics' technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 'BRCAness', the presence of the androgen receptor, and several rare genomic alterations. Whether these alterations are molecular 'drivers', however, has not been clearly established. A subgroup of TNBCs shows a high degree of tumour-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. In this Review, we discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities derived from these data.

Efficacy of primary tumor resection for metastatic colorectal cancer with unresectable metastases: a Meta analysis

Objective To evaluate the efficacy and safety of primary tumor resection for metastatic colorectal cancer with unresectable metastases. Methods Database including PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedicine and Wanfang Database were searched with the key words of asymptomatic, primary, resection, metastatic, stage Ⅳ, cancer, colon, colorectal, rectal, 无症状性, 原发灶切除, 转移性, 4期(Ⅳ期), 结直肠癌, 结肠癌, 直肠癌between the database establishment and August 2015. Literatures about primary tumor resection or systemic treatment as first-line treatment for asymptomatic patients with unresectable metastatic colorectal cancer were retrieved, and data were extracted and evaluated by 2 independent researchers. Patients with primary tumor resection as first-line treatment were allocated to the primary tumor resection group and patients with systemic treatment as first-line treatment were allocated into the systemic treatment group. The overall survival rate and median survival time were compared between the 2 groups. The incidence of perioperative complications and mortality in the primary tumor resection group as well as the incidences of intestinal obstruction and emergency operation in the systemic treatment group were evaluated. Survival data were presented by the odds ratio (OR) and 95% confidence interval (CI). Single rate data were presented as rate (r) and 95%CI. The median survival time was analyzed using the mean difference (MD) and 95%CI. Heterogeneity of the publication was analyzed using the I2 test. Results Ten retrospective control studies including 1 434 patients were retrieved. There were 770 patients in the primary tumor resection group and 664 patients in the systemic treatment group. The results of Meta analysis showed that overall survival rate of patients in the primary tumor resection group was better than that in the systemic treatment group (OR=1.35, 95 %CI: 1.01-1.79, P<0.05), and there was a longer median survival time of 3.8 months in the primary tumor resection group (MD=3.78, 95% CI: 3.60-3.97, P<0.05). The incidence of perioperative complications and mortality in the primary tumor resection group were 22% (95%CI: 0.13-0.30) and 1% (95%CI: 0.00-0.03), respectively. The incidences of intestinal obstruction and emergency surgery were 18% (95%CI: 0.14-0.21) and 11% (95%CI: 0.06-0.16) in the systemic treatment group, respectively. Conclusions For asymptomatic patients with unresectable metastatic colorectal cancer, resection of the primary tumor is safe and feasible, and it can improve the overall survival rate of patients and median survival time. The incidence of intestinal obstruction is higher among asymptomatic patients who do not receive primary tumor resection. Key words: Colorectal neoplasms; Unresectable metastases; Primary tumor resection; Meta-analysis