Systemic Therapy For Breast Cancer Research Articles

Neoadjuvant Therapy for Breast Cancer: Updates and Proceedings From the Seventh Annual Meeting of the Canadian Consortium for Locally Advanced Breast Cancer

Therapy for breast cancer involves a complex interplay of three main treatment modalities: surgery, systemic therapy, and radiation therapy. The Canadian Consortium for Locally Advanced Breast Cancer (LABC) was established with the goal to convene a strong multidisciplinary team of breast oncology clinicians and scientists who are dedicated to the advancement of LABC research and treatment, with a vision to drive progress through increased collaboration across disciplines and throughout Canada. The most recent meeting in May 2017 highlighted the latest evidence and literature about the optimal use of neoadjuvant systemic therapy in breast cancer. There is a need for increased clinical and scientific collaboration and the development of guidelines for the use of emerging treatment strategies. The interactive meeting sessions fostered unique opportunities for academic debate and nurtured collaboration between the attendees.

Validation of CPS+EG, Neo-Bioscore, and modified Neo-Bioscore staging systems after preoperative systemic therapy of breast cancer: Protocol of a retrospective multicenter cohort study in China.

Prognostic assessment after preoperative systemic therapy (PST) is critical to develop a therapeutic strategy for breast cancer management. Currently, a clinical–pathologic staging system that incorporates ER status and nuclear grading (CPS + EG), and the Neo‐Bioscore system that includes HER2 status into CPS + EG, are used to predict outcomes in patients with breast cancer after PST. While HER2‐positive is recognized as a favorable factor in the Neo‐Bioscore system based on results in patients administered one year of trastuzumab as anti‐HER2 therapy, most HER2‐positive cases have difficulty accessing anti‐HER2 treatment in China. Therefore, it is crucial that a modified Neo‐Bioscore staging system is developed that incorporates an additional factor of poor prognosis, HER2‐positive status without trastuzumab treatment, to determine accurate prognosis. We propose a retrospective multicenter cohort study in China to validate CPS + EG, Neo‐Bioscore, and the modified Neo‐Bioscore system and determine the accuracy of prediction. Primary breast cancer patients without metastasis treated with PST and surgery in academic institutions or hospitals of provincial level in China will be included. Disease‐free, disease specific, and overall survival will be calculated using the Kaplan–Meier Method, stratified by CPS + EG, Neo‐Bioscore, and the modified Neo‐Bioscore staging system. Areas under the curve of each staging system will be calculated. Multivariate analysis using Wald testing and maximum likelihood estimates in a Cox proportional hazards model will be conducted.

Progress in adjuvant systemic therapy for breast cancer.

The prognosis of patients with early stage breast cancer has greatly improved in the past three decades. Following the first adjuvant endocrine therapy and chemotherapy trials, continuous improvements of clinical outcomes have been achieved through intense therapeutic escalation, albeit with increased health-care costs and treatment-related toxicities. In contrast to the advances achieved in surgery or radiotherapy, the identification of the patient subgroups that will derive clinical benefit from therapeutic escalation has proved to be a daunting process hindered by a lack of collaboration between scientific groups and by the pace of drug development. In the past few decades, initiatives towards de-escalation of systemic adjuvant treatment have achieved success. Herein, we summarize attempts to escalate and de-escalate adjuvant systemic treatment for patients with breast cancer and argue that new, creative trial designs focused on patients' actual needs rather than on maximizing drug market size are needed. Ultimately, the adoption of effective treatments that do not needlessly expose patients and health-care systems to harm demands extensive international collaboration between academic groups, governments, and pharmaceutical companies.

Impact of pathology reporting times on decision-making for neoadjuvant systemic therapy in breast cancer

Impact of pathology reporting times on decision-making for neoadjuvant systemic therapy in breast cancer

The experience of the usage of intraoperative radiation therapy after neoadjuvant systemic therapy for breast cancer.

e12621Background: to evaluate the usage of intraoperative radiation therapy with the INTRABEAM device in breast cancer patients after neoadjuvant therapy when conservative surgery is allowed. Metho...

Institutional practice patterns for the use of neoadjuvant systemic therapy for breast cancer: A retrospective analysis.

e12637Background: Neoadjuvant systemic therapy (NAST) has traditionally been used in patients (pts) with locally advanced breast cancer (LABC). An increasing number of pts with early-stage operable...

Validation of the CPS+EG and Neo-Bioscore staging systems after preoperative systemic therapy for breast cancer in a single center in China

BackgroundPrognostic assessment after preoperative systemic therapy (PST) plays a vital role in determining treatment in breast cancer patients. Many researchers have sought to develop a system to quantitate residual tumor and its correlation with prognosis after PST. This retrospective study validated the CPS + EG staging system and Neo-Bioscore in a single center in China. MethodsData from patients with non-metastatic primary breast cancer who were treated with PST and surgery from Jan. 2008 to Dec. 2014 at the Breast Disease Center of Peking University First Hospital, China, were reviewed. DFS, DSS and OS were calculated using the K-M curve and AUC. Multivariate analysis was used for a Cox proportional hazards model. All calculations were performed with SAS 9.4. ResultsA total of 403 patients were enrolled in this study. The median follow-up period was 45 (range 11–107) months. The five-year DFS, DSS and OS rates were 86.4%, 91.2% and 90.5%, respectively. The CS, PS, CPS + EG staging system and Neo-Bioscore stratified patients according to DFS, DSS, and OS after PST, with all P values < 0.0001. The CPS + EG staging system and Neo-Bioscore stratified prognosis after PST better than CS. HER2-positive patients without trastuzumab treatment had obviously worse DFS and OS than other subgroups with different HER2 statuses that scored a 3 in the Neo-Bioscore system. ConclusionsThe CPS + EG staging system and Neo-Bioscore can improve prognostic prediction in non-pCR breast cancer patients after PST and, provided unfavorable prognostic factors such as insufficient treatment are incorporated, will have broader clinical applicability.

Role of cooperative groups and funding source in clinical trials supporting guidelines for systemic therapy of breast cancer.

IntroductionClinical research is conducted by academia, cooperative groups (CGs) or pharmaceutical industry. Here, we evaluate the role of CGs and funding sources in the development of guidelines for breast cancer therapies.ResultsWe identified 94 studies. CGs were involved in 28 (30%) studies while industry either partially or fully sponsored 64 (68%) studies. The number of industry funded studies increased over time (from 0% in 1976 to 100% in 2014; p for trend = 0.048). Only 10 (11%) government or academic studies were identified. Studies conducted by GCs included a greater number of subjects (median 448 vs. 284; p = 0.015), were more common in the neo/adjuvant setting (p < 0.0001), and were more often randomized (p = 0.018) phase III (p < 0.0001) trials. Phase III trial remained significant predictor for CG-sponsored trials (OR 7.1 p = 0.004) in a multivariable analysis. Industry funding was associated with higher likelihood of positive outcomes favoring the sponsored experimental arm (p = 0.013) but this relationship was not seen for CG-sponsored trials (p = 0.53).Materials and MethodsASCO, ESMO, and NCCN guidelines were searched to identify systemic anti-cancer therapies for early-stage and metastatic breast cancer. Trial characteristics and outcomes were collected. We identified sponsors and/or the funding source(s) and determined whether CGs, industry, or government or academic institutions were involved. Chi-square tests were used for comparison between studies.ConclusionsIndustry funding is present in the majority of studies providing the basis for which recommendations about treatment of breast cancer are made. Industry funding, but not CG-based funding, was associated with higher likelihood of positive outcomes in clinical studies supporting guidelines for systemic therapy.

Taste and smell perception and quality of life during and after systemic therapy for breast cancer

PurposeThe purpose of the study was to assess self-reported taste and smell perception after chemotherapy in breast cancer patients compared with women without cancer, and to assess whether taste and smell perception is associated with quality of life after the end of chemotherapy.MethodsWe included 135 newly diagnosed breast cancer patients who completed chemotherapy and 114 women without cancer. Questionnaires on taste, smell, and quality of life were completed shortly after and 6 months after chemotherapy (patients) or at two moments with 6 months’ time window in between (comparisons).ResultsSelf-reported taste and smell perception were significantly lower in patients shortly after chemotherapy compared to the comparison group. Most patients recovered 6 months after chemotherapy, although patients who were still receiving trastuzumab then reported a lower taste and smell perception compared to patients who were not. A lower self-reported taste and smell were statistically significantly associated with a worse quality of life, social, emotional, and role functioning shortly after chemotherapy. Six months after chemotherapy, taste and smell were statistically significantly associated with quality of life, social and role functioning, but only in patients receiving trastuzumab.ConclusionsMost taste and smell alterations recovered within 6 months after the end of chemotherapy for breast cancer, but not for patients receiving trastuzumab. These results highlight the importance of monitoring taste and smell alterations during and after treatment with chemotherapy and trastuzumab, as they may impact quality of life.

Abstract GS1-01: Increasing the dose density of adjuvant chemotherapy by shortening intervals between courses or by sequential drug administration significantly reduces both disease recurrence and breast cancer mortality: An EBCTCG meta-analysis of 21,000 women in 16 randomised trials

Abstract Background: Much contemporary adjuvant chemotherapy uses conventional 3-weekly scheduling. Yet, cytokinetic modelling suggests that increasing the dose density of cytotoxic therapy by shortening the intervals between courses, or by using sequential rather than concurrent treatment schedules may enhance efficacy.1 At least 15 randomised trials have directly tested this hypothesis and this meta-analysis by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) brings together the worldwide evidence to clarify the balance of risks and benefits of dose-dense chemotherapy. Methods: Individual patient data were provided for 98% (21,537/21,944) of women randomised in relevant trials: 7 randomised trials (10,004 women, 2240 breast cancer recurrences, 1481 breast cancer deaths) that compared 2-weekly dose-dense chemotherapy versus the same chemotherapy given 3-weekly, and 9 trials (11,533 women, 2773 breast cancer recurrences, 1711 breast cancer deaths) that compared sequential with concurrent anthracycline and taxane-based chemotherapy. Primary outcomes were time to recurrence and breast cancer mortality. Results: Highly significant reductions in disease recurrence [rate ratio (RR)=0.83 (95%CI 0.76-0.91), p=0.00004] were seen with 2-weekly compared with 3-weekly chemotherapy, and 10 year breast cancer mortality was 3.0% lower [16.7% vs 19.7%: RR=0.85 (95% CI 0.76-0.95), p=0.003]. Overall survival was also improved [RR=0·86 (95% CI 0·78−0·95), p=0.003]. Similarly, for sequential versus concurrent taxane plus anthracycline chemotherapy the rate ratio for disease recurrence was 0.86 (95% CI 0.79-0.93, p=0.0001), 10-year breast-cancer mortality was 2.3% lower [19.2% vs 21.5%: RR=0.87 (95% CI 0.79-0.96), p=0.005], and overall survival was improved [RR=0·85 (0·78−0·94), p=0.0008]. The proportional reductions in recurrence with dose-dense chemotherapy were similar and highly significant (both p&amp;lt;0.002) in ER-positive and in ER-negative disease, and did not differ significantly by any other patient or tumour characteristics, including age, HER2 status, nodal status, tumour size, or grade. Increasing dose density did not have any material adverse effect on non-breast-cancer mortality, which was similar with 2-weekly and with 3-weekly chemotherapy [RR=0·93 (95% CI 0·74−1·17), p=0.6] and was if anything lower with sequential than with concurrent chemotherapy [RR=0·73 (95% CI 0·55−0·97), p=0.03]. Trial publications also indicate that, with haematopoietic growth factor support, dose-dense chemotherapy does not substantially increase toxicity. Conclusion: Increasing the dose density of adjuvant chemotherapy is safe and results in fewer disease recurrences and fewer deaths from breast cancer. Reference: 1 Norton, L. Evolving concepts in the systemic therapy of breast cancer. Seminars in Oncology, 1997: S10-3 – S10-10. Citation Format: Gray R, Bradley R, Braybrooke J, Davies C, Pan H, Peto R, Bliss J, Cameron D, Mackey J, Del Mastro L, Swain S, Untch M, Bergh J, Pritchard K, Norton L, for the EBCTCG. Increasing the dose density of adjuvant chemotherapy by shortening intervals between courses or by sequential drug administration significantly reduces both disease recurrence and breast cancer mortality: An EBCTCG meta-analysis of 21,000 women in 16 randomised trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS1-01.

Expression of NK Cell Surface Receptors in Breast Cancer Tissue as Predictors of Resistance to Antineoplastic Treatment

Background:Currently, one of the most used strategies for the treatment of newly diagnosed patients with breast cancer is neoadjuvant chemotherapy based on the application of taxanes and anthracyclines. However, despite the high number of patients who develop a complete pathological clinical response, resistance and relapse following this therapy continue to be a clinical challenge. As a component of the innate immune system, the cytotoxic function of Natural Killer (NK) cells plays an important role in the elimination of tumor cells. However, the role of NK cells in resistance to systemic therapy in breast cancer remains unclear. The present project aims to evaluate the gene expression profile of human NK cells in breast cancer tissue resistant to treatment with taxanes–anthracyclines.Methods:Biopsies from tumor tissues were obtained from patients with breast cancer without prior treatment. Histopathological analysis and ex vivo exposure to antineoplastic chemotherapeutics were carried out. Alamar blue and lactate dehydrogenase release assays were performed for quantitative analysis of tumor viability. Gene expression profiles from tumor tissues without prior exposure to therapeutic drugs were analyzed by gene expression microarrays and verified by polymerase chain reaction.Results:A significant decrease in gene expression of cell-surface receptors related to NK cells was observed in tumor samples resistant to antineoplastic treatment compared with those that were sensitive to treatment.Conclusion:A decrease in NK cell infiltration into tumor tissue might be a predictive marker for failure of chemotherapeutic treatment in breast cancer.

MP-4 - A major breakthrough in systemic therapy for breast cancer over the fifteen years

MP-4 - A major breakthrough in systemic therapy for breast cancer over the fifteen years

Neoadjuvant systemic therapy in breast cancer: use and trends in radiotherapy practice.

The use of neoadjuvant systemic therapy (nast) in the treatment of breast cancer is increasing, and the role of adjuvant radiation therapy (rt) in that setting is uncertain. We sought to review and report the use of nast, its trends over time, and its relationship with the prescribing patterns of locoregional rt in a provincial cancer system. Patients with stages i-iii breast cancer diagnosed during 2007-2012 were identified using a provincial database. Patient, tumour, and treatment characteristics were extracted. Multivariable logistic regression analyses were used to assess associations with the use of nast. Kaplan-Meier and Cox regression were used for survival analyses. Of the 11,658 patients who met the inclusion criteria, 602 (5%) had received nast. Use of nast was more frequent in stage iii patients (53%) than in stages i and ii patients (2%). In clinically lymph-node positive patients, a pathology assessment was made approximately 50% of the time. Higher clinical tumour stage and increasing clinical nodal stage predicted for increasing use of nast and of nodal rt after nast, but pathologic nodal status after nast was not associated with use of nodal rt. A statistically significant survival difference was observed between patients in the nast and no-nast groups, but that significance disappeared in a multivariable Cox regression analysis. This population-based study demonstrated 5% use of nast for breast cancer. Most patients received nodal rt after nast, and nodal rt was not associated with pathologic stage after nast. Findings likely reflect the realities of clinical practice and show that reliance on clinical nodal staging results in outcomes similar to those reported in the literature.

Neoadjuvant systemic therapy for breast cancer: the Westmead experience.

Neoadjuvant systemic therapy (NAST) can be used to treat breast cancer. Pathologic complete response (pCR) is a surrogate marker for improved survival. This study examined response in the breast and axilla to NAST and identified features associated with pCR. Patients undergoing NAST and surgery between January 2012 and June 2016 by surgeons at Westmead Breast Cancer Institute were identified. Patients with inflammatory or metastatic disease were excluded. Data were analysed to identify factors predictive of pCR. Ninety-one patients were identified. Mean age was 49 years. Forty-one patients had axillary metastases identified prior to NAST. Eighty-three patients received chemotherapy alone, six endocrine therapy alone and two had both. Thirty-seven patients had mastectomy and 54 had breast-conserving surgery. The overall breast pCR rate was 29% higher in patients with triple-negative (50%) or HER2-positive (39%) disease and lower in luminal disease (11.6%, P = 0.001). Forty percent of node-positive patients became node negative. The only variable associated with pCR was tumour biology. Patients with HER2-positive breast cancer were more likely to have axillary pCR than those with luminal cancer (odds ratio: 28, P = 0.00005). pCR in either the breast or axilla was most likely to be achieved in patients with HER2-positive or triple-negative breast cancers. In patients with luminal cancers, the goal of NAST is best considered to facilitate surgical options rather than obtaining a pCR.

1431P - Primary results of a study to evaluate a decision aid for women offered neoadjuvant systemic therapy for breast cancer

1431P - Primary results of a study to evaluate a decision aid for women offered neoadjuvant systemic therapy for breast cancer

Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials

We hypothesized that increased baseline BMI and BMI change would negatively impact clinical outcomes with adjuvant breast cancer systemic therapy. Data from chemotherapy trials MA.5 and MA.21; endocrine therapy MA.12, MA.14 and MA.27; and trastuzumab HERA/MA.24 were analyzed. The primary objective was to examine the effect of BMI change on breast cancer-free interval (BCFI) landmarked at 5 years; secondary objectives included BMI changes at 1 and 3 years; BMI changes on disease-specific survival (DSS) and overall survival (OS); and effects of baseline BMI. Stratified analyses included trial therapy and composite trial stratification factors. In pre-/peri-/early post-menopausal chemotherapy trials (N = 2793), baseline BMI did not impact any endpoint and increased BMI from baseline did not significantly affect BCFI (P = 0.85) after 5 years although it was associated with worse BCFI (P = 0.03) and DSS (P = 0.07) after 1 year. BMI increase by 3 and 5 years was associated with better DSS (P = 0.01; 0.01) and OS (P = 0.003; 0.05). In pre-menopausal endocrine therapy trial MA.12 (N = 672), patients with higher baseline BMI had worse BCFI (P = 0.02) after 1 year, worse DSS (P = 0.05; 0.004) after 1 and 5 years and worse OS (P = 0.01) after 5 years. Increased BMI did not impact BCFI (P = 0.90) after 5 years, although it was associated with worse BCFI (P = 0.01) after 1 year. In post-menopausal endocrine therapy trials MA.14 and MA.27 (N = 8236), baseline BMI did not significantly impact outcome for any endpoint. BMI change did not impact BCFI or DSS after 1 or 3 years, although a mean increased BMI of 0.3 was associated with better OS (P = 0.02) after 1 year. With the administration of trastuzumab (N = 1395) baseline BMI and BMI change did not significantly impact outcomes. Higher baseline BMI and BMI increases negatively affected outcomes only in pre-/peri-/early post-menopausal trial patients. Otherwise, BMI increases similar to those expected in healthy women either did not impact outcome or were associated with better outcomes. CAN-NCIC-MA5; National Cancer Institute (NCI)-V90-0027; MA.12-NCT00002542; MA.14-NCT00002864; MA.21-NCT00014222; HERA, NCT00045032;CAN-NCIC-MA24; MA-27-NCT00066573.

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications.

Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC.

PEARLY: A randomized, multicenter, open-label, phase III trial comparing anthracyclines followed by taxane versus anthracyclines followed by taxane plus carboplatin as (neo)adjuvant therapy in patients with early triple-negative breast cancer.

TPS587 Background: Triple-negative breast cancer (TNBC) is an aggressive tumor with poor prognosis. There are no molecular targets for TNBC, and there is an unmet need to provide new drugs to patients with TNBC. Platinum agents are known to have an anti-tumor activity in TNBC, especially in BRCA-mutated tumor. Addition of carboplatin significantly increased pathologic complete response rates with neoadjuvant chemotherapy in recent randomized studies. There are no data about adjuvant role of carboplatin for TNBC in a randomized trial. Methods: PEARLY is a randomized, multicenter, open-label, phase III trial comparing anthracyclines followed by taxane versus anthracyclines followed by taxane plus carboplatin as (neo)adjuvant therapy in patients with triple-negative breast cancer (TNBC). Patients with stage II or III TNBC who need adjuvant or neoadjuvant chemotherapy were included. Any prior systemic therapy for breast cancer was not allowed. Bilateral, metastatic, and inflammatory breast cancer are excluded. A total of 840 patients will be enrolled for 3 years. Patients were randomized 1:1, stratified based on the node positivity (N0 vs N+), institution, treatment setting (neoadjuvant vs. adjuvant), and BRCA mutation status (positive vs. negative). Standard arm treatment consists of doxorubicin 60 mg/m2 IV + cyclophosphamide 600 mg/m2 IV every 3 weeks for 4 cycles followed by taxane treatment (paclitaxel 80 mg/m2 IV weekly for 12 doses or docetaxel 75mg/m2 IV every 3 weeks for 4 cycles). Experimental arm added carboplatin AUC5 IV every 3 weeks for 4 cycles during taxane treatment. The primary objective was to evaluate 5-year event free survival (EFS) rate. Secondary objectives included overall survival, distant recurrence free survival, pathologic complete response, and tolerability. The analysis is planned at 248 EFS events, which provides approximately 80% power to detect superiority of standard treatment plus carboplatin versus standard treatment using a log-rank test, assuming a hazard ratio of 0.7 at a two sided alpha of 0.05. Data is expected in 2023. Clinical trial information: NCT02441933.

Editorial: Primary Systemic Therapy for Breast Cancer

Editorial: Primary Systemic Therapy for Breast Cancer

Highlights from the 15th St Gallen International Breast Cancer Conference 15-18 March, 2017, Vienna: tailored treatments for patients with early breast cancer.

The 15th St Gallen International Breast Cancer Conference was held in Vienna for the second time, from 15th–18th March 2017. 4000 people from 105 countries all over the world were invited to take part in the event. The real highlight of the conference was the last day with the International Consensus Session which was chaired by around 50 experts on breast cancer worldwide. With reference to data from scientific research, the consensus panel tried to offer guidelines for the management of breast cancer with the aim of providing patients with optimal treatment. The topics covered focused on the treatment of breast cancer, consideration of surgery, radiotherapy, neo-adjuvant, and adjuvant systemic therapy for breast cancer, as well as genetics and prevention of breast cancer.In particular, in terms of precision medicine, an important topic of the conference was ‘is it possible to think that it could become routine in clinical practice to use immunotherapy and targeted therapy based on genetic signatures?’In view of personalised therapy, it is important to take into consideration women’s treatment preferences. It is also important not only to offer guidelines which help breast cancer experts all over the world to choose the proper treatment for women with breast cancer but also to discuss the pros and cons of the therapy with the patient. This allows for a better understanding of the disease.‘From the maximum tolerable to the minimum effective treatment: it is essential to escalate treatment when necessary and to de-escalate when unnecessary’. These few words could summarise the meaning of the 15th St Gallen International Breast Cancer Conference. Prof Martine Piccart-Gebhart was awarded with the St Gallen International Breast Cancer Award 2017 for her fundamental clinical research contribution and Prof Giuseppe Curigliano with the Umberto Veronesi Memorial Award which aims to recognise a physician’s leading role in advancing the science and care of breast cancer patients. Curigliano, in his lecture, spoke about the revolutionary immunotherapy in the clinical management of breast cancer (BC). For the development of these therapies, it is necessary to identify the genetic determinants of BC immune phenotypes in which The Cancer Genome Atlas (TCGA) has contributed towards this.For example, the T helper (Th-1) phenotype (ICR4), which also exhibits upregulation of immune-regulatory transcripts (eg. PDL1, PD1, FOXP3, IDO1, and CTLA4), was associated with prolonged patients’ survival. Chromosome segment 4q21, which includes genes encoding the Th-1 chemokines CXCL9-11, was significantly amplified only in the immune favourable phenotype (ICR4). The mutation and neo-antigen load progressively decreased from ICR4 to ICR1 but could not explain immune phenotypic differences. Mutations of TP53 were enriched in the immune favourable phenotype (ICR4). Instead, the presence of MAP3K1 and MAP2K4 mutations were closely associated with an immune unfavourable phenotype (ICR1). Using both the TCGA and the validation dataset, the degree of MAPK deregulation segregates BC according to their immune disposition. These findings suggest that mutational-driven deregulation of MAPK pathways is linked to the negative regulation of intratumoural immune response in BC.The main themes of this congress were: 1) Surgery of the primary tumour and margins; 2) Surgery of the axilla; 3) Radiotherapy: hypofractionated, ‘boost’ to tumour bed, partial breast, regional node, after mastectomy, advanced technology; 4) Pathology: subtypes, TILs; 5) Multi-gene signatures and therapy; 6) Endocrine therapy: pre- and post-menopausal and duration; 7) Chemotherapy: subtypes, stages; 8) Anti-HER-2 therapy; 9) Neo-adjuvant therapy; 10) Adjuvant bisphosponates; 11) Adjuvant diet and exercise.