Search

Enrichment analysis from TCGA RNA-seq and RPPA data comparing CREBBPaltered versus wild-type patients.

Supplementary Figures and legends

Triple-negative breast cancers (TNBC) are resistant to standard-of-care chemotherapy and lack known targetable driver gene alterations. Identification of novel drivers could aid the discovery of new treatment strategies for this hard-to-treat patient population, yet studies using high-throughput and accurate models to define the functions of driver genes in TNBC to date have been limited. Here, we employed unbiased functional genomics screening of the 200 most frequently mutated genes in breast cancer, using spheroid cultures to model in vivo–like conditions, and identified the histone acetyltransferase CREBBP as a novel tumor suppressor in TNBC. CREBBP protein expression in patient tumor samples was absent in 8% of TNBCs and at a high frequency in other tumors, including squamous lung cancer, where CREBBP-inactivating mutations are common. In TNBC, CREBBP alterations were associated with higher genomic heterogeneity and poorer patient survival and resulted in upregulation and dependency on a FOXM1 proliferative program. Targeting FOXM1-driven proliferation indirectly with clinical CDK4/6 inhibitors (CDK4/6i) selectively impaired growth in spheroids, cell line xenografts, and patient-derived models from multiple tumor types with CREBBP mutations or loss of protein expression. In conclusion, we have identified CREBBP as a novel driver in aggressive TNBC and identified an associated genetic vulnerability in tumor cells with alterations in CREBBP and provide a preclinical rationale for assessing CREBBP alterations as a biomarker of CDK4/6i response in a new patient population.Significance:This study demonstrates that CREBBP genomic alterations drive aggressive TNBC, lung cancer, and lymphomas and may be selectively treated with clinical CDK4/6 inhibitors.

Supplementary Materials and Methods

Gender disparities in scientific publications have been identified in oncological research. Oral research presentations at major conferences enhance visibility of presenters. The share of women presenting at such podia is unknown. We aim to identify gender‐based differences in contributions to presentations at two major oncological conferences. Abstracts presented at plenary sessions of the American Society of Clinical Oncology (ASCO) Annual Meetings and European Society for Medical Oncology (ESMO) Congresses were collected. Trend analyses were used to analyze female contribution over time. The association between presenter's sex, study outcome (positive/negative) and journals' impact factors (IFs) of subsequently published papers was assessed using Chi‐square and Mann–Whitney U tests. Of 166 consecutive abstracts presented at ASCO in 2011–2018 (n = 34) and ESMO in 2008–2018 (n = 132), 21% had female presenters, all originating from Northern America (n = 17) or Europe (n = 18). The distribution of presenter's sex was similar over time (p = 0.70). Of 2,425 contributing authors to these presented abstracts, 28% were women. The proportion of female abstract authors increased over time (p, What's new? Presenting one's research at a conference is a great way to get your name and ideas heard within the professional community. In this study, the authors investigated how often women served as presenters at plenary sessions of ASCO Annual Meetings and ESMO Congresses. Looking through 166 abstracts over a period of 8 years, they found that 21% had female presenters, while 28% of study authors were female. Lack of visibility for female researchers at conferences can slow their career progress, and greater representation should be encouraged.

Triple-negative breast cancers (TNBC) are resistant to standard-of-care chemotherapy and lack known targetable driver gene alterations. Identification of novel drivers could aid the discovery of new treatment strategies for this hard-to-treat patient population, yet studies using high-throughput and accurate models to define the functions of driver genes in TNBC to date have been limited. Here, we employed unbiased functional genomics screening of the 200 most frequently mutated genes in breast cancer, using spheroid cultures to model in vivo–like conditions, and identified the histone acetyltransferase CREBBP as a novel tumor suppressor in TNBC. CREBBP protein expression in patient tumor samples was absent in 8% of TNBCs and at a high frequency in other tumors, including squamous lung cancer, where CREBBP-inactivating mutations are common. In TNBC, CREBBP alterations were associated with higher genomic heterogeneity and poorer patient survival and resulted in upregulation and dependency on a FOXM1 proliferative program. Targeting FOXM1-driven proliferation indirectly with clinical CDK4/6 inhibitors (CDK4/6i) selectively impaired growth in spheroids, cell line xenografts, and patient-derived models from multiple tumor types with CREBBP mutations or loss of protein expression. In conclusion, we have identified CREBBP as a novel driver in aggressive TNBC and identified an associated genetic vulnerability in tumor cells with alterations in CREBBP and provide a preclinical rationale for assessing CREBBP alterations as a biomarker of CDK4/6i response in a new patient population. Significance: This study demonstrates that CREBBP genomic alterations drive aggressive TNBC, lung cancer, and lymphomas and may be selectively treated with clinical CDK4/6 inhibitors.

High computational cost associated with digital pathology image analysis approaches is a challenge towards their translation in routine pathology clinic. Here, we propose a computationally efficient framework (SuperHistopath), designed to map global context features reflecting the rich tumor morphological heterogeneity. SuperHistopath efficiently combines i) a segmentation approach using the linear iterative clustering (SLIC) superpixels algorithm applied directly on the whole-slide images at low resolution (5x magnification) to adhere to region boundaries and form homogeneous spatial units at tissue-level, followed by ii) classification of superpixels using a convolution neural network (CNN). To demonstrate how versatile SuperHistopath was in accomplishing histopathology tasks, we classified tumor tissue, stroma, necrosis, lymphocytes clusters, differentiating regions, fat, hemorrhage and normal tissue, in 127 melanomas, 23 triple-negative breast cancers, and 73 samples from transgenic mouse models of high-risk childhood neuroblastoma with high accuracy (98.8%, 93.1% and 98.3% respectively). Furthermore, SuperHistopath enabled discovery of significant differences in tumor phenotype of neuroblastoma mouse models emulating genomic variants of high-risk disease, and stratification of melanoma patients (high ratio of lymphocyte-to-tumor superpixels (p = 0.015) and low stroma-to-tumor ratio (p = 0.028) were associated with a favorable prognosis). Finally, SuperHistopath is efficient for annotation of ground-truth datasets (as there is no need of boundary delineation), training and application (~5 min for classifying a whole-slide image and as low as ~30 min for network training). These attributes make SuperHistopath particularly attractive for research in rich datasets and could also facilitate its adoption in the clinic to accelerate pathologist workflow with the quantification of phenotypes, predictive/prognosis markers.

Summary The purpose of this study was to improve the prognostic value of tumour histopathology image analysis methodology by image preprocessing. Key image qualities were modified including contrast, sharpness and brightness. The texture information was subsequently extracted from images of haematoxylin/eosin-stained tumour tissue sections by GLCM, monofractal and multifractal algorithms without any analytical limitation to predefined structures. Images were derived from patient groups with invasive breast carcinoma (BC, 93 patients) and inflammatory breast carcinoma (IBC, 51 patients). The prognostic performance was indeed significantly enhanced by preprocessing with the average AUCs of individual texture features improving from 0.68 ± 0.05 for original to 0.78 ± 0.01 for preprocessed images in the BC group and 0.75 ± 0.01 to 0.80 ± 0.02 in the IBC group. Image preprocessing also improved the prognostic independence of texture features as indicated by multivariate analysis. Surprisingly, the tonal histogram compression by the nonnormalisation preprocessing has prognostically outperformed the tested contrast normalisation algorithms. Generally, features without prognostic value showed higher susceptibility to prognostic enhancement by preprocessing whereas IDM texture feature was exceptionally susceptible. The obtained results are suggestive of the existence of distinct texture prognostic clues in the two examined types of breast cancer. The obtained enhancement of prognostic performance is essential for the anticipated clinical use of this method as a simple and cost-effective prognosticator of cancer outcome.

BackgroundThanks to immense improvements in technology over the past few decades, we have witnessed a major shift towards the idea that breast cancer results from a combined effect of multiple common alleles conferring low risk. This study investigates the role of 3 nonsynonymous SNPs in the DNA repair genes XRCC1 (R399Q), RAD51 (G135C) and TP53 (Arg72Pro) in breast cancer in Serbian women.Patients and MethodsCases of BRCA1/2-negative hereditary breast cancer (n = 52), sporadic breast cancer (n = 106) and age-matched cancer-free female controls (n = 104) were obtained from the Institute for Oncology and Radiology of Serbia's blood bank. Restriction fragment length polymorphism analysis was used for genotyping. Descriptive analyses included genotype and allelic frequencies; the odds ratio and 95% confidence interval were calculated as an estimate of the relative risk.ResultsA significant difference in QQ+RQ versus RR genotype distribution of XRCC1 was observed between hereditary breast cancer patients and cancer-free controls. The association was confirmed among young breast cancer patients from these high-risk families. The existence of 3 recessive alleles in the RAD51 and XRCC1 genotype combination showed an association with hereditary breast cancer. Odds ratio analysis indicated a strong protective role of the RAD51 GG + TP53 ArgArg + XRCC1 RR combined genotype against hereditary breast cancer negative for BRCA1/2 mutations.ConclusionsThe XRCC1 R399Q polymorphism showed an association with increased breast cancer risk in Serbia, especially in the hereditary form of the disease and in young breast cancer patients. Dominant alleles of RAD51, TP53 and XRCC1 combined genotypes indicated a strong protective role against hereditary breast cancer.

Carcinoid tumors are rare tumors most commonly found in the gastrointestinal tract. They represent the most common malignancies of the appendix. As a distinct entity from both adenocarcinomas and carcinoids, Goblet cell carcinoid (GCC) was initially described in the literature in 1969. The GCC is almost exclusive to the appendix, but rarely can be found in rectum, ileum and colon. More than 50% of the patients at the time of diagnosis already have advancedstage disease. The most common metastatic sites are the peritoneal surfaces of the pelvis and abdominal cavity, and ovaries in women. Surgery is the main form of treatment in patients with GCC.A 49-year-old woman was treated at the Institute of Oncology and Radiology of Serbia with histopathological findings of GCC. In a 8-year period the patient was treated with initial appendectomy and three more operations because of locoregional disease progression. The last operation was performed in March 2016 because of endometrial metastases. Since then the patient is on regular follow up without disease progression.GCC is a very rare entity. Multidisciplinary approach is necessary for adequate patient treatment.

Breast cancer (BC) is the most common malignancy among women, while isolated operable liver metastases (LMs) from BC are very rare and occur in only 1-5% of the patients. Besides, positive steroid receptor (SR) status for oestrogen and/or progesterone is known as a factor which improves disease free survival (DFS) and overall survival (OS). The primary aim of this study was to examine the impact of SR status on DFS and OS after liver metastasectomy in female patients with primary BC.We analyzed 32 medical records of female patients diagnosed and treated for primary BC with LMS as the first and only site of disease progression, at the Institute of Oncology and Radiology of Serbia (IORS), during 2006- 2009. All of them underwent primary BC surgery as well as LMs resection.Patients with metachronous BC and LMs and positive SR status in both BC and LM (BC+/LM+) had a median time from BC to LM occurrence (TTLM) of 36 months, compared to BC+/LM- and BC-/LM- subgroups, whose medians for TTLM were 30.5 and 14.5 months, respectively (p0.01). For all patients, positive SR status showed high correlation with longer DFS and OS after LM resection (medians according survival analysis for DFS/OS in subgroups BC-/LM-, BC+/LM- and BC+-LM+ were 10/19, 25/45, 50/not reached months respectively; p0.01 for DFS/ OS). Cox regression analysis confirmed that the subgroup of patients with BC-/LM- had 10.8 and 18.8 higher risk of events for DFS (disease relapse or death) and event for OS (death only), respectively, compared to BC+/LM+ subgroup of patients.Positive SR status in BC and LM has a high impact not only on time from BC to LM occurrence, but also on longer DFS and OS after LM resection.

Breast cancer prognosis is a subject undergoing intense study due to its high clinical relevance for effective therapeutic management and a great patient interest in disease progression. Prognostic value of fractal and gray level co-occurrence matrix texture analysis algorithms has been previously established on tumour histology images, but without any direct performance comparison. Therefore, this study was designed to compare the prognostic power of the monofractal, multifractal and co-occurrence algorithms on the same set of images. The investigation was retrospective, with 51 patients selected on account of non-metastatic IBC diagnosis, stage IIIB. Image analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Bootstrap-corrected Cox proportional hazards regression P-values indicated a significant association with metastasis outcome of at least one of the features within each group. AUC values were far better for co-occurrence (0.66-0.77) then for fractal features (0.60-0.64). Correction by the split-sample cross-validation likewise indicated the generalizability only for the co-occurrence features, with their classification accuracies ranging between 67 and 72 %, while accuracies of monofractal and multifractal features were reduced to nearly random 52-55 %. These findings indicate for the first time that the prognostic value of texture analysis of tumour histology is less dependent on the morphological complexity of the image as measured by fractal analysis, but predominantly on the spatial distribution of the gray pixel intensities as calculated by the co-occurrence features.

Erysipelas is a bacterial cellulitis usually associated with Streptococcal infection. It may appear as a complication following mastectomy and radiotherapy for breast cancer. The study involved 17 cases of erysipelas of the upper limbs with a median age of 62 years. Here we described the clinical, therapeutic and evolutionary aspects of erysipelas. Our results indicated that the erysipelas appeared with an average of 9 years after mastectomy and was recurrent in three patients (17.64%). It is associated with obesity in 42% and arterial hypertension in 52.9% of patients with breast cancer after radical mastectomy. Breast cancer patients in advance stages of disease at presentation (T2+ T3) are significantly more subject to erysipelas in comparison to those patients with locoregional stage of disease at presentation (T1), Mann Whitney U-test, (p

Introduction. Hepatocellular carcinoma (HCC) is the most frequent primary malignant tumor of the liver. It is usually seen in the 6th and 7th decades of life and chronic hepatitis B is the most frequent cause. Extrahepatic metastasis of HCC is an indicator of a poor prognosis and the most common sites are lungs, bones, lymph nodes, kidneys and adrenal glands. We reported a case of isolated metastasis in the right maxilla, which had been found initially, before the tumor in the liver was diagnosed. Case report. A 70-year-old man underwent dental surgery of the upper right molar. Prolonged bleeding control was difficult for up to two weeks, so the biopsy was performed. Histopathological analysis revealed a metastatic hepatocellular carcinoma. Computerized tomography (CT) of the abdomen revealed a diffusely heterogeneous liver parenchyma with irregular borders and two foci of mass lesions. There were metastasis in the spleen and also two pathological retroperitoneal lymph nodes were detected, but no ascit, liver cirrhosis, cholestasis or portal vein thrombosis were seen. CT of the orbital and maxillary regions revealed a tumor mass in the right maxillary sinus, spreading to the alveolar sinus, nasal cavity and partially infratemporal space. A tumor mass was in the right orbit as well, infiltrating the surrounding bones and muscles. Clinically, there was proptosis of the right eye accompanied by amaurosis. The treatment started with chemotherapy based on 5-fluorouracil (sorafenib was not available). After three cycles, control CTs showed a stable disease in the liver, but progression in the right maxillary sinus and orbit. Enucleation of the right eye was performed and postoperative radiotherapy was planed. The patient deteriorated rapidly and died, about 6 months after the disease had been diagnosed. Conclusion. Extrahepatic metastasis of HCC represents a progressive phase of the disease with poor prognosis, so the main aim of the treatment should be palliation and care of symptoms.

Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The purpose of this study was to determine the value of microscopic tumour histomorphology texture for prognosis of local and systemic recurrence at the time of initial IBC diagnosis. This retrospective study included a group of 52 patients selected on the basis of non-metastatic IBC diagnosis, stage IIIB. Gray-Level-Co-Occurrence-Matrix (GLCM) texture analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Obtained values were categorized by use of both data- and outcome-based methods. All five acquired GLCM texture features significantly associated with metastasis outcome. By accuracies of 69-81% and AUCs of 0.71-0.81, prognostic performance of GLCM parameters exceeded that of standard major IBC clinical prognosticators such as tumour grade and response to induction chemotherapy. Furthermore, a composite score consisting of tumour grade, contrast and correlation as independent features resulted in further enhancement of prognostic performance by accuracy of 89%, discrimination efficiency by AUC of 0.93 and an outstanding hazard ratio of 71.6 (95%CI, 41.7-148.4). Internal validation was successfully performed by bootstrap and split-sample cross-validation, suggesting that the model is generalizable. This study indicates for the first time the potential use of primary breast tumour histology texture as a highly accurate, simple and cost-effective prognostic indicator of metastasis risk in IBC. Clinical relevance of the obtained results rests on the role of prognosis in decisions on induction chemotherapy and the resulting impact on quality of life and survival.

e12509 Background: Contrary to well recognized higher incidence of brain metastases (BM) in HER2 3+ and triple negative (TN) BC, correlation with BC molecular subtypes and cerebellar metastases is not well explored. Methods: From January 2007 to Jun 2016, 269 patients with BCBM have been prospectively registered at the Institute for Oncology and Radiology of Serbia. We analyzed metastases localization within brain, and identified 28 patients with cerebellar metastases. Correlation with molecular subtype of primary BC, median time to cerebellar metastases development, treatment and survival were also analyzed Results: 28 patients (10.4%) of median 47 years (29-63) had cerebellar metastases as the only brain metastatic site confirmed by CT/MRI. Median time to cerebellar BM was 21 months (range 0-141). Cerebellum was the first distant metastatic site in 20/28 patients (71.4%), and 8 (28. 5%) patients had inoperable BC and/or distant metastases before cerebellar metastases development. Molecular subtype of primary BC was known for 27/28 pts (96.4%): 21 pts (77.7%) had HER2 3+BC; 14 (52%) had ER/PR negative BC and there were no TNBC. Fifteen patients (53.5%) were treated with brain surgery + postoperative WBRT, 4 (14%) with gamma knife, while remaining 9 pts (32%) underwent WBRT only. Patients with good performance (PS 0-2) also received various systemic treatments +/- trastuzumab/ lapatinib. Mean survival upon cerebellar metastases was 19.2 months (median 9, range 2-123+ months); 39% patients were alive after 12 months; 21% after 24 months; 14% after 36 months. One patient (3.6%) is alive without relapse/progression 123 months+ after cerebellar metastases extirpation; trastuzumab is ongoing through all that period. Conclusions: Majority of analyzed patients with cerebellar metastases had HER2 3+ BC (77.7%). It is also interesting that none of patients within this group had TNBC Therefore, it seems reasonable to speculate that some still unrecognized BC and/or cerebellar soil characteristic, contribute to HER2 3+ BC predilection to cerebellum in this rare patient subgroup.

e12523 Background: Because there is no cumulative dose, trastuzumab could be given until disease progression. However, characteristics of patients with long term benefit of trastuzumab treatment are seldom reported. Methods: Trastuzumab become available for HER2 3+ MBC at November 2005 at the Institute for Oncology and Radiology of Serbia. Since then, we have registered 42 patients with HER2 3+ MBC and/or inoperable loco-regional recurrent BC treated with first line trastuzumab for at least 24 months (range 24-123+). Results: Median age was 53 years (range 35-76). 30/42 patients (71%) had ER/PR positive BC. MBC was initial presentation in 14 patients (33%), and as relapse in 28 (67%) patients. Only 7/28 (25%) patients received neoadjuvant/adjuvant trastuzumab, therefore majority have been trastuzumab naive (83.3%). Metastases were present in the liver (9), lungs (9), bones (16), soft tissue (6), CNS (1), while 20 (48%) patients had multiple metastatic sites. After antracyclines based chemotherapy, patients have been treated with first line weekly taxane concurrently with three weekly trastuzumab. After taxanes (up to 24 doses), trastuzumab was continued +/-hormonal therapy. Objective response was achieved in 29 (69%) patients with 17 patients (40%) achieving complete response. Median duration of response was 32+ months; 11 patients are still in remission 5 years after trastuzumab initiation. The longest complete remission duration is 123+ months, in patient with initially inoperable BC and solitary cerebellar metastasis. During observational period 10 patients stopped trastuzumab predominantly because of disease progression (8/42 19%) and 2 (4.8%) because of decreased ejection fraction (EF≤ 50%) that occurred as a rather late effect, after 34 and 49 months of continuous trastuzumab treatment. Three patients are lost from follow-up (7%); 39 (93%) patients included in this analysis are alive, still receiving trastuzumab for median 37 cycles (range 29-172+). Conclusions: A subgroup of patient with HER2 3+ MBC has a long-term benefit of trastuzumab treatment. In this analysis majority (71%) had also ER/PR positive MBC and majority have not been treated with neoadjuvant/adjuvant trastuzumab (83.3%).

Introduction. Metastases to the thyroid gland are very rare. They are usually seen in malignant melanoma, kidney, breast cancer and lung cancer. Case report. We presented a 54- years-old female patient with breast cancer diagnosed in 2002. The adequate surgical procedure was done and the tumor and axillary lymph nodes were removed. The patient also received adjuvant postoperative chemotherapy. After seven years of a disease free period, the first relapse of the disease was detected as thyroid gland tumor with axillary lymphadenopathy. The patient had a good response to systemic treatment so the surgical removal of thyroid gland and enlarged lymph nodes was performed. Histopathological analysis confirmed metastasis with breast cancer origin. Radical mastectomy was also preformed. Second relapse of the disease was detected 10 months later, while the patient was on hormonal therapy. It was manifested as the appearance of bone and skin metastases, pleural effusion and lymphadenopathy. Conclusion. This case report emphasized the importance of detailed examination of any new onset of thyroid swelling in a patient with previous history of malignancy.

e21030 Background: Contra-lateral breast cancer (CBC) is considered to be the most frequent new malignancy after primary breast cancer (PBC) However, there are few reports whether the histology and other major molecular characteristics differs between PBC and CBC. The aim of this paper is toevaluate and compare PBC/CBC histology according to the time to CBC development. Also, age at CBC and major molecular characteristics (tumor grade, estrogen/progesterone receptors, HER2) have been analyzed. Methods: A cohort of 113 patients with CBC, without distant metastases, has been prospectively registered during 28 months. Patients are divided in 2 groups according to the time of CBC diagnose: 1. Synchronous, if the CBC (S-CBC) was diagnosed either simultaneously or within 6 months after PBC; 2. Metachronous (M-CBC) if CBC was diagnosed > 6 months after PBC. Results: Results are presented in Table 1. Median age was calculated at the time of CBC diagnose. Patient with S-CBC are median 7 years older than patients with M- CBC that is statistically significant difference (p-0.007) S-CBC is more likely to be of the same histological type (76%) than M-CBC (56%) (p 0.006) In the whole analyzed group, and each subgroup separately, lobular carcinoma is registered in higher percentage (41%) than expected (~20%) For all other analyzed BC characteristics, statistical difference was not confirmed, however ~ 25% of specimens were not available for testing. Conclusions: Although it is still unclear what could be the clinical significance of these findings, genetic susceptibility to particular histology type of BC might be reasonably speculated. [Table: see text]

Inflammatory breast carcinoma (IBC) is a rare but aggressive breast cancer (BC) subtype. General prognosis is poor with higher incidence of axillary node involvement and metastatic disease at presentation (~30 %) as compared with common BC (~10 %). The typical IBC is characterised by rapid onset of localised or generalised skin redness, involving at least one-third of the breast, warmth and usually presence of skin oedema (peau d’orange), often without an underlying tumour mass. This clinical presentation of skin inflammation is a consequence of pathological plugging of the dermal lymphatic of the breast with tumour emboli. Dermal lymphatic invasion (DLI), although not mandatory for IBC diagnosis, is one of the hallmarks of this malignancy and can be proven in up to 75–80 % of IBCs. Surprisingly, there are very few data regarding whether the presence of DLI independently contributes to IBC prognosis as compared with IBC without DLI.

e21112 Background: HER2 overexpression is present in ∼20% of all breast carcinoma (BC) but it is not quite known whether this percentage is maintained in potentially radiotherapy induced BC. Radiot...

1106 Background: Inflammatory breast carcinoma (IBC) is rare but aggressive form of breast cancer. Up to 38% of IBC are HER-2+. According to literature, complete remission (CR) can be achived in more than 50% of patients with combinatination of chemotherapy and trastuzumab. However, trastuzumab is still not available in all countries. The aim of this study was to evaluate the rate and duration of CR to induction chemotherapy alone, without trastuzumab, in HER-2+ and HER-2- IBC pts and compare our results to literature data. Methods: The data were analized for 3,452 breast carcinoma patients registered at the Institute for Oncology and Radiology of Serbia (IORS) during one year. Among them, 281 pts had IBC, defined as pathologically confirmed skin lymphangiosis or BC with classical clinical signs of cancer mastitis. Responses have been evaluated clinically and by mammography after every 3–4 cycles of chemotherapy. CR was estimated as a complete disappearance of previously palpable breast tumour; no clinical and mammography signs of cancer mastitis; no enlarged regional lymph nodes and disappearance of all metastatic sites in stage IV. HER-2 status (IHC, Dako) was assessed in 88 patients (70.9%) and 25/88 (28.4%) were HER-2 3+. Results: We investigated 124 IBC pts with complete medical records. The overall incidence of IBC was 8.1%. Median age at diagnosis was 59 (ranges 35–81). The rate of CR is evaluated separately in subset of HER2+ and HER2- IBC. 100 pts received FAC induction chemotherapy (median number of cycles was 6) and remainder received CMF regimen (median number of cycles was 5), trastuzumab none. Only seven pts (5,6%), all treated with FAC achieved CR. Among them, four had HER-2 3+ (4/25; CR 16%) and three HER2 negative IBC (3/99; CR 3%). Median duration of CR in HER-2+ subset was 15 months (range 7–36+) and in HER-2- 18 months (range 7–101+). Conclusions: Our study shows that incidence of IBC in Serbia is higher than reported in the literature, 8,1% vs 1–4%. Also, it has been shown that very low percentage of IBC patients achieved CR after chemotherapy alone, esspecialy in HER-2- subset of IBC-only 3%, compared to 16% in HER-2+ group, even in the absence of trastuzumab, while the duration of CR in both groups were similar. No significant financial relationships to disclose.