Protein Corona Gold Nanoparticles Fingerprinting Reveals a Profile of Blood Coagulation Proteins in the Serum of HER2-Overexpressing Breast Cancer Patients

Breast cancer (BC) is a molecularly heterogeneous disease that encompasses five major molecular subtypes (luminal A (LA), luminal B HER2 negative (LB-), luminal B HER2 positive (LB+), HER2 positive (HER2+) and triple negative breast cancer (TNBC)). BC treatment mainly depends on the identification of the specific subtype. Despite the correct identification, therapies could fail in some patients. Thus, further insights into the genetic and molecular status of the different BC subtypes could be very useful to improve the response of BC patients to the range of available therapies. In this way, we used gold nanoparticles (AuNPs, 12.96 ± 0.72 nm) as a scavenging tool in combination with Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) to quantitatively analyze the serum proteome alterations in the different breast cancer intrinsic subtypes. The differentially regulated proteins specific of each subtype were further analyzed with the bioinformatic tools STRING and PANTHER to identify the major molecular function, biological processes, cellular origin, protein class and biological pathways altered due to the heterogeneity in proteome of the different BC subtypes. Importantly, a profile of blood coagulation proteins was identified in the serum of HER2-overexpressing BC patients.

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Prognostic subset of metastatic and non-metastatic luminal B breast cancer (LBBC) subtype based on Ki67 index.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12570 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12570-e12570

Author(s):

Lalnun Puii ◽

Lalram Sangi ◽

Hrishi Varayathu ◽

Samuel Luke Koramati ◽

Beulah Elsa Thomas ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Disease ◽

Ki67 Index ◽

Breast Cancer Patients ◽

Luminal A ◽

Her2 Positive ◽

Ki 67 ◽

Luminal B ◽

Therapeutic Implications ◽

Significant Difference

e12570 Background: Gene expression profiling for breast cancer has classified ER positive subtype into luminal A and luminal B. Luminal B breast cancer (LBBC) have a higher proliferation and poorer prognosis than luminal A tumors. Ki-67 index is the commonly used proliferation marker in breast cancer; however Ki67 expression can also be used to identify a subset of patients among LB with a favorable prognosis. This study attempts to verify this subset of LBBC patients based on DFS and PFS in non-metastatic and metastatic patients respectively. Methods: We retrospectively analyzed 80 IDC breast cancer patients diagnosed in 2013-2016 with complete follow-up till January-2021. We defined LBBC as ER+, PR+ or PR- , HER2+ or HER2- with a Ki67 index >20%. PFS was considered as the endpoint in patients presenting with metastatic disease whereas DFS was used in non-metastatic disease. The cut-off for ki67 was calculated using an X-tile plot (version 3.6.1, Yale University) by dividing Ki67 data into two populations: low and high, with randomized 1:1 “training” and “validation” cohorts. Results: Median age was 51.5 years. 18.7% (n=15) presented with metastasis at the time of diagnosis and their overall median PFS was found to be 25.8 months. The incidence of HER2 positive LBBC was found to be 15% (n=12) and none of them were found to be presented with metastasis. Survival and frequency of various sub groups in our study are enlisted in the given table. We estimated a Ki67 cut-off of 30% in patients with upfront metastatic disease and PFS was found to be higher in <30% compared to a Ki67 index >30% (38.9 months vs 19.7 months, p-0.002). Overall median DFS was not achieved in non-metastatic group (Mean DFS: 64.7 months) where as a statistically significant difference was observed in the survival of HER2 positive (median DFS: 53.5 months, mean DFS: 50.9) than HER2 negative patients (median DFS not achieved, mean: 66.97 months) ( p-0.021). We obtained a Ki67 cut-off of 32% in non- metastatic group and mean DFS was found to be higher in Ki67<32% (69 months) compared to Ki67>32% (61.4 months), however it failed to exhibit a statistically significant relationship ( p-0.373). Conclusions: Our study indicates that a subset of patients exists within metastatic and non-metastatic LBBC with differing prognosis based on Ki67. Larger studies are further required to confirm the findings and therapeutic implications.[Table: see text]

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BREAST CANCER TYPING USING RT-PCR ASSAY

Siberian Journal of Oncology ◽

10.21294/1814-4861-2019-18-5-61-67 ◽

2019 ◽

Vol 18 (5) ◽

pp. 61-67

Author(s):

V. K. Bozhenko ◽

I. D. Trotsenko ◽

E. A. Kudimnova ◽

S. G. Vardanyan ◽

M. V. Zakharenko ◽

...

Keyword(s):

Breast Cancer ◽

Systemic Therapy ◽

Breast Cancer Patients ◽

Rt Pcr ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Diagnostic Measures ◽

Total Percentage ◽

Response To Chemotherapy

Introduction. Adjuvant systemic therapy remains one of the main options for treating breast cancer. Results of standard immunohistochemical studies are not always a criterion for selecting systemic therapy. Nowadays, multigene expression analysis is actively used to predict the response to chemotherapy in patients with earlystage breast cancer. We studied a 24-gene multi-gene panel for typing breast cancer.Material and Methods. A prospective analysis of 199 breast cancer patients (T1–3N0–3M0) was carried out. Surgical specimens were studied using the standard immunohistochemistry (IHC) and RT-PCR for detecting expression of 24 genes.Results. According to the IHC results, breast cancer was divided into 5 molecular subtypes: luminal A was detected in 59 (30 %) patients; luminal B (HER2-negative) in 52 (26 %); luminal B (HER2-positive) in 19 (9 %); triple-negative in 28 (14 %); HER2-positive 41 (21 %). RT-PCR showed that ST K15, MYC, MYBL2, BIRCC 5, BCL2, TERT, ESRP1, PGR, HER2, GBR7, MGB1 and MMP11 were the most significant genes in subtype distribution. The total percentage of matches between the two studies was 61.7 %.Conclusion. Studies have shown the need to add additional typing methods for breast cancer to a standard IHC study, which will undoubtedly increase the information content of diagnostic measures and will improve the effectiveness of the treatment.

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Comparative analysis of the receptor status of the primary focus and synchronous axillary metastases in breast cancer patients

Russian Journal of Oncology ◽

10.18821/1028-9984-2019-24-3-6-74-78 ◽

2020 ◽

Vol 24 (3-6) ◽

pp. 74-78

Author(s):

Yu. S. Krumin’ ◽

V. A. Khailenko ◽

N. A. Kozlov ◽

G. Yu. Cheremis ◽

D. V. Khailenko ◽

...

Keyword(s):

Breast Cancer ◽

Proliferative Activity ◽

Molecular Subtype ◽

Her2 Status ◽

Breast Cancer Patients ◽

Luminal A ◽

Her2 Positive ◽

Axillary Metastases ◽

Receptor Status ◽

Luminal B

The aim of the investigation. To study concordance of surrogate molecular subtype in the pairs of primary and synchronous axillary metastases in patients with invasive breast cancer (IBC). Materials and methods. Retrospective analysis included 80 patients aged 28 to 90 years (average age 40.35.3 years) with a first-time diagnosed IBC who underwent surgical treatment at the N.N. Blokhin National Medical Research Center of Oncology during 20162018 years. None of the patients received any neoadjuvant drug therapy. The pathological evaluation of the estrogen receptors (ER), progesterone receptor (PR), HER2 expression and estimation of proliferative activity (Ki-67 index) with subsequent assignment to surrogate subtypes were performed according to ASCO/CAP protocols and the recommendations of the 20132019 San-Gallen Conference on treatment of Early Breast Cancer. Results. Preliminary results of our study revealed therapeutically significant changes in hormone receptor status, HER2-status and proliferative activity in 12.5% of cases of Luminal A type IBC, 20% of Luminal B/HER2-positive and 4% of Luminal B/Her2-negative subtypes of IBC.

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Prognostic factor Ki67 for breast cancer patients in each subgroup.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.565 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 565-565

Author(s):

Naoki Niikura ◽

Shinobu Masuda ◽

Mizuho Terada ◽

Mayako Terao ◽

Nobue Kumaki ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative ◽

Predictive Marker ◽

Rank Test ◽

Breast Cancer Patients ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Er Positive

565 Background: Immunohistochemical (IHC) Ki67 has described it as a prognostic and predictive marker for breast cancer. The St. Gallen Consensus Meeting determined that Ki67 labeling index is chiefly important for distinguishing between “Luminal A” and “Luminal B (HER2 negative)” subtypes and is a predictive marker for chemotherapeutic efficacy. However, the high and low cutoff points remain controversial. Our objective is to compare survival in patients with low, intermediate, and high Ki67 levels in each subgroup. Methods: We retrospectively identified all the patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000, and December 31, 2010. Ki67 was defined as low if <10% Ki67 was detected, as Intermediate if 10–20% Ki67 was detected, and as high if >20% Ki67 was detected. To assess Ki67 levels and survival outcomes, survival curves were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: We identified 1331 primary breast cancer patients without metastasis, of whom 686 received neoadjuvant or adjuvant chemotherapy. Patients with high Ki67 had poorer relapse-free survival (RFS) than patients with intermediate (p = 0.009) and low Ki67 (p < 0.001). Patients with intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001). In ER-positive cases (n = 1059), patients with high and intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001 and p = 0.002, respectively). In HER2-positive and ER-negative cases (n = 103), patients with high Ki67 had poorer RFS than patients with low Ki67 (p = 0.002). In triple-negative cases (n = 164), patients with high Ki67 tended to have poorer RFS than patients with low Ki67 (p = 0.064). Conclusions: Our data demonstrated that low, intermediate, and high Ki67 levels may be used to differentiate prognosis in ER-positive cancer patients as well as HER2-positive and triple-negative cancer patients.

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Biologic subtypes and first relapse pattern in curative surgery performed breast cancer patients: Study of Anatolian Society of Medical Oncology.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11559 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11559-e11559

Author(s):

Muhammet Ali Kaplan ◽

Ülkü Yalçintas Arslan ◽

Abdurrahman Isikdogan ◽

Berna Oksuzoglu ◽

Mevlude Inanc ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Distant Recurrence ◽

Breast Cancer Patients ◽

Luminal A ◽

Her2 Positive ◽

Curative Surgery ◽

Luminal B ◽

First Relapse

e11559 Background: Relapse is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in patients with curative surgery performed breast cancer. Methods: We retrospectively evaluated clinical data from 1126 breast cancer patients with relapses after their curative surgery between 1998 and 2012 from referral centers of Turkey. Study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression.Patients were divided into four biological subtypes according to IHC: triple negative (ER negative, PR negative, and HER2 negative), HER2 overexpressing (ER negative, PR negative, and HER2 positive), luminal B (ER and/or PR positive, HER2 positive), and luminal A (ER and/or PR positive, HER2 negative). Results: The proportion of patients with luminal A, Luminal B, HER2-overexpressing, and triple negative breast cancer was 42.0% (n=473), 23.0% (n=259), 13.3% (n=150), and 21,7% (n=244), respectively. Median time to relapse was 26.6 months. 22.5% of the patients (n=253) had multiple relapse sites. The incidence of first distant recurrence site was significantly different among the subtypes. Liver (31.8% vs. 22.4%, p=0.008), bone (42.2% vs 37.0%, p<0.001), and lung metastases (30.9% vs. 22.2%, p=0.019) were increased in HER2 overexpressing, luminal A and triple negative group as first relapse site compared with other groups, respectively. Brain metastasis was increased in HER2 overexpressing and triple negative groups (17.7%), compared with Luminal A and B groups (8.0%, p<0.001). Conclusions: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.

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Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

Tumori Journal ◽

10.1177/03008916211012341 ◽

2021 ◽

Vol 107 (1_suppl) ◽

pp. 12-12

Author(s):

D Aissaoui ◽

M Bohli ◽

R Ben Amor ◽

J Yahyaoui ◽

A Hamdoun ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Response ◽

Inflammatory Breast Cancer ◽

Hormone Receptor ◽

Triple Negative ◽

Molecular Subtypes ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

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Trends in breast cancer mortality according to molecular subtypes: A population-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.572 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 572-572

Author(s):

Yunan Han ◽

Shuai Xu ◽

Graham A. Colditz ◽

Adetunji T. Toriola

Keyword(s):

Breast Cancer ◽

Cancer Mortality ◽

Triple Negative ◽

Molecular Subtypes ◽

Breast Cancer Mortality ◽

Treatment Strategies ◽

Luminal A ◽

Her2 Positive ◽

Mortality Trends ◽

Luminal B

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p<0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p<0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p<0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.

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Analysis of prolactin receptor expression in breast cancer subtypes

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20206601089 ◽

2020 ◽

Vol 66 (1) ◽

pp. 89-94

Author(s):

T.S. Kalinina ◽

V.V. Kononchuk ◽

S.V. Sidorov ◽

L.F. Gulyaeva

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Prolactin Receptor ◽

Mrna Level ◽

Receptor Expression ◽

Mrna Levels ◽

Luminal A ◽

Her2 Positive ◽

Tissue Samples ◽

Luminal B

Breast cancer (BC) is the most common cancer among women. It is known that the prolactin receptor (PRLR) may play a role in breast carcinogenesis, but the available data are often contradictory. To get a more complete picture of the relationship between the receptor and mammary gland carcinogenesis, we examined the association between changes in PRLR expression level and tumor subtype (and its main characteristics). To do this, using real-time PCR, we evaluated the level of PRLR mRNA in BC tissue samples and untransformed adjoining tissue samples (89 pairs). Since the androgen receptor (AR) has begun to be seen as a prognostic marker in breast cancer, we also evaluated the association between mRNA levels of AR and PRLR. We found a significant increase in PRLR expression in luminal subtypes; the highest level of PRLR mRNA was detected in luminal A subtype. In HER2-positive ER-, PR-negative BC, the PRLR mRNA level decreases in tumor tissues compared with untransformed tissues. High PRLR expression is also associated with smaller tumor size in luminal B HER2-negative subtype. In ER-, PR-negative tumors, PRLR expression is associated with AR expression: PRLR mRNA level is increased when AR mRNA level is reduced by more than 8 times in triple-negative tumors; in contrast, in HER2-positive subtype it decreases more significantly when AR expression is reduced by more than 3 times. A tendency towards an increase in PRLR expression with an increase in the AR mRNA level was also discovered in luminal subtypes. The level of PRLR expression depends on the age of patients. In luminal A, PRLR expression is higher in patients under 65 years. In contrast, in luminal B HER2-negative and triple-negative BC, reduced PRLR expression was observed in patients under the age of 40 years and under the age of 50 years, respectively. In this group of patients under the age of 40 years with luminal B HER2-negative BC, ER expression was also reduced (0-4 score according to the IHC assay). Thus, PRLR probably plays a different role in the development and progression of BC: in luminal A and luminal B HER2-positive subtypes PRLR may act as an oncogen, and in luminal B HER2-negative and ER-, PR-negative subtypes can play a tumor suppressor role.

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Relationship between tumor size and metastatic site in patients with stage IV breast cancer: A large SEER-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13065 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13065-e13065

Author(s):

Qian Dong ◽

Mi Zhang ◽

Da Jiang

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Size ◽

Stage Iv ◽

Breast Cancer Patients ◽

Luminal A ◽

Chi Square ◽

Metastatic Site ◽

Luminal B ◽

Stage Iv Breast Cancer

e13065 Background: To analyze the correlation between tumor size and metastatic site in first-diagnosed stage IV breast cancer patients. Methods: Stage IV breast cancer patients diagnosed from 2010 to 2015 were screened by the Surveillance, Epidemiology, and End Results (SEER) database. The characteristics of clinical variables were represented by a frequency table, and the Chi-square test was used for comparison. At the same time, the Chi-square test was used to analyze the relationship between tumor size and organ metastasis. Correlation between tumor size and the prognosis of patients was contributed by KM curve and Log-rank test. Results: Regardless of tumor size, the proportion of bone metastasis was higher and brain metastasis was lower in breast cancer patients. There were significant differences in the site of metastases based on different subtype. Luminal A and Luminal B breast cancer had the highest proportion of bone metastases; brain metastasis accounted for the highest proportion in triple-negative breast cancer (TNBC); while the incidence of liver metastasis was the highest in Her-2(+) breast cancer. At the same time, the results indicated that Luminal A breast cancer with a tumor size > 5 cm was more likely to develop multi-site metastasis and lung metastasis, while Luminal B breast cancer with a tumor size ≤ 5 cm was more likely to develop liver metastasis. The results also revealed that TNBC patients with a tumor size of 0 - 2cm were more likely to develop bone metastasis than those with a tumor size > 5 cm, and the incidence of lung metastasis in triple-negative patients showed an increasing trend with the increase of tumor size. Conclusions: Based on subtype, we found that there was a significant difference between tumor size and metastatic site in patients with stage IV breast cancer, and the difference was statistically significant. This study provided evidence-based basis for decision-making of stage IV breast cancer treatment.

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Treatment effectiveness in advanced breast cancer patients in Italy: Ten years experience.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11573 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11573-e11573

Author(s):

Sandro Barni ◽

Ilaria Vallini ◽

Marta Bonotto ◽

Antonella Brunello ◽

Monica Indelli ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Prognostic Factors ◽

Soft Tissue ◽

Triple Negative ◽

Demographic Data ◽

Breast Cancer Patients ◽

Luminal A ◽

Luminal B ◽

Oncology Unit

e11573 Background: Several studies suggest that newer therapies can improve survival in MBC, but a different impact on overall survival (OS) is observed according to histology, extension of disease and prognostic factors. This survey was performed for evaluate Italian experience in cancer treatment in the last ten years. Methods: We collected data from 13 Italian Medical Oncology Unit; we registered all consecutive patients (pts) with breast cancer who have developed metastasis between 2000 and 2008. Demographic data, pathological characteristics and treatment were reported. OS was calculated from time of recurrence and stratified according to biological characteristics and to recurrence date. Results: 1542 pts was suitable for analysis; median age 61,7 (range 22-94); MBC at diagnosis 21,8%. Site of disease recurrence: bone 26,2%, visceral 25,4%, bone and visceral 20,7%, soft tissue 11,5%, soft tissue and visceral 8,4%, bone and soft tissue 7,8%. Molecolar classification: luminal A 66,3%, luminal B 14,5%, triple negative 11,5%, HER2+ like 7,7%. Pts received a median of 2 lines of chemotherapy (range 0-10) and 1 line of hormonal therapy (range 0-7); 22,5% received biological drugs. 15,5% of metastatic pts were enrolled in clinical trials. After a median follow up of 7.1 years 84,1% pts died (1297/1542 pts) and median OS was 2,7 years (range 2,6-2,9). We did not observe difference in OS for pts divided into 3 groups according to recurrence date (2000-2002, 2003-2005, 2006-2008). A longer median OS was observed in luminal B (3,8 years) versus luminal A and HER2+ like (2,8 years) and triple negative disease (1,2 years). Conclusions: Our survey describe a large number of MBC pts treated in 13 Italian Oncology Unit. OS analysis did not show significant differences according to recurrence date, but for different prognostic factors. OS data are superimposable to literature ones, showing a good transfer from clinical trials to clinical practice.

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