Negative Hormonal Status Research Articles

Relation Between Baseline CXCR1 Expression And Neoadjuvant Chemotherapy Response In Breast Cancer Patients.

To examine the C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues prior to neo-adjuvant chemotherapy, and its relationship to neo-adjuvant chemotherapy effectiveness and other prognostic variables. The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2018 to March 2021, and comprised patients with recent histopathologically proven breast cancer cases eligible for chemotherapy. Paraffin blocks of tumourspecimens were stained by immunohistochemicalstain using concentrating rabbit anti-human C-X-C Motif Chemokine Receptor 1 polyclonal antibody kits. C-X-C Motif Chemokine Receptor 1 expression was classified into low and high categories. Patients were followed for 2 years for treatment response, disease recurrence and mortality. Data was analysed using SPSS 25. Of the 100 females with mean age 50.2±12.1 years, 52(52%) had their left side affected, while 48(48%) had their rightside affected. There were 52(52%) cases with mean age 49.2±12.9 years having high C-X-C Motif Chemokine Receptor 1 expresssion, while 48(48%) with mean age 51.4±11.2 years had low expression. There was a significant association between high expression and advanced tumour grade, advanced tumourstage, higher frequency of triple negative breast cancer and higher frequency of Ki-67-positive cancers (p<0.05). Patients with high C-X-C Motif Chemokine Receptor 1 expression had significantly lower frequency of complete pathological response when compared with patients with low expression (p<0.001). Patients with high expression had higher frequency of recurrence, shorter disease-free survival, higher mortality and shorter overall survival, but the difference was not significant (p>0.05). Multivariate logistic regression analysis identified triple negative hormonal status (p=0.031) and high baseline C-X-C Motif Chemokine Receptor 1 expression (p<0.001) as significant predictors of complete pathological response. There was found to be a link between baseline C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues and pathological response to neoadjuvant therapy in breast cancer patients.

Expression of BRCA1 by immunohistochemistry and its association with ER, PR, Her2neu status in infiltrative ductal carcinoma of breast.

Breast cancer is a heterogeneous disease, which differs in its clinical behaviors and responses to treatment and outcome. The prognosis of breast cancer depends on histopathological parameters and molecular subtypes. Among more than 300 genes, which are involved in the pathogenesis of breast cancer tumor suppressor gene such as BRCA1 is known to play a significant role in hereditary cancers. However, its role in sporadic cases of infiltrating ductal carcinoma is yet to be established. To evaluate the expression of BRCA1 in infiltrative ductal carcinoma and to analyze the association of BRCA1 with histopathological parameters and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (Her2) neu expression. This was a laboratory-based exploratory study in which 56 patients with infiltrative ductal carcinoma who underwent radical mastectomy from October 2019 to July 2021 were included. Patients with chemotherapy and radiotherapy, trucut biopsies, and incomplete patient details were excluded. Immunostaining for BRCA1 was performed. Individual clinicopathological parameters were compared with the BRCA1 mutation. Statistical analysis was done using SPSS 22. A P value of < 0.05 was considered statistically significant. Among 56 cases of IDC, 18 cases (32.1%) showed BRCA1 mutation. BRCA1 mutation was associated with postmenopausal age, larger tumor size, lower tumor grade, and higher tumor staging. When we analyzed the biomarkers with BRCA1 mutation, it showed a negative association with ER, PR, and Her2 neu and a high Ki67 proliferation index. No family history of breast carcinoma was seen in 34/56 patients where history was available. Our study showed BRCA1 mutation in 32.1% and associated with postmenopausal age group, larger tumor size, and higher staging and negative hormonal status of breast carcinoma.

An intriguing journey of encapsulated apocrine papillary carcinoma of the breast

BackgroundEncapsulated Apocrine Papillary Carcinoma (EAPC) of the breast are very rare tumors. They usually present as a cystic mass with mural nodule in women aged 44–84 years. Affected patients may be asymptomatic or complain of breast swelling, or nipple discharge. Mammographic features are nonspecific. The tumor appears as a high-density round or oval mass with circumscribed or spiculated margins on mammography. On Ultrasonography (US) a classical lesion appears as predominantly cystic mass with intracystic solid papillary projections and area of vascularity within it. Contrast Enhanced Breast MRI helps to further characterize the lesion by showing intense contrast enhancement in early phase along with washout curve. Histological features of these tumors are similar to those of classical encapsulated papillary neoplasm, in that myoepithelial cells are absent within the papillary structures and at the periphery of the cyst. They show variable degree of cytological atypia and mitotic activity. Such tumors consist of abundant granular eosinophilic cytoplasm and large nuclei with prominent nucleoli and are androgen receptor positive. However, a multidisciplinary approach is crucial for diagnosis and tissue histology is essential to suitably formulate treatment guidelines. Surgical excision is the preferred treating option for these tumors. Little consensus is available about local radiation and adjuvant therapy for the treatment of such tumors, yet they have been reported to have good prognosis.Case presentationThis rare case report describes the intriguing journey towards the diagnosis of an encapsulated intracystic apocrine papillary carcinoma in a 52-year-old premenopausal female who presented with palpable breast swelling in left breast. The patient underwent mammography, breast ultrasound and breast MRI concluding it to be a BIRADS 4A lesion. Then the patient was subjected to trucut core biopsy and finally surgical excision was performed. On Histopathology this lesion was diagnosed as encapsulated apocrine papillary carcinoma with androgen receptor positivity and triple negative hormonal status. At present patient is on regular follow-up.ConclusionsEncapsulated intracystic apocrine papillary carcinoma has a favorable prognosis with low recurrence rate and excellent long-term survival regardless of its invasive nature. Therefore, we present this rare entity to highlight the importance of radiological and histopathology findings in its diagnosis.

Cancer-Testis Antigens in Triple-Negative Breast Cancer: Role and Potential Utility in Clinical Practice.

Simple SummaryTriple-negative breast cancer (TNBC) has been associated with worse prognoses due to the limited treatment options. Thus, there is a need to characterise new biomarkers or treatment targets to improve patient outcomes. Cancer testis antigens (CTAs) are a group of antigens that are preferentially expressed in tumours and exhibit strong immunogenicity, as such, CTAs hold great promise as potential treatment targets and biomarkers in cancer. Previous reports have implicated roles for CTAs in different subtypes of breast cancer, including TNBC. Multiple clinical trials are in progress investigating CTAs as treatment targets in various cancers. This review aims to discuss the roles of CTAs in TNBC and discuss the potential applications and benefits of incorporating CTAs in clinical practice. Breast cancer cells commonly express tumour-associated antigens that can induce immune responses to eradicate the tumour. Triple-negative breast cancer (TNBC) is a form of breast cancer lacking the expression of hormone receptors and cerbB2 (HER2) and tends to be more aggressive and associated with poorer prognoses due to the limited treatment options. Characterisation of biomarkers or treatment targets is thus of great significance in revealing additional therapeutic options. Cancer-testis antigens (CTAs) are tumour-associated antigens that have garnered strong attention as potential clinical biomarkers in targeted immunotherapy due to their cancer-restricted expressions and robust immunogenicity. Previous clinical studies reported that CTAs correlated with negative hormonal status, advanced tumour behaviour and a poor prognosis in a variety of cancers. Various studies also demonstrated the oncogenic potential of CTAs in cell proliferation by inhibiting cell death and inducing metastasis. Multiple clinical trials are in progress to evaluate the role of CTAs as treatment targets in various cancers. CTAs hold great promise as potential treatment targets and biomarkers in cancer, and further research could be conducted on elucidating the mechanism of actions of CTAs in breast cancer or combination therapy with other immune modulators. In the current review, we summarise the current understandings of CTAs in TNBC, addressing the role and utility of CTAs in TNBC, as well as discussing the potential applications and advantage of incorporating CTAs in clinical practise.

LDL-c as a predictor of hormonal status and determining factor for therapy of breast cancer patients

Background: Immunohistochemical testing is important in determining clinical diagnosis and therapy, and is useful as a prognostic and predictive factor, but it is not easy to do and is not always available. Breast cancer patient with higher low-density-lipoprotein cholesterol [LDL-c]. level tends to have larger tumor size, higher grade, higher proliferation rate, positive Human Epidermal growth factor Receptor-2 (HER2-neu) and occasionally come at late stage. High LDL-c receptors are found on the surface of breast cancer cells, where cancer cells will take up cholesterol in serum, and a metabolite of 27-hydroxycholesterol cholesterol will affect Estrogen Receptor-α. Methods: Analytical observational study by cross sectional method, during July 2020 – November 2020, at Oncology Clinic Dr. Soetomo Hospital Surabaya with a total sample size of 42. The data obtained were analyzed using the SPSS version 23.0 program, regression test and Chi-Square were performed for characteristic analysis and Chi-Square Fischer’s Exact Test were performed for correlation test between lipid profiles with hormonal status. Results: The mean value of LDL-c was 117.88 ± 33.89 mg/dL. In the analysis of the correlation between LDL-c and hormonal status, it was found that the majority of patients who had positive hormonal status had LDL-c levels of ≤160 mg/dL with p value = 0.049. ROC analysis shown LDL-c cut-off point of 132 mg/dL, p value = 0.034 (OR 5.031, 95% CI 1.159-21.848), sensitivity 46.7% and specificity 83.35%. Conclusion: There is a statistically significant relationship between LDL-c levels and hormonal status with the cut-off point of 132 mg/dL. The increase in LDL-c in serum increases the tendency of negative hormonal status, therefore LDL-c levels can be considerate in determining the therapy for breast cancer patients.

Impact of hormonal status on ductal carcinoma in situ of the breast: Outcome and prognostic factors.

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease which is increasingly diagnosed through improved screening measures. Multiple prognostic scores have been devised to predict the risk of local recurrence (LR), and the optimal adjuvant management for DCIS is still debated. Hence, the aim of this analysis is to investigate the factors contributing to the prognosis of DCIS, in particular the role of its hormonal status. From 2005 to 2016, a total of 1221 female patients diagnosed with DCIS at the National Cancer Centre Singapore and Singapore General Hospital were studied. The mean age of diagnosis was 54years of age (sd=11.0), with estrogen receptor (ER)-positive DCIS tumors presenting earlier (mean age 54 vs 57years of age; P<.001). DCIS with negative hormonal status (HS) correlates significantly with a larger size (mean 23.5mm vs 13.0mm, P<.001) and higher grade of tumor (P<.001). Patients with positive HS were more likely to undergo breast conservation surgery over a mastectomy, in contrast to patients with negative HS (P<.001). Patients with negative HS had a poorer prognosis, with a shorter time of overall survival time (HR=26.3, P=.020). In conclusion, our study shows that the hormonal status, age of diagnosis, and positive margins are important prognostic factors for DCIS, at least in our Asian population.

Cancer testis antigens as immunogenic and oncogenic targets in breast cancer.

Breast cancer cells frequently express tumor-associated antigens that can elicit immune responses to eradicate cancer. Cancer-testis antigens (CTAs) are a group of tumor-associated antigens that might serve as ideal targets for cancer immunotherapy because of their cancer-restricted expression and robust immunogenicity. Previous clinical studies reported that CTAs are associated with negative hormonal status, aggressive tumor behavior and poor survival. Furthermore, experimental studies have shown the ability of CTAs to induce both cellular and humoral immune responses. They also demonstrated the implication of CTAs in promoting cancer cell growth, inhibiting apoptosis and inducing cancer cell invasion and migration. In the current review, we attempt to address the immunogenic and oncogenic potential of CTAs and their current utilization in therapeutic interventions for breast cancer.

Predictive factors for sentinel node metastases in primary invasive breast cancer: a population-based cohort study of 2552 consecutive patients

BackgroundAxillary lymph node status is one of the most important prognostic factors for breast cancer. The aim of this study was to determine predictive factors for metastasis to sentinel node (SN) in primary invasive breast cancer.MethodThis is a study of 3979 patients with primary breast cancer during 2008–2013 in Malmö and Lund scheduled for surgery and included in the information retrieved from Information Network for Cancer Care (INCA). The final study population included 2552 patients with primary invasive breast cancer. The risk of metastases to SN were examined in relation to potential clinicopathological factors such as age, screening mammography, tumor size, tumor type, histological grade, estrogen status, progesterone status, Her-2 status, multifocality, and lymphovascular invasion. Binary logistic regression was used; adjusted analyses yielded odds ratio (OR) with 95% confidence interval.ResultsTumors detected by mammography screening were less likely to be associated with metastases to SN compared to those not found by mammography screening (0.63; 0.51–0.80). Negative hormonal status for estrogen associated with lower risk for SN metastases compared to tumor with positive estrogen status (0.64; 0.42–0.99). Tumors with a size more than 20 mm had higher risk to metastasize to SN (1.84; 1.47–2.33) compared to tumors less than 20 mm. Multifocality (1.90; 1.45–2.47) and lymphovascular invasion (3.74; 2.66–5.27) were also strong predictive factors for SN metastases.ConclusionSN metastasis is less likely to occur in women with invasive breast cancer diagnosed by screening mammogram. Tumors with negative estrogen status are associated with low risk for SN metastases. Tumors larger than 20 mm, multifocality, or lymphovascular invasion are also factors associated with high risk for SN metastases.

Identification of single nucleotide polymorphism of PI3k-AKT-TOR pathway as a risk factor of central nervous system metastasis in metastatic breast cancer.

2007 Background: Although new therapeutic options are available, an early diagnosis of central nervous system (CNS) metastasis may be needed to improve the prognosis. The PI3k-Akt-mTor pathway has been shown to be relevant in the development of CNS metastasis. Our aim was to identify risk-associated single nucleotide polymorphisms (SNP) of the PI3K Akt-mTOR pathway in the development of CNS metastasis in patients with metastatic breast cancer. Methods: We performed a secondary analysis in a subpopulation of patients from the GENEOM study (NCT00959556). In this previous study, blood samples were collected from 914 breast cancer patients treated by chemotherapy in the neoadjuvant, adjuvant or metastatic setting for genomic analysis. We identified CNS metastatic patients (both leptomeningeal and parenchymal) and non-CNS metastatic patients (no neurological symptoms or normal brain MRI before death or during 5-years metastatic period). Based on the literature, 88 SNPs of the PI3K-Akt-mTOR pathway were analyzed, including AKT1 (17 SNPs), AKT2 (4), FGFR1 (2), mTOR (7), PDK1 (4), PI3KR1 (11), PI3KCA (20), PTEN (17), RPS6KB1 (6). Results: Of the 342 patients with metastases in the GENEOM cohort, 100 patients with CNS metastasis (parenchymal lesions only, n = 51; leptomeningeal lesions only, n = 18; both, n = 31) and 107 patients without CNS metastasis were included. Negative hormonal status (p = 0.002) and presence of vascular emboli on breast cancer samples (p = 0.006) were associated with CNS metastasis. In univariate analysis, genotypes CC of AKT1 rs3803304, AA of AKT2 rs3730050, CC of AKT2 rs8100018, TT of PDK1 rs1168690, GG of PDK1 rs11904366 and GG of PI3KR1 rs251408 were associated with CNS metastasis at the p &lt; 0.05 threshold. Only genotype TT of PI3KR1-rs706716 was statistically associated with CNS metastasis after Bonferroni correction (p = 0.0003, &lt; 0.00085). Conclusions: PI3KR1-rs706716 is associated with CNS metastasis in metastatic breast cancer patients, in addition to negative hormonal status and presence of vascular emboli and could be combined in a composite score to predict the risk of and to detect early CNS metastasis in this population.

Serum HER2 in combination with CA 15-3 as a parameter for prognosis in patients with early breast cancer

AimHER2 in breast cancer tissue is a marker of high prognostic and predictive relevance. Soluble HER2, the extracellular domain of the HER2/neu receptor (HER2 ECD), which is shed into the blood, has been suggested to be a helpful tumor marker. We investigated the relationship between the concentrations of HER2 ECD, CEA and CA 15-3, the association of these markers with clinicopathological features and the impact of HER2 ECD alone and in combination with known prognostic factors on disease free survival (DFS) and cancer specific survival (CSS) in untreated early breast cancer patients. Patients and methodsHER2 ECD (ADVIA, Bayer), CEA (AxSYM, Abbott) and CA 15-3 (Elecsys, Roche) were measured at time of primary diagnosis in the pre-therapeutic (pre-operative) sera of 241 breast cancer patients and were correlated with clinicopathological parameters and outcome. ResultsHigher HER2 ECD levels were significantly correlated with postmenopausal status (p=0.016) and tissue HER2-overexpression (p<0.0001). Higher serum levels of CA 15-3 were associated with larger tumor size (p=0.019), positive lymph nodes (p=0.019), UICC stage III (p<0.01), positive tissue HER2-overexpression (p<0.05) and negative hormone receptor status (p=0.016). In multivariate analysis, serum HER2 ECD levels, CA 15-3 levels, large tumor size and negative hormonal status were independent prognostic factors in DFS. Patients with both high levels of HER2 ECD (>15ng/mL) and high serum levels of CA 15-3 (>24U/mL) had the poorest prognosis with a DFS after 3years of 50.0%. Patients without elevated serum levels had a better outcome with a DFS of 91.2%. ConclusionsIn our retrospective analysis, HER2 ECD and CA 15-3 were independent and better prognostic tools than HER2 in tissue. Prospective validation is necessary to confirm their usefulness in clinical practice.

Association of Fascin and matrix metalloproteinase-9 expression with poor prognostic parameters in breast carcinoma of Egyptian women.

BackgroundThe effects of fascin on cell invasiveness involve changes in cell motility and matrix metalloproteinase-9 (MMP-9) activity. Previous studies on the prognostic value of fascin and MMP-9 in breast carcinoma revealed conflicting results. To date, no immunohistochemical studies have been performed to assess the possible association between them in breast carcinoma. This study is designed to correlate their expression with prognostic parameters in breast carcinoma and assess the relationship between them.MethodsImmunohistochemical expression of fascin and MMP-9 was evaluated semi quantitatively in 67 cases of breast carcinoma regarding the percentage of positive cells. Chi square test and Fisher’s exact test were used to examine the relationship between categorical variables. Kappa statistics was used to compute the measure of agreement between two investigational methods.ResultsFascin and MMP-9 expressions were detected in 43.28% and 50.75% of breast carcinomas (respectively). Regarding the normal breast tissue, fascin expression was observed in myoepithelial cells and luminal cells of few ducts and acini. However, normal tissue showed negative MMP-9 expression. A significant relationship was observed between fascin and MMP-9 expression and lymph node metastases (p = 0.001 and 0.002 respectively), advanced tumor stage (p = 0.004 and 0.005 respectively), estrogen receptor negative (p = 0.002 and 0.005 respectively), progesterone receptor negative (p = 0.001 and 0.003 respectively) hormonal status and molecular subtypes (p = 0.0007 and 0.014 respectively). A significant strong agreement was detected between fascin and MMP-9 expression (p = 0.0001). More intense immunostaining of fascin and MMP-9 was observed at the invasive fronts compared with other areas of the tumor. Moreover, a significant moderate agreement between fascin and MMP-9 was found regarding the site of predominant intensity.ConclusionFascin and MMP-9 proteins are associated with parameters of poor prognosis in breast cancer. The significant strong agreement between the two markers supports the role of fascin in cell invasiveness by activating matrix proteases besides increasing cell motility. Both proteins may represent potential therapeutic targets for patients with breast cancer especially those with hormone receptor–negative status.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1421167695121127.

Breast cancer in the young (≤35 years): A single center study from the All India Institute of Medical Sciences.

e12539 Background: Breast cancer in young women (&lt;/= 35 years) is uncommon and accounts for 1-2 % of all breast cancer in the West. There is limited data on breast cancer in the young from India. The aim of our study was to assess clinical, pathological parameters and outcome in young breast cancer patients. Methods: We carried out an analysis of 271 patients of young breast cancer patients (&lt;/=35 years) registered between 2000 to 2012 at I.R.C.H, AIIMS, New Delhi, India. Results: The median age was 31 years (range 18-35). The median duration of symptoms was 10 months (range 0.25-60). Breast lump was the commonest (93%) presenting symptom (left &gt;right side). Ninety percent of patients were married and median age at first child birth was 23 years. Positive family history was elicited in only 15 patients. The TNM stage distribution was: stage I was 3 %, stage II- 20%, stage III- 55%, and stage IV- 22%. The median clinical tumour size was 5.1 cm. Modified radical mastectomy was the commonest surgical procedure and this was done in 80 % of cases. The histopathological analysis showed 93% had infiltrating ductal carcinoma. Thirty percent of tumours were high grade and 55% had pathological node positive disease. ER/PR and her-2neu positivity was 33% and 30% respectively. Triple negative breast cancer (TNBC) constituted 33%. Fifty five patients presented with metastasis. A combination of anthracycline and taxanes were used in the majority of patients and Trastuzumab could be used only in 6 cases out of 72 patients who were Her-2 neu positive. With a median follow up of 30 months (non metastatic group), three years disease free survival (DFS) and overall survival (OS) was 50% and 60%. Higher nodal stage, tumour size (&gt;5 cm), negative hormonal status (triple negative) and visceral metastasis at baseline predicted poor outcome. Conclusions: Young women constituted 8 % of breast cancer cases, this proportion is much higher than the published Western figures of 1-2 % and reflects younger age of our population. Even in this young group ER/ PR positivity was 33% and almost a third were her-2 neu positive. Higher nodal stage, tumour size (&gt;5 cm), triple negativity and visceral metastasis at baseline predicted poor outcome.

Characteristics and clinical outcome of T1 breast cancer: A national multicenter retrospective cohort study.

566 Background: T1N0M0 breast cancer (BC) are generally considered as carrying good prognosis and cancer-specific survival rates after 5 to 10 years are as high as 90 or 95% in many studies. However, they constitute a heterogeneous group and many studies identified biologically-defined at-risk patients within T1 BC. The objectives of our study were to describe the main characteristics of T1a, b, and c (11-15mm) BC and to identify prognostic factors for survival. Methods: We retrospectively collected the medical files of all patients diagnosed with BC who underwent sentinel lymph node biopsy (SLNB) between January 1999 and December 2008 in 13 French sites and examined overall survival (OS) and Relapse-free survival (RFS) in T1a, T1b and T1c 11-15 mm. Results: Among 8,100 women operated, 5,423 had T1 tumors (708 T1a, 2,208 T1b and 2,508 T1c 11-15mm). T1a differed significantly from T1b tumors with respect to several parameters : younger age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion (LVI), exhibiting a mix of favorable and poor prognosis factors. After a median follow-up of 60.5 months, OS rate was 97.6% (95CI: 97.1-98) at 60 months, 95.4%(94.5-96.4) at 84 months and 90.7% (85.2-96.4) at 120 months. No significant difference was observed between T1a, T1b and T1c tumors (p=0.335). RFS rates were 94% (95CI: 93.8-95.2), 92.1% [91.1-93.2] and 83.8% (77.6-90.5) at 60, 84 and 120 months respectively. RFS was significantly higher in T1b tumors (95.9%, 95CI: 95-96.9) as compared to T1a (93.2%, 91-95.4) or T1c tumors (93.8%, 92.8-94.9), p=0.0099. In multivariate analysis, SBR tumor grade, hormone therapy and LVI were independent prognostic factors for RFS, while hormone therapy and SBR grade were independently associated with OS. Conclusions: Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of adjuvant systemic therapy (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 breast cancer.

1398P - Clinico-Pathological Characteristics and Treatment Outcome of Young Breast Cancer Patients: an Institutional Study

ABSTRACT Background Breast cancer in young women ( Methods This analysis was carried out in 250 patients aged 35 years or less, who were registered in our clinic between 2000-2011 at I.R.C.H, A.I.I.M.S. This constituted about 7.5% of all new cases. Patients' records were analyzed from computer database using ICD code (C-50). Results The median age was 31 years (range 18-35). The median duration of symptoms was 10 (range 0.25-60). Breast lump was the commonest (93%) presenting symptom (left >right side). Ninety percent of patients were married and median age at first child birth was 23 years. Positive family history was elicited in 10 patients. Five patients presented with synchronous malignancy. The TNM (7th edition) stage distribution was stage I - 2.5 %, stage II - 30%, stage III - 46.5%, and stage IV - 22%. The median clinical tumor size was 5.0 cm. Modified radical mastectomy was the commonest surgical procedure and this was done in 83 % of cases. The histopathological analysis showed 94% had infiltrating ductal carcinoma. Thirty percent of tumors were high grade and 70% had pathological node-positive disease. ER/PR and Her2neu positivity was 33% and 29%, respectively. Triple-negative breast cancer (TNBC) constituted 31%. A combination of anthracyclines and taxanes were used in the majority of patients and trastuzumab was used only in 3 % of cases. With a median follow up of 28 months (non-metastatic group), 3-year disease-free survival (DFS) and overall survival (OS) was 50% and 60%. Higher Nodal stage, tumor size (>5 cm), negative hormonal status (triple negative) and visceral metastasis at baseline predicted poor outcome. Conclusion Young women constituted 7.5 % of breast cancer cases. The proportion of triple negative (nearly one third) was also higher than the Western population. Higher stage and triple negative status results in poorer outcome. Disclosure All authors have declared no conflicts of interest.

1P Trastuzumab in the Adjuvant Setting: Retrospective Study

ABSTRACT Background 25% of primitive breast cancers overexpress the HER2 oncoreceptor which is a poor prognostic factor, indicating a rapid tumor growth and causing a higher incidence of recurrence and metastasis with reduced survival. In Algeria, there are about 6000 new cases of breast cancer per year, about 25% overexpress HER2. Methods A retrospective study of 210 patients with breast cancer in the adjuvant setting at the department of medical oncology between 2006 and 2009. Results Median age of patients was 46 years (range 23 to 75) (15% less than 36 years). In more than half of our patients: tumor size was between 2-5cm, Stage IIB-IIIB, SBR grade II-III (88%), with a predominance of infiltrating ductal carcinoma associated with lymph node dissemination and capsular rupture. Almost half of our series has a positive hormonal status. The delay of the treatment with trastuzumab was between 1-18 months post radiotherapy. Cardiac toxicity has occurred in 3 patients (dilated cardiomyopathy and severe mitral insufficiency) requiring to stop the treatment. 10% of patients relapsed (especially liver, bone) after 25-36 months (6 months after completion of trastuzumab for the most part): they are mainly over 35 years (71%), a negative hormonal status, with lymph node dissemination and capsular rupture for almost majority. Patients under 36 years are mainly stage IIB, SBR II-III, with lymph node dissemination and capsular rupture for all, a negative HR status in more than 55%. There were two deaths (beyond 36 months). Conclusion Trastuzumab is a remarkable progress in the treatment of breast cancer. It provides, in combination with chemotherapy, a higher response rate, prolonged remission and a significant advantage for survival, reducing the risk of recurrence in the adjuvant setting. Disclosure All authors have declared no conflicts of interest.

Clinico-Pathological Characteristics of Triple Negative and Non Triple Negative High Grade Breast Carcinomas with and without Basal Marker (CK5/6 and EGFR) Expression at a Rural Tertiary Hospital in India

Aims of the study were to evaluate the expression Cytokeratin 5/6(CK5/6) and Epidermal Growth Factor Receptor (EGFR) among triple negative breast cancers and high grade infiltrating duct carcinomas. Further to probe if triple negative phenotype can be a surrogate marker for basal phenotype and to correlate the expression of basal markers with disease free survivals among triple negative phenotype and high grade infiltrating duct carcinomas.MethodsExpression of CK5/6 and EGFR were studied by Immunohistochemistry (IHC) in 31 triple negative and 19 non-triple negative high grade breast carcinomas.Results21 of the 31 triple negative phenotype (67.7%) breast carcinomas and 7 out of 19 non-triple negative (36.8%) breast carcinomas showed expression of basal markers (CK5/6 and/or over-expression of EGFR). There were statistically significant associations of all the basal-like tumors with negative hormonal status. The basal markers positive phenotype subjects had a shorter disease free interval as compared to basal markers negative phenotype subjects.ConclusionBasal-like breast carcinomas constitute a unique clinical and pathological entity, characterized by high tumor grade and a propensity for lack of ER, PR and HER2 expression. Basal phenotypes have a more aggressive course than non-basal phenotype. “Triple negative” status cannot be used as a surrogate for “basal marker expression”.

P2-12-14: Prognostic Value of HER2 Positivity and Negative Hormonal Status in Patients with Small Tumor (&amp;lt;1cm) and Node-Negative Breast Cancer.

Abstract Introduction. Human epidermal growth factor receptor 2 (HER2) amplification has become the prototype biomarker to develop tailored biological treatment. Many studies suggested that HER2 positivity is an independent predictor of disease recurrence and breast cancer mortality. Trastuzumab has been introduced into clinical practice for high-risk HER2−positive patients who have completed the standard adjuvant treatment. However, small (&amp;lt;1cm), node-negative tumors remain a subgroup of HER2−positive patients who are currently ineligible for trastuzumab treatment, as clinically they have been deemed to have no requirement for standard adjuvant chemotherapy. The aim of our analysis was to evaluate the prognostic factors of local and distant recurrence in patients diagnosed with T1a-b, node-negative, HER-2 positive breast cancer. Materials and methods. A total of 704 patients were diagnosed at Florence University between November 1999 and December 2008 with node-negative, invasive BC that were 1 cm or smaller. Patients with ductal carcinoma in situ, with recurrent BC at presentation and patients that received adjuvant chemotherapy were excluded from analysis. Results. Mean follow-up was 4.9 years (0.5−10.8 years); we recorded a total of 19 recurrences, including 10 distant recurrences. Mean time to local relapse occurrence was 3.8 years (0.4−7.3 years); mean time to distant metastases diagnosis was 4.4 years (1.4−7.6 years). Among all patients, the recurrence-free survival (RFS) was 93.7%. The only parameter that emerged as significant predictor of events is the age (p=0.02). The distant recurrence-free survival (DRFS) rate was 96.5%. Patients who had HER2−positive BC had worse DRFS than patients who had HER2−negative BC (92.0% v 96.9%; p=0.045). In addition to HER2, also HR status was significantly associated with DRFS (p=0.026). Patients who had HR negative status had worse DRFS than patients who had HR positive status (91.4% v 97.4%; p=0.045). Conclusions. Patients with T1a-b, node-negative, breast cancer have a low risk of distant and local recurrence. Women with HER2−positive and negative hormonal status have a significant risk of distant recurrence and should be considered for anti-HER2 adjuvant therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-14.

Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy

To assess the prognostic and predictive significance of p53 and Bcl-2 protein expression in high risk patients with breast cancer treated with dose-dense sequential chemotherapy. From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (P) 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. p53 and Bcl-2 expression was investigated by immunohistochemistry in 392 and 397 patients respectively. Positive expression of p53 was detected in 104 (26.5%) patients and was significantly associated with negative hormonal status, worse histologic grade, higher incidence of disease relapse and higher rate of death. p53 positive expression was a significant negative predictor of overall survival (OS) (P = 0.002) and disease-free survival (DFS) (P = 0.001). Negative expression of Bcl-2 was detected in 203 (51%) patients and was significantly associated with negative hormonal status. Multivariate analysis revealed that, positive p53 expression, higher number of positive nodes and worse tumor grade were related to significantly poorer OS and DFS. For both treatments, p53 positive expression was a significant negative prognostic factor for OS and DFS while Bcl-2 was not. No predictive ability of p53 status or Bcl-2 status for paclitaxel treatment was evident.

Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose–dense sequential adjuvant chemotherapy

To assess the prognostic and predictive significance of HER-2 overexpression and high expression of VEGF in high-risk patients with breast cancer treated with dose-dense sequential chemotherapy. From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (T) 250 mg/m2 followed by three cycles of "intensified" CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. HER-2 was assessed by immunohistochemistry (IHC) in 394 patients, and by fluorescence in situ hybridization (FISH) in cases scored as 2+ by IHC. VEGF was evaluated in 323 patients by IHC. HER-2 overexpression was detected in 123 patients (31%) and high expression of VEGF in 233 (72%). The rate of HER-2 overexpression was significantly higher in patients with positive VEGF staining (35% vs. 21%, p=0.02). Overexpression of HER-2 was significantly associated with negative hormonal status, high histologic grade and larger tumors. HER-2 overexpression was a significant negative predictor of DFS (p=0.002), but not of OS. Adjusting for HER-2 overexpression, DFS and OS did not significantly differ between treatment groups. Positive VEGF staining was not associated with receptor status, number of positive nodes, grade, tumor size, incidence of relapse or death. For both treatments, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident.

Flow cytometric analysis of Ki-67 in invasive ductal carcinoma of the breast: correlation with tumor and patient characteristics.

Of all markers associated with cellular proliferation in breast carcinoma, Ki-67 has more often been correlated with prognosis in patients with these tumors than others. To investigate the relevance of Ki-67 determination at each phase of the cell cycle in the biological assessment of mammary carcinoma we applied bivariate Ki-67/DNA content analysis on samples from 154 resected primary lesions. Three Ki-67-derived indices including an overall and G1 and S+G2M indices were generated. These values were correlated with similar indices derived from flow cytometric DNA/RNA analysis and traditional clinicopathologic factors. The results show that overall Ki-67 indices do not correlate with flow cytometric values and clinicopathologic factors. Flow-derived Ki-67 and DNA S+G2M indices were positively correlated (p<0.0001, r=0.58). High indices for the S+G2M phase derived by both Ki-67 and DNA analysis were significantly correlated with DNA aneuploidy, high tumor grade, and negative hormonal status. We conclude that the proliferative fraction (S+G2M) by either Ki-67 or DNA analyses offers more practical and clinically relevant information in assessing the proliferative activity in mammary carcinoma.