Evaluation of Association between Tumor Markers, Hormonal Receptors, Inflammatory Biomarkers and Breast Cancer

158 Background: In female breast cancer, estrogen receptor (ER) and/or progesterone receptor (PR) positivity confers a favorable prognosis; however, the effect of these hormone receptors (HR) on survival in male breast cancer (MBC) is controversial. The aim of this study isto determine if there is a difference in the 5 year cancer specific survival (CSS) rate of patients in different HR subgroups of MBC using the SEER database. Methods: We included patients with MBC ≥ 18 years of age in the SEER database from 1990 to 2011. Patients with unknown or borderline ER or PR status were excluded. Patients were divided into four subgroups based on HR status: ER+/PR+, ER+/PR-, ER-/PR+, ER-/PR-. Univariate analysis was done using t-test and chi-square. Multivariate Cox regression analysis was used to evaluate hazard ratios and determine the significance of covariates. Kaplan -Meier method was used to estimate survival. Results: We included 3,341 patients. The mean age was 64.9 years (SD 12.7) and most (2736, 81.9%) were Caucasians. The majority (2770, 82.9%) had ER+/PR+ tumors, 377 (11.3%) had ER+/PR- , 33 (1.0 %) had ER-/PR+ and 161(4.8%) had ER-/PR- tumors. Caucasians were more likely to have MBC positive for both ER and PR compared to African-Americans (84.1% versus 74.3%, P< 0.001). ER-/PR- tumors were more likely to be poorly differentiated compared to ER+/PR+ , ER+/PR- and ER-/PR+ (62.7%, 32.2%, 44.8%, 36.4% respectively , P<0.001). There was a significant difference in 5 year CSS of HR subgroups only in stage III and IV, with subgroups positive for ER consistently showing improved survival compared to ER-/PR- (Table). On multivariate analysis, positive ER or PR status was independently associated with decreased hazard of death (Hazard Ratio: 0.68 (p = 0.03); 0.78 (p = 0.04) respectively). Conclusions: Our study showed a significant difference in the 5 year CSS rate of patients in different HR subgroups of advanced stages (III and IV) of MBC. Positive HR status was associated with a better prognosis. [Table: see text]

A very broad definition of a tumor marker is: a tool that enables the clinician to answer clinically relevant questions regarding a cancer disease (1). However, most researchers in this field would probably prefer the following more specific definition of a tumor marker: a molecule, a process, or a substance that is altered quantitatively or qualitatively in precancerous or cancerous conditions, the alteration being detectable by an assay (2). Alterations can be produced either by the tumor itself or by the surrounding normal tissue as a response to tumor cells (2). Regardless of which definition is preferred, the tumor marker itself can be DNA, mRNA, protein, or processes (apoptosis, angiogenesis, proliferation, etc.) measured quantitatively or qualitatively by an appropriate assay. In addition, the types of specimen in which the tumor marker is detected can be different; tissue, blood (plasma/ serum), saliva, urine, etc. are all used. The tumor marker assays can be of very different formats ranging from complex animal models to immunohistochemical test kits. The most commonly used format is probably the immunoassay, which is a well-characterized methodology. However, this field is progressing rapidly, and new and advanced assays such as microarrays and mass spectrometry are becoming established technologies in tumor marker research. The first known tumor marker was described in 1846, when Henry Bence-Jones reported the precipitation of a protein in acidified urine from patients with multiple myeloma. Detection of the monoclonal immunoglobulin light chain in this disease is still in use, and since then numerous potential tumor markers have been reported on in the literature (1). Examples of such markers in clinical use are: alpha-fetoprotein for tumors of the liver, testis, and other germ cell line tumors, CA125 for ovarian cancer, prostate specific antigen (PSA) for prostate cancer, and steroid hormone receptors (estrogen and progesterone receptor) used in management of breast cancer. However, as the field of tumor markers has expanded rapidly over the last two decades with a concomitant increase in published reports, it has become increasingly apparent that a strong need exists for establishment of consensus guidelines for development and use of tumor markers. Such guidelines should be internationally accepted if any of these potential new markers are ever to reach a stage where they will benefit the patients. The guidelines should define the potential specific clinical uses of tumor markers, define specific requirements for the technical development of tumor marker assays, and state specific requirements that are to be fulfilled before clinical implementation of a tumor marker. Suggestions for such guidelines have been made; in 1996, a tumor marker expert panel convened by the American Society of Clinical Oncology proposed a framework to be used for evaluation of tumor marker studies: the tumor marker utility grading system (TMUGS), which also includes a framework for rating published evidence (2). The TMUGS framework is further discussed in “Clinical Testing.” However, work in this field is still ongoing, and some important aspects to consider in the process of designing such guidelines will be covered in this review. The possible clinical uses of tumor markers are manifold, and several categories of markers can be defined. A diagnostic tumor marker is a marker that will aid in detection of malignant disease in an individual. Preferably, the marker should be tissue specific and not be influenced by benign diseases of the particular tissue/organ. Thus, a diagnostic marker should exhibit both high levels of diagnostic sensitivity and specificity (see below) to be of clinical value, especially if the marker is to be used for (mass) screening purposes. A fundamental prerequisite for development of any diagnostic (screening) tumor marker lies in the nature of the disease From the ‡Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Ridebanevej 9, DK-1870 Frederiksberg C, Copenhagen, Denmark, §Department of Chemical Endocrinology, University Medical Centre Nijmegen, P.O. Box 9101, Geert Groteplein 10, NL-6500 HB Nijmegen, The Netherlands, ¶Clinical Research Unit, Department of Obstetrics & Gynaecology, Technical University of Munich, Ismaninger Strasse 22, D-81675 Munchen, Germany, and Rotterdam Cancer Institute (Daniel der Hoed Klinik), Josephine Nefkens Building, Nr. BE 426, Dr. Molewaterplein 50, NL-3015 GE Rotterdam, The Netherlands Received, June 9, 2003 Published, MCP Papers in Press, June 17, 2003, DOI 10.1074/mcp.R300006-MCP200 1 The abbreviations used are: PSA, prostate specific antigen; TMUGS, tumor marker utility grading system; CEA, carcino-embryonic antigen; uPA, urokinase-type plasminogen activator; PAI-1, plasminogen activator inhibitor type-1; EORTC, European Organisation for Research and Treatment of Cancer; RBG, Receptor and Biomarker Group; ER, estrogen receptor; PgR, progesterone receptor; HCG, human chorionic gonadotropin; QC, quality control; LOE, level of evidence. Review

Purpose: Male breast cancer (MBC) is extremely rare, accounting for less than 1% of all malignancies in men and only 1% of all breast carcinomas. The treatment and surveillance guidelines on male breast cancers are less recognized. The aim of this study is to evaluate our single institution's experience with MBC over the past 15 years and to contrast differences between female and MBC. Methods: MBC diagnosed from 1994 to 2010 at the Department of Surgery, Samsung Medical Center (Seoul, Korea) was retrospectively analyzed. Clinical data and tumor characteristics were examined. Each MBC was matched with female counterparts by 1:N varied matching ratio that showed accordance in seven variables (year of diagnosis, age, tumor stage, nodal stage, tumor grade, estrogen receptor(ER), progesterone receptor(PR)). Results: 39 male/184 female matched-pairs were available for analysis. The median duration of follow-up was 3.8 years. The median age of MBC patients was 50 years and the median size of tumor was 2.0cm. The proportion of positivity of ER and PR status was 97.4% and 84.6%, respectively. Despite of higher positive rate of hormone receptor, the rate of hormone therapy in MBC patients was significant lower than female conterpart (p = 0.002). Men and women with breast cancer had similar disease-free survival (DFS) and disease-specific overall survival (DSS). Five MBC patients had a recurrence during follow up period and 4 of them were expired. The 10-years DFS was 73.1% in men and 80.5% in women (p = 0.348). The 10-years DSS was 74.1% in men and 87.1% in women, respectively (p = 0.207). Conclusion: This study showed no disease free and overall survival differences between male and female breast cancer patients and revealed that gender is no predictor for survival in breast cancer. Male patients receive obviously less adjuvant treatment compared their female matched patients. It would be better to do more aggressive treatment in MBC to improve the survival outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-11-01.

In 2011, carcinoma of the breast in men accounted for ∼1% of all breast cancers in the US, and approximately 450 male patients died from this disease. Although breast carcinomas in both genders share certain pathological features, notable differences have been observed regarding incidence, prognosis and survival. Results from microarray analyses in our studies and those of other reports were used to select 33 candidate genes to investigate in male breast carcinomas. Tumor marker results for 99 male breast cancers and ∼18,000 female breast carcinomas were extracted from our IRB-approved comprehensive database. Estrogen receptor (ER) and progestin receptor (PR) levels were determined by either radio-ligand binding (NEN/DuPont) or enzyme immunoassay (Abbott Labs). HER-2/neu levels were determined by either ELISA (Oncogene Science) or EIA (Triton Biosciences), and epidermal growth factor receptor (EGFR) levels were determined by an in-house radio-ligand competition assay. RNA was isolated from tissue sections of de-identified frozen biopsies from 12 male patients and 233 female patients using the RNeasy Mini kit (Qiagen) and analyzed for quality and quantity (Agilent Bioanalyzer). cDNA for qPCR measurements was prepared in Tris-HCl buffer with KCl, MgCl2, DTT (Invitrogen), dNTPs (Invitrogen), RNasin (Promega) and Superscript RT III (Invitrogen). qPCR reactions were performed using Power Sybr Green PCR Master Mix (Applied Biosystems), forward/reverse primers and cDNA obtained from the reverse transcription reaction. Relative gene expression was calculated by the ddCt method using β-actin as a reference and Universal Human Reference RNA (Stratagene) as a calibrator. Among 99 male breast cancers, 82 were ER positive and 78 exhibited PR. Levels of ER (P = 0.013) and PR (P < 0.001) protein were greater in male breast cancers compared to biopsies from female patients, although no difference was observed in the expression of ESR1 and PGR genes that encode these receptors. In contrast, no differences were observed in either of the other conventional breast cancer biomarkers, HER-2/neu or EGFR protein, nor in patient age at diagnosis. However, there was a difference in the binding affinities (Kd value) of PR (P = 0.004) between the genders, which was not observed in ER between male and female breast cancer tissues. Furthermore, expression levels of six genes (NAT1, TBC1D9, IL6ST, RABEP1, PLK1 and LRBA) that we and others have suggested serve as indicators of risk of recurrence, were elevated in male breast cancer biopsies compared to those from female patients (P < 0.05). Preliminary results suggest that over-expression of the protein product of one or more of the genes identified represents a molecular target that warrants further exploration for development of a gender specific therapeutic and companion diagnostic. Supported in part by a grant from Phi Beta Psi Charity Trust and a CTSP Award from the Commonwealth of Kentucky. Citation Format: Sarah A. Andres, Irina A. Smolenkova, James L. Wittliff. Gender-associated expression of tumor markers and a small gene set in breast carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3457. doi:10.1158/1538-7445.AM2013-3457

Metastatic Carcinoma of the Breast Resembling Early Gastric Carcinoma

Male breast cancer (MBC) is rare and poorly characterized. Like the female counterpart, most MBCs are hormonally driven, but relapse after hormonal treatment is also noted. The pan-hormonal action of steroid hormonal receptors, including estrogen receptor alpha (ERα), androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) in this understudied tumor type remains wholly unexamined. This study reveals genomic cross-talk of steroid hormone receptor action and interplay in human tumors, here in the context of MBC, in relation to the female disease and patient outcome. Here we report the characterization of human breast tumors of both genders for cistromic make-up of hormonal regulation in human tumors, revealing genome-wide chromatin binding landscapes of ERα, AR, PR, GR, FOXA1, and GATA3 and enhancer-enriched histone mark H3K4me1. We integrate these data with transcriptomics to reveal gender-selective and genomic location-specific hormone receptor actions, which associate with survival in MBC patients.

Background: Male breast cancer (MaBC) is an uncommon disease, and population-based information regarding prognostic factors is limited. Most MaBC are hormone receptor (HR) positive, however, the association of tumor subtypes with overall survival (OS) and breast cancer-specific survival (BCSS) is unclear. The aim of this study was to analyze the characteristics of each tumor subtype and its impact on OS and BCSS. Methods: Using Surveillance, Epidemiology, and End Results (SEER) data, we identified men with invasive breast cancer between 2010 and 2014 with known estrogen receptor and progesterone receptor (together HR) status and human epidermal growth factor receptor 2 (HER2) status. Tumor subtypes were classified as: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple negative (TN). We examined tumor subtypes by patient (pt) characteristics and performed multivariate Cox proportional hazards analyses to determine the associations of each variable with OS and BCSS. Results: We included 1508 pts with a median follow-up of 24 months (range 0-60). Median age was 65 years (range 26-97). At diagnosis, 86.6% of tumors were ductal, 97.1% HR+, 42.1% T1, 55.7% N0, 7.9% M1. Tumor subtype distribution was: 85.5% HR+/HER2-, 11.6% HR+/HER2+, 0.9% HR-/HER2+ and 2% TN. Compared with other subtypes, pts with TN tumors had higher grade disease, presented with more advanced stage and died more often from breast cancer (all p<0.0001); whereas pts with HR+/HER2- tumors were older (p=0.02) and more often white (p=0.02). In univariate analysis, OS at 5 years for all HER2- and all HER2+ was 74.2% and 64.1%, respectively (p=0.002); while BCSS at 5 years for all HER2- and all HER2+ was 88.4% and 78.8%, respectively (p=0.009). Of all subtypes, TN had the worst OS and BCSS (p<0.0001). Breast cancer was the cause of death in 43.7% of HR+/HER2-, 54.2% of all HER2+ and 100% of TN (p<0.0001). In multivariate analyses for OS, older pts (Hazard ratio [HaR] 3 vs. <50 years; p=0.001), stage IV (HaR 9 vs. stage I; p<0.001), HR+/HER2+ tumors (HaR 1.9 vs. HR+/HER2-; p=0.003), TN tumors (HaR 8.5 vs. HR+/HER2-; p<0.001) and unmarried pts (HaR 1.9 vs. married; p=0.002) had significantly worse survival. In multivariate analyses for BCSS, stage IV (HaR 25.7 vs. stage I; p<0.001), HR+/HER2+ tumors (HaR 2.1 vs. HR+/HER2-; p=0.019), TN tumors (HaR 17 vs. HR+/HER2-; p<0.001) and unmarried pts (HaR 2.2 vs. married; p=0.009) had significantly worse survival. Conclusion: We observed significant differences in outcomes by tumor type in men with breast cancer which mirror those previously observed for women with breast cancer. Among the limited numbers of men with HER2+ and TN disease in our sample, outcomes were poor, suggesting possible under-treatment, aggressive tumor biology, and/or more advanced of disease at presentation. Studies to better understand the inferior survival for men with these subtypes are warranted and efforts to ensure appropriate treatment are paramount. Citation Format: Leone J, Freedman RA, Zwenger AO, Lin NU, Tolaney SM, Vallejo CT, Leone BA, Winer EP, Leone JP. Tumor subtypes and survival in male breast cancer: SEER 2010-2014 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-19-02.

Objective. The aim of the present study was: (a) to measure levels of the tumor markers, Carcinoembryonic antigen (CEA), Cancer antigen 19-9 (CA19-9), Cancer antigen 125 (CA125), Neuron specific enolase (NSE) and Cytokeratin fragments 19 (CYFRA21-1); (b) to investigate any correlation between them and the inflammatory biomarkers C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR) and white blood cells count (WBC), in patients with chronic obstructive pulmonary disease (COPD) exacerbation, who belong in groups of severity C and D, as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD); (c) and finally, to compare these results in these two groups. Material and methods. Fifty-two patients with COPD exacerbation [35 male/17 female, mean age (± SD) 68.3 ± 6.4 years] were the study subjects, and were classified in severity groups C (n = 27) and D (n = 25), based on the spirometric classification, the number of exacerbations in the preceding year and the assessment of their symptoms by GOLD. Results. CEA and CA125 were increased in group D. In group C, there was a significant correlation between CRP and CA125 (p = 0.05). In group D, there was a significant correlation between WBC and NSE (p = 0.02), between CRP and CA19-9 (p = 0.02) and NSE (p < 0.001), and between the ESR and NSE (p = 0.03). CA125 (p = 0.01) and CA19-9 (p = 0.01) were significantly higher in group D compared to group C. In contrast, there was no significant difference in two groups for NSE, CEA and CYFRA21-1. Conclusion. Certain tumor markers were increased and were associated with increased levels of inflammatory biomarkers and with the disease severity. Inflammation might have a key pathogenetic role linking the above tumor markers with the severity of COPD.

Male breast cancer is rare, and something different from female breast cancer. The characteristics of molecular subtype in male breast cancer is unclear and lack of large-sample study. A retrospective study was conducted to investigate the characteristics and prognosis of patients with male breast cancer using the data recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2014. A total of 1,597 cases were enrolled with median age of 66 years. The study endpoint was considered as patient death. The molecular subtype was defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, hormone receptor (HR) positive was defined as ER positive with or without PR positive, including 1,373 cases of HR+/HER2- tumor (86%), 182 cases of HR+/HER2+ tumor (11.4%), 13 cases of HR-/HER2+ tumor (0.8%) and 29 cases with triple negative (TN) tumor (1.8%), respectively. There were significant differences in distributions of age, race, grade, tumor size and American Joint Committee on Cancer (AJCC) stage between different molecular subtypes. Patients of different molecular subtypes differed significantly in 5 years overall survival and cause-specific survival (CSS). Five-year CSS (5y-CSS) rates of different molecular subtypes was 89.2% (HER2-/HR+), 78.4% (HER2+/HR+), 72.6% (HER2+/HR-) and 43.2% (TN), respectively. According to Cox regression, age ≥65 years [P=0.001, hazard ratio (HR) =2.136 (1.372, 3.324)], ER negative [P=0.02, HR =2.481 (1.159, 5.319)], PR negative [P=0.007, HR =2.294 (1.256, 4.184)], TN subtype [P<0.001, HR =10.676 (4.441, 25.665)], AJCC stage IV [P<0.001, HR =21.222 (10.377, 43.4)], tumor size >5 cm or T4 [P<0.001, HR =2.577 (0.978, 6.792)], Stage M1 [P=0.001, HR =4.519 (1.929, 10.587)] and Black race [P=0.002, HR =2.322 (1.442, 3.74)] were independent prognostic factors for poorer CSS. Just like female, molecular subtypes also varied in male breast cancer. It could be a predictor for survival and improve the strategy making in clinical practice.

Male breast cancer (MBC) is a rare and poorly characterized disease. In the present study we used a novel biomathematical model to further characterize MBC and to identify differences between male and female breast cancer (FBC). A total of 134 cases of MBC were stained immunohistochemically for 13 key oncoproteins, and staining percentages were used in a mathematical model to identify dependency patterns between these proteins. The results were compared with a large group of FBC (n = 728). MBC and FBC clearly differed on the molecular level. In detail, the results suggest a different role for progesterone receptor (PR) compared to oestrogen receptor (ER) in MBC, while in FBC ER and PR show a similar pattern. In addition, Androgen receptor (AR) seems to be a more powerful effector in MBC. Grades 1 and 2 tumours were clearly separated from grade 3 tumours, and luminal types A and B tumours also showed a different pattern. Defined morphological and molecular phenotypes can be identified in MBC, but these seem to be the result of different molecular mechanisms and perhaps multiple genetic pathways, as characterized previously in FBC, emphasizing the rising concept that MBC and FBC should be regarded as different and unique diseases.

Tumor markers such as carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are widely used for monitoring breast cancer. However, the prognostic efficacy of preoperative elevations of CEA and CA15-3 levels in breast cancer patients remains controversial. We retrospectively analyzed the clinicopathological parameters of 149,238 patients in the Korean Breast Cancer Society Registry Database who underwent surgery between January 2000 and December 2015. The patients with elevated CA15-3/CEA levels had worse overall survival (OS) than the patients with normal CA15-3/CEA levels. For the luminal A subtype, the CA15-3- and CEA-elevated group had a hazard ratio (HR) of 2.14 (95% CI 1.01-4.55). The CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68) compared to the normal group. For the luminal B subtype, the CA15-3- and CEA-elevated group had an HR of 3.99 (95% CI 2.23-7.16), whereas the CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68). For the HER2 subtype, elevated CEA level was the only independent prognostic factor. However, for the triple-negative breast cancer (TNBC) subtype, elevated preoperative CEA and CA15-3 levels were not significant prognostic factors for OS. Preoperative CEA and CA15-3 levels showed varying prognostic ability according to breast cancer subtype. Preoperative CA15-3 and CEA elevation are significant prognostic factors for luminal breast cancer, but they were not significant factors for TNBC.

1069 Background: The outcomes of male breast cancer (MBC) and female breast cancer (FBC) according to tumor subtype are poorly known. Our group previously reported the prognostic significance of tumor subtypes in MBC. The aim of this study was to analyze differences in OS between MBC and FBC according to tumor subtype compared with other factors. Methods: We evaluated men and women with microscopically confirmed invasive breast cancer between 2010 and 2013 with known estrogen receptor (ER) and progesterone receptor (PR) (together hormone receptor [HR]) status and human epidermal growth factor receptor 2 (HER2) status reported to the SEER program. Patients (pts) with other primary either before or after breast cancer were excluded. Pt characteristics were compared between MBC and FBC. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Results: We included 1,187 MBC and 166,054 FBC pts. Median age for MBC was 65 years (range 26-97) and for FBC was 60 years (range 18-108). Median follow-up was 21 months (range 1-48) for both groups. OS at 3 years for MBC and FBC was 85.6% and 90.4%, respectively (p = 0.0002). MBC pts were more frequently ductal, had higher grade, presented with more advanced stage and were more often HR+/HER2- (all p &lt; 0.0001). MBC had worse OS than FBC in HR+/HER2- (Hazard ratio [HaR] 1.5; p = 0.0005), HR+/HER2+ (HaR 2.8; p &lt; 0.0001) and triple negative (TN) (HaR 4.3; p &lt; 0.0001) (p for interaction &lt; 0.02). MBC had significantly worse OS than FBC in stage I and II, but similar OS in stage III and IV (p for interaction &lt; 0.01). In multivariate analysis adjusted for age, race, grade, stage, surgery, radiation and marital status; HR+/HER2+ was the only subtype with significant differences in OS between MBC and FBC (HaR 2.0; p = 0.002). Conclusions: In this cohort, we observed significant differences in the distribution of tumor subtypes between MBC and FBC. OS was significantly different in both groups. Men had worse OS in stage I and II while similar OS in stage III and IV. There were significant differences in OS according to tumor subtype; compared with women, men with HR+/HER2+ tumors had twice the risk of death.

587 Background: The incidence of MBC continues to rise. Few studies have addressed the differences between MBC and female breast cancer (FBC). Treatment for MBC has ben extrapolated from FBC regimens. The VA cancer registry (VACCR) provides a unique source to study MBC. This retrospective analysis aims at comparing the characteristics and outcome of MBC and FBC in the VA population. Methods: We reviewed the VACCR database between 1995 and 2005, for 120 VA medical centers. Primary breast cancer site codes were identified (500–508). Data was entered and analyzed using bio-statistical software SPSS. Results: A total of 3025 patients :612 MBC and 2413 FBC were compared. Mean age at diagnosis was 67 for MBC and 57 for FBC (p &lt;0.005). More MBC patients were black. MBC patients presented with a significantly higher stage of disease, more node positive(N+) and larger tumor size. In MBC, ductal histology was more common while lobular and ductal carcinoma in situ were less common than in FBC. ER + and PR + tumors were significantly more common in MBC (60% vs 52% and 53% vs 47%, P&lt; 0.005). MBC patients received less chemotherapy while no statistical difference in hormonal treatment was observed. The median overall survival (OS) was lower for MBC (7 years vs 9.8 years, p&lt;0.005). OS was not significantly different for stage III and IV while OS was inferior for MBC in stage I (7 yr vs not reached, p 0.005) and stage II (6 vs 8.6yr, p 0.001). In N- tumors, OS was inferior in MBC (6.1 vs 14.6 yr, p&lt;0.005) but not statistically different for N+ tumors . In ER + and PR + tumors, OS was inferior in MBC (7yr vs 8yr and 7.3 yr vs 9.8 yr p&lt;0.005); however, no statistical significance was observed in ER - or PR - tumors. Using Cox regression analysis age, sex, clinical stage, nodal status were statistically independent prognostic factors while race, histology and grade were not. Conclusion: This study suggests differences in the biology, pathology, presentation, and survival between male and female VA breast cancer patients. Survival of MBC patients appears inferior in early stage disease and N- tumors suggesting gender differences in the tumor pathogenesis and biology. In hormone receptor + MBC, survival was also inferior despite similar hormonal treatment practices. This observational study calls for different approach and treatment strategies in MBC. No significant financial relationships to disclose.

Steroid hormone receptor expression in male breast cancer

Context The rate of male breast cancer is a small fraction of that observed in females, thus severely limiting our understanding of the pathogenesis of this condition. It remains unclear whether the biological behavior and tumor progression associated with male breast cancer parallel that of the female form. Objectives To evaluate the immunohistochemical profile of male breast carcinomas and to compare this profile with that of stage-matched female breast cancers. Design Seventy-five cases of primary male breast cancer were identified using the records of the Saskatchewan Cancer Foundation over a period of 26 years (1970-1996). Fifty-nine of these cases had formalin-fixed, paraffin-embedded tissue blocks available for the purposes of this study. All cases were reviewed and a standardized modified Bloom-Richardson grading criterion was applied. Estrogen receptor status, progesterone receptor status, c-Erb-B2 expression, p53 expression, and Bcl-2 expression were evaluated by immunohistochemistry. Results from 240 consecutive cases of stage-matched female breast cancers analyzed in the same laboratory were used as a standard set for comparison. Results Male breast cancers tended to be high grade (85% grade 3) in comparison with the female breast cancers (50% grade 3). In descriptive analysis across all stages of disease, male carcinomas were more frequently estrogen receptor positive (81% vs 69%) than their female counterparts. Despite their high grade, they were less likely to overexpress p53 (9% vs 28%) and Erb-B2 (5% vs 17%) than the female counterparts. There was no significant difference in either progesterone receptor (63% vs 56%) or Bcl-2 (79% vs 76%) overexpression. Stratified analysis by stage-matched controls showed no statistically significant differences among the men and women with stage I disease. However, in stage II-matched samples, statistically significant differences were observed between the 2 groups. The male cancers were more likely to overexpress estrogen receptor (81.6% vs 64.4%, P = .04), progesterone receptor (71.1% vs 47.5%, P = .01), and Bcl-2 (78.9% vs 69.4%, P = .20). They also showed statistically significant lower expression of p53 (7.9% vs 36.3%, P = .001) and Erb-B2 (5.3% vs 23.8% P = .01). Conclusion Male breast cancers display distinct immunophenotypic differences from those occurring in women, implying a different pathogenesis in the evolution and progression of this disease. Such differences may play key roles in therapeutic management, warranting different treatment strategies in comparison to female breast cancers.