Prognostic value of estrogen receptor α and progesterone receptor conversion in distant breast cancer metastases

BACKGROUND:

Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor α (ERα) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ERα and PR on survival in a large group of distant non‐bone breast cancer metastases.

METHODS:

Receptor conversion was studied by immunohistochemistry in a group of 233 metastatic breast cancer patients. Kaplan‐Meier overall survival curves were plotted, and differences between the curves were analyzed by log‐rank analysis. The additional prognostic value of conversion to established prognosticators was studied by Cox regression.

RESULTS:

Overall survival of patients showing conversion from positive to negative ERα or PR, or from negative to positive ERα or PR, or remaining receptor negative was comparable, and significantly worse than patients remaining receptor positive. ERα or PR receptor conversion from positive in the primary breast tumor to negative in distant metastases has independent negative prognostic value.

CONCLUSIONS:

ERα or PR receptor conversion from positive in the primary breast cancer to negative in distant metastases has negative prognostic value. Cancer 2012. © 2012 American Cancer Society.     

The prognostic significance of lymphovascular invasion in invasive breast carcinoma

BACKGROUND:

Although lymphovascular invasion (LVI) has been associated with a poor outcome in patients with breast cancer, it is not included in most internationally recognized staging systems, including the American Joint Committee on Cancer tumor, lymph node, metastasis (TNM) classification. This is mainly because it remains unclear whether the presence of LVI is an independent, high‐risk criterion in clinically relevant staging subgroups.

METHODS:

The current study was based on a large and well characterized consecutive series of patients who had operable (pathologic T1 [pT1]‐pT2, pathologic N0 [pN0]‐pN3, M0) breast cancer (3812 informative cases) who were treated according to standard protocols at a single institution and who had long‐term follow‐up to assess the prognostic value of definite LVI in clinically and molecularly relevant staging subgroups.

RESULTS:

LVI was strongly associated with both breast cancer‐specific survival (BCSS) and distant metastasis‐free survival (DMFS) in the entire series and in different subgroups. Multivariate analyses identified LVI as an independent predictor of both BCSS and DMFS in patients with operable breast cancer overall; in the TNM clinical subgroups pT1a‐pT1c/pN0 and pT2/pN0; and in the molecular classes estrogen receptor (ER)‐positive, ER‐negative, human epidermal growth factor 2 [HER2]‐negative, and triple‐negative. In patients who had lymph node‐negative tumors, LVI could be used as a high‐risk criterion providing survival disadvantage equivalent to that provided by 1 or 2 involved lymph nodes (pN0 to pN1) and to that provided by 1 size category (pT1 to pT2). The use of immunohistochemistry for detecting an endothelial‐specific marker contributed to the prognostic significance of LVI when applied to routine LVI negative/possible cases.

CONCLUSIONS:

LVI provided a strong predictor of outcome in patients with invasive breast cancer and should be incorporated into breast cancer staging systems. Cancer 2012. © 2011 American Cancer Society.     

Survival in patients with metastatic recurrent breast cancer after adjuvant chemotherapy

BACKGROUND:

Population‐based studies have shown improved survival for patients diagnosed with metastatic breast cancer over time, presumably because of the availability of new and more effective therapies. The objective of the current study was to determine whether survival improved for patients who developed distant recurrence of breast cancer after receiving adjuvant therapy.

METHODS:

Adjuvant chemotherapy trials coordinated by the Eastern Cooperative Oncology Group that accrued patients between 1978 and 2002 were reviewed. Survival after distant disease recurrence was estimated for progressive time periods, and adjusted for baseline covariates in a Cox proportional hazards model.

RESULTS:

Of the 13,785 patients who received adjuvant chemotherapy in 11 trials, 3447 (25%) developed distant disease recurrence; the median survival after recurrence was 20 months (95% confidence interval, 19 months‐21 months). Factors associated with inferior survival included a shorter distant recurrence‐free interval (DRFI), estrogen receptor‐negative and progesterone receptor‐negative disease, the number of positive axillary lymph nodes present at the time of diagnosis, and black race (P < .0001 for all). When the time period of recurrence was added to the model, it was not found to be significantly associated with survival for the general population with disease recurrence. Survival improved over time only in those patients with hormone receptor‐negative disease with a DRFI ≤ 3 years, both among the 5 most recent and the entire trial data sets (P = .01 and P = .05, respectively).

CONCLUSIONS:

In contrast to reports from population‐based studies, no general improvement in survival was observed over the last 30 years for patients who developed distant disease recurrence after adjuvant chemotherapy after adjusting for DRFI. Improved survival for patients with hormone receptor‐negative disease with a short DRFI suggests a benefit from trastuzumab. Cancer 2013. © 2012 American Cancer Society.     

Immunohistochemical surrogate markers of breast cancer molecular classes predicts response to neoadjuvant chemotherapy

BACKGROUND:

Complete pathologic response to neoadjuvant chemotherapy (NACT) is predominantly seen in “ERBB2” and “basal‐like” tumors using expression profiling. We hypothesize that a similar response could be predicted using semiquantitative immunohistochemistry for estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2).

METHODS:

ER, PR, and HER2 were used to classify 359 tumors treated with NACT into 6 groups: luminal A (strong ER+, HER2 negative), luminal B (weak to moderate ER+, HER2 negative), triple negative (negative for ER, PR, and HER2), ERBB2 (negative for ER and PR, but HER2+), luminal A‐HER2 hybrid (strong ER+ and HER2+), and luminal B‐HER2 hybrid (weak to moderate ER+ and HER2+). Complete pathologic response was defined as absence of invasive carcinoma in the breast and regional lymph nodes.

RESULTS:

Thirteen percent (48 of 359) demonstrated complete pathologic response. The highest rate of complete pathologic response was seen in ERBB2 (33%; 19 of 57) and triple negative (30%; 24 of 79) tumor classes. Among the ER+ “molecular” group, the highest rate of complete pathologic response was seen among luminal B‐HER2 hybrid tumors, 8% (2 of 24). Remainder of ER+ tumors demonstrated a very low rate of complete pathologic response, 1.5% (3 of 198). The 5‐year survival for patients achieving complete pathologic response was 96% compared with 75% in patients that failed to achieve complete pathologic response. The overall survival was worse in the ER‐negative group (ERBB2 and triple negative) compared with the ER‐positive group.

CONCLUSIONS:

We confirm the recently defined “triple negative paradox,” or rather “hormone receptor negative paradox,” that despite the best response to NACT, ERBB2 and triple negative tumors show the worst overall survival because of higher relapse among those with residual disease. Cancer 2010. © 2010 American Cancer Society.     

DEAD box 1 (DDX1) expression predicts for local control and overall survival in early stage, node-negative breast cancer

BACKGROUND:

DEAD box 1 (DDX1) is an RNA helicase with a number of roles, including translation initiation, RNA splicing and modification, and possibly DNA double‐strand break repair. Amplification of DDX1 expression has been implicated in tumors including neuroblastoma, Wilms tumor, retinoblastoma, and testicular carcinoma. The purpose of this study was to evaluate the prognostic significance of DDX1 expression in patients with breast cancer treated with breast‐conserving therapy.

METHODS:

Paraffin‐embedded specimens from 282 women with node‐negative stage 1 and 2 breast cancer treated with breast‐conserving surgery and radiation therapy were constructed into tissue microarrays and stained for DDX1. The molecular profiles were correlated with clinicopathologic factors and overall, local, and distant metastatic‐free survival.

RESULTS:

DDX1 positivity was identified in 142 (50%) patients. The median age at diagnosis was 53 years. Eighty percent of the patients had T1 disease; 11% were HER2neu‐positive, and 18% had triple‐negative disease. DDX1 negativity was strongly associated with triple‐negative phenotype (P = .01). DDX1 positivity was found to be associated with improved local relapse‐free survival (96% vs 85%, P = .0233), distant metastatic‐free survival (95% vs 85%, P = .0320), and overall survival (92% vs 84%, P = .0474) at 10 years.

CONCLUSIONS:

Node‐negative, early stage breast cancer patients with high levels of DDX1 were found to have a significant improvement in local control, distant metastatic‐free survival, and overall survival compared with patients with low levels of DDX1. Cancer 2012;. © 2011 American Cancer Society.     

Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer

BACKGROUND:

The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node‐negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status.

METHODS:

The authors reviewed 704 women with T1aT1bN0M0 BC who received treatment at the Radiation‐Oncology Center of Florence University between November 2002 and December 2008. Patients with ductal carcinoma in situ or recurrent BC at presentation and patients who received adjuvant chemotherapy were excluded from the analysis.

RESULTS:

In total, 75 patients had HER2‐positive BC (10.7%). At a mean follow‐up of 4.9 years (standard deviation, 2.6 years; range, 0.5‐10.8 years), 19 events were identified, including 10 distant recurrences. Patients with HER2‐positive BC had worse distant recurrence‐free survival (DRFS) than patients with HER2‐negative BC (hazard ratio, 3.66; 95% confidence interval, 0.94‐14.69; P = .045). Negative hormone receptor (HR) status was associated significantly with worse DRFS (hazard ratio, 0.26; 95% confidence interval, 0.07‐0.93; P = .026). In multivariate analysis, younger age was the only significant risk factor for an event of recurrence (hazard ratio, 0.61;95% confidence interval, 0.20‐1.82; P = .029).

CONCLUSIONS:

The current results indicated that patients with T1a/T1b, lymph node‐negative BC have a low risk of distant and local recurrence, but younger age is a significant risk factor for events occurrence. Young women with HER2‐positive and HR‐negative status have a significant risk of distant recurrence and should be considered for future clinical trials with anti‐HER2 adjuvant therapy. Cancer 2011. © 2011 American Cancer Society.     

Polycomb group protein EZH2 is frequently expressed in inflammatory breast cancer and is predictive of worse clinical outcome

BACKGROUND:

Enhancer of zeste homolog 2 (EZH2), a member of polycomb group proteins, is involved in the regulation of cell cycle progression and has been implicated in various human malignancies, including breast cancer, and also has been associated with aggressive tumor behavior. However, the clinical significance of EZH2 expression in inflammatory breast cancer (IBC), a rare but aggressive type of breast carcinoma, has not been explored. In this retrospective study, the authors examined EZH2 expression in IBC tumors and evaluated the relation between EZH2 expression and patient survival.

METHODS:

Tissue microarrays of 88 surgically resected IBC tumors were stained immunohistochemically for EZH2, and the authors evaluated the association of EZH2 expression status with clinicopathologic factors and clinical outcome.

RESULTS:

The median follow‐up for the entire cohort was 45.7 months, and the 5‐year overall survival (OS) rate was 45%. EZH2 was expressed frequently in IBC tumors (75.7%) and was associated significantly with unfavorable prognostic factors, such as higher tumor grade, negative estrogen receptor status, and triple‐negative status (ie, negative for the estrogen, progesterone, and human epidermal growth factor 2 receptors). Univariate survival analysis indicated that patients who had EZH2‐positive IBC had a significantly lower 5‐year OS rate than patients who had EZH2‐negative IBC (P = .01). In multivariate analysis, only positive EZH2 status remained an independent predictor of worse OS.

CONCLUSIONS:

EZH2 was expressed frequently in IBC tumors. The current results indicated that EZH2 expression status may be used to identify a subset of patients with IBC who have a relatively worse prognosis. Targeting EZH2 also may provide a novel strategy for improving the clinical outcome of patients with IBC. Cancer 2011;. © 2011 American Cancer Society.     

Activated extracellular signal‐regulated kinase is an independent prognostic factor in clinically confined renal cell carcinoma

BACKGROUND:

Extracellular signal‐regulated kinase (ERK) promotes proliferation, metastasis, and poor survival in cancers of the breast, lung, and liver. Advanced localized renal cell carcinoma (RCC) is extraordinarily treatment resistant and has high recurrence rates despite surgery. Limited data exist regarding the prognostic significance of activated (phosphorylated) ERK in RCC. The authors hypothesized that activated ERK (pERK) promotes disease progression and metastasis in localized RCC and may be of value as a biomarker to predict disease recurrence.

METHODS:

The expression profile of pERK was examined by immunocytochemistry using a tissue microarray constructed from 174 drug treatment–naive patients who had undergone radical nephrectomy for localized RCC. Levels of tumor‐cell specific pERK were scored and correlated with clinicopathologic parameters of RCC and disease‐free survival.

RESULTS:

Immunostaining for pERK was present in 36% of all RCCs, with a predominance found in the clear cell histologic subtype. High expression was associated with increased tumor size, increased TNM stage, and vascular invasion. Patients with pERK‐positive tumors had a mean disease‐free survival of 4.19 years, compared with 6.38 years for patients with pERK‐negative tumors (P < .001). Cox regression models revealed pERK to be a significant independent predictor of disease‐free survival, with a hazards score of 2.9 (P < .001), a value similar to tumor grade (hazards ratio, 3.01; P < .001).

CONCLUSIONS:

Expression of pERK is an independent prognostic factor in RCC that is associated with advanced and aggressive pathologic features of renal tumors and predicts the onset of metastasis in patients with localized disease. Cancer 2009. © 2009 American Cancer Society.     

Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women

BACKGROUND:

Breast cancers that are negative for the estrogen receptor (ER), the progesterone receptor (PR), and the HER2 (human epidermal growth factor receptor 2) marker are more prevalent among African women, and the biologically aggressive nature of these triple‐negative breast cancers (TNBCs) may be attributed to their mammary stem cell features. Little is known about expression of the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) in African women. Novel data are reported regarding ALDH1 expression in benign and cancerous breast tissue of Ghanaian women.

METHODS:

Formalin‐fixed, paraffin‐embedded specimens were transported from the Komfo Anoyke Teaching Hospital in Kumasi, Ghana to the University of Michigan for centralized histopathology study. Expression of ER, PR, HER2, and ALDH1 was assessed by immunohistochemistry. ALDH1 staining was further characterized by its presence in stromal versus epithelial and/or tumor components of tissue.

RESULTS:

A total of 173 women contributed to this study: 69 with benign breast conditions, mean age 24 years, and 104 with breast cancer, mean age 49 years. The proportion of benign breast conditions expressing stromal ALDH1 (n = 40, 58%) was significantly higher than those with cancer (n = 44, 42.3%) (P = .043). Among the cancers, TNBC had the highest prevalence of ALDH1 expression, either in stroma or in epithelial cells. More than 2‐fold higher likelihood of ALDH1 expression was observed in TNBC cases compared with other breast cancer subtypes (odds ratio = 2.38, 95% confidence interval 1.03‐5.52, P = .042).

CONCLUSIONS:

ALDH1 expression was higher in stromal components of benign compared with cancerous lesions. Of the ER‐, PR‐, and HER2‐defined subtypes of breast cancer, expression of ALDH1 was highest in TNBC. Cancer 2013. © 2012 American Cancer Society.     

Comparison of American Joint Committee on Cancer pathologic stage T3a versus T3b urothelial carcinoma: Analysis of patient outcomes

BACKGROUND:

The radical cystectomy experience at Vanderbilt University Medical Center was scrutinized to determine whether there was a difference in survival between patients with lymph node‐negative pathologic T3a versus pathologic T3b urothelial carcinoma of the bladder.

METHODS:

Pathologic and clinical data were reviewed on patients who underwent radical cystectomy for urothelial carcinoma between 1995 and 2005. We excluded patients with nontransitional cell cancer, lymph node disease, or with unknown lymph node status. Of the 790 reviewed patients, 75 patients (9.4%) were diagnosed with pathologic T3 urothelial cancer of the bladder. The impact of pathologic substaging (pT3a vs pT3b) was examined to determine the effect on overall, disease‐specific, and recurrence‐free survival.

RESULTS:

The mean age was 68.6 years (36 years to 83 years). Median overall follow‐up was 25.3 months (1.13 months to 130.17 months). Median follow‐up for patients alive at last follow‐up was 55.9 months (25.3 months to 130.2 months). Actuarial overall survival at 5 years was 29.5% for pT3a and 29.3% for pT3b (P = .79). Actuarial disease‐specific survival at 5 years was 54.1% for pT3a and 42.4% for pT3b (P = .21). Actuarial recurrence‐free survival at 5 years was 68.1% for pT3a and 71.9% for pT3b (P = .53).

CONCLUSIONS:

There were no significant differences in overall, disease‐specific, or recurrence‐free survival when comparing lymph node‐negative pT3a versus pT3b urothelial cancer of the bladder following radical cystectomy. Simplification of pathologic staging for urothelial carcinoma of the bladder should be considered at future revisions of the American Joint Committee on Cancer staging system. Cancer 2009. © 2009 American Cancer Society.     

Multifocal breast cancer documented in large‐format histology sections

BACKGROUND:

The prognostic significance of molecular phenotype in breast cancer is well established in the literature. Recent studies have demonstrated that subgross lesion distribution (unifocal, multifocal, and diffuse) and disease extent also carry prognostic significance in this disease. However, the correlation of molecular phenotypes with subgross parameters has not yet been investigated in detail.

METHODS:

In total, 444 consecutive invasive breast cancers that were documented in large‐format histology slides and worked up with detailed radiologic‐pathologic correlation were sampled into tissue microarray blocks and stained immunohistochemically to delineate the molecular subtypes.

RESULTS:

Diffuse or multifocal distribution of the invasive component of breast carcinomas in this series was associated with a 4.14‐fold respectively 2.75‐fold risk of cancer‐related death compared with unifocal tumors irrespective of molecular phenotype. Patients who had human epidermal growth factor receptor 2 (HER2)‐positive cancers; estrogen receptor‐negative, progesterone receptor‐negative, and HER2‐negative (triple‐negative) cancers; or basal‐like cancers had a 2.18‐fold, 2.33‐fold, and 4.07‐fold risk of dying of disease, respectively, compared with patients who had luminal A carcinomas. Unifocal luminal A, HER2‐positive, and basal‐like cancers were associated with significantly better long‐term survival outcomes than their multifocal or diffuse counterparts; luminal B and triple‐negative tumors also had the same tendency. In multivariate analysis, patient age, tumor size category, lymph node status, lesion distribution, and molecular phenotypes remained significant.

CONCLUSIONS:

Multifocality and diffuse distribution of the invasive component were associated with significantly poorer survival in women with breast carcinomas compared with unifocal disease in patients with luminal A, HER2 type, and basal‐like cancers. Molecular classification of breast cancer is a powerful tool but gains in power when combined with conventional and subgross morphologic parameters. Cancer 2013. © 2013 American Cancer Society.     

Fine-needle aspiration cytopathology--an accurate diagnostic modality in mammary carcinoma with osteoclast-like giant cells: a study of 8 consecutive cases

BACKGROUND:

Invasive ductal carcinoma with osteoclast‐like giant cells (OGCs) is a very rare breast tumor the main characteristic of which is the presence of multinucleated cells of histiocytic nature.

METHODS:

The authors report a study of 8 consecutive cases of fine‐needle aspiration cytopathology (FNAC) of breast nodules in which OGCs and malignant epithelial cells were associated and diagnosed as mammary carcinoma with OGCs. These cases were selected over a period of 5 years from more than 6000 patients who were examined during a weekly, single‐day, multidisciplinary breast clinic. The corresponding biopsies and surgical specimens were examined histologically in an immunohistochemical study using a histiocytic marker (cluster of differentiation 68 [CD68]).

RESULTS:

Conventional histologic analysis made it possible to diagnose 5 of the 8 cases as mammary carcinoma with OGCs; whereas, in the other 3 cases, OGCs were not detected without the help of immunohistochemistry.

CONCLUSIONS:

FNAC appeared to be a very efficient way to diagnose breast carcinoma with OGCs, because it detected forms with only a few OGCs that usually are not observed at histologic diagnosis. Consequently, the current results indicated that mammary carcinoma with OGCs may be more frequent than reported previously. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Is it useful to detect lymphovascular invasion in lymph node‐positive patients with primary operable breast cancer?

BACKGROUND:

Lymphovascular invasion (LVI) is a widely recognized prognostic factor in lymph node‐negative breast cancers. However, there are only limited and controversial data about its prognostic significance in lymph node‐positive patients.

METHODS:

Among 931 patients operated on and monitored at the authors' institution for an invasive breast carcinoma between 1989 and 1992, all 374 lymph node‐positive breast cancers entered the study (median follow‐up, 126 months).

RESULTS:

LVI was present in 46% of tumors and was associated with age ≤40 years (P = .02), high histological grade (P = .01), and negative estrogen receptor status (P = .032), but not with tumor size, number of involved lymph nodes, or HER‐2/neu status. LVI was an independent prognostic factor for distant metastases (P = .002). Furthermore, in HER‐2/neu–negative/hormone receptor‐positive (n = 287) tumors, the number of independent prognostic factors (LVI, age, histological grade, number of involved lymph nodes, and tumor size) was associated with a 5‐years metastasis‐free survival ranging from 100% if no factors (n = 25) to 89% ± 2% if 1 or 2 factors (n = 186) and 67% ± 6 if 3, 4, or 5 factors (n = 76) were present (P < .001).

CONCLUSIONS:

LVI is an independent prognostic factor in lymph node‐positive breast cancer and merits further prospective investigations as a decision tool in the adjuvant chemotherapy setting. Cancer 2010. © 2010 American Cancer Society.     

Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma

Objective: To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma (MGC) and signet-ring cell carcinoma (SRCC). Methods: Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using χ 2 test. Survival was analyzed using the Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression model (backward, stepwise). Results: A total of 181 patients with gastric cancer (74 MGC, 107 SRCC) were included. MGC, when compared with SRCC, was featured by senile patients, stage III and IV, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion (P<0.05). The overall 5-year survival rate showed no difference between the two groups (48.8% vs. 44.8%, P>0.05). However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age <60 years, negative distant metastasis, and tumor localized at upper third stomach (P<0.05). Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group. Conclusions: While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.     

Pathologic characteristics of second breast cancers after breast conservation for ductal carcinoma in situ

BACKGROUND:

The number of women diagnosed with ductal carcinoma in situ (DCIS) is increasing. Although many eventually develop a second breast cancer (SBC), little is known about the characteristics of SBCs. The authors described the characteristics of SBC and examined associations between the pathologic features of SBC and index DCIS cases.

METHODS:

Women were identified in the National Comprehensive Cancer Network Outcomes Database who were diagnosed with DCIS from 1997 to 2008 and underwent lumpectomy and who subsequently developed SBC (including DCIS or invasive disease that occurred in the ipsilateral or contralateral breast). The Fisher exact test and the Spearman test were used to examine associations between the pathologic characteristics of SBC and index DCIS cases.

RESULTS:

Among 2636 women who underwent lumpectomy for DCIS, 150 (5.7%) experienced an SBC after a median of 55.5 months of follow‐up. Of these 150 women, 105 (70%) received adjuvant radiotherapy, and 50 (33.3%) received tamoxifen for their index DCIS. SBCs were ipsilateral in 54.7% of women and invasive in 50.7% of women. Among the index DCIS cases, 60.6% were estrogen receptor (ER)‐positive, and 54% were high grade, whereas 77.5% of SBCs were ER‐positive, and 48.2% were high grade. Tumor grade (P = .003) and ER status (P = .02) were associated significantly between index DCIS and SBC, whereas tumor size was not (P = .87).

CONCLUSIONS:

After breast conservation for DCIS, SBC in either breast exhibited pathologic characteristics similar to the index DCIS, suggesting that women with DCIS may be at risk for developing subsequent breast cancers of a similar phenotype. Cancer 2012. © 2012 American Cancer Society.     

Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma

BACKGROUND.

The objective of this study was to evaluate the effect of pericyte coverage (PC) of differentiated tumor microvessels on the prognosis of patients with clear cell renal cell carcinoma (CCRCC).

METHODS.

Samples from 2 cohorts of patients with CCRCC (101 Asian patients and 524 US patients) were prepared using 2 different histologic approaches: routine sectioning versus tissue microarray. Then, the samples were immunohistochemically doubled‐stained for a pericyte marker (alpha smooth muscle actin [α‐SMA]) and a differentiated vessel marker (cluster of differentiation 34 [CD34]), followed by multispectral image capturing and computerized image analyses to quantify the microvessel density (MVD) and the PC of differentiated vessels. The correlations of PC and the MVD:PC ratio with clinicopathologic characteristics were analyzed.

RESULTS.

There was an inverse correlation between differentiated MVD and PC. Higher PC correlated with more aggressive clinicopathologic characteristics of CCRCC in both cohorts, including more advanced T‐classification, higher pathologic grades, and the occurrence of tumor necrosis. The MVD:PC ratio was an independent favorable prognostic factor for overall and recurrence‐free survival in the Asian cohort and for recurrence‐free survival in the US cohort. PC also was an independent prognostic factor, with higher PC predicting a poorer outcome. The combination of PC and MVD was better at distinguishing the outcome of patients with CCRCC. PC combined with differentiated MVD or with the MVD:PC ratio provided additional, independent prognostic information to the Leibovich risk model, and that information was used to generate improved risk models.

CONCLUSIONS.

The authors consistently observed that higher PC was correlated with more aggressive clinicopathologic characteristics. PC was an independent unfavorable prognostic factor. The authors concluded that pericytes should be considered for therapeutic targeting. Cancer 2013. © 2012 American Cancer Society.     

Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer

BACKGROUND:

Recent observational studies have shown that metformin use in diabetic patients decreases both cancer incidence and mortality. Metformin use is also independently predictive of pathologic complete response. In the current study, the authors explored the association between metformin use and survival outcomes in patients with triple receptor‐negative breast cancer (TNBC) who were receiving adjuvant chemotherapy.

METHODS:

The Breast Cancer Management System database of The University of Texas MD Anderson Cancer Center identified 1448 women who received adjuvant chemotherapy for TNBC between 1995 and 2007. Patients were categorized by diabetes status and metformin use. The Kaplan‐Meier product‐limit method was used to calculate distant metastasis‐free survival (DMFS), recurrence‐free survival (RFS), and overall survival (OS). Cox proportional hazards models were fit to determine the association between metformin use and survival outcomes.

RESULTS:

The study cohort was comprised of 63 diabetic patients receiving treatment with metformin, 67 diabetic patients not receiving metformin, and 1318 nondiabetic patients. Patients in the diabetic groups tended to be older (P = .005); more diabetic patients were postmenopausal (P = .0007), black (P = .0001), and obese (P < .0001). At a median follow‐up of 62 months, there were no significant differences with regard to 5‐year DMFS (P = .23), RFS (P = .38), and OS (P = .58) between the 3 groups. Compared with the metformin group, patients who did not receive metformin (hazard ratio [HR], 1.63; 95% confidence interval [95% CI], 0.87‐3.06 [P = .13]) and nondiabetic patients (HR, 1.62; 95% CI, 0.97‐2.71 [P = .06]) tended to have a higher risk of distant metastases.

CONCLUSIONS:

The findings of the current study suggest that metformin use during adjuvant chemotherapy does not significantly impact survival outcomes in diabetic patients with TNBC. Cancer 2012;. © 2011 American Cancer Society.     

Isolated Contralateral Axillary Lymph Node Involvement in Breast Cancer Represents a Locally Advanced Disease Not Distant Metastases

Background

Breast cancer metastases to an ipsilateral supraclavicular lymph node is assigned a N3 status in the TNM system and thus classified as stage III disease in the American Joint Commission on Cancer staging manual. Breast cancer metastatic to contralateral axillary lymph node (CAM) without metastases to any other distant organ is currently assigned M1 status (stage IV) instead of N3 (stage III).