Ipsilateral breast tumor recurrence (IBTR) in patients with operable breast cancer who undergo breast-conserving treatment after receiving neoadjuvant chemotherapy: Risk factors of IBTR and validation of the MD Anderson Prognostic Index

BACKGROUND:

There is limited information about the risk factors for ipsilateral breast tumor recurrence (IBTR) after patients undergo breast‐conserving surgery plus radiotherapy (breast‐conserving treatment [BCT]) subsequent to neoadjuvant chemotherapy (NAC). The objective of the current study was to analyze these risk factors.

METHODS:

The authors collected data from 375 patients who underwent BCT and received NAC and analyzed the risk of IBTR associated with undergoing BCT after NAC. The usefulness of the MD Anderson Prognostic Index (MDAPI) for IBTR also was validated using the current data set.

RESULTS:

The median follow‐up was 47.8 months, and the 4‐year IBTR‐free survival rate was 95.6%. Multivariate analysis demonstrated that estrogen receptor (ER) status and multifocality of the residual tumor were associated significantly with IBTR‐free survival. In addition, patients who had ER‐positive and human epidermal growth factor 2 (HER2)‐negative tumors did not develop IBTR during the observation period. Although prognostic stratification according to MDAPI was relatively good for the prediction of IBTR in the study patients, the IBTR rate in the high‐risk group was not very high and was lower than that in the intermediate‐risk group. Multivariate analyses demonstrated that IBTR was an independent predictive factor for overall survival.

CONCLUSIONS:

ER status and multifocality of the residual tumor after NAC were independent predictors of IBTR after BCT. The MDAPI was barely adaptable to the study patients in terms of predicting IBTR. Patients with ER‐positive and HER2‐negative tumors had a favorable prognosis, whereas patients who developed IBTR after NAC had significantly worse overall survival. The authors propose a new IBTR prognostic index using the 2 factors that were identified as predictive of IBTR: ER status and multifocality of the residual tumor. Cancer 2012. © 2012 American Cancer Society.     

Evaluating cognitive complaints in breast cancer survivors with the FACT-Cog and quantitative electroencephalography

Purpose

In contrast to other countries, the Dutch breast cancer guideline does not recommend re-excision for focally positive margins after breast-conserving surgery (BCS) in invasive tumor and does recommend whole-breast irradiation including boost. We investigated whether omitting re-excision as compared to performing re-excision affects prognosis with a retrospective population-based cohort study.

Methods

The total cohort included 32,119 women with primary BCS for T1–T3 breast cancer diagnosed between 2003 and 2008 from the nationwide Netherlands cancer registry. The subcohort included 10,433 patients in whom the resection margins were registered. Outcome measures were 5-year ipsilateral breast tumor recurrence (IBTR) rate, 5-year disease-free survival (DFS) rate, and 10-year overall survival (OS) rate.

Results

In the total cohort, 25,878 (80.6%) did not have re-excision, 2368 (7.4%) had re-excision by BCS, and 3873 (12.1%) had re-excision by mastectomy. Five-year IBTR rates were 2.1, 2.8, and 2.9%, respectively (p = 0.001). In the subcohort, 7820 (75.0%) had negative margins without re-excision, 492 (4.7%) had focally positive margins without re-excision, 586 (5.6%) had focally positive margins and underwent re-excision, and 1535 (14.7%) had extensively positive margins and underwent re-excision. Five-year IBTR rate was 2.3, 2.9, 1.1, and 2.9%, respectively (p = 0.099). Compared to omitting re-excision, performing re-excision for focally positive margins was associated with lower risk of IBTR (adjusted HR 0.30, 95% CI 0.11–0.82), but not with DFS (adjusted HR 0.83 95% CI 0.59–1.17) nor with OS (adjusted HR 1.17 95% CI 0.87–1.59).

Conclusion

Omitting re-excision in breast cancer patients for focally positive margins after BCS does not impair DFS and OS, provided that whole-breast irradiation including boost is given.

     

Concurrent lobular neoplasia increases the risk of ipsilateral breast cancer recurrence in patients with ductal carcinoma in situ treated with breast‐conserving therapy

BACKGROUND:

Multiple clinicopathologic factors have been analyzed for their association with an increased risk of ipsilateral breast tumor recurrence (IBTR) after women receive breast‐conserving treatment (BCT) for ductal carcinoma in situ (DCIS). The reported incidence of proliferative lesions, such as atypical ductal hyperplasia (ADH), columnar cell changes (CCC), and lobular neoplasia associated with breast cancer, has been as high as 23%; however, the relevance of these lesions on the natural history of DCIS and the risk of IBTR remains unknown.

METHODS:

Two hundred ninety‐four patients with DCIS who received BCT between 1991 and 1995 were identified from the authors' institutional database. Slides were reviewed by a dedicated breast pathologist with particular attention to the presence of lobular neoplasia, ADH, and CCC. The actuarial 5‐, 10‐, and 15‐year IBTR rates were calculated using the Kaplan‐Meier method and were compared using the log‐rank test.

RESULTS:

Concurrent lobular neoplasia was present in 41 of 294 patients (14%), ADH was present in 37 of 294 patients (13%), and CCC was present in 71 of 294 patients (24%). The median follow‐up was 11 years. IBTR occurred in 40 of 227 patients without lobular neoplasia (18%) versus 15 of 41 patients with lobular neoplasia (37%; P=.005; hazard ratio [HR], 2.49). The 5‐, 10‐, and 15‐year cumulative incidence rates of IBTR were twice as high in women who had DCIS and lobular neoplasia compared with women who had DCIS alone (P=.002). Concomitant ADH (HR, 1.53) and CCC (HR, 1.24) were not associated significantly with IBTR (P=.20 and P=.44, respectively).

CONCLUSIONS:

Concurrent lobular neoplasia is associated with a significantly higher risk of IBTR in women with DCIS who received BCT. Women with coexisting DCIS and lobular neoplasia who receive BCT should consider using additional risk‐reducing strategies. Cancer 2009. © 2009 American Cancer Society.     

Pathologic complete response in breast cancer patients receiving anthracycline‐ and taxane‐based neoadjuvant chemotherapy

BACKGROUND:

The current study was conducted to evaluate the influence of race/ethnicity and tumor subtype in pathologic complete response (pCR) following treatment with neoadjuvant chemotherapy.

METHODS:

A total of 2074 patients diagnosed with breast cancer between 1994 and 2008 who were treated with neoadjuvant anthracycline‐ and taxane‐based chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axilla. The Kaplan‐Meier product‐limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome.

RESULTS:

The median patient age was 50 years; 14.6% of patients were black, were 15.2% Hispanic, 64.3% were white, and 5.9% were of other race. There were no differences in pCR rates among race/ethnicity (12.3% in black, 14.2% in Hispanics, 12.3% in whites, and 11.5% in others, P = .788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse recurrence‐free survival (RFS) and overall survival (OS) (P ≤ .0001). Differences in RFS by race/ethnicity were noted in the patients with hormone receptor‐positive disease (P = .007). On multivariate analysis, Hispanics had improved RFS (hazard ratio [HR], 0.69; 95% confidence interval [95% CI], 0.49‐0.97) and OS (HR, 0.63; 95% CI, 0.41‐0.97); blacks had a trend toward worse outcomes (RFS: HR, 1.28 [95% CI, 0.97‐1.68] and OS: HR, 1.32 [95% CI, 0.97‐1.81]) when compared with whites.

CONCLUSIONS:

In this cohort of patients, race/ethnicity was not found to be significantly associated with pCR rates. On a multivariate analysis, improved outcomes were observed in Hispanics and a trend toward worse outcomes in black patients, when compared with white patients. Further research was needed to explore the potential differences in biology and outcomes. Cancer 2010. © 2010 American Cancer Society.     

Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers

PURPOSE:

To evaluate the impact of low estrogen/progesterone receptor (ER/PR) expression and effect of endocrine therapy on survival outcomes in human epidermal growth factor receptor 2 (HER2)‐negative tumors with ER/PR <10%, previously labeled as triple negative.

METHODS:

In a retrospective review, 1257 patients were categorized according their ER/PR percentages into 3 groups, ER/PR <1% (group A), ER/PR 1% to 5% (group B), and ER/PR 6% to 10% (group C). Kaplan‐Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics.

RESULTS

Groups A, B, and C had 897 (71.4%), 241 (19.2%), and 119 (9.4%) patients, respectively. After a median follow‐up of 40 months there was no significant difference in 3‐year recurrence‐free survival (RFS): 64%, 67%, and 77% (P = .34) or overall survival (OS): 79%, 81%, and 88% (P = .33) for groups A, B, and C, respectively. ER/PR expression was not an independent predictor for RFS (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.86‐1.39; P = .46 for group B, and HR, 0.96; 95% CI, 0.66‐1.38; P = .81 for group C, compared with group A), or OS (HR, 1.11; 95% CI, 0.84‐1.46; P = .46 for group B, and HR, 0.94; 95% CI, 0.63‐1.42; P = .78 for group C, compared with group A). Endocrine therapy had no impact on survival outcomes (RFS: P = .10; OS: P = .45) among groups.

CONCLUSIONS:

In this cohort, a low ER/PR level (1%‐5%) does not appear to have any significant impact on survival outcomes. There was a tendency for survival advantages in the ER/PR 6% to 10% is seen. Benefit of endocrine therapy in these patients is unclear. Cancer 2011;. © 2011 American Cancer Society.     

Long-term Survival Comparison of Repeated Breast-conserving Surgery Versus Mastectomy for Patients with DCIS with Ipsilateral Breast Tumor Recurrence: A Real-world Longitudinal Study

BackgroundAlthough patients diagnosed with ductal carcinoma in situ (DCIS) harbor excellent overall survival (OS) after breast-conserving therapy, the evidence regarding to surgical management for ipsilateral breast tumor recurrence (IBTR) is scarce. This study aimed to assess the prognosis of repeated breast-conserving surgery (BCS) versus mastectomy for IBTR in DCIS survivors.Materials and MethodsHerein, 5344 DCIS cases with IBTR were identified during 702,748 person-years of follow-up, 3532 (66.09%) received mastectomy, and 1812 (33.91%) received repeated BCS. Cox regression and competing risk regression were employed to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and breast cancer–specific survival (BCSS), which was respectively calculated within spontaneous and matched cohorts.ResultsAfter adjustment for confounders, no statistically significant survival difference was observed between the repeated BCS and mastectomy for patients with DCIS with IBTR. The stratified analyses further revealed that patients with DCIS with IBTR receiving repeated BCS combined with radiation therapy were associated with both superior OS (HR, 0.79; CI, 0.64-0.98; P = .04) and BCSS (HR, 0.54; CI, 0.33-0.90; P = .02) compared with counterparts undergoing mastectomy. Furthermore, patients with DCIS who were age older than 60 years at IBTR diagnosis benefit from repeated BCS with radiotherapy (HR, 0.44; CI, 0.24-0.84; P = .01) than mastectomy.ConclusionWe suggest that repeated BCS with radiation therapy deserves consideration when DCIS survivors suffered IBTR. The choice of surgical management should be tailored based on patients’ age at IBTR diagnosis and size of recurrent disease.     

Male breast cancer according to tumor subtype and race

BACKGROUND:

Breast cancer occurs rarely in men. To the authors' knowledge, no population‐based estimates of the incidence of human epidermal growth factor receptor 2 (HER2)‐positive breast cancer or of the distribution of breast cancer subtypes among male breast cancer patients have been published to date. Therefore, the objective of the current study was to explore breast tumor subtype distribution by race/ethnicity among men in the large, ethnically diverse population of California.

METHODS:

This study included men who were diagnosed with invasive breast cancer between 2005 and 2009 with known estrogen receptor (ER) and progesterone receptor (PR) (together, hormone receptor [HR]) status and HER2 status reported to the California Cancer Registry. Among the men with HR‐positive tumors, survival probabilities between groups were compared using log‐rank tests.

RESULTS:

Six hundred six patients were included. The median age at diagnosis was 68 years. Four hundred ninety‐four men (81.5%) had HR‐positive tumors (defined as ER‐positive and/or PR‐positive and HER2‐negative). Ninety men (14.9%) had HER2‐positive tumors, and 22 (3.6%) had triple receptor‐negative (TN) tumors. Among the patients with HR‐positive tumors, non‐Hispanic black men and Hispanic men were more likely to have PR‐negative tumors than non‐Hispanic white men. No statistically significant differences in survival were observed according to tumor subtype (P = .08). Differences in survival according to race/ethnicity were observed among all patients (P = .087) and among those with HR‐positive tumors (P = .0170), and non‐Hispanic black men had poorer outcomes.

CONCLUSIONS:

In this large, representative cohort of men with breast cancer, the distribution of tumor subtypes was different from that reported for women and varied by patient race/ethnicity. Non‐Hispanic black men were more likely to have TN tumors and ER‐positive/PR‐negative tumors than white men. Cancer 2013. © 2013 American Cancer Society.     

Predictive clinical outcome of the intratumoral CD66b-positive neutrophil-to-CD8-positive T-cell ratio in patients with resectable nonsmall cell lung cancer

BACKGROUND:

The role of the interaction between tumor cells and inflammatory cells in nonsmall cell lung carcinoma (NSCLC) is unclear. In this study, the authors assessed the prognostic impact of intratumoral cluster of differentiation 66b (carcinoembryonic antigen‐related cell adhesion molecule 8 [CD66b])‐positive neutrophils and of the intratumoral CD66b‐positive neutrophil‐to‐cluster of differentiation 8 (cell surface antigen T8 [CD8])‐positive lymphocytes (the CD66b‐positive neutrophil‐to‐CD8‐positive lymphocyte ratio [iNTR]) in patients with resectable NSCLC.

METHODS:

Expression levels of CD66b and CD8 were evaluated by immunohistochemistry on tissue microarrays consisting of 632 NSCLC specimens from patients who underwent curative surgery. The relation between clinicopathologic variables and patient outcome was assessed.

RESULTS:

Intratumoral CD66b‐positive neutrophils were elevated in 318 patients (50%). In univariate analysis, an increase in CD66b‐positive cells was associated with a high cumulative incidence of relapse (CIR) (median CIR, 51 months for low CD66b‐positive cell density; 36 months for high CD66b‐positive cell density; P = .002) and trended toward worse overall survival (OS) (median OS, 57 months for low CD66b‐positive cell density; 54 months for high CD66b‐positive cell density; P = .088). The iNTR was elevated in 190 patients (30%). An increased iNTR was strongly associated with both a high CIR (median CIR: 43 months for an iNTR ≤1; 34 months for an iNTR >1; P < .0001) and poor OS (median OS: 60 months for an iNTR ≤1; 46 months for an iNTR >1; P < .0001). In multivariate analysis, independent prognostic factors for a higher CIR were high iNTR (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.56‐0.90; P = .005) and tumor stage >I, (HR, 0.39; 95% CI, 0.30‐0.52; P < .0001). Independent prognostic factors for worse OS were a high iNTR (HR, 0.70; 95% CI, 0.54‐0.91; P = .007) and tumor stage >I (HR, 0.35; 95% CI, 0.26‐0.47; P < .0001).

CONCLUSIONS:

The current results indicated that the iNTR is a novel, independent prognostic factor for a high rate of disease recurrence and poor OS in patients with resectable NSCLC. Cancer 2011;. © 2011 American Cancer Society.     

Five‐year outcome of patients classified using the American Society for Radiation Oncology consensus statement guidelines for the application of accelerated partial breast irradiation

BACKGROUND:

The American Society for Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) was applied to patients who were treated with this technique on the American Society of Breast Surgeons MammoSite Registry Trial to determine potential differences in clinical outcome based on classification group.

METHODS:

Patients were classified based on the CS groups of “suitable,” “cautionary,” and “unsuitable.” Rates of ipsilateral breast tumor recurrence (IBTR), regional lymph node failure, distant metastases, disease‐free survival, cause‐specific survival, and overall survival were assessed.

RESULTS:

Of the 1449 cases who were treated, 1025 patients (71%) could be classified according to the CS groupings, including 419 patients (41%) who fit the “suitable” criteria, 430 patients (42%) who fit the “cautionary” criteria, and 176 patients (17%) who fit the “unsuitable” criteria. At a median follow‐up of 53.5 months, the 5‐year actuarial rates of IBTR for the “suitable,” “cautionary,” and “unsuitable” groups were 2.59%, 5.43%, and 5.28%, respectively (P = .1884). Univariate analysis of factors potentially associated with IBTR indicated that negative estrogen receptor status was the only variable associated with IBTR among patients with invasive breast cancer (odds ratio [OR], 4.01; P = .0003). Larger tumor size was associated with a greater risk of distant metastasis (OR, 3.05; P = .0001). Among patients with ductal carcinoma in situ, only age <50 years and close‐positive margins were associated with IBTR (OR, 1.12 [P = .0079] and OR, 7.81 [P = .0131], respectively).

CONCLUSIONS:

The ASTRO CS groupings did not differentiate a subset of patients with a significantly worse rate of IBTR when they were treated with the MammoSite breast brachytherapy catheter to deliver APBI. Cancer 2010. © 2010 American Cancer Society.     

Multifactorial,site‐specific recurrence model after radical cystectomy for urothelial carcinoma

BACKGROUND:

A scoring algorithm of site‐specific disease recurrence after cystectomy for urothelial carcinoma was designed.

METHODS:

Identified were 1388 patients who underwent radical cystectomy for nonmetastatic urothelial carcinoma between 1980 and 1998. Clinical, surgical, and pathologic features were evaluated for associations with 4 locations of site‐specific disease recurrence: upper urinary tract, abdomen/pelvis, thoracic region, and bone. Recurrence‐free survival rates were estimated using the Kaplan‐Meier method. Cox proportional hazards models were fit to test associations with disease recurrence.

RESULTS:

A total of 493 (35.5%) patients experienced at least 1 recurrence. There were 67, 388, 143, and 145 patients with recurrences to the upper tract, abdomen/pelvis, thoracic region, and bone at a median of 3.1 years, 1.1 years, 1.3 years, and 1.0 years, respectively. Pathologic T4 stage (hazard ratio [HR], 2.84; P = .006), positive ureteral margins (HR, 5.71; P < .001), and multifocality (HR, 2.07; P = .009) were found to be independent predictors of upper tract recurrence. Pathologic T3 (HR, 2.30; P < .001) and T4 stage (HR, 3.55; P < .001), lymph node invasion (HR, 1.97; P < .001), extent of lymphadenectomy (pNx [HR, 1.66; P = .002] and <10 lymph nodes [HR, 1.52; P < .001]), multifocality (HR, 1.80; P < .001), and prostatic involvement (HR, 1.45; P = .019) were found to be independent predictors of abdominal/pelvic recurrence. Features independently associated with thoracic recurrence included pathologic T3 (HR, 2.61; P < .001) and T4 (HR, 3.39; P < .001), lymph node invasion (HR, 2.64; P < .001), extent of lymphadenectomy (pNx [HR, 1.89; P = .019] and <10 lymph nodes [HR, 1.58; P < .030]), and multifocality (HR, 1.79; P < .001). Pathologic T3 (HR, 3.45; P < .001) and T4 stage (HR, 3.87; P < .001), lymph node invasion (HR, 1.79; P = .006), occupational exposure to radiation (HR, 2.97; P = .003), and a positive urethral margin (HR, 2.28; P = .039) were found to be independent predictors of osseous recurrence. Macroscopic hematuria (HR, 0.52; P = .009) and obesity (HR, 0.59; P = .027) were found to be protective and negatively associated with upper tract and osseous recurrence, respectively. Scoring algorithms to predict the likelihood of disease recurrence to these sites were developed using regression coefficients from the multivariable models.

CONCLUSIONS:

Scoring algorithms based on independent predictors of site‐specific recurrence were presented. These models may be used to tailor postoperative surveillance to the individual patient based upon clinicopathologic features at the time of cystectomy. Cancer 2010. © 2010 American Cancer Society.     

Clinicopathologic features and prognoses of different histologic types of triple-negative breast cancer: A large population-based analysis

Purpose

To examine the clinicopathologic characteristics and survival outcomes of different histologic types of triple-negative breast cancer (TNBC).

African American patients with breast cancer have worse prognosis than white patients in certain subtypes and stages

Purpose

Racial disparity of breast cancer in each subtype and substage is not clear.

Methods

We reviewed 156,938 patients with breast cancer from 2010 to 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Breast cancer was subtyped by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status as HR+/HER2?, HR+/HER2+, HR?/HER2+, and HR?/HER2?.

Results

African American (AA) patients had worse overall survival (OS) and breast cancer cause-specific survival (BCSS) in HR+/HER2? stages III and IV breast cancer and HR?/HER2+ stage IV cancer; they had worse OS but not BCSS in HR+ /HER2? stage II cancer and HR?/HER2? stage II cancer.

Conclusion

AA patients with breast cancer had worse survival in certain subtype and stage, especially in ER+ breast cancer.

     

Long‐term outcomes for patients with limited stage follicular lymphoma

BACKGROUND:

Given the indolent behavior of follicular lymphoma (FL), it is controversial whether limited stage FL can be cured using radiotherapy (RT). Furthermore, the optimal RT field size is unclear. The authors of this report investigated the long‐term outcomes of patients with limited stage FL who received RT alone and studied the impact of reducing the RT field size from involved regional RT (IRRT) to involved node RT with margins up to 5 cm (INRT≤5 cm).

METHODS:

Eligible patients had limited stage, grade 1 through 3A FL diagnosed between 1986 and 2006 and treated were with curative‐intent RT alone. IRRT encompassed the involved lymph node group plus ≥1 adjacent, uninvolved lymph node group(s). INRT≤5 cm covered the involved lymph node(s) with margins ≤5 cm.

RESULTS:

In total, 237 patients were identified (median follow‐up, 7.3 years) and included 48% men, 54% aged >60 years, stage IA disease in 76% of patients, elevated lactate dehydrogenase (LDH) in 7% of patients, grade 3A tumors in 12% of patients, and lymph node size ≥5 cm in 19% of patients. The 2 RT groups were IRRT (142 patients; 60%) and INRT≤5 cm (95 patients; 40%). At 10 years, the progression‐free survival (PFS) rate was 49%, and the overall survival (OS) rate was 66%. Only 2 patients developed recurrent disease beyond 10 years. The most common pattern of first failure was a distant recurrence only, which developed in 38% of patients who received IRRT and in 32% of patients who received INRT≤5 cm. After INRT≤5 cm, 1% of patients had a regional‐only recurrence. Significant risk factors for PFS were lymph nodes ≥5 cm (P = .008) and male gender (P = .042). Risk factors for OS were age >60 years (P < .001), elevated LDH (P = .007), lymph nodes ≥5 cm (P = .016), and grade 3A tumors (P = .036). RT field size did not have an impact on PFS or OS.

CONCLUSIONS:

Disease recurrence after 10 years was uncommon in patients who had limited stage FL, suggesting that a cure is possible. Reducing RT fields to INRT≤5 cm did not compromise long‐term outcomes. Cancer 2010. © 2010 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.     

Prognostic impact of O6‐methylguanine‐DNA methyltransferase silencing in patients with recurrent glioblastoma multiforme who undergo surgery and carmustine wafer implantation

BACKGROUND:

O⁶‐methylguanine‐DNA methyltransferase (MGMT) is a key enzyme in the DNA repair process after alkylating agent action. Epigenetic silencing of the MGMT gene by promoter methylation has been associated with longer survival in patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. In this study, the authors evaluated the prognostic value of different biomarkers in recurrent GBM and analyzed the changes in MGMT status between primary tumors and recurrent tumors.

METHODS:

Twenty‐two patients who had recurrent GBM and who underwent surgery with carmustine wafer implantation were enrolled prospectively between 2005 and 2007. The authors investigated the correlation between MGMT silencing in the tumor at recurrence and survival taking into account other clinically recognized prognostic factors. MGMT status was determined by using methylation‐specific polymerase chain reaction analysis, a high‐throughput quantitative methylation assay, and immunohistochemistry. In addition, expression analyses of human mutL homolog 1, human mutS homolog 2, and tumor necrosis factor α‐induced protein 3 at recurrence were conducted with regard to their prognostic impact.

RESULTS:

The median progression‐free survival (PFS) and overall survival (OS) rates after recurrence were 3.6 months and 9.9 months, respectively, and the 6‐month PFS rate after recurrence was 27.2%. On multivariate analysis, only age (P = .04) and MGMT promoter hypermethylation at recurrence, as determined by MethyLight technology (P = .0012) and methylation‐specific polymerase chain reaction (MSP) analysis (P = .004), were correlated with better PFS. On multivariate analysis, only MGMT promoter hypermethylation at recurrence, as determined by using MethyLight technology (P = .019) and MSP analysis (P = .046), was associated with better OS.

CONCLUSIONS:

MGMT methylation status was an important prognostic factor in patients with recurrent GBM who underwent surgery plus carmustine wafer implantation; therefore, it was useful in predicting the outcome of GBM therapy at recurrence. Cancer 2009. © 2009 American Cancer Society.     

Factors predicting in-breast tumor recurrence after breast-conserving surgery

Purpose: The main objectives of this study were to identify risk factors for local in-breast tumor recurrence after breast-conservation and to evaluate the impact of IBTR (in-breast tumor recurrence) on overall survival. Methods: A total of 335 consecutive patients with 346 invasive and in situ breast cancers were treated with breast conserving therapy. Univariate and multivariate statistical analysis were performed and survival rates were calculated and analyzed using the Kaplan–Meier method. Results: With a median follow-up period of 70.6 months 14 patients (4%) developed an IBTR. Overall survival and the disease-free 8-year actuarial survival of patients were 95% and 93%, respectively. The overall survival of patients with tumour recurrence on any site was significantly shorter than of those without recurrence (64% versus 85% after 8 years of follow-up; P < 0.0001). Similarly, overall survival was significantly reduced in patients with distant metastases compared to all others without distant disease (88% versus 40% after 8 years; P < 0.0001). In contrast, overall survival of patients who experienced IBTR did not differ significantly from the group of patients who never developed IBTR (87% versus 70% after 8 years of follow-up). By univariate analysis, lobular carcinoma, high grade tumours, multifocality, concomitant LCIS and DCIS, the absence of estrogene and progesterone receptor status, as well as R1-status, were significant predictors of IBTR. By multivariate analysis, only R1-status (P < 0.002) and the presence of LCIS around the invasive tumour (P < 0.03) remained as significant factors predicting IBTR. Conclusions: Concomitant lobular carcinomas in situ, as well as R1 surgical status are independent significant risk factors for in breast tumor recurrence after breast conserving therapy.     

Outcomes of radical nephroureterectomy: A series from the Upper Tract Urothelial Carcinoma Collaboration

BACKGROUND:

The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified.

METHODS:

Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re‐reviewed by genitourinary pathologists according to strict criteria.

RESULTS:

Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high‐grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) ‐positive. Over a mean follow‐up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5‐year recurrence‐free and cancer‐specific survival probabilities (±SD) were 69% ± 1% and 73% ± 1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P < .001), advancing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.8, P < .001), infiltrative growth pattern (HR: 1.5, P < .001), and LVI (HR: 1.2, P = .041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P = .001), high tumor grade (HR: 1.7, P = .001), increasing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.7, P < .001), sessile architecture (HR: 1.5, P = .002), and LVI (HR: 1.4, P = .02) were independently associated with cancer‐specific survival.

CONCLUSIONS:

Radical nephroureterectomy provided durable local control and cancer‐specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy. Cancer 2009. © 2009 American Cancer Society.     

Osteosarcoma of the jaw/craniofacial region

BACKGROUND:

The current study was performed to evaluate outcomes in patients with osteosarcoma of the head and neck (OHN) who were treated with surgery with or without radiotherapy (RT).

METHODS:

Between 1960 and 2007, 119 patients with OHN underwent macroscopic total resection with or without RT. The median age of the patients was 33 years (range, 7‐77 years). Of these 119 patients 92 (77%) underwent surgery alone whereas 27 (23%) patients were treated with combined modality treatment (CMT) comprised of surgery and RT (median dose, 60 Gray [Gy]; range, 50‐66 Gy).

RESULTS:

The median follow‐up was 5.8 years. Overall survival (OS) rates at 5 years and 10 years were 63% and 55%, respectively. Corresponding disease?specific survival (DSS) rates were 67% and 61%, respectively. Stratified analysis by resection margin status demonstrated that CMT compared with surgery alone improved OS (80% vs 31%; P = .02) and DSS (80% vs 35%; P = .02) for patients with positive/uncertain resection margins. Multivariate analysis indicated that CMT for patients with positive/uncertain resection margins improved OS (P < .0001). A total of 44 (37%) patients experienced local disease recurrence (LR) and 25 (21%) developed distant metastases (DM). There was no difference noted with regard to DSS if disease recurrence was isolated (LR vs DM: 26% vs 29%, respectively, at 5 years; P = .48) The use of CMT versus surgery alone improved local control (LC) (75% vs 24%; P = .006) for patients with positive/uncertain resection margins. The rate of surgical complications was 28% at 5 years. The rates of RT‐associated complications were 40% and 47% at 5 years and 10 years, respectively.

CONCLUSIONS:

The results of the current study indicated that RT in addition to surgery improves OS, DSS, and LC for patients with OHN who have positive/uncertain resection margins. Cancer 2009. © 2009 American Cancer Society.     

Increased use of regional radiotherapy is associated with improved outcome in a population-based cohort of women with breast cancer with 1-3 positive nodes

Purpose

To examine use of and outcomes from adjuvant locoregional radiotherapy (LRRT) after breast-conserving surgery (BCS) for women with breast cancer with 1-3 positive nodes (1-3 N+) before and after the 1997 publication of randomised trial evidence of a survival advantage from post-mastectomy LRRT.

Methods

Data were analysed for 2768 women diagnosed between 1989 and 2005 and referred to the British Columbia Cancer Agency with newly diagnosed pT1-3 breast cancer with 1-3 N+, treated with BCS and RT. LRRT use was analysed over time. Ten-year Kaplan-Meier locoregional control (LRC), breast cancer-specific survival (BCSS) and overall survival (OS) curves were compared using the log-rank test. Cox regression modeling of LRC and BCSS were performed.

Results

LRRT use in patients with 1-3 N+ increased from 23% before 1997 to 57% after 1997. LRRT was associated with significant improvements in LRC, but not in DRFS, BCSS, or OS. 10--year LRC was 89% with local RT alone and 93% with LRRT (p = 0.006). On multivariable analysis, LRRT was associated with improved LRC compared to local RT alone (HR 0.55, 95% CI: 0.40-0.77), but not with significant BCSS differences. Margin status, grade, % positive nodes, and hormonal therapy were significant predictors for LRC, while tumour size, grade, % positive nodes, and hormonal therapy significantly affected BCSS.

Conclusion

Post-BCS LRRT use in British Columbia increased almost threefold in patients with 1-3 N+ after 1997. Adjuvant LRRT was associated with improved LRC, but not with improved BCSS compared to breast RT alone.