The overall rates of BCS have remained stable or slightly increased over the past decade in the United States. The CPM rates have markedly increased while unilateral mastectomy rates have decreased. Increasingly, more women are not receiving RT after BCS, particularly high-risk women. These trends have important potential untoward consequences. Strategies are being developed to ensure adequate local therapy for breast cancer patients.

PURPOSE The Intergroup 0116 trial has demonstrated that postoperative chemoradiotherapy (CRT) improves survival in gastric cancer. We retrospectively compared survival and recurrence patterns in two phase I/II studies evaluating more intensified postoperative CRT with those from the Dutch Gastric Cancer Group Trial (DGCT) that randomly assigned patients between D1 and D2 lymphadenectomy. PATIENTS AND METHODS Survival and recurrence patterns of 91 patients with adenocarcinoma of the stomach who had received surgery followed by radiotherapy combined with fluorouracil and leucovorin (n = 5), capecitabine (n = 39), or capecitabine and cisplatin (n = 47) were analyzed and compared with survival and recurrence patterns of 694 patients from the DGCT (D1, n = 369; D2, n = 325). For both groups, the Maruyama Index of Unresected Disease (MI) was calculated and correlated with survival and recurrence patterns. RESULTS With a median follow-up of 19 months in the CRT group, local recurrence rate after 2 years was significantly higher in the surgery only (DGCT) group (17% v 5%; P =.0015). Separate analysis of CRT patients who underwent a D1 dissection (n = 39) versus DGCT-D1 (n = 369) showed fewer local recurrences after chemoradiotherapy (2% v 8%; P =.001), whereas comparison of CRT-D2 (n = 25) versus DGCT-D2 (n = 325) demonstrated no significant difference. CRT significantly improved survival after a microscopically irradical (R1) resection. The MI was found to be a strong independent predictor of survival. CONCLUSION After D1 surgery, the addition of postoperative CRT had a major impact on local recurrence in resectable gastric cancer.

PURPOSE In the absence of high-level evidence or clinical guidelines supporting any given active treatment approach over another for localized prostate cancer, clinician and patient preferences may lead to substantial variation in treatment use. METHODS Data were analyzed from 36 clinical sites that contributed data to the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Distribution of primary treatment use was measured over time. Prostate cancer risk was assessed using the D'Amico risk groups and the Cancer of the Prostate Risk Assessment (CAPRA) score. Descriptive analyses were performed, and a hierarchical model was constructed that controlled for year of diagnosis, cancer risk variables, and other patient factors to estimate the proportion of variation in primary treatment selection explicable by practice site. Results Among 11,892 men analyzed, 6.8% elected surveillance, 49.9% prostatectomy, 11.6% external-beam radiation, 13.3% brachytherapy, 4.0% cryoablation, and 14.4% androgen deprivation monotherapy. Prostate cancer risk drives treatment selection, but the data suggest both overtreatment of low-risk disease and undertreatment of high-risk disease. The former trend appears to be improving over time, while the latter is worsening. Treatment varies with age, comorbidity, and socioeconomic status. However, treatment patterns vary markedly across clinical sites, and this variation is not explained by case-mix variability or known patient factors. Practice site explains a proportion of this variation ranging from 13% for androgen deprivation monotherapy to 74% for cryoablation. CONCLUSION Substantial variation exists in management of localized prostate cancer that is not explained by measurable factors. A critical need exists for high-quality comparative effectiveness research in localized prostate cancer to help guide treatment decision making.

ABSTRACT:(105 words) Early breast cancer treatment is based on a multimodality approach with the application of clinical and histological prognostic factors to determine locoregional and systemic treatments. The entire scientific community is strongly involved in the management of this disease: radiologists for screening and early diagnosis, gynecologists, surgical oncologists and radiation oncologists for locoregional treatment, pathologists and biologists for personalized characterization, genetic counsellors for BRCA mutation history and medical oncologists for systemic therapies. Recently, new biological tools have established various prognostic subsets of breast cancer and developed predictive markers for miscellaneous treatments. The aim of this article is to highlight the contribution of biological tools in the locoregional management of early breast cancer.

PURPOSE IBTR! version 1.0 is a web-based tool that uses literature-derived relative risk ratios for seven clinicopathologic variables to predict ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT). Preliminary testing demonstrated over-estimation in high-risk subgroups. This study uses two independent population-based datasets to create and validate a modified nomogram, IBTR! version 2.0. METHODS Cox regression modeling was performed on 7,811 patients treated with BCT at the British Columbia Cancer Agency (median follow-up, 9.4 years). Population-based hazard ratios were generated for the seven variables in the original nomogram. A modified nomogram was then tested against 664 patients from Massachusetts General Hospital (median follow-up, 9.3 years). The mean predicted and observed 10-year estimates were compared for the entire cohort and for four groups predefined by nomogram-predicted risks: group 1: less than 3%; group 2: 3% to 5%; group 3: 5% to 10%; and group 4: more than 10%. Results IBTR! version 2.0 predicted an overall 10-year IBTR estimate of 4.0%(95% CI, 3.8 to 4.2), while the observed estimate was 2.8%(95% CI, 1.6 to 4.7; P =.10). The predicted and observed IBTR estimates were: group 1 (n = 283): 2.2% versus 1.3%, P =.40; group 2 (n = 237): 3.8% versus 3.5%, P =.80; group 3 (n = 111): 6.7% versus 3.2%, P =.05; and group 4 (n = 33): 12.5% versus 8.7%, P =.50. CONCLUSION IBTR! version 2.0 is accurate in the majority of patients with a low to moderate risk of in-breast recurrence. The nomogram still overestimates risk in a minority of patients with higher risk features. Validation in a larger prospective data set is warranted.

To determine which web-based model best identifies women at low risk of further axillary disease after a positive sentinel lymph node (SLN+) biopsy. 673 women with T1-2cN0M0 SNB+ breast cancer who underwent completion axillary dissection (AxD) were identified. A subgroup not eligible to avoid AxD as part of the Z0011 study was defined (Z0011 exclusion group). Predicted risk of further axillary disease was generated using seven web-based models."Low risk" was defined as a ≤10% risk of further axillary disease. False negative ("low risk" prediction but AxD+) rates (FNRs), area under the receiver operating characteristic curve (AUC), and Brier score were determined for each model. 6 of 7 models identified "low risk" patients but FNRs ranged from 14 to 30%. The Stanford and Memorial Sloan-Kettering (MSKCC) models had the best FNRs. FNRs were lower with SLN micrometastasis (7-15%) and higher in the Z0011 exclusion group (21-41%). All models under-predicted further nodal disease in low risk patients and over-predicted in higher-risk patients. The Stanford and MSKCC models were able to identify women with SLN micrometastasis with a ≤10% FNR. Models were not able to accurately identify low risk women from a cohort that would have been excluded from Z0011.

PURPOSE The standard of care for patients with a positive (+) sentinel lymph node (SLN) is axillary dissection; however, for various reasons, some SLN+ patients do not undergo dissection. The purpose of this study was to define possible predictors of having four or more involved nodes to provide information for clinicians and patients making decisions about adjuvant chemotherapy and radiation. PATIENTS AND METHODS We reviewed the records of 402 patients with invasive breast cancer and one to three involved SLNs who underwent completion axillary dissection at two academic cancer centers. None of these patients received neoadjuvant chemotherapy. Factors associated with having four or more involved axillary nodes (SLNs and non-SLNs) were evaluated by univariate and multivariate logistic regression analysis. RESULTS Eighty-seven patients had four or more positive nodes. On multivariate analysis, having four or more SLNs was associated with tumor histology, primary tumor size, lymphovascular space invasion, extranodal extension, the number of involved SLNs, the number of uninvolved SLNs, and the size of the largest SLN metastasis. A nomogram to predict the probability of having four or more nodes based on patients' pathologic data was developed from the multivariate logistic regression model. A separate previously published data set of 206 SLN+ patients treated at a community hospital in another city was used to validate this model. CONCLUSION Patients with a low probability of having four or more nodes can be identified from known pathologic features. The nomogram developed will be helpful to clinicians making adjuvant treatment recommendations.

PURPOSE To assess the need for adjuvant radiotherapy following mastectomy for patients with node-negative breast tumors 5 cm or larger. METHODS AND MATERIALS Between 1981 and 2002, a total of 70 patients with node-negative breast cancer and tumors 5 cm or larger were treated with mastectomy and adjuvant systemic therapies but without radiotherapy at three institutions. We retrospectively assessed rates and risk factors for locoregional failure (LRF), overall survival (OS), and disease-free survival (DFS) in these patients. RESULTS With a median follow-up of 85 months, the 5-year actuarial LRF rate was 7.6%(95% confidence interval, 3%-16%). LRF was primarily in the chest wall (4/5 local failures), and lymphatic-vascular invasion (LVI) was statistically significantly associated with LRF risk by the log-rank test (p=0.017) and in Cox proportional hazards analysis (p=0.038). The 5-year OS and DFS rates were 83% and 86% respectively. LVI was also significantly associated with OS and DFS in both univariate and multivariate analysis. CONCLUSIONS This series demonstrates a low LRF rate of 7.6% among breast cancer patients with node-negative tumors 5 cm and larger after mastectomy and adjuvant systemic therapy. Our data indicate that further adjuvant radiation therapy to increase local control may not be indicated by tumor size alone in the absence of positive lymph nodes. LVI was significantly associated with LRF in our series, indicating that patients with this risk factor require careful consideration with regard to further local therapy.

PURPOSE To evaluate the effect of radiotherapy (RT) omission on survival in older breast cancer patients treated with breast-conserving surgery. METHODS Data were analyzed for 4836 women aged 50 to 89 with T1-T2, N0-N1, M0 breast cancer. Tumor and treatment factors, relapse rates, and overall survival (OS) and breast cancer-specific survival (BCSS) were compared between women treated with and without RT in 3 age categories: 50 to 64 (n = 2398), 65 to 74 (n = 1665), and > or = 75 years (n = 773). RESULTS Median follow-up was 7.5 years. Rates of RT omission significantly increased with advancing age (7%, 9%, and 26% in age 50-64, 65-74, and > or = 75 years respectively, P <.0001). RT omission was associated with significantly reduced local control, BCSS, and OS. Despite similar tumor characteristics and higher rates of systemic therapy use, women aged > or = 75 years were observed to have lower 5-year OS and BCSS when RT was omitted. CONCLUSION These findings support the hypothesis that inadequate local therapy is associated with reduced survival in elderly women treated with breast-conserving therapy.

OBJECTIVE To examine time intervals between diagnosis and treatment of limited stage small cell lung cancer (L-SCLC) and to evaluate its effect on clinical outcomes. MATERIALS AND METHODS Data on 166 patients with L-SCLC referred to a regional cancer center between January 1991 and December 1999 were analyzed. The time intervals studied were defined as: interval A, first abnormal chest x-ray to pathologic diagnosis: interval B, diagnosis to first oncology consultation; interval C, oncology consultation to first day of thoracic radiotherapy (RT); interval D, oncology consultation to first day of chemotherapy; and interval E, first day of chemo to first day of RT. Cox proportional hazards models were used to examine associations between the time intervals and thoracic relapse (TR) and overall survival (OS) outcomes. Logistic regression analysis was used to model associations between time and complete response (CR) rates. RESULTS The median time duration of intervals A to E were 20, 12, 63.5, 15, and 48 days, respectively. When time was analyzed as a continuous variable, no statistically significant association between the interval lengths and outcomes studied was observed. Dichotomizing each interval using the median value as cut-off revealed that interval A >20 days was significantly associated with improved CR (odds ratio = 3.573; P = 0.027) whereas interval B >12 days was associated with a trend toward lower CR (odds ratio = 0.348; P = 0.073). CONCLUSIONS Short median times from first abnormal chest x-ray to diagnosis and from diagnosis to oncology consultation indicate that L-SCLC patients were diagnosed and referred promptly in the community setting. OS and TR appeared independent of the time intervals analyzed. Individual variations in disease presentation and tumor biology may explain the observed associations between early pathologic diagnosis and inferior CR rates.

PURPOSE To identify patient subsets with T1-T2N0 breast cancer at high risk of locoregional recurrence (LRR) who may warrant consideration for postmastectomy radiotherapy. METHODS AND MATERIALS Data were analyzed for 1505 women referred between 1989 and 1999 with pathologic T1-T2N0M0 breast cancer treated with mastectomy with clear margins and no adjuvant radiotherapy. Logistic regression analysis was performed to identify statistically significant factors associated with LRR. Recursive partitioning was used to develop a classification tree model for LRR given the prognostic variables. RESULTS The median follow-up was 7.0 years. The 10-year Kaplan-Meier LRR rate was 7.8%. On logistic regression analysis, the statistically significant factors predicting LRR were histologic grade (p <0.0001), lymphovascular invasion (LVI)(p <0.0001), T stage (p = 0.05), and systemic therapy use (p = 0.01). In the recursive partitioning model, the first split in the classification tree was histologic grade. For 972 patients without high-grade histologic features, the 10-year Kaplan-Meier LRR rate was 5.5%. For 533 patients with Grade 3 disease (LRR rate 12.1%), the concomitant presence of LVI was associated with a LRR rate of 21.2%(n = 126). In patients with Grade 3 disease without LVI, T2 tumors conferred a LRR rate of 13.4%(n = 194), which increased to 23.2% for patients who did not receive systemic therapy (n = 63). CONCLUSION Women with pT1-T2N0 breast cancer experienced a LRR risk of approximately 20% in the presence of Grade 3 disease with LVI or Grade 3 disease, T2 tumors, and no systemic therapy. These subsets of node-negative patients warrant consideration of for postmastectomy radiotherapy.

PURPOSE To determine the value of the intent to include internal mammary nodes (IMNs) in the radiation therapy (RT) volume for patients receiving adjuvant locoregional (breast or chest wall plus axillary and supraclavicular fossa) RT for breast cancer. METHODS AND MATERIALS 2413 women with node-positive or T3/4N0 invasive breast cancer, treated with locoregional RT from 2001 to 2006, were identified in a prospectively maintained, population-based database. Intent to include IMNs in RT volume was determined through review of patient charts and RT plans. Distant relapse free survival (D-RFS), breast cancer-specific survival (BCSS), and overall survival (OS) were compared between the two groups. Prespecified pN1 subgroup analyses were performed. RESULTS The median follow-up time was 6.2 years. Forty-one percent of study participants received IMN RT. The 5-year D-RFS for IMN inclusion and exclusion groups were 82% vs. 82%(p = 0.82), BCSS was 87% vs. 87%(p = 0.81), and OS was 85% vs. 83%(p = 0.06). In the pN1 subgroup, D-RFS was 90% vs. 88%(p = 0.31), BCSS was 94% vs. 92%(p = 0.18), and OS was 91% vs. 88%(p = 0.01). After potential confounding variables were controlled for, women who received IMN RT did not have significantly different D-RFS (hazard ratio [HR] = 1.02 (95% confidence interval [CI], 0.84-1.24; p = 0.85), BCSS (HR = 0.98 (95% CI, 0.79-1.22; p = 0.88), or OS (HR = 0.95; 95% CI, 0.78-1.15; p = 0.57). In the pN1 subgroup, IMN RT was associated with trends for improved survival that were not statistically significant: D-RFS (HR = 0.87; 95% CI, 0.63-1.22; p = 0.42), BCSS (HR = 0.85; 95% CI, 0.57-1.25; p = 0.39), and OS (HR = 0.78; 95% CI, 0.56-1.09; p = 0.14). CONCLUSIONS After a median follow-up time of 6.2 years, although intentional IMN RT was not associated with a significant improvement in survival, this population-based study suggests that IMN RT may contribute to improved outcomes in selected patients with N1 disease.

PURPOSE: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. METHODS AND MATERIALS: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. RESULTS: The median follow-up time was 1.9 years. LRT consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14%(p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46%(p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009). CONCLUSION: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease, clear margins, and distant disease limited to one subsite, bone-only involvement, or fewer than five metastatic lesions.

PURPOSE There is controversy about whether patients with synchronous bilateral breast cancer (SBBC) have similar or worse outcomes compared with patients with unilateral breast cancer. The purpose of this study was to determine whether survival outcomes for patients with SBBC can be estimated from the characteristics of their individual cancers. PATIENTS AND METHODS Patients had invasive breast cancer, without metastases or inflammatory disease, diagnosed in British Columbia between 1989 and 2000. There were 207 cases with SBBC (diagnosed ≤ 2 months apart) and 15,497 with unilateral breast cancer. By using 10-year breast cancer-specific survival (BCSS) estimates, the higher-risk cancer of each SBBC case was determined and matched with three breast cancers from the unilateral cohort to select 621 high-risk matches. The priority sequence of matching the prognostic and predictive variables was positive lymph node number, primary tumor size, age, grade, lymphovascular invasion, estrogen receptor status, local therapy used, margin status, treating clinic, diagnosis year, and type of systemic therapy used. RESULTS With a median follow-up of 10.2 years, the overall 10-year BCSS was significantly higher for the unilateral cohort (81%; 95% CI, 81% to 82%) than for the SBBC cases (71%; 95% CI, 63% to 77%). The SBBC cases had significantly higher mean age and stage at presentation. The 10-year BCSS was 74%(95% CI, 69% to 77%) for the high-risk matches. CONCLUSION BCSS was not significantly different between the SBBC cases and their high-risk matches.

PURPOSE Prior results of breast-conserving therapy (BCT) have shown substantial rates of local recurrence (LR) in young patients with breast cancer (BC). PATIENTS AND METHODS We studied 1,434 consecutive patients with invasive BC who received BCT from December 1997 to July 2006. Ninety-one percent received adjuvant systemic therapy; no patients received trastuzumab. Five BC subtypes were approximated: estrogen receptor (ER) or progesterone receptor (PR) positive, HER2 negative, and grades 1 to 2 (ie, luminal A); ER positive or PR positive, HER2 negative, and grade 3 (ie, luminal B); ER or PR positive, and HER2 positive (ie, luminal HER2); ER negative, PR negative, and HER2 positive (ie, HER2); and ER negative, PR negative, and HER2 negative (ie, triple negative). Actuarial rates of LR were calculated by using the Kaplan-Meier method. RESULTS Median follow-up was 85 months. Overall 5-year cumulative incidence of LR was 2.1%(95% CI, 1.4% to 3.0%). The 5-year cumulative incidence of LR was 5.0%(95% CI, 3.0% to 8.3%) for age quartile 23 to 46 years; 2.2%(95% CI, 1.0% to 4.6%) for ages 47 to 54 years; 0.9%(95% CI, 0.3% to 2.6%) for ages 55 to 63 years; and 0.6%(95% CI, 0.1% to 2.2%) for ages 64 to 88 years. The 5-year cumulative incidence of LR was 0.8%(95% CI, 0.4% to 1.8%) for luminal A; 2.3%(95% CI, 0.8% to 5.9%) for luminal B; 1.1%(95% CI, 0.2% 7.4%) for luminal HER2; 10.8%(95% CI, 4.6% to 24.4%) for HER2; and 6.7%(95% CI, 3.6% to 12.2%) for triple negative. On multivariable analysis, increasing age was associated with decreased risk of LR (adjusted hazard ratio, 0.97; 95% CI, 0.94 to 0.99; P =.009). CONCLUSION In the era of systemic therapy and BC subtyping, age remains an independent prognostic factor after BCT. However, the risk of LR for young women appears acceptably low.

BACKGROUND AND PURPOSE: This study aims to explain the unexpected weak association between the width of the negative surgical margin and the risk of local recurrence in breast conserving therapy. MATERIALS AND METHODS: We utilized a classical tumor-control probability (TCP) model to estimate the risk of local recurrence, considering the heterogeneity of microscopic disease spread observed around the invasive index tumor in a pathology dataset (N=60). The estimated result was compared with the true risk observed in the EORTC boost-versus-no-boost trial (N=1616). RESULTS: The disease volume beyond any given distance from the edge of the index tumor varied considerably among patients. Adopting this disease volume variation in the TCP model accurately reproduced the local recurrence rate as function of surgical margin width in the boost-versus-no-boost trial (Pearson's correlation coefficients are 0.652 and 0.862, and significant at the 0.05 and 0.01 level for absence and presence of a radiation boost, respectively). CONCLUSIONS: The impact of a negative margin width on local recurrence is limited due to the large variation of microscopic disease that can reach large quantities beyond any given distance from the edge of the index tumor across the patient population of breast-conserving therapy.

BACKGROUND: Management of mammographically detected ductal carcinoma in situ (DCIS) at a single institution was reviewed to determine long-term clinical outcomes after treatment with breast-conserving therapy (BCT). METHODS: Data from all patient-cases with DCIS who received BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for their effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included breast-conserving surgery followed by external-beam radiotherapy to the whole breast, with 86 % of patients receiving a lumpectomy cavity boost. The median dose to the whole breast was 50 Gy and 60.4 Gy to the lumpectomy cavity. RESULTS: A total of 129 cases were evaluated; the median follow-up was 19.3 years. Twenty-one patients developed an ipsilateral breast tumor recurrence (IBTR), 76.2 % of which were invasive (n = 16). Fourteen recurrences (66 %) were within the same breast quadrant (true recurrence), while an additional 7 cases developed an IBTR elsewhere in the breast. True recurrences were more prevalent in women <45 years of age (20 %/24 % vs. 5.1 %/8 %) at 10 and 20 years (p = 0.02). The 5-, 10-, 15-, and 20-year actuarial rates of IBTR for this cohort were 8.7, 10.4, 12.1, and 16.3 %(IBTR), while overall survival at 5, 10, and 20 years was 97.6, 96.8, and 96.8 %, respectively. CONCLUSIONS: Mammographically detected DCIS remains a clinically distinct subset of noninvasive breast cancer. With 20 year follow-up, local control and overall survival are excellent after BCT.

BACKGROUND: Mastectomy is still considered the treatment of first choice in patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and whole-breast radiotherapy. METHODS: We retrospectively evaluated 161 patients with invasive IBTR who underwent a second BCS in order to describe prognosis, determine predictive factors of outcome, and select the subset of patients with the best local control. Median follow-up after IBTR was 81 months. RESULTS: Median age at IBTR was 53 years. Five-year overall survival after IBTR was 84 %(95 % confidence interval [CI] 78-89). Five-year cumulative incidence of a second local event after IBTR was 29 %(95 % CI 22-37). At the multivariate analysis, IBTR size >2 cm and time to relapse ≤48 months significantly increased the risk of local reappearance (hazard ratio [HR] 3.3, 95 % CI 1.6-7.0; and HR 1.9, 95 % CI 1.1-3.5). The 5-year cumulative incidence of a further local reappearance of the tumor after repeating BCS was 15.2 % in the patients with IBTR ≤2 cm and time to IBTR >48 months, 31.2 % in the patients with IBTR ≤2 cm and time to IBTR ≤48 months, and 71.2 % in patients with IBTR >2 cm (P < 0.001). CONCLUSIONS: The best candidates for a second BCS are those with small (≤2 cm) and late (>48 months) IBTR. The information about the risk of a further local reappearance after repeating BCS should be shared with the patients in the decision making process.

PURPOSE To determine 20-year rates of local control and outcome-associated factors for ductal carcinoma in situ (DCIS) after breast-conserving therapy (BCT). METHODS AND MATERIALS All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. RESULTS One hundred forty-five cases were evaluated; the median follow-up time was 19.3 years. IBTR developed in 25 patients, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. One third of IBTRs were elsewhere failures, and 68% of IBTRs occurred <10 years after diagnosis. Young age and cancerization of lobules predicted for IBTR at <10 years, and increased slide involvement and atypical ductal hyperplasia were associated with IBTR at later time points. CONCLUSIONS Patients with DCIS treated with BCT have excellent long-term rates of local control. Predictors of IBTR vary over time, and the risk of recurrence seems highest within 10 to 12 years after diagnosis.

OBJECTIVES There are limited data on the outcomes of patients treated with repeat lumpectomy at the time of ipsilateral breast tumor recurrence (IBTR). METHODS We retrospectively analyzed 78 patients who underwent repeat lumpectomy after IBTR. The risk factors for second IBTR were assessed. RESULTS The median follow-up period was 40 months. The 5-year second IBTR-free survival rate was 78.8%. Patients with estrogen receptor (ER)-positive or unknown tumors at IBTR had a significantly better second IBTR-free survival rate than those with ER-negative tumors at IBTR (88.3 vs. 55.4%, respectively; p = 0.0022). Multivariate analysis revealed that the ER status of IBTR was a significantly independent predictive factor for second IBTR-free survival (p = 0.0177). The low-risk group for second IBTR was detected using the ER status, disease-free interval, margin status of IBTR, and age at diagnosis (5-year cumulative incidence, 7.0%). CONCLUSION The ER status of IBTR was a significantly independent predictive factor for second IBTR-free survival. Some patients could safely undergo repeat lumpectomy for IBTR.

PURPOSE Prediction of patients at highest risk for ipsilateral breast tumor recurrence (IBTR) after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The aim of our study was to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center to predict for risk of IBTR in patients with DCIS from our institution. PATIENTS AND METHODS We retrospectively identified 794 patients with a diagnosis of DCIS who had undergone local excision from 1990 through 2007 at the MD Anderson Cancer Center (MDACC). Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients who had complete data. RESULTS There was a marked difference with respect to tumor grade, prevalence of necrosis, initial presentation, final margins, and receipt of endocrine therapy between the two cohorts. The biggest difference was that more patients received radiation in the MDACC cohort (75% at MDACC v 49% at MSKCC; P <.001). Follow-up time in the MDACC cohort was longer than in the MSKCC cohort (median 7.1 years v 5.6 years), and the recurrence rate was lower in the MDACC cohort (7.9% v 11%). The median 5-year probability of recurrence was 5%, and the median 10-year probability of recurrence was 7%. The nomogram for prediction of 5- and 10-year IBTR probabilities demonstrated imperfect calibration and discrimination, with a concordance index of 0.63. CONCLUSION Predictive models for IBTR in patients with DCIS who were treated with local excision are imperfect. Our current ability to accurately predict recurrence on the basis of clinical parameters alone is limited.

The diagnosis of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy is of great interest to breast physicians. The present study compared the utility of gray-scale sonography standardized by a breast imaging reporting and data system (BI-RADS) and power Doppler sonography for differentiating between benign scar formation and IBTR after breast-conserving therapy. Gray-scale sonography detected 83 solid breast lesions classified as BI-RADS categories 3-5 in 272 patients after breast-conserving therapy, and these lesions were entered into the study (53 lesions as category 3, probably benign; 30 lesions as categories 4-5, suspected malignancy). Power Doppler sonography revealed intratumoral flow in 19 of 83 solid breast lesions. BI-RADS category 3 was accepted as probably benign and BI-RADS categories 4-5 were considered as suspicious for breast tumor recurrence in the gray-scale ultrasound criteria. Positive and negative intratumoral flow were employed as suspicious for breast tumor recurrence and probably benign, respectively, in the power Doppler sonography criteria. Sensitivity was higher for power Doppler sonography (94.7±10.0%) than for gray-scale sonography (57.9±22.2%). Specificity was also higher for power Doppler sonography (98.4±3.0%) than for gray-scale sonography (70.3±0.6%). These results suggest that power Doppler sonography can complement gray-scale sonography standardized by BI-RADS in differentiating between IBTR and benign scar lesions.

BACKGROUND We previously developed a prognostic index for assessing local-regional recurrence (LRR) risk in patients undergoing breast conservation therapy (BCT) after neoadjuvant chemotherapy. The prognostic index assigns a point for each of the following variables: clinical N2/N3 disease, lymphovascular invasion, residual pathologic tumor size >2 cm, and multifocal residual disease on pathology. The current study was undertaken to evaluate this prognostic index in an independent cohort. METHODS We identified 551 patients treated from 2001 to 2005 with neoadjuvant chemotherapy, mastectomy or BCT, and radiation. These patients were not used in the original development of the prognostic index. Outcomes were stratified by prognostic index. The 5-year LRR-free survival was calculated using the Kaplan-Meier method, and differences were compared using the log-rank test. RESULTS For patients undergoing BCT, the 5-year LRR-free survival rates were 92, 92, 84, and 69% when the prognostic index was 0 (n = 91), 1 (n = 82), 2 (n = 38), or 3-4 (n = 13)(P = 0.01). The 5-year LRR-free survival rates were similar between patients undergoing mastectomy or BCT when the prognostic index score was 0, 1, or 2. When the prognostic index score was 3-4, the 5-year LRR-free survival was significantly lower for patients treated with BCT compared with mastectomy (69 vs. 93%, P = 0.007). CONCLUSION The previously developed prognostic index was successful in stratifying patients with respect to LRR in an independent cohort undergoing BCT after neoadjuvant chemotherapy. The prognostic index can be used to identify patients at high risk for LRR who may be considered for more extensive surgery or enrollment into clinical trials evaluating novel strategies for local-regional control.

Young breast cancer patients are more likely than old patients to experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS). However, the pathological processes underlying this relationship have not been elucidated. We investigated the effect of young age on IBTR in a Korean cohort of women with different molecular subtypes of breast cancer. We analyzed data of 2,102 consecutive breast cancer patients who underwent BCS and post-surgical radiation therapy (RT) at two Korean institutions between 2000 and 2005. Patients were classified as young (≤ 40 years; N = 513) or old (> 40 years; N = 1,589). Breast cancer subtype was determined by estrogen receptor (ER), progesterone receptor (PR), and HER2. Median follow-up duration was 61 months. The 5-year IBTR rate was 3.4% in young patients and 1.1% in old patients (P < 0.001). Univariate analysis indicated that IBTR rate in young patients with luminal A and HER2 subtypes was significantly greater than in old patients with these subtypes (P = 0.015 and P < 0.001, respectively). Multivariate analysis, which used luminal A subtype in old patients as reference, indicated that HER2 subtype in young patients was associated with increased risk of IBTR (hazard ratio, HR = 12.24; 95% CI: 2.54-57.96). Among old patients, HER2 subtype was not associated with increased IBTR. In conclusion, young women had a higher rate of IBTR after BCS and RT than old women. This difference is mainly among women with HER2 subtype. Aggressive local control and adjuvant therapy should be considered for young women with HER2 subtype breast cancer.

BACKGROUND AND PURPOSE The EORTC 22881-10882 trial showed that for patients treated with breast conserving therapy (BCT), a 16Gy boost dose significantly improved local control, but increased the risk of breast fibrosis. A model to estimate the risk of ipsilateral breast relapse (IBR) already exists, but now a model has been developed which takes boost treatment into account and is based on centrally reviewed pathology. MATERIALS AND METHODS A Cox model was developed based on central pathology review data and clinical data of 1603 patients from the EORTC 22881-10882 trial with a median follow-up of 11.5years. From a predefined set of variables, predictors with a maximal effect on 10-year IBR rate >4% were retained in the model. Bootstrap re-sampling was used to assess model calibration and discrimination. The results are presented in the form of a nomogram. RESULTS Apart from young age and no boost, presence of DCIS adjacent to the invasive tumor was associated with increased risk of IBR (HR 1.96, p=0.001). Patients with high grade invasive tumors were younger than patients with low/intermediate grade (p<0.0001). The nomogram includes histologic grade, DCIS, tumor diameter, age, tamoxifen, chemotherapy, and boost with a concordance probability estimate of 0.68. CONCLUSIONS The nomogram for predicting IBR 10years after BCT includes seven factors, with young age, presence of DCIS and boost treatment as the most dominant factors. The nomogram estimates IBR and confirms the importance of a boost dose. Combined with a model to predict fibrosis published previously, the nomogram presented here may assist in decision making for individual patients.