Incidence Of Local-regional Recurrence Research Articles

The Presence of Extensive Lymphovascular Invasion (LVI) is Associated with Higher Risk of Recurrence in Curatively Treated Breast Cancer Patients

Lymphovascular invasion (LVI) is a pathological feature seen in breast cancer that may be an important step in cancer metastasis. Multiple datasets have demonstrated a correlation between LVI and local-regional recurrence (LRR). Whether the extent of LVI is an incremental determinant of LRR risk is unknown. We describe clinical outcomes in women with invasive breast cancer stratified by: 1) absence of LVI (neg), 2) LVI focal or suspicious (FS-LVI), 3) usual (non-extensive) LVI (LVI) and 4) extensive LVI (E-LVI). Between December 2009 and August 2021, there were 8,837 patients with early-stage breast cancer (T1-2 and N0-2a) were treated with curative intent and were evaluable. Clinical-pathological details were abstracted by retrospective review. The description of LVI was abstracted from pathology reports. Recurrence and survival outcomes were compared based on the extent of LVI. Of the 8837 patients studied, 5584 were neg, 461 had FS-LVI, 2315 had LVI, and 477 had E-LVI. The E-LVI cohort had baseline characteristics suggestive of higher risk such as younger median age, higher proportion of grade 3, more nodal positivity, more mastectomy (67% vs 48%), and higher use of chemotherapy compared to LVI. The cumulative incidence of LRR and DM was highest in the E-LVI group. Using LVI as the reference, the presence of E-LVI, age, tumor size, ER status, grade, mastectomy, and close/positive margins were independent variables for LRR on Cox multivariable regression (Table 1). To assess the effect with an alternate statistical method, we created propensity matched cohorts (matched for age, size, receptors, grade, surgery type, margins and chemotherapy/RT use); a statistical difference in OS was noted between groups with LVI vs E-LVI (HR 1.44 (CI 1.06-1.96, p = 0.018), but not in LRR (HR 1.31 (CI 0.87-1.97, p = 0.2) or DM (HR 1.16 (CI 0.88-1.53, p = 0.3). Our work suggests that patients with E-LVI are at a higher risk for LRR compared to patients with usual LVI, despite maximal standard of care treatment. This is important because E-LVI can be determined from breast specimens, and may help define indications for RNI/PMRT when nodal information is not available.

Application of the ACOSOG Z0011 criteria to Chinese patients with breast cancer: a prospective study

BackgroundAlthough the ACOSOG Z0011 study showed that axillary lymph node dissection (ALND) could be avoided in a specific population of sentinel lymph node-positive patients, it is not widely accepted by Chinese surgeons. We conducted a prospective single-arm study to confirm whether or not the results of Z0011 are applicable to Chinese patients.MethodsPatients conforming to the Z0011 criteria were prospectively enrolled at the Peking University People’s Hospital Breast Center from November 2014 to June 2019. The clinicopathological features of the study group were compared with those of the Z0011 study group. Lymphedema after surgery, the incidence of local-regional recurrence, and survival were analyzed.ResultsOne hundred forty-two patients who met the Z0011 eligibility criteria were enrolled in this study; 115 underwent sentinel lymph node biopsy (SLNB) alone. Compared with the Z0011 trial, younger patients were included (median age, 52 [26–82] years vs 54 [25–90] years; P = 0.03). For clinical T stage, tumor histology, hormone status, lymphovascular invasion, and the number of positive sentinel lymph nodes (SLNs), no statistically significant differences were observed. More patients received adjuvant chemotherapy and endocrine therapy in this study (90.85% vs 58.0% and 80.99% vs 46.6% respectively, P <0.001). A similar percentage of patients received radiotherapy, but more nodal radiotherapy procedures were carried out in our study (54.5% vs 16.9%). After a median follow-up of 29 months, only 1 patient (0.9%) had ipsilateral breast tumor recurrence, and no regional recurrence occurred.ConclusionOur study showed that it is achievable to avoid ALND in patients eligible for Z0011 in China.Trial registrationClinicalTrials.gov. Registration number NCT03606616. Retrospectively registered on 31 July 2018.

Abstract PS6-26: Recurindex® predicts local regional recurrence for n1 breast cancer after mastectomy

Abstract Background: Post-mastectomy radiation therapy (PMRT) is part of standard regimen in the management of breast cancer. It has been shown to decrease the incidence of local regional recurrence (LRR) and improve breast cancer survival. Yet, its role in patients with 1-3 positive lymph nodes (N1) remains unclear. The lack of biological markers to evaluate the efficacy of PMRT for N1 patients leads to excessive treatment of low-risk patients and ignore of those at high risk. A clinical-genomic model RecurIndex® (RI-LR), based on a genomic database from mRNA expression as well as clinical factors (lymph node involvement, ER status,age at diagnosis, and lymphovascular invasion), is mainly developed for predicting the LRR in early stage breast cancer patients. Method: The preliminary result enrolled 107 breast cancer patients with N1 involvement in a retrospective study atthe fourth hospital of Hebei Medical University. Kaplan Meier method is used to calculate the survival rates in terms of LRR-free interval (LRFI). The log rank test and cox regression model are applied for the survival difference between two independent groups, and for investigating prognostic factors related to high-risk patients. The primary endpoint is LRFI. Results: With a median follow-up of 84 [IQR 64-84] months, RI-LR partitioned these N1 patients into 70% high-risk group and 30% low-risk group. LRR rate was 14.7% in the high-risk group whereas only 3.1% in the low-risk group. The survival curve clearly showed a partitioned trend of two groups (5-year LRFI 87.5%vs 100%, p = 0.085). Patients identified in the RI-LR high-risk group showed significantly higher LRFI if they had PMRT compared to those without PMRT (5-year LRFI 94% vs 70%, p =0.043), suggesting that higher radiosensitive patients could be identified by RI-LR. Multivariate analysis revealed that high-risk patients treated with PMRT has a 71 % reduction of LRR compared to those without PMRT (HR 0.29, 95%CI: 0.08-1.00, p = 0.051). Conclusions:The present study provided robust evidence that RI-LR could partition N1 breast cancer patients into good and poor prognosis of LRR. RI-LR is capable of identifying high-risk patients who would benefit from PMRT. This observation warrants to validate in a larger cohort. Key words: Early breast cancer, genomic assay, recurrence index (RI), local-regional recurrence (LRR), post mastectomy radiotherapy (PMRT) Citation Format: Li-Na Zhang, Yue-Ping Liu, Chun-Xiao Li, Chao Song, Ning Wang, Ji-Yu Tang, Meng-Li Zhou, Ting-Hao Chen, Ming-Shuo Chen, Skye Hung-Chun Cheng, Cui-Zhi Geng. Recurindex® predicts local regional recurrence for n1 breast cancer after mastectomy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-26.

Effectiveness of image-guided radiotherapy for rectal cancer patients treated with neoadjuvant concurrent chemoradiotherapy: A population-based propensity score-matched analysis.

The effects of image-guided radiotherapy (IGRT, an advanced RT technology) have been debated in the literature. We compared the outcomes of locally advanced rectal cancer (LARC) patients treated with neoadjuvant concurrent chemoradiotherapy (NCCRT; with vs without IGRT) in a large population-based propensity score (PS)-matched analysis. We identified LARC patients diagnosed between 2007 and 2015 via the Taiwan cancer registry (TCR) and constructed a PS-matched cohort to balance observable potential confounders. Outcomes (R0 resection, overall survival, incidence of local regional recurrence [ILRR], rectal cancer mortality [IRCM], other cancer mortality [IOCM] and cardiovascular mortality [ICVM]) were obtained from TCR and the national death registry. We compared the hazard ratio (HR) of death and other endpoints between IGRT and non-IGRT groups. We performed supplementary analysis (SA) to evaluate the robustness of these results in a subgroup, taking an additional potential confounder into account. Our study population comprised of 586 patients that were balanced with regard to observed covariables. There was no significant difference in HR for death (0.99; 95% confidence interval 0.70-1.39; P=0.94) between IGRT and non-IGRT groups. There were also no significant differences in R0 resection, ILRR, IRCM, IOCM or ICVM. The results of our SA were consistent with these findings. For LARC patients treated with NCCRT, the treatment outcome was not significantly different among patients treated with and without IGRT. Further study is needed to clarify these results with consideration to additional potential confounding factors and toxicity profiles at endpoints.

Strategies of surgical and comprehensive management of breast cancer patients with local regional recurrence

Breast conserving surgery and sentinel lymph node biopsy are widely used in early breast cancer treatment. Right now, the mode of local regional recurrence (LRR) has significantly changed and the rate of ipsilateral breast tumor recurrence and axillary lymph node recurrence are steadily increasing. Due to its relatively low incidence of LRR compared with distant metastasis, inconsistent of pre-recurrence treatment, difficulty in surgical treatment, and few prospective clinical studies, there are rising new challenges for clinical management of LRR patients. In this article, based on new theory of LRR, clinical diagnosis and treatment progress, and our own clinical practice experience for LRR breast cancer patients, we propose that we should make pathological diagnosis and do systemic evaluation for LRR disease, then considering it as a curable disease, and integrating local and systemic comprehensive treatment for LRR patients, thus to improve their disease outcome.

The sequencing of chemotherapy and radiotherapy in breast cancer patients after mastectomy.

The purpose of the study was to retrospectively evaluate the outcome according to the sequencing of radiotherapy and chemotherapy after mastectomy in high-risk patients with breast cancer. From January 1986 through September 2000, 275 women with stage I-IIIB breast cancer were treated with chemotherapy and radiotherapy after mastectomy. The patients were divided into four groups. Chemotherapy was given first in 116 patients (CTRT), concurrent chemoradiotherapy in 77 (CCRT), sandwich therapy in 65 (SAND), and radiotherapy first in 17 (RTCT). Prognostic factors such as age, primary tumor size and nodal status were not statistically different among the four groups. There was a higher proportion of patients with close or positive margins in CCRT and RTCT groups than in the CTRT and SAND groups (22/77, 5/17 vs 3/116, 2/65, P <0.001). Median follow-up was 145 months (range, 10-210). Five-year overall and disease-free survival were 69.4% and 56.1%, respectively. Survival outcomes were not statistically different among the four groups (5-year overall/disease-free survival, 68.0%/63.0%, 71.3%/60.8%, 65.0%/48.1%, 81.9%/58.8%, in CTRT, CCRT, SAND, and RTCT, respectively) (P = 0.3422/P = 0.6333). The incidence of local-regional recurrence was not different in the early radiotherapy group (CCRT/RTCT, 11%/12%) and delayed radiotherapy group (CTRT/SAND, 7%/8%). This study suggests that in these high-risk breast cancer patients after mastectomy, delay in the start of radiotherapy does not increase local-regional recurrence, and the final survival outcomes are not affected by the sequencing of chemotherapy and radiotherapy.

Indications for Postmastectomy Radiation After Neoadjuvant Chemotherapy in ypN0 and ypN1-3 Axillary Node-Positive Women

IntroductionDownstaging with neoadjuvant chemotherapy (NAC) might obscure indications for postmastectomy radiation (PMRT). The degree of downstaging that results in local-regional recurrence (LRR) rates low enough to omit PMRT remains controversial. We examined the rate of LRR in women who received NAC who underwent mastectomy without PMRT. Patients and MethodsBetween 2004 and 2013, 81 women with stage I to IIIA breast cancer had NAC and mastectomy; 48 patients (59%) were clinical N0 and 33 patients (41%) were clinical N1; median age was 45 years; 33 patients (41%) had hormone receptor-positive (HR+)HER2−, 21 patients (26%) HR+HER2+, 19 patients (23%) HR− HER2−, and 7 patients (9%) HR−HER2+ disease. We explored how LRR rates varied with age, BRCA status, Grade, receptor status, clinical N status, pathologic response, lymphovascular invasion, and mastectomy margins. Median follow-up was 4.9 years. ResultsAfter NAC, 35 patients (43%) had a pathologic complete response (pCR), 33 patients (41%) were ypN0, and 13 patients (16%) were ypN1-3+. There were 8 LRRs (6 chest wall, 1 axillary, 1 supraclavicular node). The 5-year cumulative incidence of LRR was 8% for all patients, 3% for pCR, 16% for ypN0, 10% for ypN1-3+, 6% for HR+HER2−, 25% for HR+HER2+, 0% for HR−HER2−, and 0% for HR−HER2+. LRR was 31% in the ypN0 and 33% in the ypN1-3+ HR+HER2+ women, and 12% in the ypN0 and 0% in the ypN1 to ypN3+ HR+HER2− patients. ConclusionThis study is unique. All HER2+ patients received trastuzumab and LRR was analyzed according to treatment response, clinicopathologic factors, and receptor status. pCR patients including young women and clinical stage IIIA had low LRR rates. However, ypN0 and ypN1-3+ HR+HER2+ patients had higher rates of LRR compared with other receptor subgroups and on the basis of limited data should be considered for PMRT.

Abstract P3-10-06: Patterns of failure in patients with inflammatory breast cancer: the case for aggressive local/regional treatment

Abstract Background: While the survival of patients with inflammatory breast cancer (IBC) is dictated by the status of their distant metastases, local/regional control remains an important component of quality of life. We have sought to determine patterns of local/regional recurrence (LRR) in patients presenting with inflammatory breast cancer. Methods: The medical records of 92 patients (pts) diagnosed with IBC from 1997 until 2007 were reviewed. Pt cohorts were stratified by disease burden at presentation (metastatic or local/regional) and their tumor, treatment, and disease course were analyzed. Primary outcomes were time from diagnosis to LRR, time to distant recurrence, and overall survival (OS). Median follow-up (MFU) for the entire cohort was 6 years (yrs) (range 0.1 to 12.7 yrs); for those patients who presented with metastatic disease versus only local/regional disease, MFU is 2 yrs and 6 yrs, respectively. This study was approved by the hospital institutional review board. Results: Median age at diagnosis was 49 yrs (range 24 to 72). 68 (74%) patients were without evidence of metastatic disease on presentation. With 6yr MFU, 40/68 (59%) had disease recurrence at either local or distant sites, and 15/68 (22%) had documented LRR, either as the first or subsequent site of recurrence. Estimated 5yr OS is 64%. 24 (26%) pts presented with metastatic disease (lung, liver, distant lymph nodes, pleura). All of the 24 pts presenting with metastatic disease developed systemic disease progression; 12/24 (50%) also developed LRR, and for 9/12 pts the LRR was first progression or concurrent with distant progression. Eleven of the 24 pts did not receive radiation or surgery; and within this cohort, 7 (64%) pts developed LLR at a median time of 9 months after diagnosis. Six pts received radiation therapy without surgery; 3/6 (50%) developed LRR. One pt had surgery alone; this patient was not known to have LRR, although had limited follow-up. Six pts received radiation therapy and surgery; 1 for palliation and 5 to prevent LRR. Of these 5 pts, 1/5 (20%) developed LRR that extended to the contralateral breast at 1.2y after diagnosis. Among the 24 patients, the cumulative incidence of LRR was 29%, 37%, and 43% at 1yr, 2yr, and 3yr (accounting for competing risk of death). The median OS was 2.9 yrs and estimated 5yr OS was 36%. Conclusions: Pts with inflammatory breast carcinoma presenting with metastatic disease are at high risk for local/regional disease progression. Aggressive local therapy should be considered to prevent symptoms of uncontrolled local disease, despite an uncertain impact upon OS. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-06.

Risk of locoregional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post-mastectomy radiation

We assessed differences in locoregional outcome based on receptor status combinations in a cohort of stage II-III breast cancer patients treated with modern trimodality therapy. Medical records of 582 consecutively treated patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 were reviewed. Rate of local regional recurrence (LRR) was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Gray's test and by Fine and Gray's modeling approach. Median follow-up was 44.7 months. Five-year progression-free survival (PFS) was 73.9% and overall survival (OS) was 84%. The cumulative 5-year incidence of LRR as first site of failure was 6.2% (95% CI 4.2-8.7). Five-year cumulative incidence of LRR was 8.6 versus 4.4% for estrogen receptor (ER) negative versus ER positive (P = 0.017), 8.5 versus 3.4% for progesterone receptor (PR) negative versus PR positive (P = 0.011), and 1.7 versus 7.5% for HER2 positive (86% received trastuzamab) versus HER2 negative (P = 0.032). Five-year cumulative incidence of LRR was 11.8% for the triple negative subtype and 3.9% for other receptor combinations (P < 0.001). Among patients whose disease is ER positive, 5-year LRR rate was 7.8 versus 3.4% for PR negative versus PR positive (P = 0.130). The prognostic value of the triple negative and HER2 negative subtypes was maintained on multivariate analysis. In the era of HER-2 targeted therapy, tumors that are HER-2 over expressing and are treated with trastuzumab have a very low rate of LRR. ER negative, PR negative, and triple negative status are associated with increased risk of LRR.

Abstract 4910: Identification of putative epigenetic markers for head and neck squamous cell carinoma recurrence

Abstract Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent types of cancer but the lack of early detection and high incidence of local-regional recurrence lead to high mortality. Therefore, it is important to develop new molecular markers to be used as diagnostic and prognostic indicators. An important mechanism for gene transcriptional inactivation is hypermethylation at the CpG islands within the promoter regions. The presence of hypermethylation might be useful as a molecular marker for tumor cell detection which could be useful for early detection of tumor recurrence. The aim of this study was to evaluate promoter hypermethylation of suppressor genes via quantitative methylation-specific PCR (Q-MSP) in tumor and body fluid samples (saliva) as a means to detect epigenetic alterations specific to HNSCC. Tumor samples and salivary rinse were collected before and after the last curative treatment from 180 consecutive HNSCC cases and every 6 months during the patient follow-up. The pattern of aberrant methylation of 24 genes was analyzed and allowed the selection of a panel of 5 genes that have a specificity of 95% and a sensitivity of 38% in the detection of hypermethylated cells in saliva samples from recently diagnosed HNSCC patients. The efficacy of this panel may be useful in early diagnosis of HNSCC recurrence is being evaluated. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4910.

The Sequencing of Chemotherapy and Radiotherapy in Breast Cancer Patients after Mastectomy

The purpose of the study was to retrospectively evaluate the outcome according to the sequencing of radiotherapy and chemotherapy after mastectomy in high-risk patients with breast cancer. From January 1986 through September 2000, 275 women with stage I-IIIB breast cancer were treated with chemotherapy and radiotherapy after mastectomy. The patients were divided into four groups. Chemotherapy was given first in 116 patients (CTRT), concurrent chemoradiotherapy in 77 (CCRT), sandwich therapy in 65 (SAND), and radiotherapy first in 17 (RTCT). Prognostic factors such as age, primary tumor size and nodal status were not statistically different among the four groups. There was a higher proportion of patients with close or positive margins in CCRT and RTCT groups than in the CTRT and SAND groups (22/77, 5/17 vs 3/116, 2/65, P <0.001). Median follow-up was 145 months (range, 10-210). Five-year overall and disease-free survival were 69.4% and 56.1%, respectively. Survival outcomes were not statistically different among the four groups (5-year overall/disease-free survival, 68.0%/63.0%, 71.3%/60.8%, 65.0%/48.1%, 81.9%/58.8%, in CTRT, CCRT, SAND, and RTCT, respectively) (P = 0.3422/P = 0.6333). The incidence of local-regional recurrence was not different in the early radiotherapy group (CCRT/RTCT, 11%/12%) and delayed radiotherapy group (CTRT/SAND, 7%/8%). This study suggests that in these high-risk breast cancer patients after mastectomy, delay in the start of radiotherapy does not increase local-regional recurrence, and the final survival outcomes are not affected by the sequencing of chemotherapy and radiotherapy.

The Effect of Radiotherapy on Local Regional Recurrence among Patients with Pathologic Complete Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

Abstract Background: Radiotherapy has been shown to reduce local recurrence rates of breast cancer after treatment with surgery and adjuvant chemotherapy. Indications for postmastectomy radiation have historically been based on pathology, but indications for radiation in the setting of pathologic complete response (pCR) to neoadjuvant chemotherapy are not well defined. The aim of this study was to evaluate the rates of local regional recurrence (LRR) among patients with pCR to neoadjuvant chemotherapy followed by surgery with or without radiation (XRT).Patients and Methods: The case histories of 337 patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, surgery with or without radiation from October 1997 to December 2006 were analyzed. Median age at diagnosis was 50.6 years (range: 25-84). The clinical stage at diagnosis was I in 3 (1%), IIA in 105 (31%), IIB in 94 (28%), and III in 135 (40%) patients. All patients received preoperative systemic therapy with a doxorubicin-based regimen (92%) or a single-agent taxane regimen (7%) or CMF (1%). A total of 272 patients received radiation following surgery and 65 did not receive any radiation. Median follow-up time was 40 months among all patients. The Kaplan-Meier method and log rank test were used to evaluate LRR rates and overall survival among both groups.Results: Patients treated with neoadjuvant chemotherapy followed by surgery and XRT had a lower incidence of LRR at 3 years with 24 cases of local recurrence among 272 patients who received XRT compared with 12 cases of local recurrence among the 65 patients who did not receive XRT (8.9% v 18.5%, P=0.02). Radiation also reduced local regional recurrence at 3 years among a subset of patients with clinical stage T2N1 disease (4.9% v 28.6%, P=0.03). There was no difference in overall survival or disease free survival among patients who received XRT compared to patients who did not receive XRT. There were 62 (18%) patients who achieved a pCR to neoadjuvant chemotherapy. Among patients with a pathologic complete response, radiation appeared to reduce the risk of LRR compared to patients who did not receive XRT (7.4% v 25%, P=0.17).Conclusion: Radiotherapy significantly reduced local regional recurrence rate among patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and surgery. Of particular interest, patients who achieve a pathologic complete response to neoadjuvant chemotherapy still had high LRR rates and may benefit from radiotherapy by lowering the risk of local regional recurrence. Further studies on the significance of LRR and overall survival among these patients are needed. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4114.

Local-regional and distant recurrence rates in skin-sparing mastectomies compared with non-skin-sparing mastectomies.

Abstract Abstract #4138 Background: Although skin-sparing mastectomies (SSMs) are becoming more common, there are few data regarding the local-regional and distant recurrence rates. The aim of this study was to examine the incidence of local-regional recurrence, distant recurrence, and survival in breast cancer patients who underwent SSMs or non-skin-sparing mastectomies (NSSMs) at our institution.&amp;#x2028; Methods: We reviewed records of patients with primary breast carcinoma stage 0 to III who underwent total mastectomies with or without complete axillary dissection at our center from January 2000 to December 2005. After excluding patients with bilateral breast cancer, mastectomies for recurrent breast cancer, and patients with less than two-year follow-up, there were 1623 patients for study. Patient and tumor characteristics were evaluated and comparisons undertaken between the SSM and NSSM groups with univariate and multivariate logistic analyses. Kaplan-Meier curves and log-rank test were used to evaluate the overall and disease-free survival in the two groups.&amp;#x2028; RESULTS: Of the 1623 patients, 465 (28.7%) patients underwent SSM and 1158 (71.3%) underwent NSSM. Patients who underwent NSSM were older (55.6 vs. 48.9, p&amp;lt;0.0001) and had more advanced stage tumor (stage II or high: 48.3% vs. 28%, p&amp;lt;0.0001). Significantly more patients in the NSSM group received systemic chemotherapy (p=0.045), radiation therapy (p&amp;lt;0.0001), and endocrine therapy (p=0.002). At a median follow-up of 24.4 months (range 1.1-95.3), 138 patients (4.6%) had local-regional or distant recurrence. Specifically, 7 patients (1.5%) in the SSM group and 34 patients (2.9%) in the NSSM group had local-regional recurrences (p=0.097). The distant recurrence rate in patients undergoing SSM or NSSM was 14 (3.0%) and 110 (9.5%) patients (p&amp;lt;0.0001) at median follow-up time of 29.2 and 25.4 months, respectively. There is no difference in disease-free survival between the SSM group and NSSM after adjusting for tumor TNM stage and final nodal status at a median follow-up time of 54.3 months and 53.2 months, respectively.&amp;#x2028; CONCLUSIONS: SSM is safe and effective in appropriately selected patients with breast carcinoma. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4138.

Locoregional control in locally advanced breast cancer using neoadjuvant chemotherapy followed by breast conservation

539 Background: Neoadjuvant chemotherapy is commonly employed in the treatment of locally advanced breast cancer. However, the difference in local-regional recurrence (LRR) rates between those undergoing BCT and those with mastectomy is not well defined. The purpose of this study was to examine the incidence of LRR in these two groups after neoadjuvant chemotherapy at a single institution. Methods: Under IRB approval, a prospective database was utilized to identify all patients with locally advanced Stage II and III breast cancer undergoing neoadjuvant chemotherapy from 1991 to 2005. Patients presenting with stage IV disease or T4d primary breast cancer were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy by log-rank test and Cox regression analysis was utilized to evaluate individual variables associated with LRR. Results: 236 patients were included, 94 (40%) underwent BCT and 142 (60%) mastectomy. 93/94 (99%) of the BCT and 115/142 (81%) of the mastectomy patients received postoperative radiation. Pathologic complete response (CR) was seen in 60 patients, of which 34 underwent BCT. Those achieving BCT were more likely to have T2 or smaller tumors before treatment (p=0.0053) and smaller tumors post-treatment (p<0.0001) and were more likely to have a pathologic CR (p=0.0035) than those with mastectomy. At a median f/u of 58 months, the rate of LRR was 5% (5/94) in the BCT group and 9% (13/142) in the mastectomy group (p=0.32). Univariate Cox modeling showed ER status (p=0.01), number of positive axillary nodes (p=0.039), post-treatment T stage (p=0.02), tumor size post-treatment (p=0.04) and pathologic stage (p=0.008) were independent predictors of LRR. Pre-treatment T and N stage were not associated with LRR. Five-year overall survival was 90% in the BCT group and 69% in the mastectomy group (p=0.01). Conclusions: In this series of locally advanced breast cancer patients undergoing neoadjuvant chemotherapy, the rate of LRR was very low and was not significantly different between those undergoing BCT as compared to mastectomy. However, overall survival was improved in those achieving BCT, suggesting this may be a surrogate for prognosis. No significant financial relationships to disclose.

Locally recurrent breast cancer after conservation therapy

Background Today, the majority of small invasive and noninvasive breast cancers are treated with breast conservation therapy (BCT). The incidence of local-regional recurrence (LRR) after BCT for stage 0, I, and II patients ranges between 5% and 22%. Methods A literature search for BCT, local recurrence, and regional recurrence was performed. Data from over 50 articles pertaining to the characteristics, risk factors, detection, management, and prognosis of these patients with LRR after BCT were collected and analyzed. Results Positive margins, high-grade ductal carcinoma in situ (DCIS), young age, and the absence of radiation therapy after BCT increase the risk for LRR. Prognosis at LRR is impacted by invasive versus noninvasive histology, size and stage, method of detection, and involvement of skin and/or axillary lymph nodes. The standard treatment is salvage mastectomy. Conclusions The prognosis for LRR after BCT is favorable compared with patients with postmastectomy chest wall recurrence.

Comparison of Clinical Stage, Therapy Response, and Patient Outcome Between Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus

To analyze the differences in clinical stage, pathologic response to chemoradiotherapy, patterns of failure, and overall survival (OS) between patients with squamous cell carcinoma (SCC) and adenocarcinoma (ACA) of the esophagus. We stratified patients by two histologies, ACA and SCC, and statistically compared their clinical stage, post-therapy pathologic response, patterns of failure, and OS. Of the 235 patients who underwent preoperative chemoradiotherapy, 42 (18%) had SCC and 193 (82%) had ACA. Among the ACA patients, a significantly larger proportion was male (93% vs 7%; p <0.001), whereas sex was distributed similarly among SCC patients (55% male vs 45% female; p = 0.5). A significantly larger percentage of SCC patients were classified as lower TN and overall stage than ACA patients (T2 = 41% vs 28%, p <0.0001; N0 = 69% vs 48%, p = 0.01; stage II = 76% vs 55%, p <0.001). A significantly greater portion of SCCs was categorized as pathologic N0 after treatment (71% vs 65%; p = 0.02). Among the pathCR patients in clinical stage II, there were significantly greater proportion of SCC patients (77% vs 63%; p <0.001) than ACA patients. Among the pathCR patients in clinical stage III patients, a significantly greater proportion were ACA patients (38% vs 23%; p <0.001) than SCC patients. The median and 5-yr OS was 53 +/- 11 mo and 39% for ACA patients and 35 +/- 14 mo and 37% for SCC (median OS, p = 0.3). Among pathCR patients, median OS of ACA patients (133 mo) was longer than that of SCC patients but nonsignificant (29 mo; p = 0.07); results were similar for non-pathCR patients. DFS results were similar in all subgroups. Among the whole cohort, incidence of local-regional recurrence and distant metastases did not vary significantly. The median time to distant metastases did not vary significantly for pathCR and non-pathCR patients. We believe this is the first study that compares failure outcome of ACA and SCC patients with similar clinical stage after trimodality therapy. Our data suggest that significant differences in clinical stage and post-therapy pathologic stage exist between ACA and SCC. Frequent presence of malignant nodes in the resected specimens of ACA patients resulted in a shorter time-to-metastases suggesting that ACA patients need better systemic control.

Irradiation as an alternative to mastectomy

The conventional treatment of clinical Stage I and II breast cancer has been the radical or modified radical mastectomy. This presentation will review the available data to support the use of lumpectomy and irradiation as an alternative to mastectomy. Points of discussion will include patient selection, the role of pretreatment mammography, and surgical technique, i.e. incisional versus excisional biopsy, delineation of the biopsy site and extent of axillary surgery. Emphasis will be placed on radiotherapy technique, i.e. the role of regional lymphatic irradiation in pathologically NO patients, fractionation and total dose, field arrangement and the role of the boost . Results will be analyzed in terms of 5 and 10 year survival, the incidence of local-regional recurrence, complications, and the incidence of malignancy developing in the contralateral breast. Comparison will be made to those results achieved with mastectomy. Factors related to local-regional recurrence will be outlined. The influence of surgery and radiotherapy technique on cosmetic outcome will be discussed. The abi I ity to combine adjuvant chemotherapy with primary radiotherapy for patients with histologically positive axillary nodes will be reviewed in terms of the selection and sequencing of agents, the ability to deliver optimal doses of chemotherapy and the effect of chemotherapy on cosmesis and complications. Current treatment policy, the status of on-going studies and recommendations will be presented.