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Background: Undifferentiated pleomorphic sarcomas (UPS) present a diagnostic and therapeutic challenge. Identification of prognostic molecular markers is required for the discovery of novel treatment approaches. The purpose of this study was to correlate clinicopathologic variables, expression of tyrosine kinase receptors, and markers of cell cycle progression and survival with oncologic outcomes., Methods: A tissue microarray containing 208 primary UPS samples was analyzed by immunohistochemistry for protein markers and in situ hybridization for microRNA. Staining results were correlated with clinicopathologic features and oncologic outcomes. Univariate and multivariate analyses were conducted to assess associations between expression of protein markers, mi-RNA, and outcome., Results: At a median follow-up of 3.9 years (9 years for survivors), 5-year disease-specific survival (DSS) was 63 %. Clinical variables associated with improved DSS included age <61 years, tumor size <10 cm, margin-negative resection, and sporadic-tumor status. At the protein level, loss of cyclin D1 (p = 0.06), pEGFR (p = 0.023), pIGF-1R (p = 0.022), and PTEN (p < 0.001) and overexpression of AXL (p = 0.015) were associated with reduced DSS on univariate analysis. Ki67, PCNA, and pEGFR were more highly expressed in sporadic UPS than radiation-associated (RA-UPS), whereas RA-UPS samples expressed higher levels of both phosphorylated and total IGF-1R., Discussion: Loss of cyclin D1, overexpression of AXL, and loss of PTEN are associated with poor cancer-specific outcomes and warrant further investigation in UPS. The differences in protein expression in sporadic versus RA-UPS may indicate that the activated molecular signaling nodes may be different for each specific histology and also could explain the aggressive phenotype seen in RA-UPS compared with the sporadic lesions.

Background: Radiation therapy is used increasingly as a component of multidisciplinary treatment for many solid tumors. One complication of such treatment is the development of radiation-associated sarcoma (RAS). Undifferentiated pleomorphic sarcoma (UPS), previously termed "malignant fibrous histiocytoma" (MFH) is the most common histologic subtype of RAS. This study investigated the clinical outcomes for patients with radiation-associated UPS (RA-UPS/MFH)., Methods: The study identified 1068 patients with UPS/MFH treated at the authors' institution. Patient and tumor factors were collected and compared. Regression analysis was performed to identify independent predictors of survival. A matched-cohort survival and recurrence analysis was performed for radiation-associated and sporadic UPS/MFH., Results: The findings showed that RA-UPS/MFH comprised 5.1 % of the UPS population. The median latency to the development of RA-UPS/MFH was 9.3 years. The 5-year disease-specific survival (DSS) was 52.2 % for patients identified with RA-UPS/MFH (n = 55) compared with 76.4 % for patients with unmatched sporadic UPS/MFH (n = 1,013; p < 0.001). A matched-cohort analysis also demonstrated that the 5-year DSS was significantly worse for RA-UPS/MFH (52.2 vs 73.4 %; p = 0.002). Furthermore, higher local recurrence rates were observed for patients with RA-UPS/MFH than for patients with sporadic lesions (54.5 vs 23.5 %; p < 0.001). Radiation-associated status and incomplete resection were identified as independent predictors of local recurrence., Conclusion: This study demonstrated worse clinical outcomes for patients with RA-UPS/MFH than for patients with sporadic UPS/MFH. Local recurrence was significantly higher for patients with RA-UPS/MFH, suggesting a unique tumor biology for this challenging disease.

Background: Surgery is the primary treatment for all subtypes of retroperitoneal liposarcoma, but neoadjuvant therapy may be warranted in cases of dedifferentiated liposarcoma (DDLS), which has an increased risk of recurrence and metastasis. Therefore, an accurate subtype-specific diagnosis is vital for appropriate consideration of neoadjuvant therapy. Previous studies assessing the subtype-specific accuracy of percutaneous biopsy are limited. We aimed to analyze the accuracy of preoperative percutaneous biopsy in the subtype-specific diagnosis of retroperitoneal liposarcoma and thus the reliability of percutaneous biopsy in guiding decisions about neoadjuvant treatment., Methods: We retrospectively reviewed the medical records, including the pathologic reports, interventional radiology reports, and operative reports, of patients registered in the retroperitoneal/well-differentiated liposarcoma (WDLS/DDLS) database at The University of Texas MD Anderson Cancer Center between 1993 and 2013., Results: We identified 120 patients who underwent 137 preoperative percutaneous biopsies followed by surgical resections. Pathologic examination following resection indicated that 74 of the patients had WDLS and 63 had DDLS. The overall diagnostic accuracy of percutaneous biopsy for identifying the subtype of liposarcoma was 62.8 % (86/137); the accuracy for identifying WDLS was significantly higher (85.1 %; 63/74) than that for identifying DDLS (36.5 %; 23/63) (p < 0.01)., Conclusions: Percutaneous biopsy has low accuracy in the diagnosis of retroperitoneal DDLS. This can potentially mislead physicians in the decision to implement neoadjuvant treatment. When developing treatment strategies, including clinical trials for patients with retroperitoneal liposarcoma, physicians should carefully consider the low accuracy of percutaneous biopsy in detecting DDLS.

Background: Treatment of distal rectal cancer remains clinically challenging and includes proctectomy and coloanal anastomosis (CAA) or abdominoperineal resection (APR). The purpose of this study is to evaluate operative and pathologic factors associated with long-term survival and local recurrence outcomes in patients treated for distal rectal cancer., Methods: A retrospective consecutive cohort study of 304 patients treated for distal rectal cancer with radical resection from 1993 to 2003 was performed. Patients were grouped by procedure (CAA or APR). Demographic, pathologic, recurrence, and survival data were analyzed utilizing chi-square analysis for comparison of proportions. Survival analysis was performed using Kaplan-Meier method and log-rank test for univariate and Cox regression for multivariate comparison., Results: The median tumor distance from the anal verge was 2 cm [interquartile range (IQR) 0.5-4 cm]. Margins were negative in all but four patients (one distal, 0.3%; three radial, 1%). The 5-year overall survival rate was 82% (88.6% stage pI, 80.5% stage pII, 67.9% stage pIII). Older age, advanced pathologic stage, presence of lymphovascular or perineural invasion, earlier treatment period, and APR surgery type were associated with worse survival on multivariate analysis. The 5-year local recurrence rate was 5.3% after CAA and 7.9% after APR (p = 0.33)., Conclusions: Low rates of local recurrence and good overall survival can be achieved after treatment of distal rectal cancer with stage-appropriate chemoradiation and proctectomy with CAA or APR. Sphincter preservation can be achieved even with distal margins less than 2 cm.

Background: Controversy exists in the literature regarding the optimal site for lymphatic mapping in breast cancer. This study was designed to characterize lymphatic drainage patterns within the same patient after subareolar (SA) and peritumoral (PT) radiopharmaceutical injections and examine the impact of reader interpretation on reported drainage., Methods: In this prospective trial, 27 women with breast cancer underwent sequential preoperative SA and PT injections of 0.5 to 2.7 mCi of technetium-99 m filtered sulfur colloid 3 days or more apart. Patterns of radiopharmaceutical uptake were reviewed independently by two nuclear medicine physicians. Inter-reader agreement and injection success were assessed in conjunction with observed drainage patterns., Results: There was near perfect inter-reader agreement observed on identification of axillary LN drainage after PT injection (P = 0.0004) and substantial agreement with SA injection (P = 0.0344). SA injection was more likely to drain to only axillary LNs, whereas PT injection appeared more likely to drain to both axillary and extra-axillary LNs, although no statistically significant differences were found. All patients with extra-axillary drainage after PT injection (n = 6 patients) had only axillary drainage after SA injection. Dual drainage was observed for six patients with PT injection and one patient with SA injection., Conclusions: Our findings suggest that radiopharmaceutical injected in the SA location has a high propensity to drain to axillary LNs only. After controlling for patient factors and demonstrating inter-reader agreement, the inability to demonstrate statistically significant differences in drainage based on injection site suggests that lymphatic drainage patterns may be a function of patient and tumor-specific features.

The purpose of this study was to determine the outcome of surgery for patients with recurrent gastric or gastroesophageal cancer. We queried records from 7,459 patients who presented with gastric or gastroesophageal cancer to our institution from 1973 through 2005 to identify those for whom resection of recurrent disease had been attempted. We assessed the associations between various clinicopathologic factors and resectability with logistic regression analysis and between clinicopathologic factors and overall survival (OS) with the Cox proportional hazards model. Sixty patients underwent attempted resection for recurrent cancer. In 31 cases (52%), recurrent disease proved unresectable at laparotomy. Factors associated with the ability to undergo re-resection included neoadjuvant treatment prior to initial resection [odds ratio (OR) 12.2, 95% confidence interval (CI) 1.9-75.6] and having an isolated local recurrence (OR 5.1, 95% CI 1.3-20.5). Of the 29 patients who underwent re-resection, 14 required adjacent organ resection, and 6 required interposition grafting. Three- and 5-year OS rates for all 60 patients were 21% and 12%, respectively; median follow-up time was 23 months. Median OS for patients undergoing resection was 25.8 months (95% CI 17.1-49.8) versus 6.0 months (95% CI 4.0-10.5) for unresectable patients (P < 0.001). Initial tumor location at the gastroesophageal junction was associated with diminished OS [hazard ratio (HR) 2.8, 95% CI 1.2-6.5] and ability to undergo resection of recurrence was associated with improved OS (HR 0.2, 95% CI 0.1-0.6). We conclude that surgical resection of select patients with recurrent gastric or gastroesophageal cancer can result in improved OS but often requires adjacent organ resection or interposition graft placement.

Background: The purpose of this study was to identify clinicopathologic factors associated with positive peritoneal cytology (PPC) in patients with gastric cancer and to compare the overall survival (OS) of patients with PPC treated with and without neoadjuvant therapy., Methods: The medical records of 3,747 patients with gastric or gastroesophageal adenocarcinoma presenting to our institution (January 1995 to December 2005) were reviewed to identify those patients who underwent diagnostic laparoscopy as a staging procedure prior to consideration for neoadjuvant therapy. Associations between various clinicopathologic factors and OS were examined with Cox proportional hazards models. Kaplan-Meier curves were created to compare OS between groups., Results: Of 381 patients who underwent diagnostic laparoscopy for staging, 39 were found to have PPC without gross metastatic disease. Linitis plastica and tumors located at the gastroesophageal junction were identified as predictors of PPC (P < 0.01). Median follow-up for living patients was 51 months. Median OS for patients with PPC and no gross metastatic disease at laparoscopy (13 months) was no different from that for patients with gross metastatic disease at laparoscopy (10 months, P = 0.06). For the 39 patients with PPC and no gross metastatic disease, use of neoadjuvant therapy resulted in a 3-year OS rate of 12% versus 0% for patients who did not receive neoadjuvant therapy., Conclusion: Outcomes for patients with PPC without gross metastatic disease are not significantly different from those patients with gross metastatic disease at laparoscopy. However, some patients can achieve long-term survival and should be considered for neoadjuvant treatment prior to attempts at surgical resection.

Background: Although completion lymph node dissection (CLND) is the standard of care for breast cancer patients with sentinel lymph node (SLN) metastases, the SLN is the only node with tumor in 40% to 60% of cases. To assist with decision-making regarding CLND, investigators at Memorial Sloan-Kettering Cancer Center devised and validated a nomogram for predicting the likelihood of non-SLN metastases. To assess the generalizable use of this nomogram, validation analysis was performed by using an external database., Methods: Eight clinicopathologic variables for 200 consecutive breast cancer patients at the University of Texas M. D. Anderson Cancer Center with SLN metastases and CLND were entered into the nomogram. The accuracy of the nomogram to predict non-SLN metastases was assessed by the receiver operating characteristic (ROC) curve and linear regression analysis. The accuracy of the nomogram with touch-imprint cytology (TIC) as a substitute variable for frozen section was also evaluated., Results: The linear correlation coefficient of the nomogram-predicted probabilities correlated with the observed incidence of non-SLN metastases for all patients (.97). The accuracy of the nomogram as measured by the area under the ROC curve was .71. When applied solely to patients who had TIC assessment of the SLN, the area under the ROC curve was .74., Conclusions: This study validated the Memorial Sloan-Kettering Cancer Center breast cancer nomogram by using an external database. TIC seems to be an acceptable substitute for frozen section as a nomogram variable. The nomogram may help predict an individual's risk of non-SLN metastases and assist in patient decision making regarding the benefit of CLND.

Background: The presence of skin involvement has been accepted as a relative contraindication to breast preservation because it is believed to be associated with an increased local failure rate. This study was conducted to assess the outcome of a carefully selected group of patients who presented with breast cancer involving the skin and who had breast conservation therapy (BCT) following neoadjuvant chemotherapy., Methods: Between 1987 and 1999, 33 patients with stage IIIB or IIIC breast cancer completed treatment consisting of four cycles of neoadjuvant chemotherapy, lumpectomy, radiation therapy, and consolidative chemotherapy. Clinicopathologic factors were analyzed and patients were followed for locoregional and distant recurrence., Results: Initial median tumor size was 7 cm. All patients had skin involvement, defined as erythema, skin edema, direct skin invasion, ulceration, or peau d'orange. Following chemotherapy, median pathologic tumor size was 2 cm. Complete resolution of skin changes occurred in 29 patients (88%). At median follow-up time of 91 months in surviving patients, 26 patients (79%) were alive without evidence of disease. The 5-year, disease-free survival rate was 70%, and the 5-year overall survival rate was 78%. The actuarial ipsilateral breast cancer recurrence rate was 6% at 5 years., Conclusions: Patients who present with T4 breast cancer who experience tumor shrinkage and resolution of skin changes with neoadjuvant chemotherapy represent a select group of patients who can have BCT. These patients have favorable rates of long-term local control and survival. Mastectomy is not mandatory for all patients with breast cancer who present with skin involvement.

Background: It is unclear which breast cancer patients with positive sentinel lymph nodes (SLNs) require a completion axillary lymph node dissection. Our aim was to determine factors that predict involvement of nonsentinel axillary nodes (NSLNs) in patients with positive SLNs., Methods: We reviewed the records of all patients with invasive breast cancer who underwent SLN biopsy at our institution between 1993 and August 2001. Multivariate analysis was used to identify clinicopathologic features in SLN-positive patients that predict involvement of NSLNs., Results: A total of 131 patients had a positive SLN and underwent completion axillary lymph node dissection. Multivariate analysis revealed that primary tumor >2 cm (P =.009), SLN metastasis >2 mm (P =.024), and lymphovascular invasion (P =.028) were independent predictors of positive NSLNs. The number of SLNs harvested was a significant negative predictor (P =.04). In our model, based on the presence of these factors, the positive predictive value was 100% for a score of 4., Conclusions: The likelihood of positive NSLNs correlates with primary tumor size, size of the largest SLN metastasis, and presence of lymphovascular invasion. A scoring system incorporating these factors may help determine which patients would benefit from additional axillary surgery.

Background: Our goal was to evaluate the role of breast-conservation therapy in early-stage breast cancer patients with a family history (FH) of breast cancer., Methods: Between 1970 and 1994, 1324 female patients with breast cancer were treated with breast-conservation therapy at our institution. From these, we identified 985 patients with stage 0-II breast cancer and who had available information on FH status. FH was considered positive in any patient who had a relative who had been previously diagnosed with breast cancer. Disease-specific survival was calculated from the date of initial diagnosis using the Kaplan-Meier method., Results: The stage distribution for the 985 patients was as follows: 0 in 65 (7%), I in 500 (51%), and II in 420 (43%). The median age was 50 years (range, 21-88), with a median follow-up time of 8.8 years (range,.25-29). The median tumor size was 1.5 cm. FH was positive in 31%. There were no significant differences in locoregional recurrence, distant recurrence, disease-specific survival, or incidence of contralateral breast cancer in patients with a positive FH versus patients with a negative FH., Conclusions: Breast-conservation therapy is not contraindicated in early-stage breast cancer patients with a positive FH.

Background: In sentinel lymph node (SLN) biopsy for breast cancer, many centers use same-day preoperative injection of technetium 99mTc-labeled sulfur colloid and intraoperative injection of blue dye for localization of SLNs. Same-day sulfur colloid injections can be problematic because of the variability in sulfur colloid migration times, which can lead to ineffective use of operating room time, and low SLN-to-background radioactivity ratios. We examined the utility of day-before-surgery injections of high dose 99mTc-labeled sulfur colloid injections., Methods: The day before surgery, high-dose 99mTc-labeled sulfur colloid was injected peritumorally, and a lymphoscintigram was obtained. Intraoperatively, after injection of blue dye, a gamma probe was used to localize SLNs. Nodes that were stained blue or were highly radioactive were considered SLNs and were removed., Results: Lymphoscintigraphy demonstrated drainage in 107 patients (91%). Transcutaneous localization of the SLN was possible in 104 patients (89%). In three patients, all of whom had no drainage demonstrated on lymphoscintigraphy, no SLN was identified at surgery (97.5% success rate for SLN identification). A mean of 2.3 SLNs per patient were identified. Twenty-five patients (21%) had at least one histologically positive SLN. In 23 of these patients, the positive SLN was the SLN with the most radioactivity, and in the remaining two patients, the positive SLN was both blue-stained and hot., Conclusion: Day-before-surgery injection of high-dose 99mTc-labeled sulfur colloid results in high rates of transcutaneous and intraoperative identification of SLNs. The delay between injection and surgery did not appear to promote significant passage of sulfur colloid to second-echelon nodes.

Background: The goals of this study were to assess the feasibility and toxicity of a regimen of preoperative chemoradiotherapy, surgery, and intraoperative radiotherapy in the treatment of patients with potentially resectable gastric cancer. A secondary objective was to assess pathologic response to chemoradiotherapy in the treated tumors., Methods: Twenty-four patients were entered in the protocol. Treatment regimen consisted of 45 Gy of external beam radiotherapy with concurrent 5-FU given as a continuous infusion at a dose of 300 mg/m2. Patients were restaged 4-6 weeks after chemoradiotherapy and then underwent surgical resection and intraoperative radiotherapy to a dose of 10 Gy., Results: Twenty-three patients (96%) completed chemoradiotherapy in accordance with the study protocol. Nineteen (83%) of 23 patients who completed chemoradiotherapy underwent surgical resection with D2 lymphadenectomy. Four patients (17%) had progressive disease and were not resected. The morbidity and mortality rates were 32% and 5%, respectively. Of the resected patients, two (11%) had complete pathologic responses while 12 (63%) had pathologic evidence of significant treatment effect., Conclusions: Preoperative chemoradiotherapy for gastric cancer can be delivered safely and is well tolerated. The rate of surgical complications is consistent with that of other recently reported prospective trials of gastrectomy alone. Preoperative chemoradiotherapy resulted in significant pathologic responses in the majority of treated tumors, and complete pathologic responses were achieved in some patients.

Background: The role of breast-conserving therapy (BCT) in the management of ductal carcinoma-in-situ (DCIS) is controversial because of reported high recurrence rates. We reviewed our experience to determine whether the rate and pattern of locoregional recurrence after BCT were similar in patients with DCIS and patients with early-stage (T1) invasive breast tumors and whether local recurrence affected survival., Methods: Between 1973 and 1994, 87 patients with DCIS alone, 22 patients with DCIS with microinvasion (DCIS-M), and 646 patients with invasive breast cancer 2 cm or smaller in diameter were treated with BCT (wide local excision with radiotherapy) at The University of Texas M. D. Anderson Cancer Center. Survival was calculated by the Kaplan-Meier method. The median follow-up times were 11 years for patients with DCIS alone, 12 years for patients with DCIS-M, and 8 years for patients with invasive breast cancer., Results: Eleven (13%) of 87 patients with DCIS and 5 (23%) of 22 patients with DCIS-M had developed locoregional recurrences at follow-up. Two patients with DCIS with locoregional recurrence died of breast cancer. Of the 646 patients with invasive breast cancer, 56 (9%) had a locoregional recurrence, and 16 (2%) died of breast cancer. The median time to locoregional recurrence was significantly longer in patients with DCIS or DCIS-M (9-10 years) than patients with invasive tumors (5 years)., Conclusions: DCIS is a favorable disease with an excellent long-term survival. The locoregional recurrence rate in patients with DCIS treated with BCT is similar to that in patients with early-stage invasive breast cancer treated with BCT, but time to locoregional recurrence is significantly longer in patients with DCIS. In patients with DCIS treated with BCT, intense surveillance for locoregional recurrence needs to be maintained for the patient's lifetime.

Background: Although preoperative chemotherapy has become the standard of care for inoperable locally advanced breast cancer, its role for downstaging resectable primary tumors is still evolving. The purpose of this study was to determine whether the prognostic information from an axillary node dissection in patients with clinical T3N0 breast cancer was altered by preoperative chemotherapy compared with surgery de novo., Methods: Between 1976 and 1994, 91 patients with clinically node-negative operable T3 breast cancer received doxorubicin-based combination chemotherapy on protocol at one institution. Fifty-three patients received both preoperative and postoperative chemotherapy (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All patients underwent axillary lymph node dissection as part of their definitive surgical treatment. There were no differences between the PreopCT and PostopCT groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative 38% vs. 32%). The median follow-up time was 7 years., Results: Patients in the PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P < .01), and a lower incidence of extranodal extension (19% vs. 42%, P = .02). By univariate analysis, the number of pathologically positive lymph nodes (P < .01) and extranodal extension (P < .01) were predictors of disease-specific survival in PreopCT patients. Multivariate analysis showed that extranodal extension was the only independent prognostic factor in PreopCT patients (P < .01). Overall, PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66% vs. 57%); however, PreopCT patients had worse disease-free (P = .01) and disease-specific survival (P = .04) when survival was compared after adjustment for the number of positive lymph nodes. Furthermore, PreopCT patients with 4-9 positive lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients with 4-9 positive nodes (17 vs. 48%, P = .04)., Conclusions: Axillary lymph node status remains prognostic after chemotherapy. Pathologically positive lymph nodes after preoperative chemotherapy are associated with a worse prognosis than the same nodal status before chemotherapy.

Background: Routine use of axillary lymph node dissection is being questioned, especially in clinically NO patients. The goal of this study was to determine whether primary tumor response to induction chemotherapy (IC) can predict the histological volume of residual axillary disease in patients who were candidates for breast conservation surgery after IC., Methods: Forty-seven patients with stage II or IIIA breast cancer who received breast conservation surgery were selected from a population of patients randomized to receive four cycles of IC. Largest clinical tumor size before and after IC was determined by physical examination, mammography, and breast ultrasound. Clinical nodal status was determined by physical examination and axillary ultrasound and compared with histological findings., Results: In patients with at least 50% reduction in primary tumor size after IC, 12 of 14 (86%) NO patients and 11 of 17 (65%) N1 patients were histologically negative. In patients with a less than 50% reduction, 0 of 3 NO patients and 2 of 13 (15%) N1 patients were histologically negative., Conclusions: There is significantly less axillary disease in responders than in nonresponders after IC. For NO responders, axillary irradiation may be an acceptable alternative to axillary lymph node dissection, and could easily be incorporated into the postsurgical radiotherapy that is standard protocol for breast conservation therapy. The more aggressive disease in nonresponders is best treated by axillary lymph node dissection, pending further study.

Background: Black women with breast cancer have significantly worse survival rates and receive diagnoses at relatively younger ages, compared with white patients with breast cancer, in the United States. Young age at diagnosis has been associated with increased risk for local recurrence (LR) after breast-conservation therapy (BCT). The goal of this study was to evaluate the impact of age and BCT on LR and survival rates among black patients with breast cancer., Methods: The records for 363 black women treated for breast cancer (excluding stage IV disease) at a comprehensive cancer center were reviewed., Results: Fifty-eight percent of patients (n = 211) had tumors < or = 5 cm in diameter. Forty-two of these patients (19.9%) received BCT; the LR rate for this group was 9.8%. A total of 168 patients (79.6%) underwent mastectomy; the LR rate for this group was 8.9%. Data on the primary operation were unavailable for one patient. Five-year disease-free survival rates were similar for patients treated with BCT and those treated with mastectomy (88% and 73%, respectively). LR was associated with significant decreases in 5-year overall survival rates for both the BCT group (67% vs. 95%, P < .01) and the mastectomy group (43% vs. 76%, P < .01). LR and 5-year disease-specific survival rates were similar for patients <50 years of age and patients > or = 50 years of age, regardless of treatment., Conclusions: LR and survival rates are not compromised by the use of BCT among black American patients. LR is associated with an increased risk of breast cancer death, regardless of treatment type. Younger age at diagnosis was not associated with an increased rate of LR after BCT in this series.

Background: The optimal management of contralateral breast cancer (CC) in patients previously treated with breast-conserving therapy (BCT) is unclear, as is whether these patients continue to choose BCT as the preferred treatment of their second breast cancer., Methods: Of 1328 patients treated with BCT at The University of Texas M. D. Anderson Cancer Center between 1958 and 1994, 63 developed a contralateral breast cancer. We reviewed the charts of these patients retrospectively, and standard demographic and treatment variables were evaluated. Survival was analyzed by the Kaplan-Meier method and subgroups by chi2 analysis., Results: Twenty-nine percent of the patients had a family history of breast cancer. First breast cancers were detected by patient or physician in 67% of cases and by mammogram in 17% of cases, compared to 59% and 36%, respectively, of CC (P = .04). Median time to development of CC was 61 months. Sixty percent of the initial tumors were AJCC stage 0 or I with a median size of 2 cm, whereas 74% of the CC were stage 0 or I (P = .02), with a median size of 1.5 cm. Eighty-seven percent of patients chose BCT for treatment of CC. There were few treatment-related complications. Recurrence rates were not significantly different from those of patients undergoing BCT for the initial cancer (P = .47), and 5- and 10-year actuarial survival rates after the first cancer were 93% and 76%, respectively. Median follow-up was 134 and 56 months from the time of diagnosis of the initial cancer and CC, respectively., Conclusions: Because contralateral breast cancer often is detected at an early stage, there are few treatment-related complications, and the risk of recurrence is no different from that for the initial cancer, BCT is an acceptable and desirable option for appropriately selected patients with metachronous or synchronous bilateral breast cancers.

Background: Induction chemotherapy has become the standard of care for patients with locally advanced breast cancer (LABC) and currently is being evaluated in prospective clinical trials in patients with earlier-stage disease. To better gauge the role of axillary lymph node dissection in patients with LABC this study was performed to assess initial axillary status on physical and ultrasound examination, axillary tumor downstaging following induction chemotherapy, and the accuracy of physical examination compared with axillary sonography in predicting which patients will have axillary lymph node metastases found on pathologic examination., Methods: Between 1992 and 1996, 147 consecutive patients with LABC were registered in a prospective trial of induction chemotherapy using 5-fluorouracil, doxorubicin, and cyclophosphamide. Physical and ultrasound examinations of the axilla were performed at diagnosis and after induction chemotherapy. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed, followed by postoperative chemotherapy and irradiation of the breast or chest wall and regional lymphatics., Results: Following induction chemotherapy, 43 (32%) of the 133 patients with clinically positive lymph nodes on initial examination had axillary tumor downstaging as assessed by physical and ultrasound examination. The sensitivity of axillary sonography in identifying axillary metastases was significantly higher than that of physical examination (62% vs. 45%, P=.012). The specificity of physical examination (84%) was higher than that of sonography (70%), but the difference did not reach statistical significance. Among the 55 patients in whom the findings of both physical and ultrasound examination of the axilla were negative following induction chemotherapy, 29 patients (53%) were found to have axillary lymph node metastases on pathologic examination of the axillary contents. However, 28 (97%) of these patients had either 1 to 3 positive lymph nodes or only micrometastases 2 to 5 mm in diameter., Conclusions: Preoperative clinical assessment of the axilla by physical examination combined with ultrasound examination is not completely accurate in predicting metastases in patients with LABC following tumor downstaging. However, patients with negative findings on both physical and ultrasound examinations of the axilla may be potential candidates for omission of axillary dissection if the axilla will be irradiated because minimal axillary disease remains. Patients who have positive findings on preoperative physical or ultrasound examinations should receive axillary dissection to ensure local control. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following induction chemotherapy is currently underway.

Background: The local recurrence (LR) rate with skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) has been reported as comparable to the LR rate after conventional mastectomy. However, limited data are available on the prognostic significance and management of LR following SSM., Methods: A prospective database maintained at the University of Texas M. D. Anderson Cancer Center identified 437 SSMs performed for 372 invasive T1/T2 breast cancers between 1986 and 1993., Results: Twenty-three LRs were identified, with a LR rate of 6.2% (23/372). Twenty-two of these (96%) presented as palpable skin-flap masses. The median time to recurrence was 25 months (range, 3 to 98 months). Fourteen patients were treated with a combination of surgery and systemic therapy. Resection of the reconstructed breast was performed in only three patients. Complete local control of the recurrent disease was achieved in 17 patients (74%). Nine patients (39%) developed distant metastatic disease. At a median follow-up of 26 months, 14 of 23 patients (61%) are alive without evidence of disease, and 7 (30%) have died from breast cancer., Conclusions: Because LR rate with SSM is low and likelihood of local control and survival is high, SSM and IBR is an acceptable treatment option for early stage breast cancer.

Background: The role of elective contralateral mastectomy (ECM) in women with early-stage breast cancer who elect or require an ipsilateral mastectomy and desire immediate bilateral breast reconstruction (IBR) is an intellectual and emotional dilemma for both patient and physician. In an attempt to clarify the rationale for this approach, we reviewed our experience with ECM and IBR and evaluated operative morbidity, the incidence of occult contralateral breast cancer, and patterns of recurrence., Patients and Methods: We retrospectively reviewed the records of 155 patients with primary unilateral breast cancer (stage 0, I, or II) and negative findings on physical and mammographic examinations of the contralateral breast who underwent ipsilateral mastectomy and simultaneous ECM with IBR between 1987 and 1995., Results: The median age of the patients was 46 years (range, 25 to 69 years). Clinical stage at diagnosis was stage 0, I, and II in 19.4%, 54.2%, and 26.4% of patients, respectively. Factors likely to influence the use of ECM were family history of breast cancer in first-degree relatives (30%), any family history of breast cancer (56%), difficulty anticipated in contralateral breast surveillance (48%), associated lobular carcinoma in situ (23%), multicentric primary tumor (28%), significant reconstructive issues (14%), and failure of mammographic identification of the primary tumor (16%). Skin-sparing mastectomies were performed in 81% of patients. Overall, 70% of patients underwent reconstruction using autogenous tissue transfer. Reoperations for suspected anastomotic thrombosis were performed in seven patients. Two patients experienced significant partial or complete flap loss. Histopathologic findings in the ECM specimen were as follows: benign, 80% of patients; atypical ductal hyperplasia, 12% of patients; lobular carcinoma in situ, 6.5% of patients; ductal carcinoma in situ, 2.7% of patients; and invasive carcinoma, 1.3% of patients. Eighteen patients (12%) had evidence of locoregional or distant recurrences, with a median follow-up of 3 years. In one patient (0.6%), invasive ductal carcinoma developed on the side of the elective mastectomy., Conclusions: The use of ECM and IBR cannot be justified if the only oncologic criterion considered is the incidence of occult synchronous contralateral disease. However, in a highly selected population of young patients with a difficult clinical or mammographic examination and an increased lifetime risk of developing a second primary tumor, ECM and IBR is a safe approach.

Background: Hemangiopericytoma is an uncommon soft tissue sarcoma. We sought to evaluate the long-term outcome of a consecutively treated patient cohort with hemangiopericytoma., Methods: The study involved 36 adult patients (older than 16 years) with hemangiopericytoma treated at The University of Texas M. D. Anderson Cancer Center between July 1975 and July 1995. Data on clinicopathologic parameters, surgical treatment, adjuvant therapy, disease recurrence, and survival were obtained from a review of medical records., Results: The median follow-up was 57 months. Twenty-eight patients (78%) underwent complete and potentially curative resection of their primary disease. Of the nine patients (32%) who had local recurrences, four (57%) had epidural tumors and three (43%) had retroperitoneal tumors, but none had extremity tumors. Extremity tumors were associated with a significantly prolonged local recurrence-free survival compared to tumors at nonextremity anatomic sites (P <.05). Ten patients had recurrences at distant sites. Of the 13 patients who experienced any form of disease recurrence, four had recurrences after a disease-free interval of more than 5 years. The 5-year actuarial survival rate for the entire group of 36 patients was 71%. Noncurative surgical treatment (P=.007) and development of distant metastatic disease (P=.013) were associated with shortened survival., Conclusion: Extended survival is common in hemangiopericytoma patients treated with curative intent. However, local and distant recurrences may occur after a prolonged disease-free interval, emphasizing the need for long-term follow-up. Retroperitoneal and meningeal tumors were associated with higher local recurrence rates; therefore, adjuvant therapies should be considered and evaluated for tumors at these sites.

Background: If cutaneous lymphoscintigraphy (CL) is accurate in predicting the draining lymph node basins at risk from primary axial melanomas, then regional metastases should only occur in those lymph node basins identified by CL., Methods: This study is a retrospective review of patients undergoing CL for primary axial melanomas from June 1, 1985, until June 31, 1992. Data retrieved included age, gender, number of basins identified, location of basins identified, management of basins, recurrence in lymphatics, development of distant disease, and long-term follow-up., Results: A total of 181 patients underwent elective LND, and 48 patients (27%) had melanoma in the nodes within the dissected basin. Of these 181 patients, seven developed nodal metastases as their site of first recurrence. All seven recurrences were seen at sites dissected or at sites indicated by CL, which the primary surgeon elected not to treat initially. Of the 116 patients observed, 16 (14%) developed lymph node metastases as their first site of recurrence. Fifteen of these 16 patients had their site of lymph node metastases predicted by CL. In this study, CL predicted 98.6% of all lymph node metastases., Conclusions: The high overall reliability of CL as demonstrated by long-term follow-up indicates that the information obtained by CL can be reliably used to guide intervention. Initial evaluation of patients with high-risk cutaneous melanomas at sites with ambiguous lymphatic drainage must include CL in order to determine the draining lymph node basins and to plan therapy.