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Positive/close margins are associated with higher in-breast failure rates after breast-conserving surgery (BCS). We investigated whether intraoperative margin assessment aids in obtaining negative margins, and to evaluate the local control thus achieved.Between 1994 and 1996, 264 patients underwent BCS for stages 0-III breast cancer [invasive, n = 200; ductal carcinoma in situ (DCIS), n = 64]. Intraoperative margin assessment included gross tissue inspection, specimen radiography, with or without frozen section.Ninety-two patients (46%) with invasive cancer and 24 (38%) with DCIS had positive/close margins on the permanent section analysis of their initial surgical specimens. Fifty-eight patients (29%) with invasive cancer and six (9%) with DCIS had initial positive/close margins, and were rendered margin-negative by intraoperative analysis and immediate re-excision. Final margins on permanent pathology were positive/close in 52 patients (20%): 34 patients (17%) with invasive cancer and 18 patients (28%) with DCIS. By multivariate analysis, excisional biopsy for diagnosis, larger tumor size, and multifocality were associated with final positive/close margins. Of these 52 patients, 23 underwent a second operation to achieve widely negative margins (13 completion mastectomies, 10 re-excisions). The 5-year ipsilateral breast recurrence-free survival rates after BCS and radiation were 99% for invasive cancer (n = 167) and 100% for DCIS (n = 27).Intraoperative assessment of margins assisted in identifying positive/close margins and allowed over a quarter of the patients to be rendered margin-negative with intraoperative re-excision at their original operation. This approach resulted in excellent local control in patients treated with BCS and radiation.

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.

BACKGROUND The purpose of the study was to determine the risk of ipsilateral breast carcinoma recurrence (IBCR) and contralateral breast carcinoma (CBC) development in patients with a concurrent diagnosis of ductal carcinoma in situ (DCIS) with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). METHODS Records of all 307 patients with DCIS treated with breast-conserving treatment (BCT) from 1968 to 1998 were analyzed. Initial pathology reports and all slides available were re-reviewed for evidence of ADH, ALH, or LCIS. Actuarial local recurrence rates were calculated. RESULTS Fifty-five cases of DCIS were associated with ADH, 11 with ALH or LCIS, and 14 with both ADH and ALH or LCIS. Overall, IBCR occurred in 14% and no significant difference in the IBCR rate was identified for patients with proliferative lesions compared with patients without these lesions (P = 0.38). Development of CBC in patients with concurrent DCIS and ADH was 4.4 times (95% confidence interval [CI], 1.44–13.63) that in patients with DCIS alone (P < 0.01). The 15-year cumulative rate of CBC development was 22.7% in patients with ALH or LCIS compared with 6.5% in patients without these lesions (P = 0.30) and 19% in patients with ADH compared with 4.1% in patients with DCIS alone (P < 0.01). CONCLUSION The risk of CBC development is higher with concurrent ADH than in patients with DCIS alone, and these patients may therefore be appropriate candidates for additional chemoprevention strategies. Concurrent ADH, ALH, or LCIS with DCIS is not a contraindication to BCT. Cancer 2006. © 2005 American Cancer Society.

Background Although underused, breast conservation therapy (BCT) is an accepted method for treatment of noninvasive and early breast cancer. The purpose of this analysis was to identify factors associated with receiving mastectomy when eligible for BCT. Methods From a recent experience, 397 patients at the University of Texas M. D. Anderson Cancer Center presented with clinical stage 0, I, or II breast cancer. Demographics and tumor characteristics of patients who underwent BCT versus mastectomy were compared. Results Of 293 BCT candidates, 203 patients (69%) underwent BCT and 90 patients (31%) received a mastectomy. Of those 90 patients, 66 patients (73%) had documented concerns about receiving BCT. Multivariate analyses showed that widow status was a factor associated with receiving mastectomy at presentation ( P = .04). Conclusions The majority of BCT candidates with early stage breast cancer undergo BCT. In our study, widow status was a predictive factor of mastectomy in BCT candidates.

Background The role of sentinel lymph node biopsy (SLNB) in patients with an initial diagnosis of ductal carcinoma in situ (DCIS) has not been well defined. The purpose of our study was to determine when the risk of finding invasive disease on final pathology in patients with an initial diagnosis of DCIS was sufficiently high to justify use of SLNB. Study design The records of 398 consecutive patients from our prospective database with an initial diagnosis of DCIS, treated between July 1999 and December 2002, were analyzed. Associations between clinical and pathologic factors and patient selection for SLNB and outcomes were analyzed for significance using univariate and multivariate analyses. Results Of the 398 patients, 80 (20%) were found to have invasive disease on final pathology. Multivariate analysis revealed 4 independent predictors of invasive cancer on final pathology: 55 years of age or younger (odds ratio [OR], 2.19; p=0.024), diagnosis by core-needle biopsy (OR, 3.76; p=0.006), mammographic DCIS size of at least 4 cm (OR, 2.92; p=0.001), and high-grade DCIS (OR, 3.06; p=0.002). A total of 141 patients (35%) underwent SLNB as a component of their initial operation. Multivariate analysis revealed that the presence of comedonecrosis (OR, 2.69; p=0.007) and larger mammographic DCIS size (OR, 1.18; p=0.0002) were independent predictors of patients' undergoing SLNB. Of these 141 patients, 103 (73%) were diagnosed by core-needle biopsy, 42 (30%) had invasive disease on final pathology, and 14 (10%) had a positive sentinel lymph node: 12 (86%) by hematoxylin and eosin staining and 2 by immunohistochemistry. The only independent predictor of a positive SLN was the presence of a palpable tumor (OR, 4.28, p=0.042). Of these 14 patients with a positive sentinel node, only 11 (79%) had invasive cancer on final pathology. Conclusions SLNB should not be performed routinely for all patients with an initial diagnosis of DCIS. Risks and benefits of SLNB should be discussed with patients who are younger, are diagnosed by core-needle biopsy, or have large or high-grade DCIS.

BACKGROUND Severe anaphylactoid reactions to isosulfan blue dye requiring resuscitation are reported to occur in 1.1% of patients with breast carcinoma undergoing sentinel lymphadenectomy. In December 2001, the authors began administering a prophylactic regimen before dye injection to determine whether prophylaxis reduced the incidence of life-threatening reactions. METHODS All patients were mapped with technetium-99m–labeled sulfur colloid. Those also receiving isosulfan blue dye were administered a glucocorticoid, diphenhydramine, and famotidine intravenously just before or at induction of anesthesia. Adverse reactions at the time of surgery were analyzed. RESULTS Between December 2001 and July 2003, 1013 consecutive patients underwent sentinel lymphadenectomy for breast carcinoma. Six hundred sixty-seven patients (65.8%) received prophylaxis and isosulfan blue dye, 33 (3.3%) received prophylaxis but no dye, 12 (1.2%) received dye but no prophylaxis, and 301 (29.7%) received no prophylaxis or dye. Blue urticaria and facial edema were observed in 3 (0.5%) of 667 patients receiving prophylaxis and dye and in 1 (8.3%) of 12 patients receiving dye but no prophylaxis. There were no episodes of hypotension, and no patients required vasopressors, ventilatory support, or intensive care observation. Adverse reactions to agents other than blue dye were observed in 2 (0.3%) of 667 patients receiving prophylaxis and dye and in 3 (1.0%) of 301 receiving no prophylaxis and no dye (P = 0.1773). CONCLUSIONS Preoperative prophylaxis was found to reduce the severity, but not the overall incidence, of adverse reactions to isosulfan blue dye. No life-threatening reactions were noted in patients treated with preoperative prophylaxis. Based on these results, the authors now routinely recommend administration of prophylaxis to patients receiving isosulfan blue for lymphatic mapping and sentinel lymph node biopsy. Cancer 2005. © 2005 American Cancer Society.

BACKGROUND: The ideal pathologic assessment of sentinel lymph nodes (SLNs) in patients with breast carcinoma remains controversial. The authors evaluated how detailed assessment of SLNs using immunohistochemistry (IHC) and serial sectioning would affect treatment decisions and outcomes in patients with breast carcinoma who had negative SLNs on standard hematoxylin and eosin staining. METHODS: The SLNs from patients who were treated between June 1998 and June, 1999 and who had negative lymph node status determined by hematoxylin and eosin staining (n = 84 patients) were evaluated further with serial sectioning and cytokeratin IHC. Patients were offered adjuvant therapy based on primary tumor factors. RESULTS: The median patient age was 57 years, and the median tumor size was 1.2 cm. At a median follow-up of 40.2 months, 81 patients (96%) were alive with no evidence of disease, 1 patient was alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. Fifteen patients (18%) had micrometastases identified on IHC. Of the total 84 patients, information regarding adjuvant therapy was not available for 5 patients. Of the remaining 79 patients, 10 patients (13%) were not offered adjuvant chemotherapy but had positive SLN status determined by IHC. SLN status based on IHC evaluation did not correlate with age (P = 0.077), tumor size (P = 0.717), grade (P = 0.148), estrogen receptor status (P = 1.000), or lymphovascular invasion (P = 0.274). Furthermore, IHC-detected positive SLN status did not correlate with distant metastasis (P = 0.372) or overall or distant metastasis-free survival (P = 0.543 and P = 0.540, respectively). CONCLUSIONS: Although the finding of SLN micrometastases by IHC may change management in > 12% of patients, preliminary results suggested that such micrometastases do not affect outcomes significantly.

The axillary lymph node status is the most important predictor of prognosis and aids in breast cancer treatment planning. Patients with breast cancer now frequently undergo sentinel lymph node (SLN) biopsy rather than axillary lymph node dissection to determine the status of the regional lymph nodes. However, the optimal timing of radionuclide injection relative to the timing of SLN biopsy remains controversial. The objective of this study was to compare the lymphatic drainage patterns on lymphoscintigraphy performed at 15 minutes to 4 hours and at 18 to 24 hours after injection of filtered Tc-99m sulfur colloid, and to determine whether, over time, radiocolloid migrates to second-echelon nodes that are not the SLNs. Fifteen women with breast cancer (mean age, 55 years; range, 38-78 years) were scheduled to undergo SLN biopsy after each received an injection of 18.5 MBq (0.5 mCi) filtered Tc-99m sulfur colloid into the breast parenchyma surrounding the tumor or biopsy cavity. Both early (15 minutes to 4 hours after radionuclide injection) and delayed (18-24 hours after radionuclide injection) lymphoscintigraphy was performed in each patient. SLN biopsy was performed, followed by completion axillary lymph node dissection and planned breast surgery. In each patient the patterns of distribution of the radionuclide in the lymph nodes were the same on early and delayed lymphoscintigrams. These findings, that the distributions of radionuclide in lymph nodes are identical on early and delayed images obtained after injection of filtered Tc-99m sulfur colloid, suggest that performing SLN biopsy on the day after injection does not diminish the accuracy of the technique in predicting the potential site of metastasis in the regional lymph nodes in patients undergoing this procedure for breast cancer.

BACKGROUND Women with unilateral breast carcinoma are at increased risk for developing contralateral breast carcinoma (CBC). The authors sought to identify predictors of malignant or moderate to high-risk histologic findings in contralateral prophylactic mastectomy (CPM) specimens, and to determine the efficacy of CPM. METHODS The authors performed a retrospective review of 239 patients with unilateral early-stage breast carcinoma who underwent CPM. The number of CBCs expected if the contralateral breast had been left intact was calculated based on CBC rates observed in the Surveillance, Epidemiology, and End Results (SEER) database and on life-table analysis by family history. RESULTS In the current study, 11 patients (4.6%) had occult contralateral malignancies (4 invasive carcinomas and 7 ductal carcinomas in situ) and 44 (18.4%) patients had moderate to high-risk pathology (8 lobular carcinoma in situ, 11 atypical lobular hyperplasia, 25 atypical ductal hyperplasia). At 1846 patient-years of follow-up, only 1 patient (0.4%) developed a new CBC compared with 11 expected cancers based on SEER data. One CBC was observed among 140 patients with a family history of breast carcinoma, compared with 16 expected cancers based on life-table analysis adjusted for adjuvant therapy. The determinants of significant findings at CPM were invasive lobular histology, estrogen and progesterone receptor positivity, additional ipsilateral moderate to high-risk pathology, and age > 40 years at cancer diagnosis. CONCLUSIONS CPM was associated with a low risk of subsequent development of breast carcinoma. Evaluation of histologic findings in the ipsilateral breast may help to predict the likelihood of significant disease in the contralateral breast and assist in risk stratification. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND Few studies in the literature address the surgical management of patients with breast carcinoma who present with associated nipple discharge. The purpose of the current study was to determine the feasibility of breast-conserving surgery (BCS) for these patients. METHODS The medical records of patients who presented with pathologic nipple discharge and underwent diagnostic or curative surgery between January 1990 and December 2002 were retrospectively reviewed. RESULTS A total of 188 patients presented with nipple discharge during the study period. Of those, 47 had breast carcinoma. One patient had metachronous bilateral nipple discharge associated with malignant disease. Therefore, medical records associated with a total of 48 cases were reviewed. The median patient age was 52 years (range, 29–87 years), and the median follow-up duration was 45 months (range, 6–109 months). Twenty-nine patients had ductal carcinoma in situ (DCIS), 14 had Stage I disease, 3 had Stage II disease, and 2 had Stage III disease. Twenty-four patients were ultimately treated with mastectomy. For 16 of these patients, mastectomy was required because extensive disease was found in reexcisional segmental mastectomy specimens. Among patients with Stage 0 or I disease, the incidence of occult nipple-areola complex (NAC) involvement was 16% (3 of 19 patients). Twenty-four patients were ultimately treated with BCS with (n = 13) or without (n = 11) adjuvant radiotherapy. Local disease recurrence was noted at 14, 28, and 40 months, respectively, in 3 patients who declined adjuvant radiotherapy after BCS for DCIS. Among patients treated with BCS, comedonecrosis, multifocality, and the absence of adjuvant radiotherapy were associated with decreased local recurrence–free survival (P = 0.0005, P = 0.045, and P = 0.013, respectively). However, disease-free survival (mean ± standard error) was similar for patients who underwent mastectomy and patients who underwent BCS (90 ± 6 months; 95% confidence interval [CI], 78–101 months vs. 82 ± 6 months; 95% CI, 69–94 months; P = 0.528). One patient with Stage I disease died of distant metastases at 99 months. CONCLUSIONS Patients with breast carcinoma accompanied by nipple discharge presented primarily with early-stage breast carcinoma associated with DCIS. Occult NAC involvement was not an uncommon finding in patients with early-stage breast carcinoma. Nonetheless, BCS can be performed safely if negative margins are achieved and if appropriate adjuvant radiotherapy or systemic therapy is administered. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND To date, the impact of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial reported in 1999 on the use of tamoxifen after surgery for ductal carcinoma in situ (DCIS) is unknown. The current study was designed to evaluate the impact of NSABP B-24 on current practices at a comprehensive cancer center. METHODS The records of 350 consecutive patients with DCIS who were treated at the authors' institution between July 1999 and June 2002 were obtained from a prospective database and analyzed. Whether patients were offered tamoxifen, whether patients accepted tamoxifen, and the associated reasons were recorded along with tamoxifen-related side effects and patient compliance with therapy. Clinical and pathologic factors were evaluated for their impact on recommendations regarding tamoxifen. Differences were assessed by chi-square analysis. RESULTS Of the 350 patients, 73 were excluded because of evidence of invasive carcinoma on final pathology review. Of the remaining 277 patients, 166 patients (60%) were offered tamoxifen, and 90 patients (54%) chose to take tamoxifen. Of 111 patients who were not offered tamoxifen, 39 patients (35%) had documented explanations, which included bilateral mastectomy (n = 25 patients), medical reasons (n = 10 patients), and already received tamoxifen for other reasons at the time of diagnosis (n = 4 patients). Of 94 patients who received tamoxifen, 20 patients (21%) discontinued use because of side effects or complications. Tamoxifen was more likely to be recommended for women who underwent segmental resection compared with women who underwent total mastectomy (P = 0.002) and for women with smaller pathologic DCIS tumors (P = 0.001). In addition, these two factors were interrelated. CONCLUSIONS Physicians and patients remain cautious regarding the use of tamoxifen after local treatment for DCIS. The current findings have implications for current trials evaluating aromatase inhibitors and other chemopreventive agents for this disease. Cancer 2004;100:942–9. © 2004 American Cancer Society.

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.

Increasing numbers of women of all ages are electing to have reduction mammaplasty for very large breasts. Breast cancer can be an incidental finding in reduction mammaplasty specimens. We report here the discovery of breast cancer in specimens from four patients who underwent elective breast reduction, three of whom had not had recent mammograms. All four patients underwent modified radical mastectomy. The role of mammography, surgical options, specimen evaluation, and practical guidelines are discussed.

Background There is no consensus about the use of the various diagnostic tests and surgical procedures available to confirm or rule out breast cancer in patients presenting with nipple discharge. This study was designed to identify patient and nipple-discharge characteristics associated with the diagnosis of breast cancer and to determine the utility of mammography, sonography, ductography, and cytology in surgical decision making in patients presenting with pathologic nipple discharge. Study design We reviewed the medical records of all patients who presented with nipple discharge at our institution between August 1993 and September 2000. Patient and nipple-discharge characteristics and findings on imaging studies and cytologic examination were analyzed. Results A total of 146 patients presented at our institution with nipple discharge during the study period. Of these, 52 had clinically benign discharge and were managed without surgical intervention; 94 patients had pathologic discharge and underwent a biopsy procedure for histologic diagnosis, treatment, or both. Logistic regression analysis identified mammographic (relative risk [RR] = 10.47, 95% confidence interval [CI] 2.36 to 46.39, p=0.0002) and sonographic (RR = 5.54, 95% CI 1.27 to 25.40, p=0.028) abnormalities as independent factors associated with a malignant diagnosis. Nineteen cancers, 62 papillomas, and 13 other benign lesions were identified among the patients with pathologic discharge. In 3 patients with cancer (15.8%) and 30 patients with a papilloma (48.4%), ductography was the only means of identifying lesions to be resected. Patients who underwent ductography-guided operation (n = 42, 50%) or any surgical procedure including a localization study (n = 66, 78.6%) were significantly more likely than patients who underwent central duct excision alone to have a specific underlying lesion identified (p = 0.045 and p=0.033, respectively). Conclusions Abnormalities on mammography and sonography in patients with nipple discharge should alert physicians to the possibility of a breast cancer diagnosis. In patients with pathologic discharge with normal findings on physical examination and other imaging studies, ductography might be the only means of localizing and resecting breast lesions associated with nipple discharge.

BACKGROUND To distinguish true local recurrences (TR) from new primary tumors (NP) and to assess whether this distinction has prognostic value in patients who develop ipsilateral breast tumor recurrences (IBTR) after breast-conserving surgery and radiotherapy. METHODS Between 1970 and 1994, 1339 patients underwent breast-conserving surgery at The University of Texas M. D. Anderson Cancer Center for ductal carcinoma in situ or invasive carcinoma. Of these patients, 139 (10.4%) had an IBTR as the first site of failure. For the 126 patients with clinical data available for retrospective review, we classified the IBTR as a TR if it was located within 3 cm of the primary tumor bed and was of the same histologic subtype. All other IBTRs were designated NP. RESULTS Of the 126 patients, 48 (38%) patients were classified as NP and 78 (62%) as TR. Mean time to disease recurrence was 7.3 years for NP versus 5.6 years for TR (P = 0.0669). The patients with NP had improved 10-year rates of overall survival (NP 77% vs. TR 46%, P = 0.0002), cause-specific survival (NP 83% vs. TR 49%, P = 0.0001), and distant disease-free survival (NP 77% vs. TR 26%, P < 0.0001). Patients with NP more often developed contralateral breast carcinoma (10-year rate: NP 29% vs. TR 8%, P = 0.0043), but were less likely to develop a second local recurrence after salvage treatment of the first IBTR (NP 2% vs. TR 18%, P = 0.008). CONCLUSIONS Patients with NP had significantly better survival rates than those with TR, but were more likely to develop contralateral breast carcinoma. Distinguishing new breast carcinomas from local disease recurrences may have importance in therapeutic decisions and chemoprevention strategies. This is because patients with new carcinomas had significantly lower rates of metastasis than those with local disease recurrence, but were more likely to develop contralateral breast carcinomas. Cancer 2002;95:2059–67. © 2002 American Cancer Society. DOI 10.1002/cncr.10952

Background: Intracystic papillary carcinoma (IPC) of the breast is a rare form of noninvasive breast cancer. An appreciation of associated pathology with IPC may be critical in surgical decision-making. Methods The medical records of all patients with IPC treated between 1985 and 2001 were retrospectively reviewed. Three patient groups were identified according to the pathologic features of the primary tumor: IPC alone, IPC with associated ductal carcinoma in situ (DCIS), and IPC with associated invasion with or without DCIS. Types of treatment and outcomes were compared between groups. Results: Forty patients were treated for IPC during the study period. Fourteen had pure IPC, 13 had IPC with DCIS, and 13 had IPC with invasion. The incidence of recurrence and the likelihood of dying of IPC did not differ between the three groups regardless of the type of surgery (mastectomy or segmental mastectomy) performed and whether radiation therapy was administered. The disease-specific survival rate was 100%. Conclusions When IPC is identified, it is frequently associated with DCIS and or invasion. Standard therapy should be based on associated pathology. The role of radiation therapy in pure IPC remains to be determined.

Objectives: To determine the characteristics of popular breast cancer related websites and whether more popular sites are of higher quality. Design: The search engine Google was used to generate a list of websites about breast cancer. Google ranks search results by measures of link popularity—the number of links to a site from other sites. The top 200 sites returned in response to the query “breast cancer” were divided into “more popular” and “less popular” subgroups by three different measures of link popularity: Google rank and number of links reported independently by Google and by AltaVista (another search engine). Main outcome measures: Type and quality of content. Results: More popular sites according to Google rank were more likely than less popular ones to contain information on ongoing clinical trials (27% v 12%, P=0.01), results of trials (12% v 3%, P=0.02), and opportunities for psychosocial adjustment (48% v 23%, P Conclusions: Popularity of websites is associated with type rather than quality of content. Sites that include content correlated with popularity may best meet the public9s desire for information about breast cancer. What is already known on this topic Patients are using the world wide web to search for health information Breast cancer is one of the most popular search topics Characteristics of popular websites may reflect the information needs of patients What this study adds Type rather than quality of content correlates with popularity of websites Measures of quality correlate with accuracy of medical information

The management of PABC is very difficult. The incidence of PABC is low, but may be increasing because of the number of women who are becoming pregnant at a later age. More investigation is needed to understand whether the biology of PABC is different from that of breast cancer in nonpregnant women. One exciting area of further research is the potential relationship between mutations in known breast cancer susceptibility genes and breast cancer development during pregnancy. Diagnosis or PABC remains challenging because of the anatomic and physiologic changes that occur in the breast during pregnancy. Understanding the generic influences on PABC may help physicians in diagnosing this disease earlier, and understanding the tumor-receptor characteristics of PABC can help physicians deliver effective treatment. The various modalities available for treatment of PABC and their risks and benefits must be discussed openly with patients and their families. Abortion is not usually recommended. Modified radical mastectomy is the recommended treatment for PABC diagnosed during the first trimester. Neoadjuvant or adjuvant chemotherapy can be given with minimal risks to the fetus during the second or third trimester. Radiation therapy is contraindicated during pregnancy because of the potential for injury to the fetus. Breast conservation therapy, with radiation treatments given after delivery or after neoadjuvant chemotherapy, is an option for women with PABC diagnosed late in pregnancy. Once the appropriate treatment modality is chosen, its implementation must not be delayed because of the pregnancy. Most of the literature shows that women with PABC have the same survival stage for stage as nonpregnant women with breast cancer. But some studies suggest that the prognosis is worse for patients who present with advanced-stage PABC. Finally, recurrence and survival in most patients previously treated for breast cancer do not appear to be adversely affected by subsequent pregnancy. Above all, the patient with breast cancer diagnosed during pregnancy is best served by early and continued involvement of a multidisciplinary cancer treatment team.

This study was performed to investigate the extent of tumor downstaging achieved in women with operable breast cancer treated with neoadjuvant chemotherapy and breast-conservation surgery, develop recommendations for effective surgical planning, and report local-regional recurrence rates with this approach.One hundred nine patients with stage II or III (T3N1) breast cancer were treated in three prospective trials utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC, n = 72) or paclitaxel (n = 37) followed by segmental resection (n = 109) and axillary node dissection (n = 94). Postoperatively, patients received 4 additional cycles of FAC followed by irradiation of the breast. The median follow-up was 53 months.The median tumor size was 4 cm (range 1.1 to 9 cm) at presentation and only 1 cm (range 0 to 4.5 cm) after four cycles of chemotherapy. The primary tumor could not be palpated after chemotherapy in 55% of 104 patients presenting with a palpable mass and therefore required needle localization or ultrasound guidance for surgical resection. Of the 34 patients clinically deemed to have no residual carcinoma in the breast after chemotherapy and before surgery, only 50% of these patients were found to have no residual carcinoma on pathologic examination after surgery. Patients with primary tumorsor =2 cm were significantly more likely than patients with larger tumors to have complete eradication of the primary tumor prior to surgery (P0.001). The 5-year local-regional recurrence rate was 5%.Tumor downstaging is marked in patients with operable breast cancer and requires close monitoring during chemotherapy. We recommend placement of metallic tumor markers when the primary tumor isor =2 cm to facilitate adequate resection and pathologic processing. Resection of the tumor bed remains necessary in women deemed to have a complete clinical response to ensure low rates of recurrence.

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: Sentinel lymph node biopsy (SLNB) is an alternative to axillary dissection for many breast cancer patients. Cases of anaphylactic reaction to the isosulfan blue dye used during SLNB have recently been reported. No study on the incidence of serious anaphylactic reactions during SLNB for breast cancer has been reported. Methods: We reviewed 639 consecutive SLNBs for breast cancer performed at our institution. Sentinel lymph node biopsy was performed using both isosulfan blue dye and technetium-99m sulfur colloid. Cases of anaphylaxis were reviewed in detail. Results: Overall, 1.1% of patients had severe anaphylactic reactions to isosulfan blue requiring vigorous resuscitation. No deaths or permanent disability occurred. In patients with anaphylaxis, 2hospital stay was prolonged by a mean of 1.6 days. In 1 patient, the anaphylactic reaction required termination of the operation. Conclusions: Prompt recognition and aggressive treatment of anaphylactic reactions to isosulfan blue are critical to prevent an adverse outcome. Lymphatic mapping with blue dye should be performed in a setting where personnel are trained to recognize and treat anaphylaxis.

Background: The objective of the study was to compare the treatment outcomes in patients with occult primary carcinoma with axillary lymph node metastasis who were treated with mastectomy or with intent to preserve the breast. Methods: From 1951 to 1998, 479 female patients were registered with axillary lymph node metastasis from an unknown primary. After clinical workup, including mammography, 45 patients retained this diagnosis and received treatment for T0 N1–2 M0 carcinoma of the breast. Clinical and pathological data were collected retrospectively, and survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. Median follow-up time was 7 years. Results: Median age was 54 years (range, 32–79). Clinical nodal status was N1 in 71% and N2 in 29% of the patients. Surgical treatment was mastectomy in 29% and an intent to preserve the breast in 71% of the patients. Locoregional radiotherapy was used in 71% and systemic chemoendocrine therapy was used in 73% of the patients. Of the 13 mastectomy patients, only one had a primary tumor discovered in the specimen. Two patients (4%) were ultimately diagnosed with lung cancer and neuroendocrine tumor. No significant difference was detected between mastectomy and breast preservation in locoregional recurrence (15% versus 13%), distant metastases (31% versus 22%), or 5-year survival (75% vs. 79%). Regardless of surgical therapy, the most important determinant of survival was the number of positive nodes. Five-year overall survival was 87% with 1–3 positive nodes compared with 42% with ≥4 positive nodes (P < .0001). Conclusions: Occult primary carcinoma with axillary metastases can be treated with preservation of the breast without a negative impact on local control or survival.

BACKGROUND Although almost half of all incidents of breast carcinoma occur in women age ≥ 65 years, not enough is known about appropriate care for patients in this age group. The objective of the current study was to evaluate the role of breast conservation therapy in the management of breast carcinoma in women age ≥ 65 years. METHODS From 1970 to 1994, 1325 patients with carcinoma of the breast were treated with breast conservation therapy (segmental mastectomy and radiation therapy with or without axillary lymph node dissection) at The University of Texas M. D. Anderson Cancer Center. From this patient group, the authors identified 184 elderly women (≥ 65 years) with Stage 0–III disease at the time of diagnosis. RESULTS The median patient age was 70 years (range, 65–88 years). The distribution of disease by stage among the women was Stage 0 disease in 12 patients (7%), Stage I disease in 107 patients (58%), Stage II disease in 63 patients (34%), and Stage III disease in 2 patients (1%). Comorbid conditions that may have influenced treatment planning were reported in 91 patients (50%). An axillary lymph node dissection was performed in 135 patients (73%), with positive axillary lymph nodes found in 30 patients (22%). Adjuvant chemotherapy was given to 10 patients (5%), and tamoxifen therapy was given to 63 patients (34%). Complications from treatment were reported in 24 patients (13%). With a median follow-up of 7.3 years (range, 0.25–23.5 years), 9 patients developed locoregional disease recurrence (5%), 10 patients developed contralateral breast carcinoma (5%), and 21 patients developed distant metastasis (11%). At last follow-up, 113 patients (61%) were alive, 15 patients (8%) were dead of disease, and 56 patients (30%) were dead of other causes. The 5-year and 10-year disease specific survival rates were 96% and 91%, respectively. CONCLUSIONS Breast conservation therapy with segmental mastectomy and postoperative radiation therapy with or without axillary lymph node dissection provides excellent local control and disease free survival in elderly women with breast carcinoma. This treatment should be considered as the standard of care for elderly patients without severe comorbid disease. Cancer 2001;92:1092–100. © 2001 American Cancer Society.

Background: Specimen radiography is an important part of breast conservation surgery for ductal carcinoma in situ (DCIS). The objective of this study was to determine whether mastectomy specimen radiography could help in obtaining negative resection margins in patients with DCIS undergoing skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR). Methods: Of 95 patients treated at our institution with SSM and IBR for DCIS, 35 had specimen radiography. The mastectomy specimen was first examined grossly and then inked, serially sectioned, and sent for radiographic assessment. Tissue slices containing calcifications were identified for pathologic evaluation. Additional tissue was excised if tumor was found near the inked margins or if calcifications were found near the radiographic margins. Results: Of the 35 patients who had specimen radiography, the radiographic margins were free of calcifications in 30 patients (86%); of these patients, the margins on the final histologic examination were free of tumor in 27 and within 1 mm in 3. The other five patients (14%) had calcifications close to the radiographic margin; four underwent an intraoperative re-excision, but the margin for one of those four patients was still positive on final histologic examination. Margins were found to be negative by both mastectomy specimen radiography and histology in 77% of the patients. Of the 95 patients with DCIS, three patients (3%), none of whom had specimen radiography, developed local recurrences. One of these was successfully re-treated, one died as a result of synchronous distant metastases, and one was lost to follow-up. At a median follow-up time of 3.7 years, 93 patients (98%) were alive and free of disease. Conclusions: Intraoperative radiography of mastectomy specimens may be useful for assessing margin status and for identifying the location of microcalcifications within tissue slices.

Black women with breast cancer have significantly poorer survival rates, a more advanced stage distribution, and are diagnosed at younger ages compared to white patients in the United States. We evaluated tumor response and survival with respect to race and age after induction chemotherapy. The study population consisted of 303 patients (229 white, 74 black) registered in two prospective trials of induction chemotherapy for locally advanced breast cancer [stage II (T >/= 4 cm), stage III (noninflammatory), and stage IV (supraclavicular lymph node involvement only)] between 1989 and 1996. Chemotherapy regimens utilized 5-fluorouracil, cyclophosphamide, and doxorubicin (FAC). Response was defined as complete (CR, no clinical/radiographic detectable disease), partial (PR, >/=50% reduction in disease), minor (MR

Historically, radical surgery was the only potentially curative treatment for cancer. Recently, neoadjuvant chemotherapy, also termed preoperative, induction, or primary chemotherapy, has assumed an increasingly important role in the management of several solid-organ malignancies, including cancers of the breast, bone, head and neck, bladder, esophagus, and lung. In breast cancer, the use of postoperative, or adjuvant, chemotherapy is inextricably linked to the improved outcomes seen over the past several decades. Neoadjuvant chemotherapy has become the standard of care for patients with locally advanced breast cancer and has rapidly come to the forefront among potential treatments for patients with earlier-stage operable disease.

Background: Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy. Patients and Methods: Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests. Results: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P = .35), and 3-year survival rates were 77% and 58%, respectively (P = .23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with highdose chemotherapy. Conclusions: No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial. [J Natl Cancer Inst 2000;92:225‐33] Patients with stage III breast cancer or patients with stage II breast cancer and multiple positive axillary lymph nodes have an approximately 80% relapse rate at 5 years if treated only with locoregional therapy (1‐3). With optimal combined modality therapies, approximately 30% of the patients with stage IIIB breast cancer, 50% of those with stage IIIA breast cancer, and

Immediate breast reconstruction (IBR) has been considered contraindicated for patients with locally advanced breast cancer (LABC). Our goal was to determine whether IBR resulted in delayed postoperative chemotherapy, increased postoperative complications, or increased risk of recurrent disease.A prospective database of 540 modified radical mastectomies performed with IBR between 1990 and 1993 identified 50 patients with LABC. Postoperative management and outcome were compared to that of 72 patients undergoing modified radical mastectomy without IBR treated on a standardized LABC protocol using preoperative chemotherapy, postoperative chemotherapy, and radiotherapy during the same time period.Results were evaluated by chi2 analysis. The median ages for the patients with IBR versus those not undergoing IBR were 44 and 46 years, respectively. The stage distribution for the IBR patients versus patients not undergoing IBR was as follows: IIB, 46% versus 17%; IIIA, 44% versus 39%; and IIIB, 10% versus 44%. The types of IBR were transverse rectus abdominis myocutaneous (TRAM) flap (68%), latissimus dorsi flap (2%), and implants (30%). Chemotherapy was given to all IBR patients: 24% preoperatively and 96% postoperatively. Radiotherapy was used in 40%. Four postoperative complications (8%) necessitated prolongation of hospitalization, including two patients requiring surgical debridement for partial flap loss; there were no complete flap losses. The incidences of major and minor wound complications in the group not undergoing IBR were 7% and 4%, respectively. Of the 15 patients receiving implant reconstruction, 7 (47%) required subsequent implant removal because of contractures or infections. The median interval between surgery and postoperative chemotherapy was 35 days for the IBR patients and 21 days for the patients not undergoing IBR. This difference was marginally significant (P =.05). With a median follow-up of 58.4 months, no significant differences in local or distant relapse rates were detected.IBR can be performed with low morbidity in patients with LABC. Use of autogenous tissue is preferable because of poor results with implants. IBR is associated with somewhat longer intervals to resumption of postoperative chemotherapy, but this does not appear to be clinically significant-the local and distant relapse rates are similar for LABC patients undergoing modified radical mastectomy with or without IBR.

In this study, the records of all patients at the University of Texas M. D. Anderson Cancer Center with T1 or T2 breast cancer who were treated between March of 1986 and November of 1990 with mastectomy followed by immediate breast reconstruction were reviewed for the presence of recurrent disease. Patients with in situ disease were not included. Patients were included in the study if a local recurrence occurred (regardless of the length of follow-up) or if a follow-up of 6 years or longer could be obtained. Patients were grouped according to the use or nonuse of skin-sparing mastectomy, by tumor stage, and by nuclear grade of the tumor. The series included 154 patients, of whom 114 had skin-sparing mastectomies and 40 had nonskin-sparing mastectomies. The local recurrence rate in the skin-sparing mastectomy group was 7.0 percent, whereas in the nonskin-sparing mastectomy group it was 7.5 percent. The sample size in the nonskin-sparing mastectomy group was too small for meaningful statistical analysis, but the data suggest that there is no clinically important difference in recurrence rates between the two groups. We conclude that the use of skin-sparing technique for early breast cancer patients does not significantly increase the risk of tumor recurrence after mastectomy.

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.The records for 363 black women treated for breast cancer (excluding stage IV disease) at a comprehensive cancer center were reviewed.Fifty-eight percent of patients (n = 211) had tumorsor = 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 patients50 years of age and patientsor = 50 years of age, regardless of treatment.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 χ2 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: 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.

Segmental resection and radiotherapy is an accepted alternative over mastectomy for small, staged breast malignancies. However, women with large, pendulous breasts have been documented to have poorer cosmetic outcomes when undergoing irradiation after breast conservative surgery compared with women with small- or medium-size breasts, thought to be caused by dose inhomogeneity. The purpose of this study was to evaluate the efficacy of combining reduction mammaplasty with breast conservative surgery to facilitate postoperative irradiation. Between 1988 and 1996, 10 women have undergone bilateral reduction mammaplasty for breast malignancy followed by radiation therapy at our center. All women wished to avoid mastectomy (average age, 59 years). All lesions were detected preoperatively on mammography. The average amount of tissue removed was 945 g per breast. A variety of reduction techniques were employed to include the malignant lesions. All patients received 50 Gy of radiation therapy delivered in 25 fractions following reduction mammaplasty during a 5-week period. Radiation therapy was usually initiated within 4 weeks following surgery. Follow-up is currently 37 months, with all patients being followed for at least 8 months. No patients have had complications from the surgery or radiation therapy. No local recurrent malignancies have been detected. Cosmesis has been good to excellent in all patients. Despite equivalent survival outcomes for mastectomy for early-stage breast cancer, certain women are not good candidates for breast conservation and radiation therapy. An alternative for women with large, pendulous breasts that combines breast conservation therapy and concurrent bilateral reduction mammaplasty should be considered. This combination, in selected women, provides good functional and cosmetic results, and at the same time minimizes the potential difficulties of radiation therapy.

Background: Antibiotic prophylaxis is controversial in patients undergoing axillary lymph node dissection (ALND). We determined whether preoperative antibiotics decreased incidence or treatment cost of infectious complications following ALND. Methods: Two hundred patients entered this prospective, randomized, double-blind trial. Patients received either placebo or cefonicid preoperatively. Loco-regional signs of infection were monitored for 4 weeks postoperatively. Results: There was a trend toward fewer infections in the prophylactic group (placebo 13% versus cefonicid 6%; P = 0.080). Cefonicid significantly decreased severe infections requiring hospitalization (placebo 8% versus cefonicid 1%; P = 0.033). Cefonicid also decreased the treatment cost of infection per patient ($49.80 versus $364.87). Conclusions: We demonstrated a trend toward fewer overall infections and significantly fewer severe infections in patients given prophylactic antibiotics, which translated into a decrease in the cost of treatment for infectious complications. These findings support antibiotic prophylaxis for patients undergoing ALND.

Background: Invasive lobular carcinoma (ILC) accounts for 5% to 10% of all invasive breast cancers. Although breast conservation therapy using local excision and postoperative irradiation is a standard therapy for early invasive ductal breast cancer, the result of this strategy in ILC is not well documented. We sought to determine the rate of locoregional recurrence after breast conservation therapy in patients with ILC. Methods: A retrospective review of 74 patients with ILC treated with breast conservation therapy at The University of Texas M. D. Anderson Cancer Center (n=43) or The John Wayne Cancer Institute (n=31) between 1977 and 1993 was performed. Results: The median age of patients was 60 years, and median follow-up was 56 months (range 1 to 207 months). Thirty-nine patients had American Joint Committee on Cancer stage I disease, 30 had stage IIa disease, and five had stage IIb disease. All patients underwent surgical resection and postoperative radiation therapy. Twelve patients received postoperative adjuvant chemotherapy, and 27 patients were treated with adjuvant hormonal therapy. The 5-year actuarial locoregional recurrence rate was 9.8%, and the median time to recurrence was 77 months (range 41 to 113 months). Patients with positive or close (⩽1 mm) surgical margins were at increased risk for local recurrence on univariate analysis (p=0.034). Of the nine patients with breast recurrence, six underwent salvage therapy with total mastectomy and are disease free at the time of this writing, two patients died of distant disease, and one is alive with local disease at the time of this report. The 5-year disease-specific survival rate was 93.7%. Conclusions: Breast conservation therapy for ILC achieves locoregional control in the majority of patients. However, long-term follow-up of patients is important because many local recurrences following breast conservation therapy are late events.

Reconstruction of abdominal-perineal wounds after tumor extirpation presents the plastic surgeon with a variety of complex reconstructive options. These options are complicated by the resection of the bony pelvis. Two cases are presented that combine the use of synthetic mesh for pelvic ring and floor reconstruction with soft tissue to protect the intraabdominal viscera. Techniques and approaches to the patient undergoing such reconstruction are reviewed.

Forty-nine women with ductal carcinoma in situ (DCIS) treated with lumpectomy and irradiation were studied retrospectively. The median age was 50 years (range, 29 to 73 years) and the median follow-up time from initiation of therapy was 86 months (range, 17 to 230 months). Twelve patients presented with palpable masses (0.4 to 4 cm), three with breast thickening, and three with nipple discharge. In 31 patients the tumors were detected by mammography. Intraoperatively, excision of lesions was confirmed by specimen x-ray (38 specimens) or gross inspection (five specimens) and was recorded to be complete. No record was available in the other six patients. Margins of excision free of DCIS were microscopically confirmed in 25 specimens. The size of impalpable DCIS lesions recorded in 25 patients ranged from 0.4 to 5.0 cm (mean, 1.5 cm). Using Lagios' classification system, there were 18 classic comedocarcinomas, high nuclear grade (NG) with necrosis; seven cribriform/papillary, high NG with necrosis; 17 cribriform/micropapillary, intermediate NG with or without necrosis; and seven cribriform/micropapillary, low NG without necrosis. In two patients residual malignant calcifications were present on the postoperative mammogram. Disease recurred in the treated breast at the site of incision in five patients at 18 months and 8, 11, and 12 (two patients) years from initial therapy. The rate of local disease recurrence was 2% at 5 years and 6% at 10 years; three recurrences showed invasive ductal carcinoma and two were DCIS. To evaluate risk factors the following characteristics were considered: necrosis, NG, histological type, periductal fibrosis, periductal lymphoid infiltrate, margin status, age, and method of tumor detection. The end points chosen were recurrence and death from any cause (because only one patient died of disease). Although the recurrences were attributed to residual disease in two patients, of the clinical and pathological parameters evaluated, only periductal fibrosis showed a significant relationship with outcome, with a P value < or = .05 by the Wilcoxon test. On the other hand, using the proportional hazards model, necrosis was a significant predictor for recurrence (P = .02), as was the pair fibrosis and tumor detection when taken together (P = .05). Fibrosis significantly associated with high NG, Lagios' histological subtypes I and II, periductal lymphoid infiltrate, and necrosis (P < or = .0006).(ABSTRACT TRUNCATED AT 400 WORDS)

While locally advanced breast cancer (LABC) represents a small fraction of patients with breast cancer in industrialized nations, in developing countries it might constitute up to 50% of incident cases. The definition includes patients with stage IIB, III, and some with limited stage IV breast cancer. Inflammatory breast cancer (IBC) is part of LABC, but it is often reported separately, because of its dismal prognosis. LABC can be considered technically operable (stage II and IIIA), or inoperable (stage IIIB, IV and IBC). For the last two decades, patients with inoperable LABC and IBC have been treated with increasing frequency with systemic therapy first, followed by regional therapy, either surgical resection or radiotherapy. Most treatment programs also included adjuvant systemic therapy. The majority of patients with LABC and IBC respond to primary chemotherapy, and most can be rendered disease-free initially. Local control rates exceed 80% with modern combined-modality treatment strategies. Since most tumors are downstaged, some patients can be treated with breast-conserving treatments. The optimal sequence of local and systemic treatments has not been defined. Combined-modality therapies improve the treatment and the outcome for patients with LABC. Whether the sequence of utilization of various treatments influences outcome remains to be established. The administration of systemic therapies first also provides a useful biological model to assess the effects of systemic treatments on the primary tumor and regional metastases, since these are available for serial non-invasive evaluation and sampling of tumor tissue.

Inflammatory breast cancer (IBC) is a rare but often fatal disease. This review discusses the following conclusions: (1) The diagnosis of IBC is based on the clinical triad of erythema, ridging with peau d'orange, and rapid onset. The importance of histologic evidence of dermal lymphatic involvement is controversial. (2) Combining doxorubicin-containing chemotherapy with mastectomy or radiation therapy improves survival over that achieved with mastectomy or irradiation alone. (3) Mastectomy after induction chemotherapy may not improve survival or decrease locoregional recurrence rates, but the surgery does provide important prognostic information on treatment response and enables use of a lower radiation dose afterward, which results in reduced long-term complications. (4) The optimal number of cycles and dose intensity of chemotherapy for IBC remain undefined.

A family history of breast cancer is present in 20% to 25% of patients with breast cancer. Except for a few families with a very high risk, however, most patients with a family history have only a two- to fivefold increased risk of breast cancer. Early onset of disease, bilaterality, and multiple affected relatives further increase this risk, and, in a small minority of patients, their lifetime risk may approach 50%. Careful, individual patient assessment is necessary to establish a particular patient’s risk, which is usually modest. This risk assessment should take into account both family history as well as other associated risk factors such as menstrual and reproductive history or the presence of benign proliferative disease.

We reviewed the medical records of 101 patients who underwent extended resection for locally advanced colorectal carcinoma between 1965 and 1989. Preoperative symptoms related to the genitourinary system were present in 46 patients. Malignant invasion of genitourinary structures by colorectal carcinoma was found in 43 of these 46 patients (93%). In contrast, 51% of the patients without such symptoms had malignant invasion of contiguous structures. Preoperative intravenous pyelography, computerized tomographic scans, and cystoscopy correctly predicted the presence or absence of malignant invasion in 89%, 83%, and 87% of patients, respectively. Tumor-positive resection margins had a negative impact on survival (mean survival: 11.4 months). The 5-year actuarial survival rate for the patients who underwent a curative extended resection (margins tumor negative) was 54%. A thorough preoperative evaluation can identify a significant number of patients with colorectal cancer extending into adjacent organs and structures. Such evaluation is vital for operative planning and patient preparation, since an appropriate extended resection can produce long-term local control and patient survival.

Between 1974 and 1986, 283 patients with ten or more positive nodes were treated in four prospective trials using doxorubicin-containing adjuvant chemotherapy. At a median follow-up of 92 months, 182 patients had had a recurrence, and 158 died. An estimated 41% and 37% were disease-free at 5 and 7 years, respectively. Patients with ten positive nodes had a significantly better disease-free survival than those with more than ten such nodes (P = 0.04). The disease-free survival rate and overall survival rate were not influenced by the estrogen receptor status of the tumor, patient age, or disease stage. Long-term data on a large number of patients treated at this institute showed the natural history of this subgroup of patients. Approximately 30% of patient survived disease-free at 10 years after treatment with the systemic therapies used in these protocols. Newer approaches are needed to alter the prognosis of this subgroup of patients further.

Background The goal of the current study was to evaluate the effect of regional anesthesia using paravertebral block (PVB) on postoperative pain after breast surgery. Methods Patients undergoing unilateral breast surgery without reconstruction were randomized to general anesthesia (GA) only or PVB with GA and pain scores assessed. Results Eighty patients were randomized (41 to GA and 39 to PVB with GA). Operative times were not significantly different between groups. Pain scores were lower after PVB compared to GA at 1 hour (1 vs 3, P = .006) and 3 hours (0 vs 2, P = .001) but not at later time points. The overall worst pain experienced was lower with PVB (3 vs 5, P = .02). More patients were pain-free in the PVB group at 1 hour (44% vs 17%, P = .014) and 3 hours (54% vs 17%, P = .005) postoperatively. Conclusions PVB significantly decreases postoperative pain up to 3 hours after breast cancer surgery.

Background We determined the incidence of positive sentinel lymph nodes (SLNs) in patients with ductal carcinoma in situ (DCIS) or microinvasive breast cancer (MIC) and the predictive factors of SLN metastasis in these patients. Methods Of 4,503 patients who underwent SLN dissection between March 1994 and March 2006 at our institution, we identified those with a preoperative diagnosis or final diagnosis of DCIS or MIC. Clinicopathologic factors were examined by logistic regression analysis. Results Of the 624 patients with a preoperative diagnosis of DCIS or MIC, 40 had positive SLNs (6.4%). Of the 475 patients with a final diagnosis of DCIS or MIC, 9 had positive SLNs (1.9%). Clinical DCIS size >5 cm was the only independent predictor of positive SLN for patients with a preoperative diagnosis and patients with a final diagnosis of DCIS or MIC. Core biopsy as the method of preoperative diagnosis and DCIS size >5 cm were independent predictors for a final diagnosis of invasive carcinoma in the 149 patients who had a preoperative diagnosis of DCIS or MIC. Conclusions SLN dissection for patients with a diagnosis of DCIS should be limited to patients who are planned for mastectomy or who have DCIS size >5 cm. Patients who have a core-needle biopsy diagnosis of DCIS have a higher risk of invasive breast cancer on final pathologic assessment of the primary tumor. This information can be used in preoperative counseling of patients with DCIS regarding the timing of SLN biopsy.

Locoregional failures after primary treatment for breast cancer include a diverse group of lesions that represent different categories of failures with various prognoses. Although patients with chest wall recurrences and regional nodal failures after traditional radical surgery have a poor prognosis, many patients can still achieve a significant degree of palliation and even long-term survival or cure with carefully orchestrated multimodal treatment. In patients who have breast failures after breast-conservation surgery and radiation, long-term salvage and cure can be achieved for the majority with prompt detection and appropriate treatment, which, like treatment for primary breast cancer, includes a consideration not only of local control but also of the risk of subsequent systemic failure and its need for treatment.

An immunocytochemical assay using a monoclonal antibody specific for estrogen receptor (ER-ICA) was performed on needle aspirates and on histologic sections (mastectomy and biopsy specimens) from 55 patients with breast cancer. A total of 82 ER-ICAs were performed, with matched cytologic and histologic specimens in 27 patients, cytology alone in 15, and histology alone in 13. ER-ICA results were described by a histochemical score (H score) based on intensity-weighted percentages of staining cells. The H scores were compared with results of sucrose density gradient (SDG) analysis of histologic specimens (mastectomy, resection, or biopsy). An H score greater than or equal to 10 and an SDG value greater than or equal to 10 fmol/mg protein were considered positive. The sensitivity of cytologic ER-ICA was 94%, the specificity 100%. The sensitivity of histologic ER-ICA was 67%, the specificity 90%. Correlating cytologic H score with Black's nuclear grade showed that grade 1 (the most anaplastic) carcinomas demonstrated the lowest H scores (mean, 7.3 +/- 29.8), whereas the highest H scores were noted in grade 3 tumors (mean, 150.0 +/- 88.1). Both SDG and ER-ICA showed ER values to be lower in premenopausal than postmenopausal women. There was no correlation between H score and presence of axillary nodal metastases or tumor size. An overall good correlation was demonstrated between immunohistochemical methods and biochemical analysis.

To evaluate the role of chemotherapy in local control of primary breast cancer, the incidence of local failure was evaluated in 768 patients treated with surgery and adjuvant, combination chemotherapy that contained fluorouracil, doxorubicin, and cyclophosphamide (FAC) at our institute between 1974 and 1982. Of these patients, 429 received postoperative irradiation (XRT) before adjuvant therapy. A group of 178 historical control patients had mastectomies and received irradiation after surgery without chemotherapy. The rates of locoregional recurrence alone in the three groups were as follows: FAC, 12%; FAC plus XRT, 5%; and XRT, 10%. The difference in recurrence rates between the FAC group and the FAC plus XRT subgroup was significant (P less than 0.01). Local failure rates were evaluated by stage and nodal status; patients with Stage III disease and those with four or more disease-positive nodes had a higher incidence of local failure than did patients with Stage II disease or those who had one to three positive nodes. Systemic chemotherapy and local therapies resulted in 50% local control at the time of locoregional recurrence in patients treated with FAC, whereas local control was achieved in 18% of patients with local recurrence in the XRT subgroups. Overall life-time local control of disease was similar whether irradiation was administered initially (in the period after operation) or at the time of local recurrence. Irradiation after mastectomy remains an integral part of a combined modality approach in selected groups of patients.

A total of 106 patients with inflammatory carcinoma of the breast underwent combined-modality treatment consisting of doxorubincin-containing chemotherapy. All patients received three cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) before local therapy. From 1974 to 1977 (group A), primary radiotherapy was the local treatment modality and chemotherapy was given for a total of 24 months. From 1978 to 1981 (group B), mastectomy became the primary local treatment modality and FAC was reinstituted within 10–14 days after surgery; after completion of FAC, consolidation radiotherapy was given. From 1982 to 1986 (group C), vincristine and prednisone were added to FAC, and doxorubicin was given by continuous infusion. The median follow-up of the three groups was 56 months. For patients alive at the time of analysis, median follow-ups were 141, 111, and 49 months in groups A, B, and C, respectively. Disease-free survival at 5 years was 35%, 22%, and 41% for groups A, B, and C, respectively, and respective overall survival at 5 years was 37%, 30%, and 48%. Mastectomy in addition to radiotherapy resulted in local control rates similar to those obtained with radiotherapy alone, but this approach would result in fewer late sequelae of high-dose irradiation and provided histologic staging for chemotherapy response. The patients treated on protocol C had slightly better disease-free and overall survival, but the differences were not statistically significant. The 5-year disease-free survival of patients achieving a clinical complete remission (CR) or partial remission (PR) was superior to that of patients whose response was less than a PR. There was no episode of doxorubicin-related cardiac toxicity in group C. Combined-modality treatment for inflammatory carcinoma of the breast resulted in improved survival.

Recent studies demonstrate improved progression-free survival (PFS) and improved overall survival (OS) with extirpation of the primary tumor in breast cancer patients who present with metastatic disease at initial diagnosis. The subset of patients who would most benefit from surgery remains unclear. This study evaluates the pathological attributes and optimum timing for surgery in patients who present with stage IV breast cancer and an intact primary.Retrospective, single-institution review of all breast cancer patients between 1997 and 2002 presenting with an intact tumor and synchronous metastatic disease. Information collected included: demographics, tumor characteristics, metastatic sites, type/timing of surgery, and radiation/systemic therapy received. Patients initiated treatment within 3 months of their diagnosis. Patients were divided into three groups based on time interval from diagnosis date to surgery date. Disease progression and vital status at last follow-up were evaluated. Analysis of metastatic PFS (defined by progression of systemic disease) benefit in relation to surgical timing was performed.Multivariate analysis revealed patients having only one site of metastasis, negative margins, and Caucasian race had improved PFS. Further analysis revealed non-Caucasian patients more often underwent surgical intervention for palliation versus surgery for curative intent, possibly explaining their worse outcome. Patients who underwent surgery in the 3-8.9 month or later period had improved metastatic PFS.Surgical extirpation of the primary tumor in patients with synchronous stage IV disease is associated with improved metastatic PFS when performed more than 3 months after diagnosis. Resection should be planned with the intent of obtaining negative margins.

Recurrent breast carcinoma is usually detected by imaging studies and biopsy. We present a case with unusual clinical presentation and discuss the diagnosis and treatment. While core needle biopsy and fine-needle aspiration are important in the diagnosis of early-stage breast cancer, physical examination and close follow-up are important in the absence of a diagnosis.