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Controversy has long existed regarding the biological implications and surgical treatment of regional lymph node metastasis in invasive breast cancer. Several factors have resulted in a renewed evaluation of axillary node dissection. First is the continuing biological controversy that axillary lymph node metastases are “indicators but not governors” of outcome in breast cancer. Indeed in all human cancers with few exceptions, this biological concept has been proved repeatedly, and in most studies addressing this issue, lymph node metastases have proved to be indicators only. Another factor that has led to resurgence of interest in the role of axillary node dissection is the downward trend in tumor size secondary to mammographic screening and the resulting decrease in proportion of patients with lymph node metastasis. Use of primary tumor characteristics and genomic patterns to aid in decisions to administer systemic chemotherapy, the failure of high-dose therapy with bone marrow support, and the increasing indications for systemic adjuvant therapy in most cases have also challenged the need for axillary node dissection. Finally, with the advent of sentinel lymph node biopsy and its widespread application, the need for complete axillary evaluation has been questioned. This chapter summarizes the role of the lymphatic system in breast cancer and factors that have led to the decreased need for surgical axillary evaluation. Alternatives to axillary lymph node dissection, including axillary observation only in patients with small tumors, treatment of the axilla with tangential whole breast radiotherapy fields or axillary radiotherapy, lymph node evaluation by four- and five-node sampling, sentinel node biopsy, and the use of ultrasound to stage the axilla are also discussed. The continuing controversy surrounding the potential value of axillary dissection in breast cancer patients is explored.

The beneficial impact of screening mammography on breast cancer outcome continues to be debated as demonstrated by guidelines published by the United States Preventive Services Task Force. A previous report from Rhode Island, which has a very high rate of mammographic screening, demonstrated significant improvements in invasive breast cancer presentation and mortality through 2001. This report updates data through 2008 to determine whether previous favorable trends continued. Rhode Island Cancer Registry data regarding invasive breast cancer presentation and mortality in 17,522 female residents diagnosed between 1987 and 2008, inclusive, were analyzed for demographic and pathological factors. Data were analyzed by four time periods: 1987–1992, 1993–1998, 1999–2003, and 2004–2008 and overall. Statistically significant improvements occurred over the four successive time periods, in mean cancer size (23.7, 20.9, 19.6, and 19.3 mm, p < 0.0001), pathologic grade (Grade I: 12, 15, 19, and 17 %; Grade III 57, 41, 36, and 35 %, p < 0.0001), breast conserving surgery (38, 56, 67, and 71 %, p < 0.0001) and mortality (37.3, 31.4, 25.1, and 22.6 per 100,000/year, p < 0.0001). The results showed that high screening rates favorably impacted presentation of and mortality from invasive breast cancer in Rhode Island. From 1987 to 2008, there has been a 39 % decline in breast cancer mortality considering 5 year periods (37.3 vs. 22.6 deaths per 100,000) and 41 % comparing the period from 1990 to 2008, which may exceed the goal of 50 % mortality reduction by 2015 established by the American Cancer Society.

Considering the declining breast cancer mortality in the United States, it is apparent that a ‘‘tipping point’’ was reached between 1986 and 1991, most apparent after 1990. For the first time since 1930, the previously unyielding ageadjusted breast cancer mortality rate began a continuous decline, starting about 5 years after the upsurge in use of mammographic screening in the 1980s (Fig. 1). This mortality decline had reached 30% in the entire United States by 2007 (Fig. 2; http://www.seer.cancer.gov) and had reached as much as 48% in Delaware, 41% in Rhode Island, and 40% in Massachusetts (http://statecancerprofiles.cancer.gov), the three highest states in mammography use recorded by the 2006 Behavioral Risk Factor Surveillance System (BRFSS) telephone surveys (http://cdc.gov/brfss/). The BRFSS estimates mammography use at least every 2 years by women over the age of 40. In contrast, mortality decline has been only 11% in Utah, 12% in Mississippi, and 14% in Oklahoma, three of the four lowest states in BRFSS reports of screening incidence (Fig. 3; http://statecancerprofiles. cancer.gov). Although the BRFSS rates may be somewhat exaggerated because they are based on women’s recall, the resultant relative ranking is undoubtedly correct because survey techniques are similar across the country. States with the greatest decline in mortality are also states with high initial incidence and mortality from breast cancer due to well-established demographic features such as older age, higher socioeconomic status, and higher education level. Because mammographic screening reduces mortality by earlier detection of a cancer with a biologically progressive disease course in most situations, a reduced rate of advanced breast cancers in a population is a surrogate for the success of screening. Here, we analyze the role of the steady change in tumor size as a result of breast cancer screening and attempt to demonstrate a temporal and possible causal relationship between changes in tumor size and the beginning of the decrease in breast cancer mortality (that is, the tipping point). The mean maximum diameter of all breast cancers was about 3.5 cm before 1950, about 3.0 cm in 1968 (just before the introduction of mammography), reached about 2.5 cm by 1987, and had a progressive further decline to less than 2.0 cm by 2006. The median maximum diameter of breast cancer, a better description of the usual presentation because it eliminates the bias of the extended ‘‘tail’’ of very large cancers, was 2.5 cm in 1968, 2.0 cm by 1987, and 1.5 cm after 2002. Accompanying this overall size decrease, the axillary lymph node metastatic rate, which was over 60% in the 1950s, usually with multiple node metastases, decreased to about 50% by 1968, and thereafter progressively declined to less than 30% by 2006. Equally important was the progressive decline in the number of lymph node metastases involved in women with invasive breast cancer through the years, so that now only one node metastasis is found in about 50% of patients who have regional nodal metastases, and all nodal metastases are limited to the excised sentinel nodes in up to two-thirds of patients. With the adoption of limited axillary node sampling by sentinel node biopsy, smaller volumes of nodal involvement have been recorded as pathologists more rigorously section and examine the few sentinel nodes submitted (median # 2), which in turn technically increases the rate of nodal metastases by up to 20%, a good example of the Society of Surgical Oncology 2011

MUC1, a tumor associated glycoprotein over-expressed in 95% of pancreatic cancers, has been shown to be associated with a worse prognosis. The objective of this study was to determine the impact of loss of MUC1 expression on pancreatic tumor growth. PANC1 human pancreatic carcinoma cells with stable "knockdown" MUC1 expression were created using a MUC1 specific short interfering RNA (siRNA). PANC1 cells with "knockdown" MUC1 expression had decreased in vitro proliferation compared with PANC1 wild type and control cells. PANC1-MUC1siRNA cells grew significantly slower in severe combined immunodeficient (SCID) mice compared with wild type and negative controls. Our data suggested that decreasing MUC1 tumor expression by RNA interference may be a novel molecular approach for the treatment of pancreatic cancer.

Chemically disordered face centered cubic (fcc) FePt nanoparticles (NPs) show the controlled release of Fe in low pH solution. The released Fe catalyzes H(2)O(2) decomposition into reactive oxygen species within cells, causing fast oxidation and deterioration of cellular membranes. Functionalized with luteinizing hormone-releasing hormone (LHRH) peptide via phospholipid, the fcc-FePt NPs can bind preferentially to the human ovarian cancer cell line (A2780) that overexpresses LHRH receptors and exhibit high toxicity to these tumor cells. In contrast, the fcc-FePt NPs pre-etched in the low pH (4.8) buffer solution show nonappreciable cytotoxicity. The work demonstrates that fcc-FePt NPs may function as a new type of agent for controlled cancer therapy.

MUC1, a tumor associated glycoprotein, is over-expressed in most cancers and can promote proliferation and metastasis. The objective of this research was to study the role of MUC1 in cancer metastasis and its potential mechanism. Pancreatic (PANC1) and breast (MCF-7) cancer cells with stable 'knockdown' of MUC1 expression were created using RNA interference. beta-Catenin and E-cadherin protein expression were upregulated in PANC1 and MCF-7 cells with decreased MUC1 expression. Downregulation of MUC1 expression also induced beta-catenin relocation from the nucleus to the cytoplasm, increased E-cadherin/beta-catenin complex formation and E-cadherin membrane localization in PANC1 cells. PANC1 cells with 'knockdown' MUC1 expression had decreased in vitro cell invasion. This study suggested that MUC1 may affect cancer cell migration by increasing E-cadherin/beta-catenin complex formation and restoring E-cadherin membrane localization.

Background Since the 1980s, Rhode Island has achieved one of the highest mammography screening rates in the nation. The objective of this study was to determine the effect of high mammography rates on breast cancer presentation and outcomes. Methods Using the Rhode Island Cancer Registry, the incidence of DCIS and invasive cancer, tumor size, stage, rate of BCS and mortality from breast cancer were determined from 1987 to 2001. Results Over 80% of Rhode Island women report routine mammography. From 1987 to 2001, there were 1,660 cases of DCIS and 11,301 cases of invasive breast cancer. Although the overall incidence of invasive cancer was stable, the median diameter decreased from 2 cm to 1.5 cm with a significant decrease in the incidence of stage III and IV cancers. There was an increase in BCS for women 50 to 64 years of age with stage I and II disease and for women older than 65 years with stage I disease. Disease-specific mortality decreased by 25%. Conclusions High mammography rates in Rhode Island are associated with smaller and earlier-stage breast cancers. This largely accounts for the decreased mortality from breast cancer and the increased rate of BCS.

This retrospective study assesses the presentation of breast cancer patients who died of disease. The goal was to estimate the proportion of patients whose cancer was detected by a screening mammogram, yet still proved fatal, and to characterize contemporary fatal breast cancers. Patients who died of breast cancer between 1995 and 2001 and were treated at three hospitals with complete, accessible information were identified using the Rhode Island Department of Health database and State Cancer Registry. Patients were classified as routinely screened, true interval, off-program, or unscreened. The median maximum diameter of fatal cancers was 2.5 cm. Sixty-nine percent of patients had lymph node metastases and 19% had stage IV disease. Fifty-seven percent were unscreened and 12% were routinely screened, with 2.5 cm and 1.5 cm median tumor diameters, respectively. Fifty-two percent of unscreened patients and no routinely screened patients had stage III or IV disease. Fifteen percent of fatal cancers were interval cancers. Only 27% of patients who died of breast cancer were participants in routine screening programs in Rhode Island, where 84% of women receive regular mammograms. This study complements randomized, population-based trials demonstrating a significant mortality reduction with an invitation to participate in screening.

Neoadjuvant therapy includes systemic chemotherapy or radiotherapy for cancer before surgery. Neoadjuvant agents may be chemotherapeutic or hormonal agents, biological response modifiers, or future genetic manipulations. Neoadjuvant therapy in breast cancer began with attempts to improve advanced local or regional disease, but it is now used in larger but operable disease and is employed in earlier operable cancers. The goals of neoadjuvant therapy included conversion of inoperable to operable disease but evolved to increase rates of breast conservation. It allows direct observation of chemotherapeutic effects and more sophisticated prognostication based on pathological analysis of response extent. Patients even with advanced or inflammatory breast cancer may have excellent long-term disease-free survival and breast conservation. Expanded research opportunities may arise from the study of cancer features before and after neoadjuvant therapy contrasting responders with nonresponders. Neoadjuvant therapy demonstrates the advantages of comprehensive multidisciplinary contemporary patient management for function preservation and cosmetic appearance without sacrificing survival.

Current standard therapy for invasive breast carcinoma is mastectomy or breast conservation with adjuvant radiation. Data from randomized trials suggest no advantage for radiotherapy after lumpectomy in highly selected patients. Selective radiotherapy would make contemporary breast cancer therapy more rational with decreased morbidity and expense.A total of 163 patients were treated by breast conservation without adjuvant radiation between 1978 and June 2003. They declined radiation after discussion or had medical contraindications. The great majority were postmenopausal and had lower-grade T1 tumors with resection marginsor = 1 cm and no nodal metastases. The goal was to identify patients with favorable prognostic features for omission of postsurgical irradiation without impaired local recurrence or survival.Twenty patients (12%) had local recurrences; 17 (10%) were invasive, and 3 (2%) were ductal carcinoma-in-situ. An ideal patient subgroup50 years of age with grade 1 or 2 cancersor =1.5 cm in diameter and with surgical marginsor = 1 cm was empirically defined. Of 80 such patients, 5 (6%) had local recurrence; 3 (3.5%) were invasive, and 2 (2.5%) were ductal carcinoma-in-situ.A defined ideal subset of older breast cancer patients with smaller, lower-grade cancers and adequate excision margins can be treated with lumpectomy without irradiation and with minimal local recurrence.

Breast cancer is a heterogenous disease with significant variations in biologic potential, ranging from small, low-grade, DCIS discovered mammographically with essentially no impact on patient survival to rapidly growing, palpable, locally advanced invasive breast cancer with clinically palpable nodal metastasis. The current challenge is to identify the clinical, pathologic, and molecular factors that determine the biologic potential of a particular breast cancer. Although size, nodal status, histologic grade, age, surgical margin, and hormone receptor status of breast cancer are the most important prognostic factors, the focus of research must be beyond these factors to other nonspecific prognostic information. Bone marrow micrometastasis may be an important factor to help predict outcome (7a) and the complement of sentinel node biopsy, bone marrow analysis, and primary tumor features may allow physicians to better select therapy. With increased understanding of the individual molecular events that control the invasive potential of a particular cancer, practitioners should be better able to predict more accurately which patients have little risk of recurrent disease or metastasis and would be best served by surgery alone versus patients who have a high risk of recurrent and metastatic disease and who should receive multimodality care.

Sentinel node biopsy to determine the presence of metastatic disease in regional lymph nodes has been described in a variety of solid tumors. Sentinel node biopsy has proven that drainage of cancer cells to the regional lymph nodes is an orderly process with metastasis predominantly to one or two nodes first before involvement of subsequent nodes. The use of this technique has resulted in the increased identification of regional metastasis suggesting that patients previously identified as node negative may have unidentified regional metastasis. The clinical significance of these microscopic tumor deposits in lymph nodes remains controversial.

Details of surgical removal of invasive breast cancer do not govern survival or cure. They do, however, control local recurrence rates and regional recurrence risk. The surgeon’s role in breast cancer in the new millenium is to produce a cosmetic and functional result that is as good as possibly can be achieved while minimizing recurrence. Guidelines for incision placement, tissue volume removal, and nodal removal are critical determinants of cosmetic and functional outcome and need to be appreciated by surgeons.

Background: The roles of breast conservation and surgical evaluation of the contralateral breast in the treatment of lobular carcinoma of the breast remain unclear. The aim of this study was to compare local recurrence, 5-year survival, and incidence of contralateral breast cancer in women with lobular carcinoma to that in women with infiltrating ductal carcinoma. Methods: Women with infiltrating ductal carcinoma (IDC) and invasive lobular breast carcinoma (ILC) diagnosed during the years 1984 to 1994 were identified through a statewide tumor registry. The women were divided into groups based on their histology and treatment (breast conservation or modified radical mastectomy). The incidences of contralateral breast cancer, local recurrence, and 5-year survival were compared within each histologic group and treatment category. Results: During the period 1984 to 1994, 4886 women were diagnosed with invasive lobular or ductal breast carcinoma. Of these, 316 (6.5%) had infiltrating lobular cancer. The 5-year survival rates were 68% and 71% for ILC and IDC, respectively (p=0.5). The local recurrence rates were 2.8% and 4.3% for ILC treated with lumpectomy and axillary nodal dissection (LAND) and modified radical mastectomy (MRM), respectively, which were not significantly different from that obtained with IDC (LAND=2.5%, MRM=2.1%). The incidence of contralateral breast cancer during the period was 6.6% and 6.5% for ILC and IDC, respectively. Conclusions: Invasive lobular carcinoma can be safely treated with breast conservation with no difference in local recurrence or survival. In the absence of a suspicious finding on clinical or radiologic examination, routine contralateral breast intervention is not recommended.

Gastroduodenal fistulas compose only a small portion of gastrointestinal fistulas. They usually occur in the postoperative setting in association with an anastomotic leak. As with all fistulas, attention to adequate supportive care is needed. Interventional endoscopy may play a role in the future. The three surgical management approaches include exclusion, resection, and closure of the fistula. The success rate of closure ranges from 25% to 75% with supportive care only to 100% with proper surgical management.

There is no ideal tumor marker for pancreatic carcinoma. Most of the tumor-associated antigens in this disease are cell surface mutins, such as CA19-9, TAG-72, CA242, CA50, CA195, and CA494. CA19-9 is the most promising marker. It is used for clinical and pathological diagnosis, prognosis, and response to chemotherapy. The other mucin antigens are currently being investigated for clinical practice. CA242 shows promise as a marker of tumor load and CA494 may play a role in immunotherapy. Oncofetal antigens such as CEA are not specific for pancreatic carcinoma and have a limited use in this disease. Malignancies associated with the endocrine pancreas secrete hormonal products which can be used as tumor markers. Fluid aspirated from pancreatic cysts can also be evaluated. Tumor antigens in aspirated fluid from pancreatic cysts should be interpreted with caution since multi-locu-lated cysts do not have a uniform expression of these markers. © 1995 Wiley-Liss, Inc.

Background Neoadjuvant chemotherapy may decrease tumor volume to allow breast conservation surgery. Its effect on estrogen and progesterone receptor (ER/PR) expression and hormone receptor (HR) status is controversial. Methods From February 2001 to July 2002, 56 breast cancer patients treated with neoadjuvant chemotherapy and 56 non-neoadjuvant therapy (control) patients with adequate tissue samples were identified. Quantitative ER/PR expression was analyzed in preneoadjuvant or preoperative core biopsies and final surgical specimens. Changes between the two groups were compared to determine if alterations were due to neoadjuvant chemotherapy or tissue sampling. Results The ER/PR expression changed in 34 (61%) neoadjuvant chemotherapy patients and 27 (48%) control patients. These expression changes resulted in HR status (positive/negative) alterations in 3 patients (5%) in both groups. Age, histology, chemotherapy regimen, and neoadjuvant response did not predict change. Conclusions Hormone receptor status changed in 5% of neoadjuvant chemotherapy and control groups due to tissue sampling. As these changes may impact treatment, HR expression reanalysis in final surgical specimens is recommended.

Background: Axillary lymph node status is important for staging and planning therapy prior to neoadjuvant chemotherapy in patients with locally advanced breast cancers (LABC). The objective of this study was to evaluate the use of axillary ultrasonography coupled with fine needle aspiration biopsy (US-FNAB) to determine lymph node status prior to initiation of neoadjuvant chemotherapy. Methods: Patients with a LABC, defined as a breast cancer clinically larger than 3.0 cm or a cytology positive axillary lymph node, were evaluated by clinical examination followed by ultrasonographic evaluation. Lymph nodes were categorized as suspicious for malignancy based on size >1.0 cm, decrease in the fatty hilum, or parenchymal echogenicity. US-FNAB was performed on all patients. Most patients received neoadjuvant chemotherapy followed by definitive surgery. Axillary surgery consisted of axillary lymph node dissection. Axillary status by clinical examination and US-FNAB was compared with that obtained by axillary node dissection. Results: From January 1998 to May 2001, 26 patients (27 axillae) presented with LABC to our institution. The median age of these patients was 48 years. The sensitivity and specificity of US-FNAB for evaluating axillary metastatic disease in patients with LABC were 100% and 100%, respectively. Conclusions: In patients with locally advanced breast cancer, axillary ultrasonography coupled with fine needle aspiration biopsy can accurately stage the axilla. It is particularly useful and should be used more frequently in patients undergoing neoadjuvant chemotherapy. The use of ultrasonography to stage the axilla in patients who present with small breast cancers should be explored.

The objective of our study was to evaluate the utility of ultrasound-guided fine-needle aspiration (FNA) of the axillary lymph nodes in breast cancer patients depending on the size of the primary tumor and the appearance of the lymph nodes.Data were collected about tumor size, lymph node appearance, and the results of ultrasound-guided FNA and axillary surgery of 224 patients with breast cancer undergoing 226 ultrasound-guided FNA. Lymph nodes were classified as benign if the cortex was even and measured3 mm, indeterminate if the cortex was even but measured ≥ 3 mm or measured3 mm but was focally thickened, and suspicious if the cortex was focally thickened and measured ≥ 3 mm or the fatty hilum was absent. The results of ultrasound-guided FNAs were analyzed by the sonographic appearance of the axillary lymph nodes and by the size of the primary tumor. The sensitivity and specificity of ultrasound-guided FNA were calculated with axillary surgery as the reference standard. The sensitivity and specificity of axillary ultrasound to predict the ultrasound-guided FNA result were calculated.Of the 224 patients, 51 patients (23%) had a positive ultrasound-guided FNA result, which yields an overall sensitivity of 59% and specificity of 100%. The sensitivity of ultrasound-guided FNA was 29% in patients with primary tumors ≤ 1 cm, 50% in patients with tumors1 to ≤ 2 cm, 69% in patients with tumors2 to ≤ 5 cm, and 100% in patients with tumors5 cm. The sensitivity of ultrasound-guided FNA in patients with normal-appearing lymph nodes was 11%; indeterminate lymph nodes, 44%; and suspicious lymph nodes, 93%. Sonographic characterization of lymph nodes as suspicious or indeterminate was 94% sensitive and 72% specific in predicting positive findings at ultrasound-guided FNA.Ultrasound-guided FNA of the axillary lymph nodes is most useful in the preoperative assessment of patients with large tumors (2 cm) or lymph nodes that appear abnormal.

To retrospectively assess the sensitivity and specificity of ultrasonographic (US)-guided fine-needle aspiration (FNA) of axillary lymph nodes for preoperative staging of breast cancer across a range of primary tumor sizes, by using histologic findings as a reference standard.Institutional review board approval was obtained for this HIPAA-compliant study; informed consent was waived. US-guided FNA results in 74 patients with breast cancer (75 axillae) were compared with final pathologic results. Lymph nodes were classified as benign, indeterminate, or suspicious on the basis of US characteristics at retrospective review. US-guided FNA in the most suspicious node at US, or the largest node if all appeared benign, was performed. Final pathologic results (sentinel lymph node biopsy [SNB] or axillary lymph node dissection [ALND]) were compared with US and preoperative US-guided FNA results. Results were assessed according to tumor size. Sensitivity, specificity, and positive predictive value of US and US-guided FNA were calculated.Primary tumor sizes were 0.3-12 cm (mean, 3 cm). Patient age range was 31-81 years (mean age, 51 years). Sensitivity of US-guided FNA for predicting positive results at ALND or SNB was 71%-75%. Specificity was 100%. Sensitivity of US-guided FNA increased with primary tumor size.US-guided FNA of axillary lymph nodes in patients with newly diagnosed breast cancer had a sensitivity that increased with increasing size of the primary tumor.

Incidence of ductal carcinoma in situ (DCIS) has increased significantly during the last decade, comprising almost 20% of all breast cancers diagnosed today. DCIS is composed of malignant breast duct epithelial cells that have clonally proliferated and accumulated within the mammary duct lumen. It comprises a group of heterogeneous tumors with varying biologic behavior rendering its classification and management challenging. By definition, DCIS does not invade through the basement membrane; it is a preinvasive malignancy and systemic disease is nonexistent. The basis of treatment is to prevent progression into an invasive cancer such as ductal carcinoma. Most current DCIS classification schemes do not predict its potential to progress to invasive disease. In this review the natural history of DCIS, as it relates to its biologic potential to progress to invasive disease, is summarized, and a broad classification system that may provide a guideline for patient management is proposed.

Background: The aim of this study was to examine the effect of measurement bias in breast cancer and to create a more rational T-size categorization in tumor-node-metastasis staging in response to smaller, screen-detected cancers and measurement bias. Methods: From 1987 to 2003, 10,853 invasive nonmetastatic breast cancers enlisted in the Rhode Island Cancer Registry with a known dimension were reviewed. Data analyzed by proposed classifications included the rate of lymph node metastases and the mortality rate from breast cancer. Results: The median diameter was 16 mm. Cancer measurements reflected the bias in pathologists' dimension recording, which is centered strongly about whole- and half-centimeter sizes. A new T classification is proposed with the following sizes and frequencies in the Rhode Island Cancer Registry: 1 to 2 mm = T1 mic (3% of registered cases); 3 to 7 mm = Tla (11%); 8 to 12 mm = T1b (23%); 13 to 17 mm = Tic (18%); 18 to 22 mm = T2a (17%); 23 to 27 mm = T2b (8%); 28 to 32 mm = T2c (8%); 33 to 42 mm = T3a (6%); 43 to 52 mm = T3b (3%), and greater than 52 mm = T3c (4%). The unadjusted odds ratio for the probability of node metastases was 1.43 (confidence interval, 1.40-1.46; P

Background As delayed childbirth increases for socioeconomic and fertility reasons, its impact on breast cancer risk needs definition. Methods From 1975 to 1981, 1,307 women with childbirth at ≥40 years of age were identified. They were divided into four groups by estimated first birth median ages (EFBMA): 23, 34, 38, and 41 years, corresponding to previous parity of more than 3, 2 or 3, 1, and zero, respectively. Cancer Registry cross-referencing identified those diagnosed with breast cancer. Results Breast cancer developed in 39 women. The EFBMA of 41 years carried a relative risk of 3.7, (95%CI: 1.30 to 10.5) compared with age 23. Odds ratio of breast cancer was 1.08 (95%CI: 1.02 to 1.14) with each year older at first birth and 0.79 (95% CI: 0.67 to 0.93) for each additional previous birth. Conclusions Increased breast cancer risk with advancing maternal age at first childbirth is supported by 3.7 relative risk in women with an EFBMA of 41 years compared with those with an EFBMA of 23 years.

Hypothesis Women with breast cancer who have casting-type microcalcifications associated with multifocal invasion and extensive ductal carcinoma in situ (DCIS) form a subset of patients with a poor prognosis. Our study aims to identify the mammographic and pathologic features of this group. Design Women with casting-type microcalcifications, multifocal invasion, and extensive DCIS were identified from our tumor board registry. Mammographic features, tumor characteristics, treatment, and survival rates were evaluated. Invasive tumors were limited to 14 mm or smaller. Setting University medical teaching hospital and breast cancer specialty clinic. Results Of the 984 patients with breast cancer treated at our center, 15 patients were identified who had extensive casting-type calcifications and DCIS. Twelve of these patients also had multifocal invasive breast cancer. All had casting-type microcalcifications occupying more than 1 breast quadrant. All but 1 of the patients were treated using mastectomy with sentinel node biopsy or axillary node dissection. All but 1 patient had extensive grade 3 DCIS. Invasive tumors were negative for estrogen receptor and progesterone receptor expression in half of the patients, and 60% were positive for the HER-2-neu receptor. Positive axillary lymph nodes were found in 33% of patients, and 75% received adjuvant chemotherapy. After a median follow-up period of 20.5 months (range, 6-72 months), 1 patient had died and 1 had distant metastases. Of the 3 patients who had DCIS without invasion, 1 experienced a recurrence with infiltrating ductal carcinoma. Conclusions In women with small multifocal breast cancers with extensive casting calcifications and DCIS, the incidence of positive lymph nodes was 33%, with a tendency for poor tumor markers. These women appear to be at substantial risk for systemic disease; lymph node sampling and adjuvant systemic therapy are recommended.

Due to the high incidence of breast cancer and associated mortality rate,the development of an effective vaccine may be beneficial for the prevention or adjuvant treatment of this malignancy. We have constructed a novel breast cancer vaccine, Bacillus Calmette-Guérin (BCG)-hIL2MUC1, that consists of BCG and expresses a truncated form of MUC1 and human interleukin (IL)-2. In vitro analysis of the BCG-hIL2MUC1 construct confirmed coexpression of MUC1 and human IL-2. The ability of BCG-hIL2MUC1 to inhibit breast cancer growth was evaluated in hu-PBL-SCID mice (severe combined immunodeficient mice reconstituted with 50 x 10(6) human peripheral blood lymphocytes) that received three biweekly injections of BCG-hIL2MUC1 (0.5 colony-forming unit). Control animals received PBS, MUC1 peptide (100 microg), or empty vector BCG-261 (0.5 colony-forming unit) vaccination. After immunization, hu-PBL-SCID mice (n = 8 in each group) were xenografted with 4 x 10(6) ZR75-1 human breast cancer cells. Whereas mice receiving the control vaccines developed a tumor, only 87% of BCG-hIL2MUC1-immunized animals developed a palpable tumor with a slower rate of tumor growth (P0.001). Histological analysis of the primary tumors in BCG-hIL2MUC1-immunized animals revealed areas of reduced MUC1 expression. CD8-positive human lymphocytes were detected only in tumors grown in BCG-hIL2MUC1-immunized animals. These results imply a critical role of coexpressed IL-2 and MUC1 in eliciting tumor-specific immune response. To our knowledge, this is the first report of BCG engineered to express a tumor-associated antigen. Our results suggest that BCG-hIL2MUC1 immunization inhibited breast cancer growth in hu-PBL-SCID mice. Therefore, BCG-hIL2MUC1 may be a promising candidate as a breast cancer vaccine.

Background: Modern breast surgery, as the primary treatment of invasive breast carcinoma, has been evolving over the last century. Aggressive radical surgery, which included chest wall resection, complete axillary clearance and internal mammary node dissection, has slowly changed to a less aggressive approach. This has been based on an improved understanding of the biology of the disease. Over the years, randomized prospective trials, performed at centers all over the world, have demonstrated that axillary dissection does not impact on the overall survival while it helps with loco-regional control of breast cancer. Its major role, at the present time, is limited to staging and prognostication; functions that are equally well served by the limited approach of a sentinel node biopsy. Sources: This review is based on the available medical literature involving the biology and organ specificity of the metastatic process, not only in breast cancer but also in other malignancies. In addition, studies pertaining to clinical breast cancer, and the role of surgery in its treatment, were reviewed. The ongoing trials on the role of sentinel node biopsy in the management of the clinically node negative patients are discussed. Conclusions: This review covers the history, pathophysiology, and clinical basis of the current role of axillary dissection for invasive breast cancer. From the data presented we hope that the medical community will agree that there is no therapeutic role for extended axillary dissection at the current time.

Although the technique of isolated pelvic perfusion dates back to the time of Creech (1959) and has been used by a variety of authors to treat unresectable neoplasms, the inherent complexity of the open procedure limited its widespread use. We simplified the technique through use of the balloon-occlusion technique for aortic and caval control. Our initial efforts used this technique for unresectable pelvic cancer, but recently we used this as preoperative therapy for advanced pelvic malignancy.Isolated pelvic perfusion was accomplished by placement of balloon-occlusion catheters (Fogerty 8) in the aorta and inferior vena cava (IVC) at L3 vertebral body level via the common femoral artery and vein and establishing inflow and outflow catheter connections to a hemodialysis pump that generated a flow rate of 150-300 ml/min. Chemotherapy drugs were infused at times 0, 10, and 20 min. 5-Fluorouracil (5-FU; 1,500 mg/M2), cis-platinum (50-100 mg/M2), and mitomycin (15-20 mg/M2) were given by normothermic perfusion over a 45-min period. Forty isolated perfusions were carried out in 25 patients. Patients were evaluated by clinical examination, biochemical tests, computed tomography (CT) and magnetic resonance imaging (MRI) scans, and surgical exploration.Pelvic perfusion generally achieved pelvic systemic exposure ratios (area under the curve) between 5 and 10:1 for all three drugs: mean ratios were 11.4 (5-FU), 6.0 (cisplatin), and 9.0 (mitomycin). The amount of leaking to the systemic circuit ranged from 28 to 38%. Of 15 patients treated for palliation, there was one objective partial response (PR). Ten patients had symptomatic improvement of pain, two had complete pain relief (CR), and eight had partial pain relief, ranging from 3 weeks to 3 months (median, 5 weeks). Six of 10 patients with adequate carcinoembryonic antigen (CEA) follow-up data had a reduction in CEA levels (mean change, 35 units). Of 10 preoperative patients, there was one CR among five rectal cancer patients; and four of five PRs among patients with other pelvic malignancies: two PRs in patients with epidermoid cancer and one PR each in patients with endometrial cancer and metastatic anorectal melanoma.Pelvic perfusion by a simplified balloon-occlusion technique provides palliation for most patients with advanced pelvic malignancy and may increase resectability and improve tumor control in patients amenable to resection.

Background The objective of this study was to determine if standard tangential breast radiation covered the sentinel lymph node in women with invasive breast cancer. Methods Women with invasive breast cancer treated by lumpectomy, radiotherapy and sentinel node biopsy at our institution were included in this study if the sentinel lymph node site had been marked with a clip. Plain films were used to determine if the clip fell within the tangential fields. Results: Between April 1999 and May 2001, 36 women with invasive breast cancer treated by lumpectomy, sentinel lymph node biopsy and breast radiation were identified. Median age was 56 years (range 34 to 80) with a median tumor size of 1.1 cm (range 0.3 to 2.9 cm). The clip marking the sentinel lymph node fell within the tangential fields in 34 of 36 (94%) of the patients. The radiation dose to the clip area was greater than 4,400 cGy in 50% of those calculated by three-dimensional techniques. Conclusions: The sentinel lymph node is located within classic tangential fields in the overwhelming majority of women with invasive breast cancer. The extent of the radiation fields, and ultimately the final dose, may need to be modified if the intent is for prophylactic treatment.

Chronic idiopathic intestinal pseudoobstruction is a diagnosis of exclusion for the rare patient with severe small bowel atony without any demonstrable organic cause. The very poor prognosis associated with this disease has been somewhat improved with the advent of parenteral nutrition; nevertheless, these patients follow a stormy course characterized by malnutrition, recurrent obstruction, infection, hemorrhage, and perforation. We describe a 16-year-old boy with this disease who presented to us with vague abdominal pain and pneumoperitoneum. Laparotomy showed pneumatosis cystoides intestinalis without intestinal perforation. The presence of free air in the abdominal cavity is an almost pathognomonic sign of intestinal perforation. Pneumatosis cystoides intestinalis is one of the very few nonsurgical causes of pneumoperitoneum. Beyond the neonatal period, in which it is the hallmark of necrotizing enterocolitis, it has been described in patients with severe obstructive lung disease, in collagenous disorders, and in the short-bowel syndrome. In the present case, it may have resulted from chronic intestinal distension, allowing air under pressure to dissect through the bowel wall. The challenge of such a unique association of conditions lies in the avoidance of unnecessary surgery in a chronic, essentially nonsurgical disease while avoiding unnecessary delay in a possibly acute surgical event.