Lori Jardines

The influence of young age on outcome in early stage breast cancer

PURPOSE To assess the impact of young age on outcome in women with early stage breast cancer undergoing conservative surgery and radiation. METHODS AND MATERIALS Between 1981 and 1991, 980 patients with Stage I and II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median follow-up was 4.6 years, with a range of 1 month to 11 years. The patients were divided into three groups, based on age at the time of diagnosis: (a) age < or = 35 years--64 patients, (b) age 36-50 years--363 patients, and (c) age > 50 years--553 patients. The comparability of the groups was assessed in terms of clinical factors (tumor size and race), histopathologic factors (histologic subtype, final resection margin, estrogen and progesterone receptor status, pathologic nodal status), and treatment related factors (reexcision, median total dose to the primary, region(s) treated with radiation, and the use of adjuvant systemic chemotherapy and/or tamoxifen). Outcome was evaluated for overall, relapse-free, and cause-specific survival and patterns of first failure (breast, regional nodes, and distant metastasis). RESULTS There were no significant differences among the three groups in terms of race, clinical tumor size, pathology of the primary tumor, pathologic nodal status, final margin of resection, progesterone receptor status, median total dose to the primary tumor, or the regions treated. However, younger women were significantly more likely to have estrogen receptor negative tumors, undergo reexcision, and receive adjuvant systemic chemotherapy without tamoxifen. Younger women were found to have a statistically significantly decreased 8-year actuarial relapse-free survival (53% vs. 67% vs. 74%, p = 0.009), cause-specific survival (73% vs. 84% vs. 90%, p = 0.02), freedom from distant metastasis (76% vs. 75% vs. 83%, p = 0.02), and a significantly increased risk of breast recurrence (24% vs. 14% vs. 12%, p = 0.001), and regional node recurrence (7% vs. 1% vs. 1%, p = 0.0002). The patients were further divided on the basis of their pathologic nodal status. There were no statistically significant differences among the three age groups for axillary node-positive patients for overall survival (75% vs. 80% vs. 74%), relapse-free survival (73% vs. 73% vs. 62%), cause-specific survival (76% vs. 85% vs. 80%), and freedom from distant metastasis (75% vs. 75% vs. 72%), or breast recurrence (0% vs. 9% vs. 6%). The findings were identical when the analysis was restricted to node-positive patients who received chemotherapy. However, for axillary node-negative women, young age was associated with a statistically significant decreased overall survival (71% vs. 83% vs. 92%), relapse-free survival (51% vs. 65% vs. 76%), cause-specific survival (71% vs. 86% vs. 93%), freedom from distant metastasis (77% vs. 76% vs. 88%), and a statistically significant increased risk of breast recurrence (40% vs. 16% vs. 13%), and regional node recurrence (3% vs. 1% vs. 0%). The risk of a breast recurrence in axillary node-negative young women was decreased by the addition of adjuvant systemic chemotherapy but not by the use of reexcision. CONCLUSIONS The present analysis demonstrates that young women with early stage breast cancer do significantly worse when compared to older women in terms of relapse-free survival, cause-specific survival, distant metastasis and breast and regional node recurrence. However, the adverse effect of young age on outcome appears to be limited to the node-negative patients. These findings suggest that node-negative early stage breast cancer in young women is a more aggressive disease, with an increased risk for all patterns of failure and a decreased survival.

neu(c-erbB-2/HER2) and the epidermal growth factor receptor (EGFR) in breast cancer.

One hundred and eighty thousand new cases of invasive breast cancer were diagnosed in 1992 within the United States. This disease affects approximately 1 out of 8 women in the US. Chemotherapy and/or hormonal therapy have shown some improved disease-free and/or overall survival rates. Unfortunately, this type of therapy is not directed specifically to the malignant cells, and systemic toxicities are observed. In order to develop site-specific treatment, the biology of the disease must be understood such that certain genes or their products which are involved in the pathogenesis of the disease can be targeted. Two structurally related tyrosine kinase growth factors, the epidermal growth factor receptor (EGFR) and c-erbB-2 (neu) have been identified in human breast cancer tissue and, in many instances, may function as oncogenes. The clinical data related to these two growth factor receptors as prognostic factors for the disease have been critically evaluated. Several problems with the critical studies were identified, and solutions were proposed to clarify the conflicting results reported in the studies which have attempted to examine whether c-erbB-2 (neu), in particular, is a prognostic indicator for breast cancer. In addition, data related to the structure of, ligands for and interaction between the proteins have been reviewed and presented with respect to their role in breast cancer development. A more thorough understanding of the genetic changes which contribute to the development of breast cancer will lead to more specific and less toxic treatment for this disease.

The development of an interactive game-based tool for learning surgical management algorithms via computer

BACKGROUND We have previously demonstrated the potential efficacy of a computer-assisted board game as a tool for medical education. The next logical step was to transfer the entire game on to the computer, thus increasing accessibility to students and allowing for a richer and more accurate simulation of patient scenarios. METHODS First, a general game model was developed using Microsoft Visual Basic. A breast module was then created using 3-D models, radiographs, and pathology and cytology images. The game was further improved by the addition of an animated facilitator, who directs the players via gestures and speech. Thirty-three students played the breast module in a variety of team configurations. After playing the game, the students completed surveys regarding its value as both an educational tool and as a form of entertainment. 10-question tests were also administered before and after playing the game, as a preliminary investigation into its impact on student learning. RESULTS After playing the game, mean test scores increased from 6.43 (SEM +/- 0.30) to 7.14 (SEM +/- 0.30; P = 0.006). The results of the five-question survey were extremely positive. Students generally agreed that the game concept has value in increasing general knowledge regarding the subject matter of breast disease and that the idea of following simultaneously the work-up of numerous patients with similar problems is a helpful way to learn a work-up algorithm. CONCLUSIONS Postgame surveys demonstrate the efficacy of our computer game model as a tool for surgical education. The game is an example of problem based learning because it provides students with an initial set of problems and requires them to collect information and reason on their own in order to solve the problems. Individual game modules can be developed to cover material from different diagnostic areas.

Factors associated with a positive reexcision after excisional biopsy for invasive breast cancer

BACKGROUND Breast-conserving therapy followed by adjuvant radiotherapy represents an alternative to mastectomy as a treatment for invasive breast cancer. When excisional biopsy has been performed outside the parent institution, reexcision is often performed, with tumor being identified in 32% to 62% of the subsequent specimens. We analyzed not only the factors associated with a positive reexcision but also those factors associated with final surgical margins that are positive for tumor. METHODS Between 1978 and 1991, 956 female patients with American Joint Committee on Cancer clinical stage I or II breast cancer were treated with breast-conserving therapy where a total of 420 patients underwent reexcision after an initial excisional biopsy. Several factors were analyzed to determine their association with a positive reexcision, the status of the final surgical margin, and the nature of the disease present within the reexcision specimen. RESULTS Factors that correlated with a positive reexcision in both univariate and multivariate analysis were clinical tumor size, method of detection, the pathologic status of the axillary lymph nodes, and the histologic appearance. Those factors associated with finding invasive disease at the time of reexcision were clinical tumor size, clinical presentation, and nodal status. The single factor associated with finding residual in situ disease at the time of reexcision was histologic appearance of the primary tumor. A final positive margin was associated with method of tumor detection, age of the patient, and the presence of axillary lymph node metastases. CONCLUSIONS The most significant factors associated with a positive reexcision are clinical tumor size, method of tumor detection, pathologic nodal status, and histologic appearance. Patients with larger tumors or those that are detected by physical examination, as well as invasive lobular carcinomas, may require a more generous initial resection to achieve negative surgical margins and avoid the likelihood of reexcision.

The role of mastectomy in patients with stage I-II breast cancer presenting with gross multifocal or multicentric disease or diffuse microcalcifications

PURPOSE Women with Stage I-II invasive breast cancer who present with gross multicentric disease or diffuse microcalcifications have a significant risk of breast recurrence when treated with conservative surgery and radiation. The purpose of this report is to present the results of mastectomy in this group of patients. METHODS AND MATERIALS Between 1982 and 1989, 88 patients with clinical Stage I-II breast cancer who presented with clinical and mammographic evidence of gross multicentric disease or diffuse microcalcifications underwent modified radical mastectomy. Median followup was 4 years for the 57 patients with gross multicentric disease and 5.6 years for 31 patients with diffuse microcalcifications. At the time of mastectomy, 42% of patients were found to have positive axillary nodes. Following mastectomy, 15 patients received post mastectomy radiation and 35 patients received adjuvant systemic chemotherapy. RESULTS When compared to a group of 1295 patients with unifocal, Stage I-II breast cancer, treated with conservative surgery and radiation during the same time period, patients with gross multicentric disease and diffuse microcalcifications had a significantly higher incidence of > or = 4 positive nodes, patients with gross multicentric disease had a lower incidence of positive resection margins following mastectomy and patients with diffuse microcalcifications were younger. The 5-year actuarial risk of an isolated local-regional recurrence was 8% for patients with gross multicentric disease or diffuse microcalcifications and 7% for patients with unifocal disease. Patients with gross multicentric disease or diffuse microcalcifications and > or = 4 positive axillary nodes who did not receive post mastectomy radiation had an increased risk for local regional recurrence. There were no significant differences in the 5-year actuarial overall or relapse-free survival (88% and 73% gross multicentric disease, 97% and 86% diffuse microcalcifications and 90% and 79% unifocal disease), freedom from distant metastasis (76% gross multicentric disease, 90% diffuse microcalcifications, 86% unifocal disease) or incidence of contralateral breast cancer (10% gross multicentric disease, 13% diffuse microcalcifications, 8% unifocal disease) among the three groups. CONCLUSION The present study demonstrates no increased risk of local-regional recurrence in patients with gross multicentric disease or diffuse microcalcifications undergoing mastectomy in contrast to the increased risk of breast recurrence in patients with gross multicentric disease undergoing conservative surgery and radiation. Indications for post mastectomy radiation include > or = 4 positive nodes or close or positive surgical margins. Despite a significantly higher incidence of > or = 4 positive nodes, patients with gross multicentric disease and diffuse microcalcifications have a 5-year actuarial overall and relapse-free survival comparable to a group of patients with unifocal disease treated with conservative surgery and radiation.

Acalculous cholecystitis in bone marrow transplant patients

Background. Acalculous cholecystitis (ACC) is an uncommon disorder of the biliary tract, accounting for approximately 6% of acute cholecystitis cases. In this study, cholecystitis was seen in 8 of 770 bone marrow transplant recipients, with ACC occurring in five (63%).

Nutritional Support of Patients with Cancer of the Gastrointestinal Tract

Malnutrition is extremely common in patients with malignant disease. Whereas the causes are multifactorial, the predominant factor is the imbalance between nutrient intake and host nutrient requirements. Furthermore, the evidence suggests that cachexia is related to abnormal changes in host intermediary metabolism induced by host-tumor interactions, and endogenous peptides such as TNF may be important mediators. The role of nutritional therapy in cancer patients remains to be defined. Clearly, patients with severe malnutrition benefit from nutritional intervention. However, the benefit of nutritional therapy in less severe cases of malnutrition as an adjuvant to oncologic therapy has yet to be established.

Conservative surgery and radiation for early-stage breast cancer

In selected patients with early-stage breast cancer, conservative surgery and radiation represent an alternative equal to mastectomy in terms of local recurrence, distant metastasis, survival, and long-term complications. Patients with early-stage breast cancer who are candidates for conservative surgery and radiation include those whose primary tumor is less than 4 to 5 cm in size without evidence of gross multicentricity or diffuse microcalcifications. Patients with an extensive intraductal component may be appropriate candidates provided that margins of resection are negative. Young age is not a contraindication to the conservative treatment. A preexisting history of collagen vascular disease or prior mantle irradiation for Hodgkins or non-Hodgkins lymphoma represents a contraindication to conservative surgery and radiation because of the potential for severe complications. An additional contraindication is the pregnant woman in whom delivery cannot be accomplished before the initiation of radiation. Mammography is essential in the pretreatment evaluation and posttreatment follow-up of the conservatively treated patient. The goal of the pretreatment mammogram is to assess the extent of disease in the ipsilateral breast as well as to evaluate the contralateral breast. In patients who present with microcalcifications, a postbiopsy mammogram before radiation is essential to document complete removal of all malignant-appearing microcalcifications. Mammography is an essential part of the follow-up program in order to detect a recurrence in the treated breast as well as a cancer in the contralateral breast cancer. The optimal interval for follow-up mammography has not been determined, although programs employing mammography on a yearly basis after treatment have been associated with the detection of early recurrences and excellent survival after salvage mastectomy for these recurrences.