Does neoadjuvant bevacizumab increase surgical complications in breast surgery?

BACKGROUND: Neoadjuvant chemotherapy is being increasingly used in operable breast cancer. There are limited data on the safety of bevacizumab (bev) in the neoadjuvant setting. We sought to explore the safety of neoadjuvant cisplatin/bev in a protocol for triple negative breast cancer (TNBC). MATERIALS AND METHODS: A total of 51 patients with confirmed TNBC were enrolled in a single-arm trial of neoadjuvant cisplatin plus bev. Of the 51 patients, 28 with confirmed TNBC were enrolled in our trial of single-agent neoadjuvant cisplatin. Two-sided Fisher exact test were used for comparing the 2 trials. RESULTS: The 51 patients received neoadjuvant protocol therapy with cisplatin/bev and underwent definitive local therapy. Breast conserving therapy (BCT) was performed in 29 (57%) and mastectomy with or without reconstruction in 22 (43%). Postoperative complications were reported in 22 patients (43%); 4 (8%) required explanation of expanders. Also, 28 patients completed neoadjuvant cisplatin therapy. BCT was performed in 13 (46%) and mastectomy with or without reconstruction in 15 (54%). Postoperative complications were reported in 11 patients (39%). None of the 5 reconstructions were lost. We compared all toxicities between the two trials (P = .81 NS), and wound healing related complications between the two trials (P = .10 NS). CONCLUSIONS: Cisplatin/bevacizumab and cisplatin alone neoadjuvant therapy resulted in a significant number of postoperative complications. Specifically, use of expanders/implants may be problematic for patients treated with bev. However, this was a single-arm trial; randomized controlled studies will be needed to determine the optimal use of bevacizumab in the timing of breast cancer surgery.

Development and implementation of a science training course for breast cancer activists: Project LEAD (leadership, education and advocacy development).

OBJECTIVE: To develop and implement Project LEAD (leadership, education, and advocacy development), a science course for breast cancer activists. POPULATION: Students were breast cancer activists and other consumers, mainly affiliated with advocacy organizations in the United States of America. SETTING: Project LEAD is offered by the National Breast Cancer Coalition; the course takes place over 5 days and is offered 4 times a year, in various cities in the United States of America. RESULTS: The Project LEAD curriculum has developed over 5 years to include lectures, problem-based study groups, case studies, interactive critical appraisal sessions, a seminar by an 'expert' scientist, role play, and homework components. A core faculty has been valuable for evaluating and revising the course and has proved necessary to provide consistent high quality teaching. Course evaluations indicated that students gained critical appraisal skills, enhanced their knowledge and developed confidence in selected areas of basic science and epidemiology. CONCLUSIONS: Project LEAD comprises a unique curriculum for training breast cancer activists in science and critical appraisal. Course evaluations indicate that students gain confidence and skills from the course.

Ductal lavage for detection of cellular atypia in women at high risk for breast cancer.

BACKGROUND: Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes. Women with atypical breast ductal epithelial cells have an increased relative risk of breast cancer. In this study, ductal lavage, a new procedure for collecting ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells. METHODS: Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by lavage of fluid-yielding ducts. All statistical tests were two-sided. RESULTS: The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7% or more. Nipple aspirate fluid (NAF) samples were evaluated cytologically for 417 women, and ductal lavage samples were evaluated for 383 women. Adequate samples for diagnosis were collected from 111 (27%) and 299 (78%) women, respectively. A median of 13,500 epithelial cells per duct (range, 43-492,000 cells) was collected by ductal lavage compared with a median of 120 epithelial cells per breast (range, 10-74,300) collected by nipple aspiration. For ductal lavage, 92 (24%) subjects had abnormal cells that were mildly (17%) or markedly (6%) atypical or malignant (<1%). For NAF, corresponding percentages were 6%, 3%, and fewer than 1%. Ductal lavage detected abnormal intraductal breast cells 3.2 times more often than nipple aspiration (79 versus 25 breasts; McNemar's test, P<.001). No serious procedure-related adverse events were reported. CONCLUSIONS: Large numbers of ductal cells can be collected by ductal lavage to detect atypical cellular changes within the breast. Ductal lavage is a safe and well-tolerated procedure and is a more sensitive method of detecting cellular atypia than nipple aspiration.

A critical pathway for electronic medical record selection.

Electronic medical records (EMRs) are increasingly becoming a necessary tool in health care. Given their potential to influence every aspect of health care, there has been surprisingly little rigorous research applied to this important piece of emerging health technology. An initial phase of the COMPETE study, which is examining the impact of EMRs on efficiency, quality of care and privacy concerns, involved a rigorous "critical pathway" approach to EMR selection for the study. A multidisciplinary team with clinical, technical and research expertise led an 8-stage evaluation process with direct input from user physicians at each stage. An iterative sequence of review of EMR specifications and features, live product demonstrations, site visits, and negotiations with vendors led to a progressive narrowing of the field of eligible EMR systems. Final scoring was based on 3 main themes of clinical usability, data quality and support/vendor issues. We believe that a rigorous, multidisciplinary process such as this is required to maximize success of any EMR implementation project.

Measuring the success of electronic medical record implementation using electronic and survey data.

Computerization of physician practices is increasing. Stakeholders are demanding demonstrated value for their Electronic Medical Record (EMR) implementations. We developed survey tools to measure medical office processes, including administrative and physician tasks pre- and post-EMR implementation. We included variables that were expected to improve with EMR implementation and those that were not expected to improve, as controls. We measured the same processes pre-EMR, at six months and 18 months post-EMR. Time required for most administrative tasks decreased within six months of EMR implementation. Staff time spent on charting increased with time, in keeping with our anecdotal observations that nurses were given more responsibility for charting in many offices. Physician time to chart increased initially by 50%, but went down to original levels by 18 months. However, this may be due to the drop-out of those physicians who had a difficult time charting electronically.

Patient preferences for axillary dissection in the management of early-stage breast cancer.

BACKGROUND: Recent data on the value of adjuvant therapy in lymph node-negative breast cancer and promising early data on less invasive strategies for managing the axilla have raised questions about the appropriate role of axillary lymph node dissection (ALND) in the management of early-stage breast cancer. We sought to evaluate how women weigh potential benefits of ALND-prognostic information, enhanced local control, and tailored therapy-against the risks of long-term morbidity that are associated with the procedure. METHODS: We used hypothetical scenarios to survey 82 randomly selected women with invasive breast cancer who had been treated with ALND and 62 women at risk for invasive breast cancer by virtue of a history of ductal carcinoma in situ (DCIS) who had not undergone ALND. RESULTS: Women in both the invasive cancer and the DCIS groups required substantial improvements in local control of the cancer (5% and 15%, respectively) and overall survival (3% and 10%, respectively) before they would opt for this procedure. Women with invasive cancer would choose ALND if it had only a 1% chance of altering treatment recommendations, whereas DCIS subjects required a 25% chance. Sixty-eight percent and 29% of women in the invasive cancer and DCIS groups, respectively, would accepted a 40% risk of arm dysfunction to gain prognostic information that would not change treatment. CONCLUSIONS: For most subjects treated previously for invasive breast cancer and almost half those at risk of the disease, the potential benefits of ALND, particularly the value of prognostic information, were sufficient to outweigh the risks of morbidity. However, women varied considerably in their preferences, highlighting the need to tailor decisions regarding management of the axilla to individual patients' values.

The care of older women with early-stage breast cancer: what is the role of surgeon gender?

BACKGROUND: Over the past decade and a half, a substantial literature has documented age-dependent variations in breast cancer care. Accumulating evidence suggests that these variations impact the health outcomes of older women with breast cancer. Surgeon gender may be an important source of age-dependent variations in care. OBJECTIVE: To examine the relationship between surgeon gender and primary tumor therapy and systemic adjuvant therapy among 303 older women with early-stage breast cancer cared for by 20 surgeons in Boston, Massachusetts. METHODS: The research design was a cross-sectional observational study. The subjects were women at least 55 years of age with newly diagnosed Stage I or II breast cancer. The main outcome measure was definitive primary tumor therapy and systemic adjuvant therapy. RESULTS: After adjustment for patient and tumor characteristics, patients of female surgeons were more likely to receive definitive treatment, with the strongest effect being observed for the receipt of both definitive primary tumor therapy and systemic adjuvant therapy (odds ratio 4.5; 95% confidence interval 2.7, 7.7). CONCLUSIONS: Women with early-stage breast cancer cared for by female surgeons are more likely to receive standard therapies. Surgeons provide the initial care, both diagnostic and therapeutic, for all women with breast cancer. Their role in breast cancer care is pivotal and has a substantial impact on the nature of breast cancer care received.

Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer.

Skin-sparing mastectomy has been advocated as an oncologically safe approach for the management of patients with early-stage breast cancer that minimizes deformity and improves cosmesis through preservation of the skin envelope of the breast. Because chest wall skin is the most frequent site of local failure after mastectomy, concerns have been raised that inadequate skin excision could result in an increased risk of local recurrence. Precise borders of the skin resection have not been well established, and long-term local recurrence rates after skin-sparing mastectomy are not known. The purpose of this study was to evaluate the oncologic safety and aesthetic results for skin-sparing mastectomy and immediate breast reconstruction with a latissimus dorsi myocutaneous flap and saline breast prosthesis. Fifty-one patients with early-stage breast cancer (26 with ductal carcinoma in situ and 25 with invasive carcinoma) undergoing primary mastectomy and immediate reconstruction with a latissimus flap were studied from 1991 through 1994. For 32 consecutive patients, skin-sparing mastectomy was defined as a 5-mm margin of skin designed around the border of the nipple-areolar complex. After the mastectomy, biopsies were obtained from the remaining native skin flap edges. Patients were followed for 44.8 months. Histologic examination of 114 native skin flap biopsy specimens failed to demonstrate breast ducts in the dermis of any of the 32 consecutive patients studied. One of 26 patients with ductal carcinoma in situ had metastases to the skin of the lateral chest wall and back. Four other patients, one with stage I disease and three with stage II-B disease, had recurrent breast carcinoma. The stage I patient had a local recurrence in the subcutaneous tissues near the mastectomy specimen. Two patients suffered axillary relapse, and one had distant metastases to the spine. The findings of this study support the technique of skin-sparing mastectomy as an oncologically safe one, based on an absence of breast ductal epithelium at the margins of the native skin flaps and a local recurrence rate of 2 percent after 45 months of follow-up. Although these results need to be confirmed with greater numbers of patients and longer follow-up, skin-sparing mastectomy and immediate breast reconstruction may be considered an excellent alternative treatment to breast conservation for patients with ductal carcinoma in situ and early-stage invasive breast cancer.

Moving towards an electronic patient record: a survey to assess the needs of community family physicians.

OBJECTIVE: To determine the needs of community family physicians regarding electronic patient records (EPRs). DESIGN: A comprehensive survey was sent to 101 community family physicians in Hamilton, Ontario, who had expressed an interest in EPRs. RESULTS: 46 physicians responded (46%). 87% felt that an EPR would result in their providing better patient care. A wide variety of items were deemed to be important to be included on the EPR "front page". Desired functionality emphasized labs, medications, consultation, hospital follow-up and health maintenance. Family physicians tended to prefer templates to other data entry methods such as typing and dictating. Respondents were more willing to view information from the hospital than to let the hospital view information from their own offices. CONCLUSION: This survey provided useful information on the perceived EPR needs of community-based family physicians. It will be repeated post-computerization.

Treatment outcome after tangential radiation therapy without axillary dissection in patients with early-stage breast cancer and clinically negative axillary nodes.

PURPOSE: To determine the risk of nodal failure in patients with early-stage invasive breast cancer with clinically negative axillary lymph nodes treated with two-field tangential breast irradiation alone, without axillary lymph node dissection or use of a third nodal field. METHODS AND MATERIALS: Between 1988 and 1993, 986 evaluable women with clinical Stage I or II invasive breast cancer were treated with breast-conserving surgery and radiation therapy. Of these, 92 patients with clinically negative nodes received tangential breast irradiation (median dose, 45 Gy) followed by a boost, without axillary dissection. The median age was 69 years (range, 49-87). Eighty-three percent had T1 tumors. Fifty-three patients received tamoxifen, 1 received chemotherapy, and 2 patients received both. Median follow-up time for the 79 survivors was 50 months (range, 15-96). Three patients (3%) have been lost to follow-up after 20-32 months. RESULTS: No isolated regional nodal failures were identified. Two patients developed recurrence in the breast only (one of whom had a single positive axillary node found pathologically after mastectomy). One patient developed simultaneous local and distant failures, and six patients developed distant failures only. One patient developed a contralateral ductal carcinoma in situ, and two patients developed other cancers. CONCLUSION: Among a group of 92 patients with early-stage breast cancer (typically T1 and also typically elderly) treated with tangential breast irradiation alone without axillary dissection, with or without systemic therapy, there were no isolated axillary or supraclavicular regional failures. These results suggest that it is feasible to treat selected clinically node-negative patients with tangential fields alone. Prospective studies of this approach are warranted.

The impact of age, marital status, and physician-patient interactions on the care of older women with breast carcinoma.

Understanding why older women with breast carcinoma do not receive definitive treatment is critical if disparities in mortality between younger and older women are to be reduced. With this in mind, the authors studied 302 women age > or =55 years with early stage breast carcinoma. Data were collected from surgical records and in telephone interviews with the women. The main outcome was receipt of definitive primary tumor therapy, defined either as modified radical mastectomy or as breast-conserving surgery with axillary dissection followed by radiation therapy. The majority (56%) of the women underwent breast-conserving surgery and axillary dissection followed by radiation therapy. After statistical control for four variables (comorbidity, physical function, tumor size, and lymph node status), patients' ages, marital status, and the number of times breast carcinoma specialists discussed treatment options were significantly associated with the receipt of definitive primary tumor therapy. The authors concluded that when older women have been newly diagnosed with breast carcinoma and there is clinical uncertainty as to the most appropriate therapies, patients may be better served if they are offered choices from among definitive therapies. In discussing therapies with them, physicians must be sensitive to their fears and concerns about the monetary costs and functional consequences of treatment in relation to the expected benefits.

Outcome assessment for clinical trials: how many adjudicators do we need? Canadian Lung Oncology Group.

Considerable effort is often expended to adjudicate outcomes in clinical trials, but little has been written on the administration of the adjudication process and its possible impact on study results. As a case study, we describe the function and performance of an adjudication committee in a large randomized trial of two diagnostic approaches to potentially operable lung cancer. Up to five independent adjudicators independently determined two primary outcomes: tumor status at death or at final follow-up and the cause of death. Patients for whom there was any disagreement were discussed in committee until a consensus was achieved. We describe the pattern of agreement among the adjudicators and with the final consensus result. Additionally, we model the adjudication process and predict the results if a smaller committee had been used. We found that reducing the number of adjudicators from five to two or three would probably have changed the consensus outcome in less than 10% of cases. Correspondingly, the effect on the final study results (comparing primary outcomes in both randomized arms) would have been altered very little. Even using a single adjudicator would not have affected the results substantially. About 90 minutes of person-time per patient was required for activities directly related to the adjudication process, or approximately 6 months of full time work for the entire study. This level of effort could be substantially reduced by using fewer adjudicators with little impact on the results. Thus, we suggest that when high observer agreement is demonstrated or anticipated, adjudication committees should consist of no more than three members. Further work is needed to evaluate if smaller committees are adequate to detect small but important treatment effects or if they compromise validity when the level of adjudicator agreement is lower.

Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy.

BACKGROUND: The relationship between the microscopic margins of resection and ipsilateral breast recurrence (IBR) after breast-conserving therapy for carcinomas with or without an extensive intraductal component (EIC) has not been adequately defined. METHODS: Of 1,790 women with unilateral clinical Stage I or II breast carcinoma treated with radiation therapy as part of breast-conserving therapy, 343 had invasive ductal histology evaluable for an extensive intraductal component (EIC), had inked margins that were evaluable for an review of their pathology slides, and received > or = 60 Gray to the tumor bed; these 343 women constitute the study population. The median follow-up was 109 months. All available slides were reviewed by one of the study pathologists. Final inked margins of excision were classified as negative > 1 mm (no invasive or in situ ductal carcinoma within 1 mm of the inked margin); negative-1 mm, or close carcinoma < or = 1 mm from the inked margin but not at the margin); or positive (carcinoma at the inked margin). A focally positive margin was defined as invasive or in situ ductal carcinoma at the margin in three or fewer low-power fields. The first site of recurrent disease was classified as either ipsilateral breast recurrence (IBR) or distant metastasis/regional lymph node failure. RESULTS: Crude rates for the first site of recurrence were calculated first for all 340 patients evaluable at 5 years, then separately for the 272 patients with EIC-negative cancers and the 68 patients with EIC-positive cancers. The 5-year rate of IBR for all patients with negative margins was 2%; and for all patients with positive margins, the rate was 16%. Among patients with negative margins, the 5-year rate of IBR was 2% for all patients with close margins (negative < or = 1 mm) and 3% for those with negative > 1 mm margins. For patients with close margins, the rates were 2% and 0% for EIC-negative and EIC-positive tumors, respectively; the corresponding rates for patients with negative margins > 1 mm were 1% and 14%. The 5-year rate of IBR for patients with focally positive margins was 9% (9% for EIC-negative and 7% for EIC-positive patients). The 5-year crude rate of IBR for patients with greater than focally positive margins was 28% (19% for EIC-negative and 42% for EIC-positive patients). CONCLUSIONS: Patients with negative margins of excision have a low rate of recurrence in the treated breast, whether the margin is > 1 mm or < or = 1 mm and whether the carcinoma is EIC-negative or EIC-positive. Among patients with positive margins, those with focally positive margins have a considerably lower risk of local recurrence than those with more than focally positive margins, and could be considered for breast-conserving therapy.

Options in the local management of invasive breast cancer.

Newly diagnosed, early-stage breast cancer confronts the patient and her clinician with multiple treatment decisions. This review examines some of these local treatment options including the choice between breast-conserving treatment (BCT) and mastectomy, how best to treat the axilla, and the optimal sequencing of local and systemic therapy. Key elements in the selection of patients for BCT or mastectomy include preoperative mammography, careful pathological evaluation, and an assessment of patient desires in order to balance the risk of local recurrence against preservation of a cosmetically acceptable breast. Although some absolute contraindications to BCT exist, most patients are candidates for BCT. The role of axillary dissection is currently being redefined, and in the future, more limited procedures may be able to identify patients who can avoid axillary dissection. The relationship between timing of breast surgery with regard to the menstrual cycle and outcome is intriguing but not yet established. As well, the appropriate sequencing of chemotherapy and radiotherapy (RT) after conservative surgery (CS) is uncertain, although randomized trials are beginning to shed some light on this issue. Whether all patients treated with CS require treatment with RT is another question that is currently under investigation. This article addresses these issues, focusing on the specifics of treatment implementation.

Interobserver variation in the computed tomographic evaluation of mediastinal lymph node size in patients with potentially resectable lung cancer. Canadian Lung Oncology Group.

OBJECTIVE: To measure the reliability of the assessment of mediastinal lymph node size in computed tomographic (CT) scans of the thorax. DESIGN: Observer agreement study in which radiologists, blinded to one anothers' interpretation, were randomized to read 30 scans each. POPULATION: Sixty scans from patients with apparently operable non-small cell carcinoma of the lung were read by radiologists responsible for clinical interpretation (clinical radiologists) and four radiologists with a special interest in thoracic CT (study radiologists). MEASUREMENTS: Radiologists measured the size of left and right superior mediastinal nodes, aortic nodes, and the subcarinal nodes and, on the basis of whether any nodes accessible to mediastinoscopy were greater than 1 cm, recommended whether mediastinoscopy be undertaken. Agreement was quantified using kappa, a measure of chance-corrected agreement. RESULTS: Among all radiologists, agreement on whether there were any nodes larger than 1 cm for right superior mediastinal nodes was 0.68; for left superior mediastinal nodes it was 0.28; for aortic pulmonary nodes it was 0.62; for subcarinal nodes it was 0.58; and for any node greater than 1 cm and accessible to mediastinoscopy it was 0.61. The agreement was very similar when the analysis was restricted to the study radiologists. CONCLUSION: Although the good level of overall agreement suggests that CT provides useful information in the evaluation of mediastinal lymph node size, the disagreement was sufficient that it likely contributes to suboptimal sensitivity and specificity of CT in detecting tumor spread reported in previous studies.