Invasive breast carcinoma remains the second leading cause of

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1 1231 The Impact of A Multidisciplinary Breast Cancer Center on Recommendations for Patient Management The University of Pennsylvania Experience John H. Chang, M.D. 1 Eugenio Vines, M.D. 1 Helaine Bertsch, M.D. 1 Douglas L. Fraker, M.D. 2 Brian J. Czerniecki, M.D., Ph.D. 2 Ernest F. Rosato, M.D. 2 Thomas Lawton, M.D. 3 Emily F. Conant, M.D. 4 Susan G. Orel, M.D. 4 Lynn Schuchter, M.D. 5 Kevin R. Fox, M.D. 5 Nancy Zieber, R.N. 5 John H. Glick, M.D. 5 Lawrence J. Solin, M.D. 1 1 Department of Radiation Oncology, University of Pennsylvania Cancer Center and School of Medicine, Philadelphia, Pennsylvania. 2 Department of Surgery, University of Pennsylvania Cancer Center and School of Medicine, Philadelphia, Pennsylvania. 3 Department of Pathology and Laboratory Medicine, University of Pennsylvania Cancer Center and School of Medicine, Philadelphia, Pennsylvania. 4 Department of Radiology, University of Pennsylvania Cancer Center and School of Medicine, Philadelphia, Pennsylvania. 5 Department of Medicine, University of Pennsylvania Cancer Center and School of Medicine, Philadelphia, Pennsylvania. Presented in part at the 41st Annual Meeting of the American Society for Therapeutic Radiology and Oncology, October 31 November 4, 1999, San Antonio, Texas. Address for reprints: Lawrence J. Solin, M.D., Department of Radiation Oncology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104; Fax: (215) ; solin@xrt.upenn.edu Received July 13, 2000; revision received December 6, 2000; accepted December 8, BACKGROUND. Advances in the diagnosis and of breast carcinoma have led to a multidisciplinary approach to management for patients with breast carcinoma. To assess the effect of this approach, the authors performed an evaluation for a cohort of patients examined in a multidisciplinary breast cancer center. METHODS. An analysis was performed for the records of 75 consecutive women with 77 breast lesions examined in consultation in a multidisciplinary breast cancer center between January and June Each patient s case was evaluated by a panel consisting of a medical oncologist, surgical oncologist, radiation oncologist, pathologist, diagnostic radiologist, and, when indicated, plastic surgeon. A comprehensive history and physical examination was performed, and the relevant mammograms, pathology slides, and medical records were reviewed. Treatment recommendations made before this evaluation were compared with the consensus recommendations made by the panel. RESULTS. For the 75 patients, the multidisciplinary panel disagreed with the recommendations from the outside physicians in 32 cases (43%), and agreed in 41 cases (55%). Two patients (3%) had no recommendation before consultation. For the 32 patients with a disagreement, the recommendations were breast-conservation instead of mastectomy (n 13; 41%) or reexcision (n 2; 6%); further workup instead of immediate definitive (n 10; 31%); based on major change in diagnosis on pathology review (n 3; 9%); addition of postmastectomy radiation (n 3; 9%); or addition of hormonal therapy (n 1; 3%). CONCLUSIONS. The multidisciplinary breast cancer evaluation program provided an integrated program in which individual patients were evaluated by a team of physicians and led to a change in recommendation for 43% (32 of 75) of the patients examined. This multidisciplinary program provided important second opinions for many patients with breast carcinoma. Cancer 2001;91: American Cancer Society. KEYWORDS: breast carcinoma, ductal carcinoma in situ, mastectomy, breastconservation, combined modality, referral and consultation. Invasive breast carcinoma remains the second leading cause of cancer-related mortality in the United States today. 1 Based on the 1997 United States mortality data, breast carcinoma was the leading cause of cancer-related death in women ages years. 1 In 2000, an estimated 182,800 new cases of breast carcinoma were diagnosed in American women, and the average lifetime risk of breast carcinoma has increased to 1 in 8 women. 1 Historically, surgery has represented the primary method for treating breast carcinomas. More recently, however, the diagnosis 2001 American Cancer Society

2 1232 CANCER April 1, 2001 / Volume 91 / Number 7 and of breast malignancies have escalated in their sophistication and complexity. With the advent of screening mammography, hormonal therapy, chemotherapy, and breast-conservation, medical and radiation oncologists now have major roles in curative. Therefore, the direction of breast carcinoma care has moved toward a multifaceted approach with the involvement of many disciplines of medicine, both diagnostic and therapeutic. The University of Pennsylvania Cancer Center offers a comprehensive multimodality program that renders diagnostic and consultation services for women with newly diagnosed breast carcinoma in one visit in one location. This evaluation process provides an optimal situation for patients with breast carcinoma seeking efficient and comprehensive care. The impact of this approach was assessed based on a review of the evaluations of patients examined consecutively over a 6-month period. MATERIALS AND METHODS In 1991, the University of Pennsylvania Cancer Center established the Breast Cancer Evaluation Center for the purpose of providing a comprehensive multispecialty program for patients with breast carcinoma. When each patient called to schedule an appointment, a secretary obtained relevant patient information and instructed the patient to send operative reports, radiology studies, pathology slides, and other pertinent information before her consultation. Just before the visit, an advanced practice nurse contacted the patient by telephone to perform an in-depth interview that included assessment of the patient s breast carcinoma information level, psychosocial history, and coping strategies. On the day of the visit, the advanced practice nurse performed a clinical evaluation, followed by a full history and physical examination by a physician. All cases subsequently were presented at a multidisciplinary conference attended by a surgical oncologist, a medical oncologist, a radiation oncologist, a radiologist, and a pathologist, along with a plastic surgeon, when indicated. All patient information, radiology films, and pathology findings were reviewed and discussed. The panel agreed on a consensus recommendation for optimal management and/or further workup. One or more physicians then discussed the panel s consensus management strategy with the patient. The consensus recommendation was based on the best collective judgment of the physician panel for each individual patient, and not based on published breast carcinoma guidelines or decision trees. For the purpose of this study, patient age, menopausal status, race, distance from the institution, and TABLE 1 Patient Characteristics at the Time of Multidisciplinary Breast Cancer Evaluation Center Consultation Characteristic Number Percentage Age (yrs) Menopausal status Premenopausal Perimenopausal 3 4 Postmenopausal Unknown 1 1 Race Caucasian African-American 8 11 Asian 3 4 Distance (miles) traveled for consultation stage of the tumor were recorded. Staging was performed according to American Joint Committee on Cancer criteria. 2 Radiographic and pathology results were scored. Outside recommendations received by the patient were recorded and compared with the Breast Cancer Evaluation Center panel s consensus recommendation. RESULTS The study population consisted of 75 consecutive women with 77 breast lesions (2 patients with bilateral disease) examined in consultation between January 1, 1998 and June 30, Demographic information is shown in Table 1. The median patient age was 49 years with a range of 26 to 82 years. The distance traveled for consultation varied greatly with a median of 24 miles and range of 1 to 880 miles. Most patients (83%; 62 of 75) who presented for multidisciplinary consultation were self-referred or referred from community hospitals not affiliated with the University of Pennsylvania Medical Center. The patients presented with a spectrum of breast diseases that included benign disease, in situ carcinoma, invasive carcinoma, and angiosarcoma. The patients presented with a predominance of noninvasive and early stage breast carcinoma (Table 2). One patient had a multicentric invasive lobular carcinoma.

3 Multidisciplinary Breast Cancer Center/Chang et al TABLE 2 AJCC Clinical Stage as Determined by the Outside Institution for 77 Breast Lesions Compared with the Clinical Stage Determined by the Breast Cancer Evaluation Center AJCC clinical stage Outside institution Breast Cancer Evaluation Center Number Percentage Number Percentage 0 LCIS DCIS I IIA IIB IIIA IIIB Other a No cancer AJCC: American Joint Committee on Cancer; LCIS: lobular carcinoma in situ; DCIS: ductal carcinoma in situ. a Includes one patient with angiosarcoma of the breast and another patient with an anaplastic spindle and giant cell carcinoma. A second patient had a 7.5-cm angiosarcoma, whereas a third patient had an anaplastic spindle and giant cell carcinoma. Two patients had bilateral disease consisting of ductal carcinoma in situ (DCIS) in one breast and invasive disease in the other breast. The results of the University of Pennsylvania Cancer Center pathology reviews were compared with the outside hospital diagnoses (Table 3). There was agreement in 74 (96%) of the 77 lesions. In the other three cases (4%), a major difference in interpretation was rendered by the pathology review compared with the outside hospital diagnosis. Changes in pathologic diagnosis led to major changes in options in all three patients. Two cases involved a diagnosis from the outside institution of lobular carcinoma in situ (LCIS) but were found on review to be atypical lobular hyperplasia in one case and invasive lobular carcinoma in the other case. The third case of difference in pathology was an outside diagnosis of DCIS with close margins found on review to have microinvasion with tumor at the inked margin of resection. Treatment recommendations made to the patients by the outside physicians were compared with the Breast Cancer Evaluation Center management recommendations (Fig. 1). In 32 patients (43%), the Breast Cancer Evaluation Center recommendations differed from the outside physicians, whereas in 41 patients (55%), the approach was unchanged. Two patients (3%) had presented with no prior recommendation. The differences in management recommendations varied greatly (Table 4). With an outside recommendation of mastectomy, 13 patients were found on evaluation to be acceptable candidates for breast-conservation (i.e., breast-conservation surgery plus radiation ). The opposite recommendation was not found; in cases of an outside recommendation of breast-conservation, the Breast Cancer Evaluation Center never offered mastectomy as being a more appropriate option. Further workup was indicated before rendering a final recommendation in 31% (10 of 32) of those patients with discordant management recommendations (Tables 4 and 5). With an outside recommendation of mastectomy alone as local therapy, three patients demonstrated the need for postmastectomy radiation due to a T3 tumor in two patients and matted axillary (N2) lymph node disease in the third patient. Another two patients had outside recommendations for reexcision of the primary site before definitive breast irradiation. However, upon evaluation, one patient had negative margins of resection, whereas the other patient had a close but clear (approximately 2 mm) margin for DCIS with negative margins for invasive disease. Thus, both patients were considered adequate candidates for breast-conservation without further resection of the primary tumor site. A change in the recommendation for systemic therapy was made for one patient, for whom the Breast Cancer Evaluation Center panel recommended hormonal therapy in addition to chemotherapy because of her positive hormone receptor status. The three patients with discordant pathology after an initial outside diagnosis of LCIS or DCIS (see above) had different recommendations when evaluated at the Breast Cancer Evaluation Center. The patient with invasive lobular carcinoma required further workup before the initiation of definitive therapy, whereas observation was recommended for the patient with only atypical lobular hyperplasia. For the patient who was found to have margins positive for microinvasive carcinoma, reexcision to attempt to obtain clear margins was recommended. DISCUSSION Mastectomy has been the traditional mainstay of localized breast carcinoma. More recently, however, accumulating evidence from large randomized trials has established the survival equivalence of breast-conservation compared with mastectomy for early stage breast carcinoma. 3 6 In June 1990, the National Institutes of Health (NIH) Consensus Development Conference recommended breastconservation for most women diagnosed with Stage I and II breast carcinoma. 7

4 1234 CANCER April 1, 2001 / Volume 91 / Number 7 TABLE 3 Comparison of Outside Pathologic Diagnoses with Breast Cancer Evaluation Center Pathology Review a Breast Cancer Evaluation Center diagnosis Outside diagnosis LCIS DCIS Invasive carcinoma Angiosarcoma No cancer LCIS 2 1 a 1 a DCIS 12 1 a Invasive carcinoma 57 Angiosarcoma 1 No cancer 2 LCIS: lobular carcinoma in situ; DCIS: ductal carcinoma in situ. a Major difference in interpretation on pathologic review in 3 (4%) of the 77 breast lesions. TABLE 4 Differences in Treatment Recommendations for the 32 Patients Who Had a Difference in Management Recommendations Outside hospital recommendation Breast Cancer Evaluation Center recommendation Number Percentage FIGURE 1. Concordance of recommendations by the multidisciplinary breast cancer center panel of physicians with the outside physicians. Notwithstanding the equivalence in survival demonstrated in randomized trials and the NIH recommendation, the rate of breast-conservation has increased only moderately. Lazovich et al. reported on the Surveillance, Epidemiology and End Results (SEER) registry data from the National Cancer Institute and determined the frequency of breast-conservation in nine areas of the United States. 8 The study period spanned the years from 1983 through The rate of breast-conservation for Stage I disease increased from 35% in the years before 1990 to 60% in For Stage II patients, the increase was from 19% to 39%. Large regional Mastectomy Immediate definitive Mastectomy and adjuvant chemotherapy Recommendation based on outside pathology Reexcision Chemotherapy Breast-conservation Breast-conservation Further workup Mastectomy, adjuvant chemotherapy, and postmastectomy radiation 3 9 Recommendation based 3 9 on change in pathology requiring change in management Breast conservation 2 6 Chemotherapy and 1 3 hormonal therapy Mastectomy 0 0 variations in the 1995 rates were noted: from 40% to 70% for Stage I and from 25% to 50% for Stage II disease. Factors predicting for an increased probability of receiving a modified radical mastectomy included increasing age, Stage II disease, residence outside the region s major urban center, decreasing education, and decreasing median income. Similarly, Riley et al. found that only 37% of women older than age 65 years who were candidates for breast-conservation actually received such. 9 Failure to inform patients of all options is one major reason why breast-conservation remains underutilized. The multidisciplinary approach, exemplified by the Breast Cancer Evaluation

5 Multidisciplinary Breast Cancer Center/Chang et al TABLE 5 Breast Cancer Evaluation Center Recommendations for the 10 Patients Who Presented with an Outside Recommendation for Definitive Treatment but Were Found to Require Further Radiologic Workup or Surgery Outside recommendation Breast-conservation Mastectomy Chemoprevention with tamoxifen MRI: magnetic resonance imaging. Breast Cancer Evaluation Center recommendation Breast MRI scan 3 Further radiologic workup for multicentric 2 or contralateral breast abnormalities Postoperative mammogram 1 Reexcision 1 Further radiologic workup for multicentric 2 or contralateral breast abnormalities Postoperative mammogram 1 Number Center, may allow patients to make better informed choices about their breast carcinoma care. Morrow et al. described their experience with 432 noninvasive and early stage breast carcinoma patients. 10 Ninetyseven patients (22.5%) had a contraindication to breast-conservation. Of the remaining patients eligible for breast-conservation, 271 (81%) women chose to pursue breast conservation. The authors attributed the high rate of breast-conservation to their policy of offering all patients a consultation with other breast carcinoma specialists (i.e., medical and radiation oncologists). Clauson et al. examined 231 patients with breast carcinoma who underwent a second surgical opinion, and the medical recommendation was found to be different for 20.3% of the patients. 11 Patient age, education, employment, income, or distance traveled did not correlate with where the patient underwent surgery. An interactive multidisciplinary approach to patient care has been advocated in many medical specialties. Several institutions have implemented the concept of a comprehensive multimodality program by providing diagnostic and consultation services in one visit in one location. The Breast Cancer Evaluation Center is an example of an integrated environment in which individual cases can be evaluated by a multidisciplinary team. The goal is provision of a service that gives every patient the full spectrum of management strategies, some of which may be overlooked by a single consultation or sequential consultations. In this review of the Breast Cancer Evaluation Center study population, lack of agreement between the initial outside recommendations and those made by the Breast Cancer Evaluation Center panel was found in 32 (43%) of the 75 patients (Fig. 1). Several of these patients otherwise would not have been aware that they were acceptable candidates for breast-conservation. Most of these patients required reexcisions for close or positive margins of resection. Among the reasons given for the outside recommendations for mastectomies, one patient had received mantle radiation for Hodgkin disease more than 16 years before her current diagnosis of breast carcinoma. Although recognizing that mastectomy is the standard management for previously irradiated patients, in this case, the panel presented breast-conservation as a potential alternative approach. In a report of the University of Pittsburgh experience, breast-conservation was performed in selected patients with a long interval from their lymphoma radiation. 12 After a median follow-up of 5 years, the side effects and cosmetic outcome appeared to be similar to other reported series of breast-conservation. A second patient also had an outside recommendation for mastectomy because of the initial size of her primary tumor (7 cm). She was treated with preoperative chemotherapy yielding a partial response with tumor regression down to 3 cm in greatest dimension. The Breast Cancer Evaluation Center recommendation was to offer this patient breast-conservation based on the National Surgical Adjuvant Breast and Bowel Project (NSABP) study B-18, which demonstrated equivalent survival in patients with primary operable breast carcinoma treated with preoperative chemotherapy compared with patients treated with postoperative chemotherapy. 13,14 In this NSABP study, more patients treated preoperatively than postoperatively underwent breast-conservation. 13,14 Postmastectomy radiation, as recommended on Breast Cancer Evaluation Center consultation, was not considered by the outside institutions for three patients in whom high risk factors were present (two patients with T3 tumors and one patient with matted lymph nodes in the axilla). The value of postmastectomy radiation to maximize local control has been well established for high risk patients, even before the time of consultation for the patients in this study. 15,16 Recent randomized trials also have demonstrated a small survival benefit with the addition of postmastectomy radiation The types of recommendations given by the Breast Cancer Evaluation Center for further evaluation are listed in Table 5. All patients requiring further workup by the Breast Cancer Evaluation Center panel had been given outside recommendations to proceed directly with definitive. Most patients re-

6 1236 CANCER April 1, 2001 / Volume 91 / Number 7 quired more radiographic studies, such as postoperative mammograms to rule out residual abnormalities or a breast magnetic resonance imaging to elucidate indeterminate findings on mammograms or ultrasound. Four patients required more extensive radiologic workup due to the discovery of multicentric or contralateral breast abnormalities on physical examination and/or radiographs. Comparison of the outside pathologic diagnoses with the Breast Cancer Evaluation Center pathology review demonstrated a major change in diagnosis for 3 (4%) of the 77 breast lesions. As discussed above, the Breast Cancer Evaluation Center recommended significant changes in management for these three patients based on the changes in pathologic diagnoses. The phenomenon of a change in pathologic diagnosis for a low percentage of cases undergoing second pathologic opinion has been reported previously. Rates of discordance between initial pathologic diagnosis and second pathologic diagnosis are reported as %. The current study has several limitations. First, no follow-up information was obtained to see whether the patients acted on the recommendations from the multidisciplinary consultation. Such follow-up information potentially could provide further evidence of the importance of multidisciplinary evaluation. Second, a cost analysis was not performed to determine whether this second opinion, multidisciplinary consultation was cost-effective. However, that 43% (32 of 75) of the patients had their management recommendations altered is strong evidence that this multidisciplinary approach was clinically important for many patients. Finally, the consensus recommendation from the multidisciplinary panel was based on the best collective judgment of the panel of physicians for each individual patient, and not based on published breast carcinoma guidelines or decision trees. As such published guidelines and decision trees become more widely available, the differences between physicians (or multidisciplinary panels of physicians) for management recommendations potentially could diminish. Breast carcinoma diagnosis and requires the coordinated services of multiple medical specialists. To have available the service and consultation from multiple specialties in one location at one time facilitates the discussion of management strategies and reduces the chance of oversight that may occur when only one medical discipline is involved. Even in the setting of sequential consultations, independent opinions are offered, often without a consensus. The current study demonstrates that there is an objective benefit to the patient from a multimodality breast carcinoma program. This benefit to the patient is delivered in the form of a recommendation by a multidisciplinary team and optimization of management strategies. In conclusion, the multidisciplinary approach is an important patient-centered strategy that provides patients with newly diagnosed breast carcinoma with evaluation and second opinion in one visit in one location. REFERENCES 1. Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, CA Cancer J Clin 2000;50: American Joint Committee on Cancer. AJCC cancer staging manual. 5th ed. Philadelphia: Lippincott-Raven, 1997: Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the of breast cancer. N Engl J Med 1995;333: Veronesi U, Salvadori B, Luini A, Greco M, Saccozzi R, del Vecchio M, et al. Breast conservation is a safe method in patients with small cancer of the breast. Long-term results of three randomised trials on 1,973 patients. 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