Impact of the International Breast Cancer Overview I. Craig Henderson, M.D., Adjunct Professor of Medicine, University of California, San Francisco, CA

Overviews of all randomized trials evaluating therapy for patients with operable breast cancer were conducted in 1985, 1990, 1995, and 2000. The last has not been published yet. These overviews or meta-analyses have demonstrated effects that could not be or, at the time of the overview, had not been demonstrated by any single study. The earliest overviews established that adjuvant tamoxifen could prolong survival in older women with receptor positive tumors and adjuvant chemotherapy in older women regardless of receptor status. This hastened the world wide acceptance of these treatments. More recent overviews have demonstrated that adjuvant radiotherapy will prolong survival, especially in women with a high risk of local recurrence, such as those with large tumors or a large number of axillary nodes. Prior to the 1st overview, ovarian ablation was considered a totally ineffective treatment in most areas of the world. That clearly has changed because of the demonstration of benefits from this therapy in the meta-analysis that were never seen in a single trial. This observation opened the door for a series of randomized trials that have recently been completed comparing ovarian ablation with chemotherapy in women who are still menstruating. In each case ovarian ablation was as good or better than adjuvant chemotherapy for those with receptor positive tumors. The year 2000 overview provided the most compelling evidence to date that improvement in local control, no matter how this is achieved, has an impact on survival. There are some places where the overviews may have effected practice inappropriate by oversimplifying important issues. These include the use of anthracycline-containing regimens compared to CMF and the combination of tamoxifen and chemotherapy compared to either treatment alone. In both of these overviews the regimens included in the analysis were very heterogeneous. The application of the summary result equally to each regimen included in the analysis may not be appropriate.

Recommendation for the use of tumor markers Daniel F. Hayes, M.D., Director, Breast Oncology Program, University of Michigan Comprehensive Cancer Center, Michigan

A tumor marker is any process or feature that can serve as a surrogate for the present or future behavior of a malignancy 1. For purposes of this presentation, “tumor marker” will be used to designate a circulating marker of tumor activity. In breast cancer, several assays for four tumor markers have been widely studied: Carcinoembyronic antigen (CEA), assays for MUC-1 (CA15-3 and CA27.29), tissue polyptide antigen, and circulating extracellular domain of HER22. These markers might be helpful for one of several uses: risk categorization of unaffected individuals (to improve screening or prevention), screening, differential diagnosis, prognosis (in the primary or adjvuvant setting), prediction of response to specific therapies (in the primary or metastatic setting), monitoring patients after primary and adjuvant therapy for recurrence, and monitoring patients with established metastases to follow clinical course. Of these, the latter is the principal utility. In the context of other clinical data, a rising marker may provide additional data that the patient is progressing and that a consideration of changing treatment is appropriate. One must be aware of the phenomonen of tumor marker spike, usually occurring in the first 4-6 weeks of therapy. Although the FDA has approved the assays for monitoring patients who are free of disease (no evidence of disease, “NED”), several Expert Guidelines Panels, including ASCOs, have not recommended that these markers be used in that setting 3.

Since HER2 seems to be associated with less benefit from hormone therapy in ER positive patients, circulating HER2 has been studied as a negative predictor of response to tamoxifen, megestrol acetate, and the aromatase inhibitors. Data are mixed, but are generally consistent with this hypothesis 4,5. However, an ER positive patient should NOT have hormone therapy withheld simply on the basis of an elevated circulating HER2.
Circulating tumor cells (identified immunologically or by RT-PCR) have been reported in patients with primary and adjuvant breast cancer 6,7. These exciting studies offer promise for future patient management, but they are currently very preliminary.

References

1. Hayes DF, Bast R, Desch CE, et al: A tumor marker utility grading system (TMUGS): a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 88:1456-66, 1996
2. Stearns V, Yamauchi H, Hayes DF: Circulating tumor markers in breast cancer: Accepted utilities and novel prospects. Breast Cancer Research and Treatment 52:239-259, 1998
3. Bast RC, Jr., Ravdin P, Hayes DF, et al: 2000 Update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the american society of clinical oncology. J Clin Oncol 19:1865-78., 2001
4. Yamauchi H, O’Neill A, Gelman R, et al: Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein. Journal of Clinical Oncology 15:2518-25, 1997
5. Leitzel K, Teramoto Y, Konrad K, et al: Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer. Journal of Clinical Oncology 13:1129-35, 1995
6. Walker TM, Hayes DF, Gross S, et al: Detection of HER-2/neu cell membrane receptor on circulating tumor cells in patients with advanced breast cancer. Proceedings of the American Association of Cancer Research 42:11a, 2001
7. Walker M, Doyle G, Allard JW, et al: Mointoring circulating epithelial cells in the peripheral lood of patients with advanced carcinoma of the breast: A pilot study. Proceedings of the American Society of Clinical Oncology 19:54b, 2001

Current trials of neoadjuvant endocrine therapy Anthony Howell, CRC Department of Medical Oncology, University of Manchester, Christie Hospital, Manchester, UK

Neoadjuvant systemic therapy was first introduced in the hope that it might have a significant therapeutic impact locally, regionally and systemically. In terms of local control it was hoped that neoadjuvant chemotherapy might shrink primary tumours thereby increasing the number of patients with operable tumours who could have breast conservation surgery or alternatively increasing the number of patients with inoperable tumours which would be coverted into an operable tumour. Secondly, in terms of the axilla it was hoped that neoadjuvant chemotherapy might downstaged axillary lymph nodes and thereby improve patients’ prognosis. As a result of this, and through a proposed direct effect on occult systemic metastases, it was hoped that neoadjuvant chemotherapy might improve overall survival.

To date neoadjuvant chemotherapy in primary breast cancer has had a more prominent position than neoadjuvant endocrine therapy. NSABP B18 reported that in terms of occult disease there was no survival benefit of neoadjuvant chemotherapy over standard adjuvant therapy. However neoadjuvant chemotherapy was a good in-vivo model of chemosensitivity and NSABP B18 did show that neoadjuvant chemotherapy induced a significant reduction of tumour volume thereby allowing more patients to have breast conserving surgery. This was achieved at the price of an increased local recurrence rate. Other disadvantages of neoadjuvant chemotherapy include alteration in the standard prognostic information obtained after chemotherapy, the side-effects of the chemotherapy which all patients receive and the fact that the chemotherapy cannot be continued during the pre and perioperative periods (the latter as a means of trying to try reduce distant seeding of tumour cells shed at surgery). In contrast neoadjuvant endocrine therapy for ER positive tumours has the advantages that it can be continued during the pre and perioperative periods and at the same time has less side-effects.

The anti-oestrogen, tamoxifen, can induce objective response in up to 75%- 80% of ER positive early breast cancers. In locally advanced primary tumours (ie >5 cms clinically) this figure is lower at around 50% which may have a significant bearing on how many patients achieve breast conserving surgery. The reason for this difference has not been fully elucidated. However with both types of tumour a major disadvantage of tamoxifen is that it usually takes 6 months to achieve objective responses. A number of recent studies have suggested that the third generation aromatase inhibitors (e.g. anastroozole, letrozole) provide a significant therapeutic advantage over tamoxifen in advanced breast cancer. One of the few, double-blind, double dummy, neoadjuvant endocrine therapy trials reported a significantly higher objective response rate to letrozole than tamoxifen (60% and 41%respectively) (p=0.004) and a higher breast conservation rate (48% and 36% respectively) (p= 0.036). Furthermore these results were achieved over a treatment period which lasted only four months. This is consistent with phase II data on both letrozole and anastrozole and raises the opportunity to establish a larger randomised trial now with survival as the primary end-point. The ability to give neoadjuvant endocrine therapy throughout the pre and perioperative period allows us to test whether the events surrounding surgery impact on patient prognosis and can or cannot be modified. At this time a preoperative trial of the pure anti-oestrogen Faslodex (PETE trial) and a neoadjuvant trial (IMPACT) involving the same three therapeutic arms as in the ATAC (ie anastrozole, tamoxifen or the combination) study are currently recruiting.

Most neoadjuvant endocrine therapy studies have investigated the biological parameters in the primary tumour which predict response to therapy. Oestrogen receptor is the most important predictive factor for therapeutic response. However a recent randomised study of letrozole versus tamoxifen suggested that erbB1 and erbB2 might explain the difference in response rate seen between the two agents used in that study. If these findings are confirmed in other studies it would provide solid data to base hypotheses about the different mechanisms of action of anti-oestrogens and aromatase inhibitors.

Few neoadjuvant studies have investigated by serial biospies the changes in tumour biology associated with endocrine agents. Most biological data of this kind comes from presurgical studies where the endocrine agent was only given for up to 3 weeks or from studies of primary medical therapy alone. From these studies it would appear that anti-oestrogens such as tamoxifen and other SERMs (selective estrogen receptor modulators) reduce ER and Ki67 expression in human breast cancer. The pure anti-oestrogen, Faslodex, has been reported to produce and even greater degree of reduction in ER expression than that seen with tamoxifen and other SERMs. The PgR data from the pre-surgical Faslodex study has suggested that Faslodex may have a novel effect on ER, and Faslodex in contra-distinction to tamoxifen and other SERMs may be devoid of agonistic activity. Furthermore, these studies have also made us re-assess whether anti-oestrogens do induce apoptosis in human breast cancer. Recent randomised, pre-surgical studies of a number of anti-oestrogens have failed to show a significant effect of different endocrine agents on apoptosis.

Data on biological changes at the time of acquired hormone resistance are much scarcer. Nevertheless it would appear that tumours do not undergo major phenotypic changes at acquired tamoxifen resistance (eg changing from ER positive to ER negative). It would appear that more subtle changes in the growth stimulatory pathways (which “cross-talk” with the ER pathway) are responsible for tumours developing acquired tamoxifen resistance. The clinical data that few tumours which are resistant to tamoxifen respond to other SERMs suggests that the molecular basis for resistance to tamoxifen and other SERMs is similar in human breast cancer.

However, a significant number of tumours which develop acquired tamoxifen resistance will respond to subsequent endocrine manouvres such as an aromatase inhibitor (eg anastrozole, letrozole) or the pure anti-oestrogen, Faslodex. Furthermore, in experimental systems inhibitors of some of these biological pathways (eg tyrosine kinase inhibitors such as Iressa) have been reported to be effective in treating tumours which have developed acquired tamoxifen resistance. These findings support the importance of cross-talk between ER and growth factor pathways. Future studies of acquired endocrine must be directed to elucidate these biological changes.

MRI in Determining Response to Pre-op Chemotherapy Steven E. Harms, MD, FACR, Professor of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, and, Medical Director, Aurora Imaging Technology, North Andover, MA

“Locally advanced cancer of the breast” refers to breast carcinomas with significant primary or nodal disease, but without documented metastases (International Union against Cancer (UICC) and American Joint Commission on Cancer Staging and End Results Reporting (AJC) stage - T3b-T4, N2 or N3, M0). These cancers have been shown to be poorly controlled by surgery alone. Patients with locally advanced disease may undergo combination chemotherapy prior to mastectomy (induction chemotherapy).(1-4) The NSABP recently performed a trial (B-21) that compared induction chemotherapy prior to breast conservation surgery to mastectomy.(5-7) The motive for administering induction chemotherapy in this proposal is to reduce the tumor burden so that breast conservation surgery is feasible. Unfortunately, chemotherapy often results in breast edema and softens the tumor, which confounds the estimation of response and extent of residual disease by clinical and mammographic methods.(5-7) An imaging examination, such as MR, that can accurately determine tumor bulk may have a role in determining the response to chemotherapy and extent of residual disease prior to breast conservation surgery. This MR examination could be used to adjust chemotherapeutic regimens if tumor response is unsatisfactory.(8-10)
The implementation of new treatment protocols for locally advanced breast cancer is currently limited by inaccurate evaluation of response to neoadjuvant chemotherapy. RODEO MRI was evaluated as a tool for determining tumor response and extent of residual disease after neoadjuvant chemotherapy. Forty breasts in 39 patients with Stage II, III, or IV breast carcinoma were evaluated prospectively by MRI, physical examination, and mammography prior to and following neoadjuvant chemotherapy. Assessment of response determined by the 3 methods was compared. In addition, detailed pathology correlation of residual disease was determined by serial sectioning of 31 mastectomy specimens from 30 patients. Nine patients had breast conservation, and were included in the response evaluation only. Estimates of tumor response were made by both surgical and medical oncologists. Independent interpretations of MRI studies without knowledge of clinical response were made by 3 radiologists. The surgical oncologists assessed complete response (CR), partial response (PR), and no response (NR) in 11, 22, and 7 cases respectively. The medical oncologists assessed CR, PR and NR in 12, 21, and 7 cases respectively. The surgical and medical oncologists clinical assessment of response agreed with the results of MRI in 52% and 55% of cases respectively and with one another in 75% (30 0f 40) of cases. Mammography correlated with MRI response in only 52% of cases. However, MRI accurately predicted the pathology determination of residual disease in 97% (30 of 31) cases. There was no disagreement in the assessments of residual disease or response among the 3 radiologists. RODEO breast MRI accurately estimated residual disease after induction chemotherapy and was found to better assess response to neoadjuvant chemotherapy than traditional methods of physical examination or mammography. The information obtained from this MRI technique may be used as an objective tool during clinical trials, and to better select patients for breast conservation after neoadjuvant chemotherapy for locally advanced disease. The objective of future research is to attempt the determination of chemotherapeutic response early in the course of therapy and to use MRI-guided localization to improve the accuracy of breast conservation surgery following induction chemotherapy.(11)

A major problem is the accurate estimation of response based upon the MRI data. These larger tumors do not typically reduce in size concentrically. Rather, islands of tumor are left amidst as sea of fibrosis and necrosis. We typically cannot make a series of measurements across the tumor volume using typical image measurement methods. The next major advance is the use of sophisticated computer algorithms to automatically analyze the MRI data to accurately determine the percent response on a voxel by voxel basis. The breast provides a challenge since the breast can change shape from one examination to the next. Add to that situation the changes in volume and water density related to the therapeutic change and there is real potential for error. New computer technology will allow the fusion of images by the evaluation of repeating patterns to allow direct comparison across images obtained at different times.

References

1. Bonadonna G. Conceptual and practical advances in the management of breast cancer. J Clin Oncol. 1989; 7, 10: 1380 1397.
2. Schwartz GF, Cantor RI, Biermann WA. Neoadjuvant chemotherapy before definitive treatment for state III carcinoma of the breast. Arch Surg 1987; 122:1430-1434.
3. Hortobagyi GN, Ames FC, Buzdar AU, Kau SW, McNeese MD, Paulus D, Hug V, et al. Management of state III primary breast cancer with primary chemotherapy, surgery, and radiation therapy. Cancer 1983; 51:2507-2516.
4. Lopez MJ, Andriole DP, Kraybill WG, Khojasteh A. Multimodal therapy in locally advanced breast carcinoma. Amer J of Surg 1990; 160:669-657.
5. Fisher B, Anderson S. Conservative surgery for the management of invasive and noninvasive carcinoma of the breast: NSABP Trials. World J of Surg 1994; 18:63-69.
6. Singletary SE, McNeese MD, Hortobagyi GN. Feasibility of breast conservation surgery after induction chemotherapy for locally advanced breast carcinoma. Cancer 1992;69:2849-2852.
7. Mauriac L, Durand M, Avril A, Dilhuydy J-M. Effects of primary chemotherapy in conservative treatment of breast cancer patients with operable tumors larger than 3 cm. A Onco 1991; 2: 347-354.
8. Gilles R, Guinebretiere JM, Toussaint C, Spielman M, Rietjens M, Petit JY, Contesso G, Maselot J, Vanel D. Locally advanced breast cancer: contrast-enhanced subtraction MR imaging of response to preoperative chemotherapy. Radiology 1994; 191:633-638.
9. Abraham DC, Jones RC, Jones SE, Cheek JH, Peters GN, Knox SM, Grant MD, Hampe DW, Savino DA, Harms SE. Evaluation of Neoadjuvant chemotherapeutic response in locally advanced breast cancer by magnetic resonance imaging. Cancer (in press)
10. Fields SI, Gomori JM, Peretz T, Livove A, Zajicek G, Degani H. Evaluation of therapeutic response with dynamic high-resolution MR imaging in patients with early breast cancer. Radiology 1994; 193(P):122.
11. Abraham DC, Jones RC, Jones SE, Cheek JH, Peters GN, Knox SM, Grant MD, Hampe DW, Savino DA, Harms SE. Evaluation of Neoadjuvant chemotherapeutic response in locally advanced breast cancer by magnetic resonance imaging. Cancer 1996;78(1):91-100.

US examination of nodal basins in locally advanced breast cancer treated with preoperative chemotherapy Bruno D. Fornage, M.D., The University of Texas M. D. Anderson Cancer Center, Houston, TX

At M. D. Anderson Cancer Center, sonography (US) is used routinely for the pretreatment staging of locally advanced breast cancer and the evaluation of the response of the primary tumor and the metastatic nodes to chemotherapy or hormonal therapy.

Pretherapeutic Staging
US is useful for measuring the size (volume) of a carcinoma-a major prognostic factor—although the accuracy of the measurement depends on the type of cancer (some cancers, e.g., invasive lobular carcinomas, are so poorly defined on sonograms that accurate measurements cannot be obtained). This measurement serves as a baseline measurement. The detection of additional foci of carcinoma-not always demonstrated by mammography, particularly in dense breasts-has a significant impact on the treatment plan if breast-conserving therapy is being considered should a locally advanced cancer undergo sufficient downstaging.

Little has been written on the use of US in evaluating the nodal basins in patients with breast cancer. For the past 10 years at M. D. Anderson Cancer Center, we have included the ipsilateral axilla and internal mammary chains in the US examination of the breast in patients who have or have had breast cancer. Suspicious US findings are usually confirmed by US-guided fine-needle aspiration.

At a time when efforts are being made to reduce unnecessary axillary node dissections, the US detection of a nonpalpable metastatic axillary lymph node (confirmed with US-guided fine-needle aspiration) has a significant impact on patient management. However, although lymph node metastases larger than 7-8 mm are accurately detected by US using state-of-the-art equipment, US, like other “non-functional” imaging modalities, cannot demonstrate metastases that are only a few millimeters in size.

The internal mammary chains represent the second pathway for lymphatic drainage of the breast. US examination of the parasternal region is a simple, fast, and effective method of detecting internal mammary lymphatic involvement. Normal internal mammary nodes are not visible. Any enlarged hypoechoic node along the internal mammary chains is suspicious for metastasis. Metastases to the internal mammary nodes are most frequently found in the first, second, and third anterior intercostal spaces. Demonstration of lymph node metastases in the internal mammary chains results in the disease being staged as stage IIIB, regardless of how small the primary tumor is.

Metastases to supraclavicular nodes are considered distant metastases. Therefore, the detection of such metastases makes the disease stage IV (as would the detection of a metastatic cervical or contralateral internal mammary node). The largest of the metastatic nodes (the index lesion) in each basin is measured in three dimensions and its volume calculated.

Evaluation of Response to Neoadjuvant Therapy and Re-staging
At the completion of preoperative therapy, the primary tumor and the largest metastatic node in each nodal basin are remeasured, and the measurements are compared with the baseline measurements. The percent changes in the volumes of the target lesions are calculated and given to the clinician.

On occasion, the primary tumor appears to break down into several pieces, and comparison with the baseline study becomes virtually impossible. It is also very important to keep in mind that in cases of tumors with both an invasive component and DCIS, US and mammography may show an impressive reduction in volume of the invasive tumor but may miss significant residual DCIS.

Tumors that shrink rapidly at the beginning of chemotherapy must be marked so that the surgeon can still remove the tumor bed should the tumor disappear completely. We use custom-made metallic markers that are implanted in the tumor under US guidance.

Metastatic nodes that respond to chemotherapy decrease in size and resume a normal appearance, reflected by the reappearance of central echogenic fat. It has been our observation that lymph nodes usually respond faster than do primary tumors.

References

* Edeiken BS, Fornage BD, Bedi DG, et al. US-guided implantation of metallic markers for permanent localization of the tumor bed in patients with breast cancer who undergo preoperative chemotherapy. Radiology 1999;213:895-900.
* Fornage BD, Toubas O, Morel M. Clinical, mammographic and sonographic determination of preoperative breast cancer size. Cancer 1987;60:765-771.
* Fornage BD, Samuels BI, Paulus DD, et al. The use of sonography in the evaluation of the response of locally advanced breast carcinoma to preoperative chemotherapy (abstract). J Ultrasound Med 1990;9:23.
* Forouhi P, Walsh JS, Anderson TJ, et al. Ultrasonography as a method of measuring breast tumour size and monitoring response to primary systemic treatment. Br J Surg 1994;81:223-225. * Kuerer HM, Newman L A, Fornage BD, et al. Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer. Ann Surg Oncol 1998;5:673-680.
* Scatarige JC, Hamper UM, Sheth S, et al. Parasternal sonography of the internal mammary vessels: technique, normal anatomy, and lymphadenopathy. Radiology 1989;172:453-457.
* Vlastos G, Fornage BD, Mirza NQ, et al. The correlation of axillary ultrasonography with histologic breast cancer downstaging after induction chemotherapy. Am J Surg 2000;179:446-452.

Pre-surgical Chemotherapy Richard Margolese, M.D., Herbert Black Professor of Surgical Oncology, McGill University, Montreal, Canada

One of the goals for pre-surgical adjuvant chemotherapy for breast cancer patients is the reduction of tumor size to favor conservative breast surgery. There is good biologic rational for this, but the clinical problems the surgeon encounters are quite different from those in traditional breast conserving surgery.

Evidence in favor of pre surgical chemotherapy is derived from experience with the primary treatment of locally advanced breast cancer where initial chemotherapy is extremely effective. Preliminary studies in head and neck tumors and sarcomas also indicate high responsiveness to presurgical therapy. Thus presurgical therapy offers advantages of reduction in size of tumor.

The patient population will include many with small or minimally palpable tumors and a substantial number of clinical complete responses will occur. Since clinical response may not assure pathological disappearance of tumor it is still necessary to perform local excision and problems in identifying the exact site of the original tumor can arise.

The National Surgical Breast Project has conducted workshops for its membership in addressing these issues and a summary of findings will be presented. These involve accurate mapping of the original site, use of preoperative needle localization for persisting microcalcifications, and specific skin markers or tattoos.

One special problem is the issue of control of margins. Tumors may not shrink in a uniform fashion similar to melting ice cubes and there is concern that downsizing the scope of the operation will not maintain the excellent local control rates now obtained in conservative breast surgery. This problem will be documented and techniques for management discussed. Correlations with original tumor size and extent of response may be useful guides to surgical technique.

Life after breast cancer: long-term effects of therapy Kathy D. Miller, M.D., Associate Professor of Medicine, Indiana University, Indianapolis, IN

Although adjuvant chemotherapy is generally well tolerated, there are some serious long-term toxicities. Cardiomyopathy is a known toxicity of anthracycline-based chemotherapy. Cardiac dysfunction correlates with the cumulative dose of doxorubicin and patient age; it is rare when the dose is limited to < 300 mg/m2 in patients under the age of 65. Treatment-related leukemia is a rare but devastating side effect of chemotherapy. Escalating the dose of cyclophosphamide clearly increases the risk of treatment-related leukemia. Premature ovarian failure is another important effect of adjuvant chemotherapy. Thirty-five percent of women under 40 years old who receive 6 cycles of CMF will suffer premature menopause compared with 90% of women over the age of 40. The incidence after four cycles of AC is 13% in women under 40 and 60% in women over 40 years old. Early menopause correlates with increases in cardiovascular disease and osteoporosis, risks that may ultimately be greater than the risk of breast cancer recurrence for many low risk women. Bothersome menopausal symptoms such as hot flashes, vaginal dryness and mood swings, while not life-threatening, certainly negatively impact quality of life. Another emerging concern is the increasing evidence for long-term cognitive deficits in women treated with chemotherapy for breast cancer.

Management of the Breast Cancer Patient at a Comprehensive Breast Care Center Rache Simmons, MD FACS, Department of Surgery, Strang Weill Cornell Breast Center, New York City, NY

The definition of a “multidisciplinary breast center”

What does the patient want or expect?

What physicians and other health professionals should be involved?

Surgical oncologist Medical oncologist Radiation oncologist Plastic surgeon Oncology nursing Physical therapy Psychology/psychiatry

Percentage of cancer versus benign patients

Referral Patterns

From which physicians are the patients referred- internists, gynecologist, radiologists, other surgeons?

Do patients self-refer?

What are patients instructed to do at the first visit or prior to first visit?

Insurance screening

Obtain films, pathology reports/slides

What is the first visit encounter?

Who initiates the visit - surgeon, medical oncologist, other? Does the patient see multiple physicians on the first visit? Patient educational tools

Follow up visits

How often, by whom? Notifications of overdue visits

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