November 29, 2007
Malignant Phyllodes Tumors: A Review of 752 Cases
By Grabowski, Julia Salzstein, Sidney L; Sadler, Georgia R; Blair, Sarah L
Malignant phyllodes tumor (MPT) is a rare breast malignancy. Because of the scarcity of the disease, there are no evidence-based treatment or follow-up guidelines established. This study evaluated the survival of MPT patients to create recommendations for management. We identified 752 cases of malignant phyllodes tumors in the California Cancer Registry from the years 1988 to 2003. Relative survival was determined using Berkson-Gage life table analysis which was then compared with the relative survival of nonphyllodes breast cancer patients. For MPT patients, the relative annual survival at 1 year was 94 per cent and at 10 years was 99.6 per cent. Thus, after 10 years, these patients are no more likely to die than the general population. At 10 years, the relative cumulative survival of the MPT patients was 87.4 per cent, whereas the nonphyllodes breast cancer patients had only a 57.2 per cent relative cumulative survival. MPT patients with localized disease had a higher 10-year relative cumulative survival than those with regional disease (90.9% vs 61.5%, PMalignant phyllodes tumors are very uncommon, especially when compared with invasive ductal breast carcinoma. There is abundant literature regarding the more common types of breast cancer, whereas the literature related to phyllodes tumors is scarce, and the bulk of studies have included both the malignant and benign form of the disease with a relatively small number of patients. Clinicians have much more experience with ductal carcinoma than with phyllodes tumors, and, consequently, in the absence of evidencebased guidelines to the contrary, they tend to manage them in a similar manner. With this study, the authors sought to delineate characteristics of malignant phyllodes tumors and the epidemiologic aspects of the dis ease using a large case series including all stages of malignant phyllodes tumors. The authors also analyzed the data to determine the prognosis of phyllodes tumor, particularly as it compares to nonphyllodes breast cancer, and to gain insights that can guide treatment regimens and follow-up practices.
The California Cancer Registry (CCR), a population-based database, was reviewed from the years 1988 to 2003. The database includes information relating to cancer type, patient demographics, stage of disease, treatment, and survival.
For this study, the malignant phyllodes data were analyzed with relation to patient age, disease stage, and relative survival. The Berkson-Gage life table analysis and life expectancy data from the National Vital Statistics Report from 20024 were used to determine relative survival. The analysis included the survival of the patients over each individual year (relative annual survival) and their survival over the entire time period (relative cumulative survival). Relative survival rates compare the mortality of a cohort of patients to a general population unaffected by the disease process in question.5 Nominal data were examined using chi^sup 2^ analysis. The CCR does not contain detailed or complete information with respect to treatment modality for all years and, therefore, it was not included in the study. Median follow-up was 5 years. As a comparison, we examined the CCR data of patients with nonphyllodes breast cancer over the same time period to evaluate and relate certain specific aspects of demographics and survival.
There were 752 patients with malignant phyllodes tumors identified between the years 1988 and 2003. All were female with a median age of 50 years at the time of presentation (range 13-103 years). Patients with nonphyllodes breast tumors (n = 314,267) were diagnosed when they were, on average, 12 years older (median age of 62 years; range 11-108 years).
The majority (80%) of malignant phyllodes tumors presented as localized disease. Regional disease, with lymph node involvement or direct extension into adjacent tissues, was present in 8.2 per cent of patients, whereas distant disease accounted for only 1.5 per cent of cases. In a similar manner, the majority of cases of nonphyllodes breast cancers presented with localized tumors (61.5%), however a significantly higher percentage of these tumors were diagnosed as regional and metastatic disease (30.7% and 4.2% respectively, P
After one year, there was an overall 94 per cent relative survival rate in patients with malignant phyllodes tumors. After 10 years, the numbers are similar with a relative annual survival of 99.6 per cent and relative cumulative survival of 87.4 per cent (see Fig. 1). Though relative survival at 1 year for patients with nonphyllodes breast cancer is similar (95%), their relative cumulative survival has a continuous downward trend and at 10 years is only 57.2 per cent (see Fig. 2).
Patients had significantly worse outcomes with regional disease as compared with localized disease. Those who presented with localized disease had a 90.9 per cent 10-year relative cumulative survival, whereas patients with regional disease had a 61.5 per cent 10year relative cumulative survival (P
Fig. 1. Relative survival rates of phyllodes tumors: annual and cumulative.
Fig. 2. Relative cumulative survival: phyllode vs all other breast cancer types.
Because malignant phyllodes tumors are rare breast tumors and little is known about their prognosis, there has not been a consensus on how to manage them. In contrast, there is abundant literature to support the evidence-based treatments advocated for other, more common, breast cancers. Though some aspects of the two tumors are quite similar, they are clearly two distinct diseases.
Phyllodes tumors affect patients of all age groups with a median age of 10 years younger than those diagnosed with all other breast cancers. Patients with nonphyllodes breast cancers present with more advanced staged tumors. This speaks to the less aggressive nature of phyllodes tumors.
The difference in overall survival between patients with phyllodes tumors and those with breast cancer can guide the creation of an evidence-based follow-up paradigm. The relative survival curve of the phyllodes patients reaches a plateau after 5 years, at which point these patients have the same survival as the general population. This is in contrast to patients with nonphyllodes breast cancer where the relative survival continues to fall through time, and patients have a higher relative mortality even 10 years after their original diagnosis. Clinicians tend to follow breast cancer patients closely and continually after their diagnosis. This study indicates that patients with localized phyllodes tumors may not require such close follow-up, particularly after 5 years.
The difference in nature of the different stages of disease may help direct management of these patients. Surgery is the mainstay of treatment for all stages of disease, and most current studies show that wide local excision with adequate margins yields equivalent results to mastectomy in terms of survival.6~" There have been small studies of patients treated with adjuvant radiation and chemotherapy. Postoperative radiation treatment has been shown in several small series to decrease local recurrence and improve overall survival.12-14 Additionally, some patients with metastatic disease have been shown to have slightly improved survival with chemotherapy.15-16 As the data in this study show, patients with advanced stage disease have a much lower survival than those with localized dis ease and perhaps this is the subset of patients that could benefit from adjuvant treatments. Clearly, further studies are warranted to determine which adjuvant therapies may best treat this patient population.
This study is limited by the fact that this is a retrospective, observational study that has inherent flaws in terms of reporting, and certain data sets, such as treatment, are incomplete. Finally, there was no available data on patient comorbidities. By using relative instead of actual survival, it was possible to compare two groups of presumably equivalent patients except for the presence of a breast tumor. Differences in relative survival reflect the impact of the cancer and should not be influenced by other, unrelated patient factors. Conclusion
Malignant phyllodes tumor is an uncommon tumor which has clear differences from ductal breast carcinoma. It affects patients of all ages and disease stage seems to be the only predictor of survival. Patients with localized phyllodes tumor have an overall good prognosis and, after 5 years from surgical treatment, they have no increased mortality relative to the general population. Clinicians should plan these patients' follow-up accordingly. Additionally, given these data and the known risks of complications associated with chemotherapy and radiation, there is limited evidence for adjuvant therapy in patients with localized disease. Further studies are needed to explore adjuvant treatments for the relatively rare patients with advanced disease.
This research was supported by the National Cancer Institute's Grant 2 R25 CA65745 and CA8564; the National Institutes of Health, Division of National Center on Minority Health and Health Disparities EXPORT Grant P60MD00220; the National Cancer Institute Minority Institution/Cancer Center Partnership Program Grants #U56 CA92079 and #U56 CA92081.
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JULIA GRABOWSKI, M.D.,* SIDNEY L. SALZSTEIN, M.D., M.P.H.,t GEORGIA R. SADLER, Ph.D.,*
SARAH L. BLAIR, M.D.*
From the Departments of *Surgery and tPathology, University of California, San Diego Medical Center,
San Diego, California
Presented at the 18th Annual Scientific Meeting of the Southern California Chapter of the American College of Surgeons in Santa Barbara, CA, January 19-21, 2007.
Address correspondence and reprint requests to Sarah Blair, M.D., Department of Surgery, University of California, San Diego Medical Center, 3855 Health Sciences Drive #0987, La Jolla, CA 92093-0987. E- mail: email@example.com
DISCLAIMER "The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code section 103885, the National Cancer Institute's Surveillance, Epidemiology and End Results Program, and the Centers for Disease Control and Prevention National Program of Cancer Registries. The ideas and opinion expressed herein are those of the authors and endorsement by the State of California, Department of Health Services, the National Cancer Institute, and the Centers for Disease Control and Prevention is not intended nor should be inferred."
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