The National Cancer Data Base report on the results of a large nonrandomized comparison of breast preservation and modified radical mastectomy
Although the conclusions reached in the National Surgical Adjuvant Bowel and Breast Protocol B-06 trial and other clinical trials appear to remain intact, questions persist regarding the equivalency of breast preservation compared with modified radical mastectomy for patients with invasive carcinoma. Documentation and assessment of comparative survival rates in a large cohort of nonrandomized breast carcinoma patients was undertaken to understand better these outcome patterns.
Information gathered from the medical records of 96,030 women diagnosed with early stage carcinoma of the breast between 1985 and 1988 was reviewed to determine the age at diagnosis; tumor stage, grade, dimension; treatment; and disease status.
Of these 96,030 Stage I and II (based on the American Joint Committee on Cancer staging system) patients, 8583 (8.9%) were treated with segmental mastectomy, axillary lymph node dissection, and radiotherapy without systemic treatment. Three thousand seven hundred and ninety-seven patients (4.0%) were treated with segmental mastectomy, axillary lymph node dissection, radiotherapy, and systemic therapy. Forty-four thousand two hundred and forty-nine patients (46.0%) were treated with modified radical mastectomy without systemic therapy, and 18,322 patients (19.1%) were treated with modified radical mastectomy with systemic therapy. Within each stage, reported survival was equal to or more favorable for patients managed with breast preservation compared with those treated with modified radical mastectomy. This comparability was observed in all subsets analyzed including those defined by age at diagnosis, histologic grade, and tumor dimension.
These findings are consistent with the hypothesis that AJCC Stage I and II patients treated with breast preservation appear to have survival rates equivalent to those treated with modified radical mastectomy. Cancer 1997; 80:162-7. © 1997 American Cancer Society.
The treatment of carcinoma of the breast has evolved into a multidisciplinary approach that optimizes survival and attempts to preserve the breast. There has been a gradual decrease in the use of radical mastectomy as proposed by William Stewart Halsted in 19071 as opposed to modified radical mastectomy and segmental mastectomy with radiotherapy. This transition has resulted from several prospective randomized trials that have compared these treatment approaches and have identified no differences in outcome.2-4
This study reports the survival of women managed with segmental mastectomy, axillary lymph node dissection, and radiotherapy compared with those treated with modified radical mastectomy using the National Cancer Data Base (NCDB) of the American College of Surgeons. This data base is a voluntary hospital-based registry that provides a large convenience sample of cancer patients treated in the U. S. Details of patterns of care for breast carcinoma using NCDB data have been described in previous reports.5-8
A goal of the NCDB is to lower the morbidity and mortality of cancer by providing information regarding cancer management and outcomes. Its major products include 1) hospital reports, 2) community and state reports, and 3) clinical publications based on national data that compare cancer management patterns and outcome with national norms. The NCDB annually collects data for all forms of cancer from throughout the U. S. to continually assess treatment trends and maintain surveillance.
The methods of the NCDB have been previously described.9, 10 These data from NCDB-participating hospitals comprise a convenience sample voluntarily submitted by hospital cancer registries. Participating hospitals submitted data on patients diagnosed with early stage breast carcinoma (pathologic [p] Stage I and II, according to the American Joint Committee on Cancer [AJCC]) during a 4-year period including 13,754 breast carcinoma cases from 1985, 14,565 cases from 1986, 27,433 cases from 1987, and 40,278 cases from 1988, totaling 96,030 cases. Approximately 96% of these cases came from facilities that are members of the Approvals Program of the Commission on Cancer.
Of the reported 96,030 Stage I and II breast carcinoma patients, the majority (81%) had their carcinomas diagnosed and also received all or part of their treatment at reporting hospitals; 18% received all or part of their treatment at reporting hospitals but had their carcinomas diagnosed elsewhere; and 1% had their carcinomas diagnosed at reporting hospitals but were treated elsewhere. In total, data from 1018 U.S. hospitals are included.
The number of participating NCDB hospitals has increased between 1985 and 1988. This increase parallels and reflects the increase of computerized hospital cancer registries during that time period. Most data were received from hospitals with a computerized cancer registry, possibly introducing hospital selection bias. Furthermore, the data are thought to represent hospital-based care, and may not comprehensively include outpatient data.
The baseline data items of the NCDB include: 1) patient characteristics (gender, age/date of birth, race/ethnicity, zip code of residence, admission date, discharge date, and class or analytic status); 2) tumor characteristics (primary site, laterality, histology, grade, regional lymph nodes positive/examined, tumor size, general summary stage, clinical [c] AJCC stage group, pAJCC stage group, date/type of recurrence, and sites of distant metastasis); 3) first course of treatment (surgery, radiation therapy, chemotherapy, hormonal therapy, or biologic modifiers); and 4) follow-up (last contact date, vital status, and tumor status). They were transmitted to the NCDB following a standard data transfer specification. The case data for each patient were coded in the traditional manner by trained cancer registrars in their respective hospitals before being transmitted to the NCDB.11
Anatomic site and histology were coded using the International Classification of Diseases for Oncology 2nd Edition Clinical Modification (ICD-O 2 CM) manual.12 Surgical procedures were coded following the Data Acquisition Manual.11 Staging was performed according to the AJCC.13
Comparisons were limited to patients treated in one of four fashions: segmental mastectomy, axillary lymph node dissection, radiotherapy, and no systemic therapy; segmental mastectomy, axillary lymph node dissection, radiotherapy, and systemic therapy; modified radical mastectomy without radiotherapy or systemic therapy; and modified radical mastectomy without radiotherapy and with systemic therapy. Survival rates were computed with relative survival methodology,13, 14 which utilizes the overall mortality status as its endpoint and adjusts observed mortality with expected mortality based on patient demographic characteristics. This approach provides the advantages of risk adjustments for gender, age, and ethnicity, and utilizes the mortality (alive/dead) status, the most reliable and frequently available survival endpoint. Although hospital cancer registry data sets do include data items for cause of death, the data are frequently missing. The use of relative methodology minimizes possible bias due to censored data. In NCDB publications, the data are generally presented in stratified form (cross-tabulations) so that possible associations can be directly assessed, without regression techniques.
An important aspect of the usefulness of the data is the quality of case reports sent to the NCDB. The accuracy of the NCDB data collected has been discussed earlier.15-17 The NCDB relies on the hospital cancer committee or its equivalent to supervise the quality control of casefinding and abstracting, internal reviews of abstracts by registry staff, hospital-based computer data edits, and the editing checks of regional or state registries to monitor accuracy. In addition, the NCDB makes editing checks for inconsistent or impossible codes to assist hospital registrars in correcting their data.
Significance tests (chi-square) are determined by sample size as well as the magnitude of differences between subsets. Furthermore, they are based on certain assumptions regarding the samples. Application of statistical testing to these analyses is problematic for several reasons. First, these are descriptive national survey data, and are not collected to evaluate a priori hypotheses. Second, the numbers of cases under analysis are so large that the statistical assumptions of significance testing are not met. Repeated chi-square testing of NCDB data at the P < 0.001 level of significance suggests that markedly more comparisons have significance than the data reasonably support. Third, the cancer population under study represents such a large part of the universe of which they are a subset that the sampling assumptions on which significance testing is based may not be valid. Thus, these data are reported without significance tests.
There were 96,030 pAJCC Stage I and II breast carcinoma patients reported in the participating registries during the 4-year period 1985 to 1988 (Table 1). Of these, 8583 (8.9%) patients were treated with breast preservation (segmental mastectomy, radiotherapy, and axillary lymph node dissection) without systemic therapy. Three thousand seven hundred and ninety-seven patients (4.0%) were treated with breast preservation and systemic therapy. An additional 7293 patients had other combinations of locoregional therapy, accounting for a total of 20.5% of NCDB subjects being treated with segmental mastectomy.
Table 1. Percent of Breast Carcinoma Patients Treated with Segmental and Modified Radical Mastectomies by Pathologic (pAJCC) Stage, 1985-1988
The analysis of women treated with modified radical mastectomy was limited to those who did not receive adjuvant radiotherapy. Forty-four thousand two hundred and forty-nine patients (46.0%) were treated with a modified radical mastectomy alone. Eighteen thousand three hundred and twenty-two patients (19.1%) also received systemic therapy. Other treatment combinations accounted for 14.4% of the patients within the data base.
Comparisons were made between women treated with breast preservation (segmental mastectomy, axillary lymph node dissection, and radiotherapy), and those treated with a modified radical mastectomy. Locoregional treatment groupings were divided into two categories: those women receiving systemic therapy and those receiving none.
The characteristics of the four comparison groups were not identical. The mean age at diagnosis for breast preservation patients was lower for all categories than the mean age for women treated with modified radical mastectomy (Table 2).
Table 2. Percent of Breast Carcinoma Patients (pAJCC Stages I and II) Treated with Segmental and Modified Radical Mastectomies by Age, and by Histologic Grade, 1985-1988
Tumor greatest was slightly smaller for Stage I and II breast preservation patients compared with those treated with mastectomy (Table 3). Stage I patients receiving breast preservation therapy had an average tumor size of 12.9 mm compared with 14.1 mm for those treated with a modified radical mastectomy. For Stage II patients, the average tumor size of those treated with breast preservation was 23.5 mm and was 27.4 for those treated with a modified radical mastectomy. Thus in this large cohort, breast conservation was more frequently selected for younger patients and patients with smaller tumors.
Table 3. Average Tumor Dimension and Frequency of Breast Carcinoma Cases Treated with Segmental and Modified Radical Mastectomy by Pathologic (pAJCC) Stage and Type of Surgery, 1985-1988
|Total|| ||(8573)|| ||(3797)|| ||(12,380)|| ||(44,249)|| ||(18,322)|| ||(62,571)|
For patients with Stages I and II breast carcinoma, the 5-year relative survival rates for women treated with segmental mastectomy were equivalent to those treated with modified radical mastectomy (Table 4). For Stage I patients, 5-year survival for those treated with segmental mastectomy without and with systemic therapy was 96% and 95%, respectively, compared with 94% and 92%, respectively, for those treated with modified radical mastectomy without and with systemic therapy. For Stage II patients, 5-year survival for those treated with segmental mastectomy without and with systemic therapy was 88% and 85%, respectively, compared with 83% and 80%, respectively, for those treated with modified radical mastectomy without and with systemic therapy.
Table 4. Five-Year Relative Survival Percent and Frequency of Breast Carcinoma Cases (No.) by Type of Treatment, pAJCC Stage, and Age, 1985-1988
Although breast preservation patients were more likely to be younger, the apparent survival equivalency persisted for breast preservation patients when the analysis was stratified to women age < 50 years at the time of diagnosis (premenopausal), and to women ≥ 50 years (postmenopausal) (Table 4).
Survival analysis stratified by tumor dimension and type of locoregional treatment did not identify any survival disadvantage for patients treated with breast preservation (Table 5). Similarly, survival stratified by tumor grade revealed either equivalent or superior survival rates for women managed with breast preservation. A pattern is generally present in these data of small advantages in the survival of patients treated without systemic treatment whether controlling for patient age (Table 4), or tumor dimension (Table 5).
Table 5. Five-Year Relative Survival Percent and Frequency of Breast Carcinoma Cases (No.) by Type of Treatment and Average Tumor Size, and by Histologic Grade, pAJCC Stages I and II, 1985-1988
Several prospective clinical trials have demonstrated equivalent survival rates for women treated with either breast preservation or with modified radical mastectomy.2-4 In addition, a recent overview analysis has confirmed these conclusions.18
This study evaluates the outcomes of 74,951 patients treated between 1985 and 1988 from a total series of 96,030 patients. These patients were from all over the U. S. and were treated at large and small community hospitals, university and other teaching hospitals, and National Cancer Institute-designated centers.
During the period of study (1985-1988), clinical trials for breast preservation therapy were in progress and most women were still being treated with a modified radical mastectomy. However, the proportion of patients treated with breast preservation has steadily increased.7
Because this is a retrospective analysis, it is not possible to control potential selection bias or risk stratifying variables. However, survival comparisons in this study did not identify any disadvantages for breast preservation patients when comparing groups defined by stage, age at diagnosis, tumor dimension, tumor grade, or the use of systemic therapy.
Although several locoregional treatment approaches were recorded during this time period, analysis was limited to segmental mastectomy with axillary lymph node dissection and radiotherapy compared with modified radical mastectomy. Limiting the analysis to these groups allows one to draw comparisons to randomized clinical trials and to minimize survival differences created by potential selection bias.
Differences in tumor dimension and age at diagnosis were identified between the four study groups. As expected, younger patients were more likely to be treated with breast preservation than were older patients. Despite this difference in age at diagnosis, a survival equivalency was still evident for breast preservation patients when controlling this variable. The same observations applied to tumor dimension. On average, breast preservation patients had smaller tumors than women treated with mastectomy. However, control for the variable of tumor dimension continued to demonstrate a survival equivalency or advantage for breast preservation patients.
Although a persistent equivalency or survival advantage was reported for all breast preservation patients while controlling for stage, tumor dimension, histologic grade, and age, an unrecognized selection bias remains a possibility. These survival results are in agreement with those reported by Fisher et al in National Surgical Adjuvant Bowel and Breast Protocol (NSABP)-06.2 In their last report, they noted survival differences in women treated with segmental mastectomy, axillary lymph node dissection, and radiotherapy compared with modified radical mastectomy patients (63% vs. 59% 12-year survival, respectively).2 Although not achieving statistical significance, Veronesi et al also reported a small survival advantage in patients treated with quadrantectomy over those treated with mastectomy (85% vs. 83%).3 Workers from the Institut Gustave-Roussy also reported a small but not statistically significant survival advantage in breast preservation patients at 5 years (95% vs. 91%).4
It is difficult to interpret the small but persistent survival advantage of those patients treated without systemic therapy. The authors believe that undetected selection bias is the most likely explanation for these differences.
This article represents a large retrospective survival analysis for patients with Stage I and II invasive carcinoma of the breast. Data from this report are derived from a large national data base representative of patients treated within the U. S. This study did not identify any survival advantage for women treated with modified radical mastectomy compared with patients managed with breast preservation. Drawing from a large and diverse national data base, these findings support conclusions reached in randomized clinical trials and their overview analysis.
Data in this report were collected by the National Cancer Data Base, a joint project of the Commission on Cancer of the American College of Surgeons, and the American Cancer Society.