| Japanese Journal of Clinical Oncology | Pages |
Natural History of Fibroadenomas Based on the Correlation Between Size and Patient Age
Introduction
Materials And Methods
Results
Discussion
References
Natural History of Fibroadenomas Based on the Correlation Between Size and Patient Age
Methods: Fifty-eight consecutive patients (age range, 17-51 years; mean, 33.9 years) with histologically confirmed fibroadenoma were enrolled in this study. The sizes of the excised fibroadenomas were analyzed in relation to the women's ages.
Results: The fibroadenomas decreased significantly in size (Y, mm) with patient age (X, years) (P = 0.0012) according to the equation Y = -0.340X + 27.0 (95% confidence limits for the slope, -0.139 to -0.540). From this equation, the mean sizes of the fibroadenoma in women aged 20, 30 and 40 years were expected to be 20.2 mm (95% confidence interval, 16.2-24.2 mm), 16.8 mm (95% confidence interval, 10.8-22.8 mm) and 13.4 mm (95% confidence interval, 5.4-21.4 mm), respectively. The mean annual decrease in the size of the fibroadenomas was 0.340 mm.
Conclusions: Our results indicate that in Japanese women fibroadenomas increase in size more frequently in younger than in older women. Moreover, it is speculated that most fibroadenomas might stop growing when they reach an approximate maximum diameter of 20 mm, after which time they might remain static or regress.
INTRODUCTION
A fibroadenoma is a lump that commonly occurs in the breasts of young women. Haagensen (1) observed that most fibroadenomas stop growing when they reach 2-3 cm in diameter. However, the natural history of fibroadenoma varies (2) and the management of fibroadenoma is controversial. Some studies (3,4) indicated that most patients with a palpable fibroadenoma prefer to have it removed. Alle et al. (5) reported that excising fibroadenomas causes minimal morbidity, allows a complete pathological examination, has high patient acceptability and results in a cure rate of 100%. However, recent reports (6-8) have shown that most fibroadenomas remain unchanged or regress in size and that conservative management is thought to be safe and acceptable. When a fibroadenoma is managed conservatively, a definitive diagnosis is never established with certainty; in fact, some masses clinically diagnosed as fibroadenomas were later reported pathologically to be other forms of benign breast disease (7,9,10). To understand the natural history of fibroadenomas, it might be important to determine their sizes in relation to women's age. The aim of the present study was to analyze the correlation between the size of the fibroadenomas and the patients' age by measuring histologically confirmed specimens.
MATERIALS AND METHODS
A database was used in the present study that consisted of a consecutive series of benign breast lumps excised with the patients under local anesthesia at an outpatient clinic. The database included 66 fibroadenomas excised from 66 women between January 1992 and December 1993. During this time period, it was recommended that all patients who satisfied the study eligibility criteria undergo lump excision. The inclusion criteria were the presence of solid palpable lumps with or without malignant features or non-palpable lesions suspected to be breast cancer. All lesions were evaluated during a physical examination; all patients underwent mammography and ultrasonography and some had fine needle aspiration cytology. According to the criteria, an open biopsy was recommended for those patients diagnosed with fibroadenomas. After 1994, the inclusion criteria were changed so that most patients diagnosed with fibroadenomas were managed conservatively.
The benign breast disorders confirmed histologically during the study period according to our study criteria are shown in Table 1. Fibrocystic disease and fibroadenomas accounted for the largest numbers of breast disorders.
Because eight of the 66 excised fibroadenomas had not undergone three-dimensional measurements, 58 cases were finally enrolled in this study. Juvenile fibroadenoma or giant fibroadenoma was not included in the 58 cases; although some cases had epithelial hyperplasia or stromal hypercellularity, they were not diagnosed as juvenile or giant fibroadenoma based on their histological findings or clinical features, which were not characteristic of those pathologies or clinical features. No phyllodes tumors were included in this study. A maximum three-dimensional diameter was taken as a representative tumor size. These 58 specimens were excised from 58 women who ranged in age from 17 to 51 years (mean age, 33.9 years) and who were enrolled in this study. The age distribution of the patients is shown in Table 2. Forty-two (72.4%) of 58 fibroadenomas were diagnosed preoperatively as fibroadenomas and 11 (19.0%), most from patients over 30 years of age, were suspected to be breast cancer. The remainder were diagnosed as other benign breast disorders such as phyllodes tumors.
Pearson's correlation analysis and linear regression analysis were used to assess the correlation of the size of the fibroadenomas with the women's age. The F-test was used to evaluate the variance of the sizes of the fibroadenomas and a one-way ANOVA was used to analyze whether there existed a significant difference in the sizes of the fibroadenomas between age groups classified by decade. The statistical analyses were performed using StatMost for Windows (DataMost, Salt Lake City, UT).
Table 1.
| Benign breast disease | No. of women |
| Fibrocystic disease | 132 |
| Fibroadenoma | 66 |
| Intraductal papilloma | 7 |
| Galactocele | 7 |
| Fat necrosis | 5 |
| Atypical epithelial hyperplasia | 4 |
| Mastitis | 4 |
| Adenoma | 4 |
| Phyllodes tumor | 2 |
Table 2.
| Age (years) | No. of women |
| [le]19 | 5 |
| 20-29 | 15 |
| 30-39 | 17 |
| [ge]40 | 21 |
RESULTS
The mean size of the 58 fibroadenomas was 15.5 mm (range, 5-42 mm). The fibroadenomas decreased in size (Y, mm) with age (X, years), a statistically significant finding (P = 0.0013), according to the equation Y = -0.340X + 27.0 (95% confidence limits for the slope, -0.139 to -0.540) (Fig. 1). This equation indicated that the mean sizes of the fibroadenomas in women aged 20, 30 and 40 years were expected to be 20.2 mm (95% confidence interval, 16.2-24.2 mm), 16.8 mm (95% confidence interval, 10.8-22.8 mm) and 13.4 mm (95% confidence interval, 5.4-21.4 mm), respectively, and the mean annual decrease in the size of the fibroadenomas was 0.340 mm.
Figure 1. The sizes (Y, mm) of the fibroadenomas correlate inversely with the women's age (X, years) (P = 0.0013) according to the equation Y = -0.340X + 27.0 (95% confidence limits for the slope, -0.139 to -0.540). When the women were divided into four age groups by decade, the mean sizes of the fibroadenomas (± standard deviation) were 28.4 ± 12.8 mm in adolescents and 15.9 ± 6.7, 14.4 ± 4.8 and 13.0 ± 6.0 mm in women aged 20-29, 30-39 and [ge]40 years, respectively (Fig. 2). There was a difference in the variance of the sizes of fibroadenomas between adolescents and women aged 20-29 years (P = 0.062), women aged 30-39 years (P = 0.0037) or women aged [ge]40 years (P = 0.019). No significant difference was found in the variance of the sizes of the fibroadenomas among the age groups over 20 years. One-way ANOVA showed that there was a statistically significant difference in the mean size between four age groups by decade (P = 0.0003). Figure 2. The mean size (±standard deviation) of the fibroadenomas was 28.4 ± 12.8 mm in adolescents and 15.9 ± 6.7, 14.4 ± 4.8 and 13.0 ± 6.0 mm in women aged 20-29, 30-39 and [ge]40 years, respectively. There was a statistically significant difference in the mean size of the fibroadenoma between the four age groups by decade (P = 0.0003). Most studies have reported that over half of patients with fibroadenomas were under 30 years of age (6-9). Compared with these studies, the mean patient age of 34 years in our study population was slightly higher. In Japan, it is recommended that women aged [ge]30 years undergo annual breast screening. Therefore, older women have a greater chance that their breast lumps will be detected, suggesting that a selection bias might have existed in the present study. Considering the natural history of fibroadenoma, the juvenile or giant fibroadenoma should be analyzed separately from the conventional fibroadenomas. Generally, they grow quickly and the breasts become distorted. Therefore, conservative management may not be realistic. The terms juvenile and giant fibroadenoma are used clinically with adolescent females and with fibroadenomas with maximum diameter >50 mm, respectively (2,3). They are not a histological entity, but tend to be more cellular with minimal lobular development (11). In our study materials, although some cases had epithelial hyperplasia or stromal hypercellularity, their histological findings or clinical features were not characteristic of those pathologies or clinical features, suggesting that our study materials consisted of conventional fibroadenomas. Therefore, the natural history of fibroadenoma discussed here was that of the conventional fibroadenoma. Our results showed a significant reduction in size of the fibroadenomas with the women's age and the most significant difference in the sizes of the fibroadenomas between adolescents and women aged over 20 years. From these results, fibroadenomas in Japanese women increased in size more frequently in younger women, especially in adolescents, compared with older women. This finding supports that reported by Dixon et al. (8), who reported that fibroadenomas grew more frequently in adolescents than in women aged [ge]20 years. Based on the results of the present study, most fibroadenomas may stop growing at about 20 mm maximum diameter and then remain static or regress. The mean annual decrease of -0.340 mm found in the present study suggests that fibroadenomas rarely regress quickly. In addition, it may be difficult to recognize the reduction in size of fibroadenomas during a short interval of conservative management. Therefore, most fibroadenomas were reported to remain unchanged when they were managed conservatively (6-8). No fibroadenomas were included from women over 51 years of age. In fact, non-palpable fibroadenomas detected only by mammography were found in older postmenopausal women during the same period (data not shown), but they were ineligible for excision. The fact that no palpable fibroadenomas were found in women over 51 years in the present study suggests that most fibroadenomas regress and become non-palpable after menopause. Regarding the etiology of fibroadenomas, the significant regression with age may not reflect the neoplastic process. Clonal analysis of fibroadenomas showed that both the epithelial and stromal cells were polyclonal, suggesting a hyperplastic lesion rather than a neoplasia (12). Therefore, fibroadenomas are thought to be an aberration of natural development (13). These data suggest that most fibroadenomas should be managed conservatively. However, if the breast lumps diagnosed clinically to be fibroadenomas increase in size during conservative management or if they are already larger than about 30 mm in diameter, they should be excised because of the increased possibility of other forms of breast disease. Physicians must explain the natural history of fibroadenomas to women in whom they are clinically diagnosed, and also the advantages and disadvantages of excision based on both the diagnostic accuracy and uncertainty of fibroadenomas. Finally, fibroadenoma management should then depend on the patient's decision about whether to undergo or forego surgery.
DISCUSSION
References
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