A Systematic Study on Fibroadenoma of the Breast

ABST RACT Introduction: Fibroadenomas are one of the main benign diseases of the breast. Though considered as a risk factor for development of breast cancer, its reporting has been overshadowed by that of breast cancer. Early diagnosis and treatment can relieve anxiety associated with non-malignant conditions of the breast. Analysis of the pattern and prevalence should provide a valuable guideline for clinicians in India for comparison with other countries. Materials and Methods: A prospective study was undertaken over a six-year period, and all cases with breast lesion underwent fine needle aspiration cytology or excision biopsy. Confirmed cases of fibroadenoma were studied for clinicopathological features. A total of 210 cases were analyzed. Results: Of the 210 cases of fibroadenoma, most were married urban women in the age group of 16-30 years (66.1%), with an average duration of symptoms of 12 months (80%). The majority of fibroadenomas (51.9%) measured 3-5 cm and were located in the upper outer quadrant (43.8%). Most of the cases (78.1%) underwent excision, and none presented with recurrence or carcinoma within the lesion. Conclusion: Fibroadenomas are the most common benign lesions of the breast, with average age of presentation of 27 years. Excision is the best treatment for women over 35 years to exclude malignancy.


INT RO DUC TI ON
There is a wide spectrum of benign breast disorders in India, but its reporting has been overshadowed by that of breast cancer. Benign breast disorders have an incidence of 1.5/1000 of total hospital admissions, 6.4/1000 of surgical admissions and 8.1/1000 of adult female admissions. A recent pathological review shows fibroadenoma as the most common lesion, followed by cystosarcoma phyllodes and fibrocystic diseases of the breast. Rangabashyam and colleagues, in their clinical study, also showed fibroadenoma as the most common breast lesion, but it was followed by inflammatory lesions and fibroadenosis [1] . We have studied the clinicopathological features of fibroadenoma in a prospective study of patients attending the surgical outpatient department at Bangalore Medical College and Research Institute, Bangalore, in south India.

MaTeRIals and MeThODs
The study was undertaken during the period November 2003 to May 2010, and patients who attended the surgical outpatient department of Victoria Hospital attached to Bangalore Medical College and Research Institute formed part of the study. Patients presenting with mastalgia or breast lump were examined and evaluated. The profile of patients were recorded in a pro forma, which included age, marital status, rural or urban background, duration of symptoms, pre-menstrual and post-menstrual symptoms, number of lumps, and size and location of lumps. All cases underwent fine needle aspiration cytology (FNAC) or specimens were sent for histopathological examination after excision. All cases with proven fibroadenoma were included in the study. A total of 210 unselected cases were studied fully and are presented here.

ResUlTs
During the study period, a total of 210 cases were confirmed as fibroadenoma.
The ages of cases ranged from 11-72 years, and the maximum number of cases [139 (66.1%)] were in the age group of 16-30 years, followed by 32-45 years, with a mean age of presentation of 27 years. The majority of cases [135 (64.2%)] were from an urban background. It was found that 130 (61.9%) of the cases were married. The duration of symptoms varied for months to three years, with a majority [168 (80%)] of them presenting within a year of symptoms, which was mainly lump in the breast. None of the cases was on oral contraceptives.
Diagnosis was based on FNAC in 68% of the cases, and the rest were confirmed by excision biopsy. A total of 46 (21.9%) of the cases were managed conservatively, and 164 (78.1%) underwent excision with no major complication. Only 40% of the cases were available for follow-up at one year, and none of them presented with recurrence (Table 1).

DIsCUssION
The rate of occurrence of fibroadenoma in women who were examined in breast clinics was 7-13% while it was 9% in another study of autopsies [2,3] .
The majority (66%) of cases diagnosed as fibroadenoma were in their second and third decades (16-30 years), which may be due to hormonal dependency, participation in lactation, and involution at menopause, which is a possible contribution to lump formation and evolution. Added to this, giant fibroadenoma is common in puberty. These finding were consistent with that of Hanna and Ashebu and Gogo-Abite [4,5] . Further, the mean age of incidence of fibroadenoma among teenagers in India as reported in the literature is 14 years compared to 11 years in Germany according to Stehr et al. [6] . This implies the occurrence of fibroadenoma seems to be more common among teenagers. Fibroadenoma was found to be more common in those with an urban compared to rural background [7] . This trend may be due to more literacy and exposure to mass media sources, which increase the awareness about breast cancer screening. Fibroadenomas are more frequent among women in higher socioeconomic classes [8,9] .
Fibroadenoma tends to occur more frequently among married than unmarried women. The possible reason may be due to early marriage and parity. The age of menarche, age of menopause, and hormonal therapy, including oral contraceptives, were shown not to alter the risk of these lesions [10] . Though there is mention of an association between oral contraceptives and fibroadenoma, none of the cases was using oral contraceptives [11] . Hence, no definitive opinion regarding the association can be made.
It is interesting to note that the duration of symptoms varies from one month to six years, perhaps due to the slow-growing tumor and painless condition of fibroadenomas [12] . Fibroadenomas were almost equally distributed in the right and left breast, in contrast to Rimsten's observation that the incidence of breast lesions is higher in the left breast than in the right [13] . Upper lateral quadrant was the most common location of fibroadenoma, which is in accordance with the findings of Ajao [14] . A fibroadenoma is most often detected incidentally during a medical examination or during self examination, usually as a discrete solitary breast mass of 1-2 cm. Fibroadenomas vary in size from 1 cm to giant forms that are 18 cm in diameter. This finding is supported by Amshel and Sibley [15] .
Fibroadenomas > 5 cm (about 4% of the total) are commonly defined as giant fibroadenomas; however, this terminology is not universally accepted. Giant fibroadenomas are usually encountered in pregnant or lactating women. When found in an adolescent girl, the term juvenile fibroadenoma is more appropriate. These lesions in young women constitute 0.5-2% of all fibroadenomas, and are rapidly growing masses that cause asymmetry of the breast, distortion of the overlying skin, and stretching of the nipple. Histologically, they appear to be more cellular and have less lobular components than do simple fibroadenomas. However, giant fibroadenomas are benign lesions that do not undergo transformation into malignancy [16] .
None of the cases reported a change in size or pain during the pre-and post-menstrual period or pregnancy. Post-menstrual changes may result in regression, calcification, or both. Fibroadenoma presented with solitary lumps to multiple multi-centric and multi-focal lumps. From 10-16% of patients with multiple fibroadenomas have 2-4 in a single breast, which may present initially or be discovered over several years. Unlike women with a single fibroadenoma, most of the patients with multiple fibroadenomas have a strong family history of these tumors [17] . A possible connection between multiple fibroadenomas and oral contraceptives was proposed but has not yet been substantiated.
FNAC was used as an investigation tool for management of fibroadenoma, due to its reliability and simplicity and because it is less time-consuming. FNAC is a preliminary investigation used to distinguish fibroadenoma from other benign breast diseases [18] . Fibroadenomas comprise about 50% of all breast biopsies, and this rate rises to 75% for biopsies in women under the age of 20 years [19] .
Age-based algorithms that allow for conservative management and that limit excision to patients in whom fibroadenomas fail to regress have been presented. This finding is in line with that of Greenblatt et al. [20] . Conservative therapy has been attempted medically with progesterone and danazol, since the most prevalent theory on the etiology of fibroadeno-ma attributes them to excessive estrogen influence or response. Unfortunately, fibroadenomas fail to respond to these antiestrogen medications [21] . In the era of modern radiology and nonsurgical tissue biopsies, conservative treatment of fibroadenoma is often considered safe and acceptable after adequate triple testing (clinical examination, radiology, and biopsy). Patients who choose conservative management need to be informed of the limitation of triple testing and must be assessed promptly if there is symptomatic or clinical change [22] . Of fibroadenoma cases that have undergone long-term periodic monitoring, anxiety and discomfort for patients and difficulties for physicians are experienced in approximately one-third. These masses will be excised, and only surgical resection is curative [22][23][24] .
Surgical excision was the preferred treatment, and simple excision was done in the majority of cases studied during the period; simple mastectomy was preferred for giant fibroadenoma. This implies surgical excision is the best option for treating fibroadenoma.
The Fibroadenoma Excision Through Periareolar Incision (FETPI) technique offers the advantage of an incision in an aesthetically acceptable area [25] . The scar can be camouflaged by the dark color of the areolar skin and the roughness of the areolar glands. The periareolar scar is esthetically superior to the overlying scar. The FETPI technique is indicated for patients with the following characteristics: an areola diameter of > 3.5-5.0 cm, a distance from the outer margin of the mass to the nearest areola edge of ≤ 5.0 cm, the largest diameter of clinically diagnosed palpable fibroadenomas of ≤ 3.0 cm, and an age ≤ 35 years.
Though none of our cases presented with recurrence or carcinoma within the fibroadenoma specimen, breast cancer risk of fibroadenoma has been estimated at 3.1 annual incidence per 1000, personyear rate, and the relative cancer risk is estimated at 7.0 [26,27] .
A more recent study designed to delineate the possible correlation between the histologic features of the fibroadenoma and the risk for subsequent breast cancer used the term "complex fibroadenoma" [28] . This term applies to fibroadenomas having the histologic characteristic of being > 3 mm in diameter, or with elements of sclerosing adenosis, epithelial calcifications, or papillary apocrine metaplasia, which were associated with a 3.1-elevated risk of breast cancer. Proliferative changes in the parenchyma adjacent to the fibroadenoma were related to a further increase of the risk to 3.88. The relative risk for women with a familial history of breast cancer and complex fibroadenoma was 3.72, compared with control women with a family history of breast cancer without fibroadenoma. In these studies, women with noncomplex fibroadenoma and no family history of breast cancer were not at a greater risk of breast cancer. The risk of missing breast cancer in women under 25 years of age who have fibroadenomas as diagnosed by physical examination, sonography, and FNA is 1 in 229 to 1 in 700 [29] . This risk remains very low in women under the age of 35 years [30] . Therefore, it has been recommended that young patients should be observed with frequent clinical evaluations, while in women over the age of 35 years, the lesions should be excised. Other investigators have suggested a cut-off age of 25 years [31] .
Malignant transformations in the epithelial components of fibroadenomas are generally considered rare. The incidence of a carcinoma evolving within a fibroadenoma was reported to be 0.002-0.0125% [32] . About 50% of these tumors were lobular carcinoma in situ (LCIS), 20% were infiltrating lobular carcinoma, 20% were ductal carcinoma in situ (DCIS), and the remaining 10% were infiltrating ductal carcinoma [33,34] . The clinical, sonographic and mammographic findings are usually similar to those of benign fibroadenomas, and the malignant changes are often noted only when the fibroadenoma is excised [35] . Hence, surgery is advocated in all questionable cases where biopsy or FNAC is inconclusive.
In conclusion, fibroadenomas are one of the most common benign diseases of the breast. They are predominantly found in urban women aged 16-45 years, of varying number and size in all quadrants of the breast. Diagnosis by FNAC is reliable, yet confirmation by biopsy is required in women > 35 years and with unusual presentation. Though conservative management or observation can be followed in young women, surgical excision by a circumareolar incision is preferred in large tumors and in patients older than 35 years to avoid missing an occult malignancy within the fibroadenoma.