Breast Carcinoma within Fibroadenoma: A Systematic Review

Abstract Introduction Fibroadenoma is the most common benign breast lesion; however, it carries a potential risk of malignant transformation. This systematic review provides an overview of the presentation, management, and outcome of carcinomas arising within fibroadenomas. Methods A systematic search on Google Scholar was conducted for English-language studies on breast carcinoma within fibroadenomas. Studies on fibroadenomas with no malignant components, review articles, pre-prints, incomplete data, and those published in suspicious journals were excluded. Results On ultrasonography, 28 masses (36.8%) appeared benign, and 20 (26.3%) were suspicious, with ultrasonographic data unavailable for the remaining tumors (36.8%). Mammography data were available for 50 tumors, revealing 27 benign lesions (54%) and 23 suspicious lesions (46%). Among the 17 lesions with available magnetic resonance imaging data, five were benign lesions (29.4%), and 12 were suspicious (70.6%). Cytology evaluation among 46 tumors revealed that 20 (43.5%) were benign, 24 (52.2%) were malignant, and two (4.3%) were suspicious. The most commonly performed surgery was wide local excision (50.7%), followed by mastectomy (32.9%). On histopathology, 11 tumors exhibited more than one pathology. Ductal carcinoma in situ was the most frequent finding (40.8%), followed by invasive ductal carcinoma (28.9%) and lobular carcinoma in situ (28.4%). Recurrence was observed in one case (1.4%), and metastasis occurred in two cases (2.8%). Conclusion Although rare, carcinomas arising within fibroadenomas may present considerable challenges in preoperative diagnosis, whether through imaging or cytology. Therefore, clinicians may find it necessary to approach fibroadenomas with increased caution. Introduction Fibroadenoma is the most common benign breast lesion comprising epithelial and stromal components [1,2]. The tumor generally manifests as a hyperplastic breast lobule, presenting as a solitary mass during a woman’s early reproductive years, with the peak incidence occurring in the second and third decades of life [3,4]. Estrogen, progesterone, pregnancy, and lactation are believed to stimulate tumor growth, although it tends to shrink during menopause as estrogen levels decline [3]. Incidence rates range from 7% to 13% in the general population, with up to 20% of cases presenting with bilateral or multiple masses [3]. Clinically, fibroadenoma presents as a palpable, mobile, solid mass with a rubbery consistency and smooth, well-defined borders [5]. It is radiologically and histologically classified into simple and complex types [2]. The tumor may exceed 3 mm in size, be associated with sclerosing adenosis or epithelial calcifications, and potentially give rise to carcinomas that can invade the surrounding breast tissue. Although cases of fibroadenomas containing malignancies are rare, malignancy tends to occur more frequently in patients 10 to 20 years older than the typical age for simple fibroadenomas [2,6]. Carcinomas within fibroadenomas are most commonly carcinoma in situ (CIS) [7,8]. Invasive carcinomas, though less common, can occur, with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) being the primary forms [6]. Carcinomas in situ signal an increased risk of developing invasive cancer if left untreated, and neoplasms arising within fibroadenomas behave similarly to those occurring independently [9]. This systematic review provides an overview of the presentation, management, and outcome of carcinomas arising within fibroadenomas. Methods Study design This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data sources and search strategy A systematic search on Google Scholar was undertaken to identify relevant English-language studies on breast carcinoma within fibroadenoma. The search strategy employed a combination of keywords, including "fibroadenoma" with terms such as (carcinoma, cancer, malignancy, malignant, carcinoma in situ, lobular carcinoma in situ (LCIS), and ductal carcinoma in situ (DCIS). Eligibility criteria The inclusion criteria were limited to studies specifically addressing breast carcinoma within fibroadenoma. Studies on fibroadenomas with no malignant components, review articles, pre-prints, incomplete data, and those published in suspicious journals were excluded [10].  Study selection and data extraction Two authors independently reviewed the titles and abstracts of the identified publications. Following this, the same two authors assessed the full texts of the remaining studies based on predefined inclusion and exclusion criteria. The extracted data included the first author’s name, the country of publication, study design, patient demographics, clinical presentation, physical examination findings, imaging and cytology findings, treatment strategies, and disease prognosis. Data analysis Microsoft Excel (2019) was employed to collect and organize the extracted data, while data analysis (descriptive statistics) was performed using the Statistical Package for Social Sciences (SPSS), version 27.0. The results are presented as frequencies, percentages, ranges, mean with standard deviation, and medians with quartile ranges. Results Study selection and characteristics A total of 317 studies were identified from the search. Thirty-six studies were excluded due to duplication (n=5) and non-English language publications (n=31). This left 281 studies for title and abstract screening. At this stage, 202 studies were excluded due to irrelevancy. As a result, 79 studies advanced to the full-text screening stage. At this point, nine studies were excluded for being meta-analyses (n=2), reviews (n=2), publications with incomplete data (n=1), and pre-prints (n=4). Nine of the remaining 70 studies were excluded for failing to meet eligibility criteria as they were published in suspicious journals [10]. Ultimately, 61 studies [1-9,11-62], encompassing 72 cases, were included (Figure 1).  Most of the studies were case reports (n=58), accompanied by three case series. Most were affiliated with Japan (19.7%) and the USA (14.7%) (Table 1). The raw data of the study has been presented in Tables 1-6. Table 1. The distribution of the reported cases among countries. Author /Year [reference] Study design No. of included case(s) Country Ni et al./2023 [14] Case report 1 China Brunetti et al./2023 [4] Case report 1 Italy Wang et al./2022 [5] Case report 1 Singapore Pang et al./2022 [2] Case report 1 Malaysia Hammood et al./2022 [3] Case report 1 Iraq Tagliati et al./2021 [1] Case report 1 Italy Shojaku et al./2021 [6] Case report 1 Japan Fujimoto et al./2021 [11] Case report 1 Japan Feijó et al./2021[8] Case report 1 Brazil Shiino et al./2020 [12] Case report 1 Japan Moreno et al./2020 [17] Case report 1 Brazil Gonthong et al./2020 [13] Case report 1 Thailand El-Essawy et al./2020 [18] Case report 1 KSA Brock et al./2020 [9] Case report 1 USA Marumoto et al./2019 [16] Case report 1 USA Zeeshan et al./2018 [19] Case report 1 Pakistan Tiwari et al./2018 [15] Case report 1 India Frisch et al./2018 [7] Case report 1 South Africa Lim et al./2017 [20] Case report 1 Korea You et al./2016 [21] Case report 1 Korea Zheng et al./2015 [22] Case report 1 China Hua et al./2015 [23] Case report 1 China Wu et al./2014 [24] Case series 6 Taiwan Mele et al./2014 [25] Case report 1 Denmark Limite et al./2014 [26] Case report 1 Italy Kwon et al./2014 [27] Case report 1 Korea Kılıç et al./2014 [28] Case report 1 Turkey Dandin et al./2014 [29] Case report 1 Turkey Buteau et al./2014 [30] Case report 1 USA Hayes et al./2013 [31] Case report 1 Ireland Jahan et al./2012 [32] Case report 1 Bangladesh Butler et al./2012 [33] Case report 1 USA Ooe et al./2011 [34] Case report 1 Japan Lin et al./2011 [35] Case report 1 Taiwan Kato et al./2011 [36] Case report 1 Japan Abu-Rahmeh et al./ 2012 [37] Case report 1 Israel Rao et al./ 2010 [38] Case report 1 India Petersson et al./2010 [39] Case report 1 Singapore Tajima et al./2009 [40] Case report 1 Japan Gashi-Luci et al./2009 [41] Case report 1 Kosova Borecky et al./2008 [42] Case series 3 Australia Tiu et al./2006 [43] Case report 1 Taiwan Shin et al./2006 [44] Case report 1 Korea Blanco et al./2005 [45] Case report 1 USA Abite et al./2005 [46] Case report 1 Nigeria Stafyla et al./2004 [47] Case report 1 Greece Abe et al./ 2004 [48] Case report 1 Japan Adelekan et al./2003 [49] Case report 1 UK Yano et al./2001 [50] Case report 1 Japan Gebrim et al./2000 [51] Case report 1 Brazil Psarianos et al./1998 [52] Case report 1 Australia Shah et al./ 1998 [53] Case report 1 USA Kurosum et al./1994 [54] Case report 1 Japan Morimoto et al./1993 [55] Case report 1 Japan Gupta et al./1992 [56] Case report 1 New Zealand Gupta et al./1991 [57] Case report 1 New Zealand Fukud et al./1989 [58] Case report 1 Japan Yoshida et al./1985 [59] Case report 1 Japan Fond et al./1979 [60] Case report 1 USA Konakry et a./1975 [61] Case series 5 USA Durso et al./1972 [62] Case report 1 USA   Table 2. Patient demography, disease presentation, and medical history. First Author /Year Age (years) Gender Presentation Laterality Duration (months) PMH FHx of breast cancer Ni et al./2023 [14] 60 F Mass UL 12 NN Neg. Brunetti et al./2023 [4] 35 F Lump UL NA NN FDR Wang et al./2022 [5] 26 F Lump UL 72 NN NA Pang et al./2022 [2] 43 F Nipple discharge UL NA BM Neg. Hammood et al./2022 [3] 49 F Lump UL 60 BM Neg. Tagliati et al./2021 [1] 49 F Lump UL NA NA Neg. Shojaku et al./2021 [6] 61 F Mass UL 60 NN Neg. Fujimoto et al./2021 [11] 31 F Mass UL 12 NN Neg. Feijó et al./2021[8] 31 F Lump UL 48 NA Neg. Shiino et al./2020 [12] 53 F Lump UL 156 NA NA Moreno et al./2020 [17] 58 F Lump UL NA NA NA Gonthong et al./2020 [13] 38 F Mass UL NA IDC NA El-Essawy et al./2020 [18] 25 F Mass UL 1 MBBM Neg. Brock et al./2020 [9] 27 F Lump UL 4 FBD NA Marumoto et al./2019 [16] 70 F Mass UL NA NA Neg. Zeeshan et al./2018 [19] 34 F Lump UL 12 NN NA Tiwari et al./2018 [15] 28 F Lump BL 96 NN Neg. Frisch et al./2018 [7] 18 F Lump UL 48 NN Neg. Lim et al./2017 [20] 20 F Nodule UL NA NN Neg. You et al./2016 [21] 38 F Incidental UL NA NA Neg. Zheng et al./2015 [22] 48 F Lump BL NA NA NA Hua et al./2015 [23] 44 F Lump BL 12 NA NA Wu et al./2014 [24]   39 F NA NA 24 NA NA 31 F NA NA 84 NA NA 30 F NA NA NA NA NA 63 F NA NA 0.5 NA NA 48 F NA NA 3 NA NA 40 F NA NA 0 NA NA Mele et al./2014 [25] 63 F NA UL NA NA Pos. Limite et al./2014 [26] 26 F Lump UL NA NA Neg. Kwon et al./2014 [27] 20 F Lump BL 1 NN Neg. Kılıç et al./2014 [28] 30 F Mass UL NA NA Neg. Dandin et al./2014 [29] 35 F Mass UL 1.5 NN Neg. Buteau et al./2014 [30] 59 F Mass UL 36 NN Neg. Hayes et al./2013 [31] 51 F Incidental NA NA NA NA Jahan et al./2012 [32] 55 F Lump BL 240 NA NA Butler et al./2012 [33] 46 F Mass NA 60 NA NA Ooe et al./2011 [34] 46 F Lump UL 60 NN Neg. Lin et al./2011 [35] 34 F Lump UL NA NN Neg. Kato et al./2011 [36] 42 F Mass UL NA NA NA Abu-Rahmeh et al./ 2012 [37] 69 F Mass UL 168 NA FDR Rao et al./ 2010 [38] 30 F Lump UL 1 NN Neg. Petersson et al./2010 [39] 49 F Incidental UL 48 NA NA Tajima et al./2009 [40] 60 F Mass UL 3 NA NA Gashi-Luci et al./2009 [41] 39 F Lump UL 2 NA Neg. Borecky et al./2008 [42] 64 F Mass UL NA NA NA 80 F Lump UL 600 NA NA 53 F NA UL NA NA NA Tiu et al./2006 [43] 45 F Lump UL 60 NN NA Shin et al./2006 [44] 51 F Mass UL 12 NN Neg. Blanco et al./2005 [45] 63 F Mass UL 60 NN Neg. Abite et al./2005 [46] 23 F Lump UL 12 NA Neg. Stafyla et al./2004 [47] 27 F Mass UL NA NA NA Abe et al./ 2004 [48] 42 F Lump UL 3 NN Neg. Adelekan et al./2003 [49] 61 F Lump BL 120, 0.75 NA NA Yano et al./2001 [50] 54 F Mass UL 36 NA Neg. Gebrim et al./2000 [51] 58 F Nodule UL NA NA NA Psarianos et al./1998 [52] 34 F Mass UL NA NA NA Shah et al./ 1998 [53] 45 F Mass UL 0.25 NA Neg. Kurosum et al./1994 [54] 42 F Lump UL 21 NA NA Morimoto et al./1993 [55] 49 F Lump UL 2 NA NA Gupta et al./1992 [56] 59 F Mass UL 0.5 NN Neg. Gupta et al./1991 [57] 49 F Mass UL 7 NA Neg. Fukud et al./1989 [58] 45 F Lump UL NA BM NA Yoshida et al./1985 [59] 58 F Lump UL 1 HTN Neg. Fond et al./1979 [60] 27 F Lump UL NA CAH SDR Konakry et a./1975 [61] 59 F NA UL NA NA NA 39 F NA UL NA NA NA 44 F NA UL NA NA NA 46 F NA UL NA DCIS NA 48 F NA UL NA NA NA Durso et al./1972 [62] 42 F Lump UL NA NA NA F: female, PMH: Past Medical History, FHx: Family History, UL: Unilateral, BL: bilateral, NA: Non-available, BM: Breast Mass, NN: Nothing Noteworthy, IDC: Invasive Ductal Carcinoma, MBBM: Multiple Bilateral Breast Mass, FBD: Fibrocystic Breast Disease, HTN: Hypertension, CAH: Congenital Adrenal Hyperplasia, DCIS: Ductal Carcinoma In Situ, FDR: First-Degree Relative, SDR: Second-Degree Relative, Neg.: Negative, Pos.: Positive.   Table 3. The characteristics of the tumors. First Author. /Year Physical examination Ax LAD Size Location Shape Margin Vascularity Calcification Surface Consistency Mobility Ni et al./2023 [14] NA NA NM Neg. 7.7 mm RUA Round Smooth NA Pos. Brunetti et al./2023 [4] NA NA M Neg. 15 mm LLA Oval Well defined NA NA Wang et al./2022 [5] NA NA NA NA 24 mm LT NA Irregular NA NA Pang et al./2022 [2] NA NA NA NA 16.7 mm ROA Oval Lobulated Moderate Neg. Hammood et al./2022 [3] Smooth Firm NM NA 9.5mm RT Oval Well defined NA NA Tagliati et al./2021 [1] NA NA NA NA 35 mm RT Oval Well defined NA NA Shojaku et al./2021 [6] NA Hard NA NA 11.9 mm LT Oval Well defined NA Neg. Fujimoto et al./2021 [11] NA NA NA Neg. 22 mm LT NA Well defined NA Pos. Feijó et al./2021[8] NA NA NA Neg. 30 mm LUOQ NA Well defined Neg. Neg. Shiino et al./2020 [12] NA Hard NA Pos. 36 mm RLIQ NA Ill defined NA Pos. Moreno et al./2020 [17] NA NA NA Pos. 9.8 mm LUOQ NA NA NA NA Gonthong et al./2020 [13] NA NA NA NA 20 mm RT Oval Microlobulated NA Pos. El-Essawy et al./2020 [18] NA NA NA NA 28.7 mm LIA NA Irregular Increased Pos. Brock et al./2020 [9] NA Firm M NA 19.8 mm LOA NA NA NA Neg. Marumoto et al./2019 [16] NA NA M Neg. 20.4 mm RUOQ NA Irregular NA Neg. Zeeshan et al./2018 [19] NA NA M NA 47.9 mm RRA NA Lobulated NA NA Tiwari et al./2018 [15] Smooth Firm M NA NA BL NA Well defined NA NA Frisch et al./2018 [7] NA NA M Neg. 39.3 mm RLIQ NA Well defined Neg. Neg. Lim et al./2017 [20] NA NA NA NA 64.8 mm RUA NA NA NA NA You et al./2016 [21] NA NA NA Neg. 6.9 mm RUIQ Oval Well defined NA Pos. Zheng et al./2015 [22] NA, Smooth NA, NA NA, M Neg., Neg. 24.5 mm, NA LUA, RUIQ NA, NA Ill defined, well defined NA, NA NA, Pos. Hua et al./2015 [23] NA NA NA NA 22.4 mm LT NA Well defined Moderate Pos. Wu et al./2014 [24] NA NA NA NA 27 mm NA NA NA NA NA NA NA NA NA 34.5 mm NA NA NA NA NA NA NA NA NA 14.5 mm NA NA NA NA NA NA NA NA NA 12 mm NA NA NA NA NA NA NA NA NA 9 mm NA NA NA NA NA NA NA NA NA 6 mm NA NA NA NA NA Mele et al./2014 [25] NA NA NA Pos. 50 mm LLOQ NA Well defined NA Pos. Limite et al./2014 [26] Smooth Hard M Neg. 1.8 mm RLA NA Ill defined NA NA Kwon et al./2014 [27] NA, NA Firm, Firm M, M Neg., Neg. 16.9 mm, 21.9 mm RT, LT NA, Oval Lobulated, Irregular NA, NA Pos., Pos. Kılıç et al./2014 [28] NA Firm NA Neg. 19.9 mm LRA NA Well defined NA Pos. Dandin et al./2014 [29] NA NA M Neg. 11.8 mm LUOQ Oval Irregular NA NA Buteau et al./2014 [30] NA NA NA Pos. 17 mm LT Lobular NA NA NA Hayes et al./2013 [31] NA NA NA NA 35 mm NA Multilobulated Circumscribed NA Pos. Jahan et al./2012 [32] NA, NA NA, NA NA, NA NA, NA 39.2 mm, 36.3 mm NA, NA NA, NA NA, NA NA, NA NA, NA Butler et al./2012 [33] NA NA NA NA 7.3 mm NA Oval Well defined NA NA Ooe et al./2011 [34] Smooth Firm M Neg. 25 mm RUOQ Oval Well defined Increased Pos. Lin et al./2011 [35] NA NA M Neg. NA RUA Oval Well defined NA Pos. Kato et al./2011 [36] NA Hard NA NA 15 mm RT Irregular NA NA Pos. Abu-Rahmeh et al./ 2012 [37] NA NA NA NA 50 mm LT NA Well defined NA NA Rao et al./ 2010 [38] NA Firm M NA 28.3 mm RUA Oval Smooth NA Pos. Petersson et al./2010 [39] NA NA NA NA 30 mm NA NA Well defined NA NA Tajima et al./2009 [40] NA NA M NA 16.6 mm RUIQ Lobular Irregular NA Pos. Gashi-Luci et al./2009 [41] NA NA NA Neg. 20 mm RUOQ NA NA NA NA Borecky et al./2008 [42] NA NA NA NA 12 mm LT NA Irregular NA Pos. NA NA NA NA 40 mm LUIQ NA Ill defined NA Pos. NA NA NA NA 17 mm NA Oval Well defined NA Pos. Tiu et al./2006 [43] NA NA M Neg. 13 mm LUOQ NA Well defined Increased NA Shin et al./2006 [44] NA NA M Neg. 12.3 mm RUIQ Oval Well defined Pos. Pos. Blanco et al./2005 [45] NA NA NA NA 17.5 mm RT Round Well defined NA Pos. Abite et al./2005 [46] NA Firm M Neg. 34.2 mm RUOQ NA Well defined NA NA Stafyla et al./2004 [47] NA NA M Neg. 34 mm RUOQ NA Well defined NA NA Abe et al./ 2004 [48] NA Firm NA Neg. 47.4 mm LUOQ Irregular Well defined NA Neg. Adelekan et al./2003 [49] NA, NA NA, NA NA, NA NA, NA 35 mm, 60 mm NA, LUIQ NA, NA NA, NA NA, NA NA, NA Yano et al./2001 [50] Smooth Hard M Neg. 18.8 mm LUIQ NA Well defined Minimal Neg. Gebrim et al./2000 [51] NA NA M Neg. 24.5 mm LT NA Well defined NA Neg. Psarianos et al./1998 [52] NA Firm M NA 29.7 mm RUIQ NA Well defined NA NA Shah et al./ 1998 [53] NA Firm M Neg. 22.4 mm RUIQ NA Well defined NA NA Kurosum et al./1994 [54] NA Rubbery NA Neg. 22.9 mm RUOQ NA Well defined NA NA Morimoto et al./1993 [55] NA Rubbery M NA 24.5 mm LUIQ NA Well defined NA NA Gupta et al./1992 [56] NA Firm NA NA 19.4 mm LT NA NA NA NA Gupta et al./1991 [57] NA Rubbery NA NA NA LUOQ NA NA NA NA Fukud et al./1989 [58] Smooth NA NA NA 39.2 mm ROA NA NA NA Neg. Yoshida et al./1985 [59] Smooth Firm PM Neg. 34.1 mm LUOQ NA Well defined High Neg. Fond et al./1979 [60] NA NA M NA 20 mm RSA NA NA NA NA Konakry et a./1975 [61] NA NA NA NA 20 mm RUOQ NA NA NA Pos. NA NA NA NA 50 mm LUOQ NA NA NA NA NA NA NA NA 20 mm LUOQ NA NA NA NA NA NA NA NA 8 mm RUOQ NA NA NA NA NA NA NA NA 31.1 mm LUOQ NA NA NA NA Durso et al./1972 [62] Smooth NA NA NA 15 mm RUIQ NA NA NA NA N/A: Non-available, mm: Millimeters, Ax LAD: Axillary Lymphadenopathy, RUA: Right Upper Aspect, LLA: Left Lower Aspect, LT: Left, RT: Right, ROA: Right Outer Aspect, LUIQ: Left Upper Inner Quadrant, RLOQ: Right Lower Outer Quadrant, LUOQ: Left Upper Outer Quadrant, RLIQ: Right Lower Inner Quadrant, LIA: Left Inner Aspect, LOA: Left Outer Aspect, RUOQ: Right Upper Outer Quadrant, RRA: Right Retro-Areolar, BL: Bilateral, RLA: Right Lower Aspect, LRA: Left Retro-Areolar, LLOQ: Left Lower Outer Quadrant, LUA: Left Upper Aspect, RIA: Right Inner Aspect, RUIQ: Right Upper Inner Quadrant, RSA: Right Subareolar Area, Neg.: Negative, Pos.: Positive, NM: Non-Mobile, M: Mobile, PM: Partially mobile.   Table 4. Summary of radiology and biopsy findings. First Author. /Year Radiological findings Pre-operative diagnosis (CNB or FNAC) U/S MMG MRI Ni et al./2023 [14] Benign Benign Suspicious N/A Brunetti et al./2023 [4] Suspicious Benign N/A DCIS Wang et al./2022 [5] Benign N/A N/A Benign Pang et al./2022 [2] Benign Benign N/A Benign Hammood et al./2022 [3] Benign Benign Benign Benign Tagliati et al./2021 [1] Benign N/A Suspicious Benign Shojaku et al./2021 [6] Benign Benign Suspicious Malignant Fujimoto et al./2021 [11] Suspicious Suspicious Benign IDC Feijó et al./2021[8] Benign N/A N/A Suspicious Shiino et al./2020 [12] Suspicious Suspicious Suspicious IDC Moreno et al./2020 [17] N/A N/A N/A N/A Gonthong et al./2020 [13] Suspicious Suspicious Suspicious DCIS El-Essawy et al./2020 [18] Suspicious Suspicious Suspicious DCIS Brock et al./2020 [9] Benign Benign N/A Benign Marumoto et al./2019 [16] Suspicious Benign N/A Benign Zeeshan et al./2018 [19] Suspicious Suspicious N/A Benign Tiwari et al./2018 [15] Benign N/A N/A Benign Frisch et al./2018 [7] Benign N/A N/A N/A Lim et al./2017 [20] N/A N/A N/A N/A You et al./2016 [21] Suspicious Suspicious N/A Suspicious Zheng et al./2015 [22] Suspicious, Benign N/A, N/A N/A, N/A N/A, N/A Hua et al./2015 [23] Suspicious Suspicious N/A Benign Wu et al./2014 [24]   N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A Mele et al./2014 [25] Benign Suspicious Suspicious IAC Limite et al./2014 [26] Benign N/A N/A N/A Kwon et al./2014 [27] Benign, Benign N/A, N/A N/A, N/A Benign, Benign Kılıç et al./2014 [28] Benign Suspicious Benign DCIS Dandin et al./2014 [29] Suspicious N/A N/A N/A Buteau et al./2014 [30] N/A Benign Benign Benign Hayes et al./2013 [31] N/A Suspicious N/A Benign Jahan et al./2012 [32] Benign, Benign N/A, N/A N/A, N/A N/A, N/A Butler et al./2012 [33] Benign Benign N/A ILC – LCIS Ooe et al./2011 [34] Suspicious Benign Suspicious DCIS Lin et al./2011 [35] Benign Suspicious N/A IDC - DCIS Kato et al./2011 [36] Suspicious Suspicious Suspicious DCIS Abu-Rahmeh et al./ 2012 [37] Benign Benign N/A IDC Rao et al./ 2010 [38] Benign Benign N/A Malignant Petersson et al./2010 [39] N/A Benign N/A N/A Tajima et al./2009 [40] Suspicious Suspicious Suspicious Malignant Gashi-Luci et al./2009 [41] Suspicious Suspicious N/A Benign Borecky et al./2008 [42] Suspicious Suspicious N/A IDC - DCIS Suspicious Suspicious N/A IC Suspicious Suspicious N/A IDC - DCIS Tiu et al./2006 [43] Benign Benign N/A Malignant Shin et al./2006 [44] Suspicious Suspicious Suspicious DCIS Blanco et al./2005 [45] N/A Benign N/A N/A Abite et al./2005 [46] N/A N/A N/A N/A Stafyla et al./2004 [47] Benign N/A N/A N/A Abe et al./ 2004 [48] Suspicious Benign N/A Benign Adelekan et al./2003 [49] N/A, N/A Benign, Benign N/A, N/A Benign, Malignant Yano et al./2001 [50] Benign Suspicious Benign Malignant Gebrim et al./2000 [51] N/A Suspicious N/A Benign Psarianos et al./1998 [52] Benign Benign N/A N/A Shah et al./ 1998 [53] N/A Benign N/A Benign Kurosum et al./1994 [54] Benign N/A N/A N/A Morimoto et al./1993 [55] N/A N/A N/A Benign Gupta et al./1992 [56] N/A Suspicious N/A Malignant Gupta et al./1991 [57] N/A Benign N/A Malignant Fukud et al./1989 [58] Benign Benign N/A N/A Yoshida et al./1985 [59] N/A Suspicious Suspicious N/A Fond et al./1979 [60] N/A N/A N/A Benign Konakry et a./1975 [61] N/A Suspicious N/A N/A N/A Benign N/A N/A N/A Benign N/A N/A N/A Benign N/A N/A N/A Benign N/A N/A Durso et al./1972 [62] N/A Benign N/A N/A N/A: non-available, U/S: Ultrasound, MMG: Mammogram, MRI: Magnetic Resonance Imaging, CNB: Core Needle Biopsy, FNAC: Fine Needle Aspiration Cytology, DCIS: Ductal Carcinoma In Situ, IDC: Invasive Ductal Carcinoma, CIS: Carcinoma In Situ, IAC: Invasive apocrine carcinoma, ILC: Invasive Lobular Carcinoma, LCIS: Lobular Carcinoma In Suspicious, IC: Invasive Carcinoma.   Table 5. Breast carcinoma management strategies. First Author /Year Management   Hormonal therapy Breast surgery Axillary surgery Chemotherapy  Radiotherapy Ni et al./2023 [14] WLE SLNB No No NA Brunetti et al./2023 [4] WLE ALND Yes NA NA Wang et al./2022 [5] EB None NA Yes Yes Pang et al./2022 [2] WLE None No NA Yes Hammood et al./2022 [3] WLE None NA NA Yes Tagliati et al./2021 [1] WLE None NA No NA Shojaku et al./2021 [6] WLE SLNB NA Yes NA Fujimoto et al./2021 [11] WLE SLNB Yes Yes NA Feijó et al./2021[8] WLE None Yes Yes NA Shiino et al./2020 [12] MX ALND Yes Yes NA Moreno et al./2020 [17] MX None NA NA NA Gonthong et al./2020 [13] MX ALND No No Yes El-Essawy et al./2020 [18] WLE None NA NA NA Brock et al./2020 [9] WLE None NA NA NA Marumoto et al./2019 [16] EB None No Yes Yes Zeeshan et al./2018 [19] WLE None NA Yes Yes Tiwari et al./2018 [15]  WLE None No No NA Frisch et al./2018 [7] WLE NA NA No Yes Lim et al./2017 [20] WLE None No No No You et al./2016 [21] WLE None NA NA Yes Zheng et al./2015 [22] MX ALND Yes NA Yes Hua et al./2015 [23] MX None NA NA Yes Wu et al./2014 [24]   WLE SLNB No No Yes MX ALND Yes No Yes WLE NA No No Yes WLE SLNB No Yes Yes WLE SLNB No No No MX SLNB No No Yes Mele et al./2014 [25] MRM ALND NA NA NA Limite et al./2014 [26] WLE SLNB No No NA Kwon et al./2014 [27] WLE None NA Yes NA Kılıç et al./2014 [28] WLE None NA NA NA Dandin et al./2014 [29] WLE ALND Yes NA NA Buteau et al./2014 [30] WLE ALND Yes Yes Yes Hayes et al./2013 [31] WLE SLNB NA NA NA Jahan et al./2012 [32] WLE None NA NA NA Butler et al./2012 [33] WLE None NA NA NA Ooe et al./2011 [34] WLE SLNB No Yes Yes Lin et al./2011 [35] MRM None NA NA NA Kato et al./2011 [36] WLE SLNB NA NA NA Abu-Rahmeh et al./ 2012 [37] NA NA NA NA NA Rao et al./ 2010 [38] MRM ALND NA NA NA Petersson et al./2010 [39] EB SLNB NA NA NA Tajima et al./2009 [40] WLE None NA NA NA Gashi-Luci et al./2009 [41] RM ALND NA NA NA Borecky et al./2008 [42] NA NA NA NA NA NA NA NA NA NA EB SLNB NA NA NA Tiu et al./2006 [43] MX None NA NA NA Shin et al./2006 [44] MX SLNB NA NA NA Blanco et al./2005 [45] WLE SLNB NA NA NA Abite et al./2005 [46] EB None NA NA NA Stafyla et al./2004 [47] EB None No No NA Abe et al./ 2004 [48] MX ALND Yes NA Yes Adelekan et al./2003 [49] EB, MRM None, ALND Yes Yes Yes Yano et al./2001 [50] WLE ALND NA Yes NA Gebrim et al./2000 [51] MX ALND NA NA NA Psarianos et al./1998 [52] EB None NA NA NA Shah et al./ 1998 [53] WLE NA NA NA NA Kurosum et al./1994 [54] WLE None NA Yes NA Morimoto et al./1993 [55] WLE None Yes NA NA Gupta et al./1992 [56] WLE None NA Yes Yes Gupta et al./1991 [57] WLE ALND NA Yes NA Fukud et al./1989 [58] MRM NA NA NA NA Yoshida et al./1985 [59] RM ALND No No NA Fond et al./1979 [60] MRM ALND NA NA NA Konakry et a./1975 [61] RM NA NA NA NA MRM NA NA NA NA MRM NA NA NA NA MX NA NA NA NA MRM NA NA NA NA Durso et al./1972 [62] EB None NA NA NA NA: non-available, WLE: Wide Local Excision, EB: Excisional Biopsy, RM: Radical Mastectomy, MRM: Modified Radical Mastectomy, MX: Mastectomy, ALND: Axillary Lymph Node Dissection, SLNB: Sentinel Lymph Node Biopsy.   Table 6. Clinical outcomes of the disease. First Author /Year Post-operative HPE Immunohistochemistry (ER-PR-HER2) Axillary status FU (months) Recurrence Metastasis Ni et al./2023 [14] DCIS ER - PR Neg. NA NA No Brunetti et al./2023 [4] IDC TN Pos. NA NA Yes Wang et al./2022 [5] ILC - LCIS ER – PR NA NA NA NA Pang et al./2022 [2] LCIS NA NA 4 No No Hammood et al./2022 [3] DCIS NA NA NA No No Tagliati et al./2021 [1] DCIS ER – PR NA 60 No No Shojaku et al./2021 [6] DCIS ER NA 24 No No Fujimoto et al./2021 [11] IDC HER2 Neg. 6 No No Feijó et al./2021[8] DCIS ER – PR NA 48 No No Shiino et al./2020 [12] IDC TN Neg. 30 No No Moreno et al./2020 [17] LCIS NA NA 120 No No Gonthong et al./2020 [13] DCIS TN Neg. 12 No No El-Essawy et al./2020 [18] NA TN NA NA NA NA Brock et al./2020 [9] LCIS NA NA NA NA NA Marumoto et al./2019 [16] DCIS ER NA 12 No No Zeeshan et al./2018 [19] DCIS ER – PR NA NA NA No Tiwari et al./2018 [15] DCIS NA NA 12 No No Frisch et al./2018 [7] DCIS ER NA NA NA No Lim et al./2017 [20] CA TN NA 21 No No You et al./2016 [21] DCIS ER – PR NA 52 No No Zheng et al./2015 [22] ILC, IDC HER2, ER-PR-HER2 Neg., Neg. 3 No No Hua et al./2015 [23] LCIS ER – PR NA 60 No No Wu et al./2014 [24]   IDC ER – PR Neg. NA NA NA IDC ER – PR Pos. NA NA NA DCIS ER – PR NA NA NA NA DCIS ER – PR Neg. NA NA NA DCIS NA Neg. NA NA NA IDC ER – PR Neg. NA NA NA Mele et al./2014 [25] IAC HER2 Pos. NA NA NA Limite et al./2014 [26] ACC (Ac) TN Neg. 8 No No Kwon et al./2014 [27] DCIS, DCIS ER – PR, ER - PR NA, NA NA, NA NA NA Kılıç et al./2014 [28] DCIS NA NA NA NA NA Dandin et al./2014 [29] IDC - ILC - DCIS PR - HER2 Neg. 6 No No Buteau et al./2014 [30] ILC NA Pos. NA No No Hayes et al./2013 [31] ILC ER Neg. NA NA NA Jahan et al./2012 [32] IDC, IDC NA, NA NA, NA NA, NA NA NA Butler et al./2012 [33] ILC - LCIS NA NA NA NA NA Ooe et al./2011 [34] DCIS ER – PR Neg. 6 No No Lin et al./2011 [35] IDC - DCIS ER – PR NA 24 No No Kato et al./2011 [36] DCIS NA Neg. NA NA NA Abu-Rahmeh et al./ 2012 [37] IDC NA NA NA NA Yes Rao et al./ 2010 [38] IDC TN Pos. NA NA NA Petersson et al./2010 [39] IDC - DCIS ER – PR Neg. 24 No No Tajima et al./2009 [40] ILC - LCIS ER NA NA NA NA Gashi-Luci et al./2009 [41] IDC - DCIS HER2 Neg. 5 Yes NA Borecky et al./2008 [42] IDC - DCIS ER – PR Neg. NA NA NA IDC NA Neg. NA NA NA IDC - DCIS NA Neg. NA NA NA Tiu et al./2006 [43] DCIS NA NA 18 No No Shin et al./2006 [44] IDC - DCIS ER – PR Neg. 16 No No Blanco et al./2005 [45] ACC (Ad) TN Neg. NA NA NA Abite et al./2005 [46] IDC NA NA NA NA NA Stafyla et al./2004 [47] LCIS NA NA 24 No No Abe et al./ 2004 [48] IDC PR Pos. 59 No No Adelekan et al./2003 [49] IC, LCIS - DCIS NA, NA NA, Pos. NA, NA NA No Yano et al./2001 [50] LCIS NA Neg. 24 No No Gebrim et al./2000 [51] ILC NA Neg. NA No No Psarianos et al./1998 [52] DCIS NA NA NA NA NA Shah et al./ 1998 [53] LCIS NA NA 25 No No Kurosum et al./1994 [54] IDC NA NA NA NA No Morimoto et al./1993 [55] LCIS NA NA 132 No No Gupta et al./1992 [56] DCIS NA NA 9 No No Gupta et al./1991 [57] CA NA Neg. 10 No No Fukud et al./1989 [58] LCIS NA NA NA No No Yoshida et al./1985 [59] ILC ER Neg. 32 No No Fond et al./1979 [60] DCIS NA Neg. NA NA NA Konakry et a./1975 [61] LCIS NA Neg. 60 No No LCIS NA Neg. 36 No No LCIS NA Neg. 36 No No LCIS NA Neg. 24 No No LCIS NA Neg. NA No No Durso et al./1972 [62] LCIS NA NA NA NA NA NA: non-available, DCIS: Ductal Carcinoma In Situ, IDC: Invasive Ductal Carcinoma,  CIS: Carcinoma In Situ, IAC: Invasive apocrine LCIS - DCIScarcinoma, ILC: Invasive Lobular Carcinoma, LCIS: Lobular Carcinoma In Suspicious, , ACC (ac): Acinic Cell Carcinoma, ACC (Ad): Adenoid Cystic Carcinoma, IC: Invasive Carcinoma, CA: Carcinoma, ER: Estrogen Receptor, PR: Progesterone Receptor, HER2: Human Epidermal Growth Factor Receptor 2, TN: Triple Negative, HPE: Histopathological Examination, Pos.: positive, Neg.: negative, FU: Follow-up. Patients and tumor characteristics The total number of patients was 72 females, with a mean age of 44.4 ± 13.6 years. Most patients presented with either a breast lump (43.1%) or a mass (30.5%), with a median presentation duration of 12 months. In 80.6% of cases, the disease was unilateral, with laterality distributed almost equally between the right side (42.1%) and the left (39.5%). The mean tumor size was 24.7 ± 13.3 millimeters. The past medical history was negative in 27.8% of cases, while seven cases (9.7%) had a positive history of other breast diseases, including breast mass in four cases and DCIS, fibrocystic breast disease, and IDC per case. The family history of breast cancer was positive in four cases (5.5%). On physical examination, information about the tumor surface was available for nine tumors (11.8%), all of which had a smooth surface. Of the 22 tumors with available data on consistency, 14 (63.6%) were firm, five (22.7%) were hard, and three (13.6%) were rubbery. Among the 28 tumors with existing mobility data, 25 (89.3%) were found to be mobile. Axillary lymphadenopathy was reported in four tumors (5.3%). On ultrasonography, 28 masses appeared benign (36.8%), and 20 cases were suspicious (26.3%), with ultrasonographic data unavailable for the remaining tumors (36.8%). Mammography data were available for 50 tumors, revealing 27 benign lesions (54%) and 23 suspicious lesions (46%). Among the 17 lesions with available magnetic resonance imaging (MRI) data, five were benign lesions (29.4%), and 12 were suspicious (70.6%). Core needle biopsy (CNB) or fine needle aspiration cytology (FNAC) revealed that 20 tumors (26.3%) were benign, 24 (31.6%) were malignant, and two (2.6%) were suspicious. The data on preoperative diagnosis was unavailable for 30 cases (39.5%). (Table 7). Table 7. Baseline characteristics summary of the included studies. Variables Frequency/ percentages Study design    Case report    Case series   58 (95.0%) 3 (5.0 %) Country    Japan    USA    Korea    Brazil    China    Italy    Taiwan    Australia    India    New Zealand    Singapore    Turkey    Others   12 (19.7%) 9 (14.7%) 4 (6.6%) 3 (4.9%) 3 (4.9%) 3 (4.9%) 3 (4.9%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 14 (22.9%) Age range (mean ± SD) 18-80 (44.4 ± 13.6) Gender    Female   72 (100%) Presentation    Lump    Mass    Incidental    Nodule    Nipple discharge    N/A   31 (43.1%) 22 (30.5%) 3 (4.1%) 2 (2.8%) 1 (1.4%) 13 (18.1%) Duration of presentation, median (Q1 - Q3), months 12 (2-60) Laterality    Unilateral    Bilateral    N/A   58 (80.6%) 6 (8.3%) 8 (11.1%) Tumor location    Right    Left    Bilateral    N/A   32 (42.1%) 30 (39.5%) 1 (1.3%) 13 (17.1%) Tumor size (mean ± SD), mm 24.7 ± 13.3 PMH    Nothing noteworthy    Breast mass    Hypertension    CAH    DCIS    Fibrocystic breast disease    IDC    N/A   20 (27.8%) 4 (5.5%) 1 (1.4%) 1 (1.4%) 1 (1.4%) 1 (1.4%) 1 (1.4%) 43 (59.7%) Family history of breast cancer    Positive    Negative    N/A   4 (5.5%) 31 (43.1%) 37 (51.4%) Surface of the mass    Smooth    N/A   9 (11.8%) 67 (88.2%) Consistency of the mass    Firm    Hard    Rubbery    N/A   14 (18.4%) 5 (6.6%) 3 (3.9%) 54 (71.1%) Mobility of the mass    Mobile    Non-mobile    Partially fixed    N/A   25 (32.9%) 2 (2.6%) 1 (1.3%) 48 (63.2%) Axillary Lymphadenopathy    Negative    Positive    N/A   27 (35.5%) 4 (5.3%) 45 (59.2%) Radiological findings   Ultrasonography    Benign    Suspicious    N/A   28 (36.8%) 20 (26.3%) 28 (36.8%) Mammography    Benign    Suspicious    N/A   27 (35.5%) 23 (30.3%) 26 (34.2%) Magnetic resonance imaging    Suspicious    Benign    N/A   12 (15.8%) 5 (6.6%) 59 (77.6%) Shape of the mass    Oval    Irregular    Lobular    Round    Multilobulated    N/A   15 (19.7%) 2 (2.6%) 2 (2.6%) 2 (2.6%) 1 (1.3%) 54 (71.1%) Margin of the mass    Well defined    Irregular    Ill-defined    Lobulated    Smooth    Microlobulated    Circumscribed    N/A   32 (42.1%) 7 (9.2%) 4 (5.3%) 3 (4%) 2 (2.6%) 1 (1.3%) 1 (1.3%) 26 (34.2%) Vascularity of the mass    Yes    No    N/A   8 (10.5%) 2 (2.6%) 66 (86.8%) Calcification    Positive    Negative    N/A   24 (31.6%) 11 (14.5%) 41 (53.9%) Cytology (CNB or FNAC)    Benign    Malignant (non-specified)    DCIS    IDC    IDC – DCIS    Suspicious    IC    ILC – LCIS    Invasive apocrine carcinoma    N/A   20 (26.3%) 8 (10.5%) 7 (9.2%) 3 (4%) 3 (4%) 2 (2.6%) 1 (1.3%) 1 (1.3%) 1 (1.3%) 30 (39.5%) Breast surgery    Wide local excision    Mastectomy    Excisional biopsy    N/A   37 (50.7%) 24 (32.9%) 9 (12.3%) 3 (4.1%) Axillary surgery    ALND    SLNB    None    N/A   17 (23.3%) 15 (20.6%) 29 (39.7%) 12 (16.4%) Chemotherapy    Yes    No    NA   11 (15.3%) 15 (20.8%) 46 (63.9%) Radiation therapy    Yes    No    NA   16 (22.2%) 14 (19.4%) 42 (58.3%) Hormonal therapy    Yes    No    NA   20 (27.8%) 2 (2.8%) 50 (69.4%) Post-operative HPE    DCIS    LCIS    IDC    IDC - DCIS    ILC    ILC - LCIS    Carcinoma (non-specified)    Acinic cell carcinoma    Adenoid cystic carcinoma    IDC - ILC - DCIS    Invasive apocrine carcinoma    LCIS – DCIS     N/A   23 (30.3%) 15 (19.7%) 15 (19.7%) 6 (7.9%) 5 (6.6%) 3 (4%) 3 (4%) 1 (1.3%) 1 (1.3%) 1 (1.3%) 1 (1.3%) 1 (1.3%) 1 (1.3%) Immunohistochemistry    ER – PR    Triple-negative    ER    HER2    ER - PR - HER2    PR - HER2    PR    N/A   19 (25%) 8 (10.5%) 6 (7.9%) 4 (5.3%) 1 (1.3%) 1 (1.3%) 1 (1.3%) 36 (47.4%) Axillary status    Positive    Negative    N/A   7 (9.2%) 32 (42.1%) 37 (48.7%) Follow-up, median (Q1-Q3), months 24 (10-36) Recurrence    No    Yes    N/A   38 (52.8%) 1 (1.4%) 33 (45.8%) Metastasis    No    Yes    N/A   43 (59.7%) 2 (2.8%) 27 (37.5%) SD: Standard Deviation, N/A: non-available, CAH: Congenital Adrenal Hyperplasia, DCIS: Ductal Carcinoma In Situ, IDC: Invasive Ductal Carcinoma, CNB: Core Needle Biopsy, FNAC: Fine Needle Aspiration Cytology, CIS: Carcinoma In Situ, IC: Invasive Carcinoma, ILC: Invasive Lobular Carcinoma, LCIS: Lobular Carcinoma In Situ, ALND: Axillary Lymph Node Dissection, SLNB: Sentinel Lymph Node Biopsy, HPE: Histopathological Examination, ER: Estrogen Receptor, PR: Progesterone Receptor, HER2: Human Epidermal Growth Factor Receptor 2, Q1:first quartile, Q3: third quartile, PMH: past medical history. Management and outcome The most commonly performed surgery was wide local excision (50.7%), followed by mastectomy (32.9%). Axillary lymph node dissection was carried out in 43.9% of cases. A total of 11 cases (15.3%) received chemotherapy, 16 cases (22.2%) underwent radiotherapy, and hormonal therapy was prescribed for 20 cases (27.8%). On histopathological examination, 11 tumors exhibited more than one pathology. DCIS was the most frequent finding (40.8%), followed by IDC (28.9%) and LCIS (28.4%). Immunohistochemical analysis showed that 20 out of 40 tumors (50%) were positive for both estrogen (ER) and progesterone receptors (PR). Of the 39 tumors with reported axillary status, 82.1% had negative axillary findings. The median follow-up period was 24 months, with quartile ranges of 10 to 36 months. Recurrence was observed in one case (1.4%), and metastasis occurred in two cases (2.8%) (Table 7). Discussion Carcinomas and high-risk lesions within fibroadenomas can either originate from the fibroadenoma itself and remain entirely encapsulated, or they can involve both the fibroadenoma and the adjacent breast tissue [2]. While rare, a small percentage of fibroadenomas may contain carcinomas or high-risk lesions, with reported incidence rates ranging from 0.002% to 0.125%. Fibroadenomas with malignant components are primarily found in patients 10 to 20 years older than the typical age for simple fibroadenomas [2]. In this systematic review, the mean age of affected patients was 44.4 years, further highlighting the trend of malignancies occurring in later decades of life. The role of fibroadenomas as a potential risk factor for breast cancer is still not fully established [8]. It has been suggested that they may represent a long-term risk factor for breast cancer, particularly in women with complex fibroadenomas, proliferative disease, or a family history of breast cancer. Specifically, complex fibroadenomas are associated with a relative breast cancer risk that is approximately 3.10 times greater [6]. Another significant indicator of potential malignant transformation in fibroadenomas is the progressive mass size and thickness increase with advancing patient age [3]. A study has reported that the average tumor diameter of breast cancer occurring within a fibroadenoma is 2.46 cm [11]. Similarly, the mean tumor size in this systematic review was 2.47 ± 13.3 cm. Frisch et al. reported that the predominant form of malignancy associated with breast cancer arising in fibroadenomas was CIS, with LCIS accounting for 66.9% and DCIS comprising 12.4%. Additionally, IDCs were more frequent among the invasive cases than ILCs [7]. Conversely, another study found that ductal and lobular carcinomas occur with equal frequency [6]. In this study, the distribution of malignancies within fibroadenomas revealed distinct differences from Frisch et al.’s study [7]. Notably, DCIS was the most frequent malignancy, accounting for 40.8% of tumors and LCIS represented 28.4% of tumors. The incidence of IDC was higher in this review at 28.9%, compared to 11% in the prior study [7]. Additionally, rarer malignancies like acinic cell carcinoma, adenoid cystic carcinoma, and invasive apocrine carcinoma were observed, suggesting a broader spectrum of tumor types associated with fibroadenomas than traditionally recognized. The neoplastic proliferation of epithelial cells within the breast lobule characterizes LCIS. It is considered a precursor to ILC, similar to the relationship between DCIS and IDC. LCIS is now recognized as a general marker for breast cancer risk rather than a definitive pre-cancerous condition. It has been indicated that neoplasms within fibroadenomas behave similarly and have comparable prognoses to those occurring independently [9]. DCIS, also known as intraductal carcinoma, is a neoplasm that does not invade the basement membrane. This type of breast carcinoma develops within the ductal system, particularly in the terminal lobular duct unit. Although DCIS cannot metastasize and is considered non-lethal, its presence indicates an increased risk of developing invasive cancer if left untreated [8]. The preoperative diagnosis of malignant transformation within fibroadenoma is difficult and often necessitates surgical intervention for definitive confirmation [3]. This challenge stems from the overlap in clinical and radiological features between benign and malignant fibroadenomas, making it difficult to distinguish between the two preoperatively [4]. However, certain imaging characteristics can help identify carcinoma within fibroadenomas.  Such malignancies tend to present with larger size, irregular shape, poorly defined margins, and abnormal calcifications, including linear, pleomorphic, or microcalcifications [12]. Sonographic evaluation of carcinomas within fibroadenomas typically reveals irregular lesions with indistinct borders. These tumors are often associated with marked hypoechoic shadowing, an echogenic halo, and distortion of surrounding tissue. Ultrasound is beneficial for tumor size assessment due to its high-resolution imaging capabilities. While mammography may reveal indistinct borders and microcalcifications, it is insufficient for diagnosing fibroadenomas with underlying carcinoma. Nonetheless, microcalcifications on mammography remain a valuable indicator of malignant transformation [3]. When calcifications are identified on mammography, ultrasound can be used to evaluate the invasiveness of the lesion and guide biopsy. Additionally, Doppler color imaging provides further insights into the internal vascularity of the tumor [13]. Dynamic MRI offers a reliable method for distinguishing malignant transformations from benign fibroadenomas by highlighting differences in vascularity. Benign fibroadenomas typically appear as round or oval masses with smooth margins on MRI, showing consistent enhancement into the late phase. In contrast, malignant lesions often display rapid early enhancement with variability in delayed enhancement, a hallmark of carcinoma [3]. Detecting malignant transformation can be particularly challenging, as clinical and radiological signs may remain masked until the tumor breaches the false capsule. As a result, definitive diagnosis is usually made through histopathological examination, emphasizing the importance of maintaining a high index of suspicion in these cases [3,4]. In the present study, of the 22 cases that reported tumor shape on imaging, 15 (68.2%) presented with an oval shape, while two cases (9.1%) showed an irregular shape. Tumor margins were well-defined in 32 out of 50 cases (64%), whereas seven (14%) exhibited irregular margins. Among the 10 cases reporting tumor vascularity, eight (80%) showed increased or high vascularity. Calcifications were observed in 24 out of 35 cases (68.6%) that provided data on this feature. Common clinical techniques for obtaining pathological information include FNAC, hollow CNB, and mass excision biopsy. However, due to the inherent heterogeneity of these lesions, FNAC and CNB may not always provide conclusive results to definitively exclude malignancy in benign breast lesions that carry an increased risk of cancer development. Consequently, an open biopsy is recommended as a more reliable method for accurate diagnosis [15]. If imaging studies of a fibroadenoma indicate enlargement or any abnormal changes during follow-up examinations, it is essential to perform a CNB to ensure a definitive assessment. For patients aged 40 years and older with clinically benign fibroadenomas, clinicians should engage in discussions with these patients regarding the potential necessity of a CNB. This proactive approach allows for a thorough evaluation of changes and ensures appropriate diagnostic measures are implemented [12]. The diagnosis of fibroadenoma with carcinoma in the breast is contingent upon several critical criteria. Firstly, there must be clear evidence of epithelial heterogeneous hyperplasia or carcinoma within the fibroadenoma. Secondly, the cancerous tissue should remain confined to the capsule of the fibroadenoma, with only minimal focal infiltration into the surrounding breast tissue. Thirdly, it is crucial to exclude the possibility of infiltration from adjacent breast cancer into the fibroadenoma, as the coexistence of breast cancer and fibroadenoma does not qualify as intra-fibroadenoma carcinoma. Finally, the diagnosis must be supported by the results of immunohistochemical markers. These criteria facilitate a thorough and accurate assessment of fibroadenoma with carcinoma [15]. In this systematic review, pre-operative tissue biopsy using either CNB or FNAC was available for 46 tumors. Malignant features were observed in 24 tumors (52.2%), two tumors (4.3%) exhibited suspicious features, and 20 tumors (43.5%) were classified as benign. These findings highlight the importance of pre-operative biopsy and the challenges in accurately identifying the presence of malignancy in fibroadenomas. Given the rarity of malignancy arising within fibroadenomas, standardized management guidelines are not well-established, leaving uncertainty as to whether these patients should be treated similarly to breast cancer patients or with a distinct approach. For benign fibroadenomas, lumpectomy remains the treatment of choice. However, if the tumor is close to or involves the resection margin, wider local excision may be necessary to ensure complete removal. Factors such as large tumor size, multifocality, and central breast location may also necessitate consideration of mastectomy [3,4,16]. If surgical margins are free of cancer, lumpectomy alone is often sufficient. The overall management strategy is dictated by the stage of the disease and the degree of metastasis, whether localized or distant. Conservative management, such as lumpectomy or wide local excision, is usually appropriate for small tumors. In cases of local metastasis, especially involving the axillary lymph nodes, axillary lymph node dissection is typically performed to ensure proper treatment [3]. Surgical intervention remains the definitive treatment and may be combined with radiotherapy or chemotherapy depending on individual case specifics [16]. In the current study, the most common procedure was wide local excision (50.7%), followed by mastectomy (32.9%). Excisional biopsy was performed in 12.3% of the cases. Axillary lymph node dissection was performed in 17 cases (23.3%), while sentinel lymph node biopsy was carried out in 15 cases (20.6%). Twenty-nine cases (39.7%) did not undergo axillary surgery. This variation in axillary management highlights the individualized approach to surgical treatment based on tumor characteristics, lymph node involvement, and disease progression. The use of radiotherapy remains a topic of debate, with chemotherapy being the preferred treatment option in cases involving nodal metastasis. Some authors suggested that breast cancer arising within a fibroadenoma exhibits similar behavior to breast cancer at the same stage. Consequently, the treatment approach should align with standard breast cancer protocols, following similar therapeutic modalities [4,5,11,17]. The positive impact of radiation therapy on both survival rates and recurrence prevention when combined with lumpectomy has been reported. This approach is regarded as the standard of care for breast-conserving therapy in cases of DCIS and breast cancer. However, radiation therapy is not without drawbacks. It carries inherent risks, financial costs, and potential negative effects on patients' quality of life. Notably, long-term complications such as lung cancer and heart disease have been associated with breast cancer radiation therapy, particularly in patients who have a history of smoking [17]. Ni et al. stated that DCIS within a fibroadenoma is a heterogeneous condition with significant variability in local recurrence risks among patients. Consequently, the overall benefits of postoperative radiation therapy differ based on individual patient risk profiles. Low-risk patients who undergo breast-conserving surgery (BCS) without subsequent radiotherapy experience limited advantages from radiation. In contrast, high-risk patients show a greater benefit from the addition of radiotherapy. For instance, it has been revealed that patients treated with BCS alone had 8-year recurrence rates of 0%, 21.5%, and 32.1% for low-, intermediate-, and high-risk groups, respectively. This highlights the need for personalized treatment approaches based on risk stratification [15]. The current National Comprehensive Cancer Network (NCCN) guidelines recommend ER testing for patients with DCIS and advise considering tamoxifen for women with ER-positive disease, particularly those who undergo BCS without radiation. The goal is to optimize treatment outcomes and minimize the chances of cancer recurrence [7]. In this study, the data on chemotherapy was available for only 26 cases, of which 11 (42.3%) underwent chemotherapy as part of their treatment regimen.  Additionally, among 30 cases with information on radiation therapy, 16 cases (53.3%) received the treatment regimen. Furthermore, 22 cases addressed hormonal therapy, and 20 (90.9%) indicated it was utilized in the treatment protocols. Some scholars indicated that breast cancer developing within a fibroadenoma is generally associated with a more favorable prognosis compared to conventional breast cancer. This is primarily attributed to the higher incidence of hormone receptor (HR)-positive tumors in this subset, along with the frequent presentation of CIS and early-stage disease at diagnosis [12]. However, the prevalence of hormone receptor positivity in these cases may not significantly differ from that seen in typical breast cancer. ER positivity has been reported at 68.8%, and PR positivity at 62.5%, figures closely aligned with those observed in conventional breast cancer [11]. Despite these favorable characteristics, it has been indicated that approximately 10% of patients diagnosed with CIS within a fibroadenoma experience recurrence or metastasis, emphasizing the need for continued surveillance and individualized treatment strategies, even in cases with seemingly better prognostic indicators [3]. In this systematic review, among the 40 tumors with available hormone receptor status, six (15%) were HR-positive. The ER was positive in 26 tumors (65%), and PR was positive in 22 tumors (55%). The median follow-up duration was 24 months, during which one case (1.4%) reported recurrence, and two cases (2.8%) experienced metastasis. The primary limitation of this study is the lack of data on several variables in the reviewed studies, which may impact the generalizability of the findings. Conclusion Although rare, carcinomas arising within fibroadenomas may present considerable challenges in preoperative diagnosis, whether through imaging or cytology. Therefore, clinicians may find it necessary to approach fibroadenomas with increased caution. Declarations Conflicts of interest: The author(s) have no conflicts of interest to disclose. Ethical approval: Not applicable, as systematic reviews do not require ethical approval. Patient consent (participation and publication): Not applicable. Funding: The present study received no financial support. Acknowledgements: None to be declared. Authors' contributions: AMS, LRAP and SL were significant contributors to the conception of the study and the literature search for related studies.  BAA, DAH, BOH, HAH, SHS, DAO, SSA and SMA were involved in the literature review, the study's design, and the critical revision of the manuscript, and they participated in data collection. MGH, MNH and HOA were involved in the literature review, study design, and manuscript writing. YMM, HAH and SSO Literature review, final approval of the manuscript, and processing of the tables. HOA and AMS confirm the authenticity of all the raw data. All authors approved the final version of the manuscript. Use of AI: AI was not used in the drafting of the manuscript, the production of graphical elements, or the collection and analysis of data. Data availability statement: Note applicable.