A Case Report of Recurrent Bilateral Giant Fibroadenomas in a Young Woman with PIK3CA Mutation

A Case Report of Recurrent Bilateral Giant Fibroadenomas in a Young Woman with PIK3CA Mutation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Case Report of Recurrent Bilateral Giant Fibroadenomas in a Young Woman with PIK3CA Mutation Yuemei Zhang, Qixing Tan, Yugui Xiao, Wenhao Wang, Shengkai Huang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6695035/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Oct, 2025 Read the published version in BMC Women's Health → Version 1 posted 13 You are reading this latest preprint version Abstract Background Breast fibroadenoma is a common benign tumor of the breast. Giant fibroadenoma accounts for about 0.5-2.0% of all breast fibroadenomas, the cause of which remains unclear. PIK3CA mediates various cellular processes and is frequently mutated in solid malignancies. However, the association between breast fibroma and gene mutations remains unclear. Case report This article reviews a case involving recurrent bilateral giant fibroadenomas with a PIK3CA mutation, exploring causative factors, treatment modalities, and post-treatment recommendations. Conclusion The etiology of giant fibroadenoma of the breast may be related to sex hormones, and in addition to surgical intervention, the recommendation is to actively seek systemic drugs as complementary treatment. Although PIK3CA mutations are rare in patients with breast fibroadenoma, their coexistence increases the risk of breast cancer. Therefore, close monitoring is essential, and once malignant breast lesions occur, rapid diagnosis and intervention are necessary. Recurrent Bilateral Giant Fibroadenomas Young Woman PIK3CA Mutation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Fibroadenomas stand as the most prevalent benign breast tumors in women [ 1 ], boasting an incidence rate of 27.6%, notably affecting young women aged 20–30 years [ 2 ]. Giant fibroadenomas, characterized by their size exceeding 5cm and weight surpassing 500g [ 3 ], occupying over 4/5 of breast volume, constitute approximately 0.5-2% of all breast fibroadenomas [ 4 ]. Certain variants, particularly those hormonally influenced, such as juvenile fibroadenomas and lactating adenomas, may manifest rapid growth [ 2 ]. Hormonal factors are believed to contribute to the pathogenesis of fibroadenomas [ 5 ]. Although the likelihood of fibroadenomas undergoing malignant transformation is rare, with rates ranging between 0.002–0.124% [ 6 ], studies suggest that their growth can profoundly affect patients' physical and psychological well-being, potentially elevating the risk of breast cancer [ 7 , 8 ]. Presently, the primary diagnostic and therapeutic strategy for giant fibroadenomas revolves around complete surgical excision, which boasts high safety and low recurrence rates [ 9 , 10 ]. PIK3CA is involved in numerous physiological processes within cells, including the promotion of cell transformation, tumor occurrence and proliferation, and resistance to apoptosis [ 11 ]. While PIK3CA mutations are commonly found in solid tumors such as gastric cancer, colorectal cancer, liver cancer, and breast cancer, they are relatively rare in breast fibroadenomas [ 12 – 15 ]. The presence of PIK3CA mutations in breast fibroadenomas was initially reported by Panagiotis A. Vorkas and colleagues [ 16 ]. We present the case of a 23-year-old woman who presented with bilateral multiple giant fibroadenomas. Despite undergoing surgical treatment, the patient experienced postoperative recurrence, the cause of which remains unknown. This recurrence has significantly impacted her quality of life and was accompanied by a PIK3CA gene mutation. This case is rare and complex, prompting further exploration and analysis of its etiology, treatment options, and follow-up recommendations. Case Report A 23-year-old female patient presented at our hospital in January 2024, approximately four years post-bilateral breast lump excision surgery, with a recurrence of bilateral breast lumps persisting for over two years. In 2019, the patient noticed multiple palpable breast lumps, each approximately 4.0×4.0cm in size. Subsequently, in July of the same year, the patient underwent excision surgery for multiple bilateral breast masses, with over 40 masses removed from each breast. Pathological examination indicated multiple fibroadenomas with intraductal papillomas and adenosis. The largest nodules measured 0.8-4.0cm and 0.7-5.5cm in diameter in the left and right breasts, respectively, accompanied by local calcifications and ductal hyperplasia. Two years later, the patient noticed recurrent breast lumps that progressively increased in size, prompting medical consultation. Her past, personal, and family medical history was unremarkable. On examination, a firm, non-tender mass approximately 7.5×3.5cm in size was palpable at the 11 o'clock position of the right breast, while a mass approximately 9.5×8.2cm in size was palpable at the 4 o'clock position of the left breast. Both breasts exhibited significant ptosis (Fig. 1 ). Preoperative investigations revealed prolactin levels of 52.5ng/ml, estradiol of 71pg/ml, and progesterone of 0.16ng/ml. Ultrasound showed multiple solid lesions in both breasts, while breast MRI revealed diffuse multiple nodules and mass shadows of varying sizes in all quadrants of both breasts, with the largest lesion measuring approximately 10.7 × 8.1× 7.0cm in the left breast. Histologically, the lesion exhibited slightly low signal intensity on TIWI and slightly high to low signal intensity on T2WI fat suppression, with progressive and sustained enhancement on dynamic contrast-enhanced scans. Diffusion-weighted imaging and apparent diffusion coefficient maps showed low signal intensity, and the time-signal intensity curve was plateau-shaped. Some nodules and masses exhibited lobulated margins, with multiple non-enhancing linear septations, some of which were closely related to the adjacent skin, without evident thickening (Fig. 2 ). To rule out neurological conditions, a cranial MRI was performed, revealing no abnormalities. Considering the patient's presentation of multiple bilateral giant breast masses with significant ptosis, she underwent bilateral breast mass excision surgery, bilateral reduction mammoplasty, breast suspension surgery, and nipple-areola reconstruction surgery on the sixth day of hospitalization. Intraoperatively, multiple masses were observed in both breasts, with approximately 70 masses in the left breast, the largest measuring approximately 12.0×8.0cm, and approximately 80 masses in the right breast, the largest measuring approximately 6.0×6.0cm. The masses were gray-white, firm in consistency, with clear margins, smooth surfaces, and intact capsules (Figs. 3 ). Postoperative pathological examination confirmed multiple fibroadenomas in both breasts, with the largest lesions measuring approximately 17×7.0×2.8cm and 16.0×11.2×4.5cm in the left and right breasts, respectively. Microscopically, some ducts exhibited irregular dilation, with ordinary-type epithelial hyperplasia focal interstitial cellularity, and scattered calcifications. The margins of the specimens were negative for tumor invasion. Immunohistochemical analysis revealed cytokeratin 5/6 positivity (patchy+), estrogen receptor positivity (moderate to strong, > 90%), and Ki-67 positivity (5–10%) in areas of ductal epithelial hyperplasia (Fig. 4 ). High-throughput sequencing (NGS) covered 437 genes with a total of 1.53Mb base sites, including exons, fusion-related introns, alternative splicing regions and specific microsatellite (MS) sites. Analysis of point mutations, small indels, gene fusions, copy number variations, microsatellite analysis, and tumor mutation burden (TMB) revealed a missense mutation c.317G > T (p.G106V) in PIK3CA, p.G106V (Fig. 5 ).The patient recovered uneventfully postoperatively, with good symmetry of the breasts (SI). Discussion Breast fibroma is a common benign lesion of the breast, often presented as a unilateral, painless mass of 1-2cm in size in young women [ 12 ]. Breast fibroadenomas that exceed 5cm, weigh more than 500mg, or occupy more than 4/5 of the breast are called giant fibroadenomas [ 17 ]. Michael Sosin et al reported that the average age of onset of giant juvenile fibroadenomas was 16.7 years old, and the average diameter of the tumors was 11.2cm [ 10 ]. While the etiology of fibroadenomas remains elusive, genetic factors may contribute [ 4 ]. Additionally, Simmons, P. S., posits that fibroadenomas are influenced by estrogen and may undergo rapid growth during puberty and pregnancy [ 18 ]. The stimulation of reproductive hormones, breast tissue hypersensitivity to estrogen, and a relative deficiency in estrogen antagonists are also postulated as potential causative factors [ 19 , 20 ]. In this case review, the patient first presented symptoms at age 15, experiencing continued rapid tumor growth into late adolescence despite normal hormone levels. Given the pivotal role of prolactin in breast development [ 21 ], central nervous system involvement was considered, prompting prolactin and estrogen testing, along with cranial MRI, which revealed no abnormalities. The precise etiology of the patient's condition remains unresolved. The diagnosis of breast fibroadenomas predominantly relies on the patient's medical history, physical examination, and imaging studies. Ultrasound serves as the preferred modality due to the high breast tissue density in young women, limiting the diagnostic efficacy of mammography. CBBCT offers a more comprehensive three-dimensional assessment of breast lesions compared to mammography and demonstrates a good correlation with pathological diagnoses. For young women presenting with breast masses, CBBCT may be recommended to assess lesion characteristics. Breast MRI boasts a sensitivity of 97% and specificity of 69% for detecting breast lesions [ 22 ]. In this particular case, breast MRI revealed multiple nodules, suggesting the primary diagnosis of multiple fibroadenomas, with the potential of phyllodes tumors not entirely excluded. Phyllodes tumors can manifest at any age in women but are more prevalent in the 35–55 age demographic [ 23 ], aiding in the initial differentiation from fibroadenomas. A definitive diagnosis hinges on histopathological examination. Given the patient's previous histological assessment following mass excision, the preoperative diagnosis remained consistent with fibroadenomas. In terms of treatment, clinical investigations have illuminated the limited efficacy of the hormone receptor antagonist tamoxifen in managing breast fibroadenomas [ 24 ], potentially attributable to endocrine resistance. The research underscores that beyond hormone-sensitive pathways, fibroadenomas activate endocrine resistance pathways [ 8 ], elucidating the suboptimal response to tamoxifen therapy. Notably, certain patients harboring multiple breast fibroadenomas exhibit heterozygous single-nucleotide polymorphisms in exon 6 of the prolactin receptor (prlr) gene, encoding an Ile146→Leu substitution in the extracellular region[ 25 ], offering a novel therapeutic avenue. Compared to their adult counterparts, fibroadenomas in adolescents display rapid growth and are conventionally addressed through surgical excision [ 10 ]. In the present case, the patient underwent surgical tumor removal without systemic pharmacotherapy. However, despite surgical intervention, recurrence ensued, necessitating a subsequent surgical procedure that culminated in favorable symmetry and recovery. The prospect of future recurrence looms, underscoring the imperative for ongoing surveillance. Consequently, adjunctive systemic pharmacotherapy assumes importance, albeit hindered by the dearth of reliable drug options. Hence, there is a pressing need for further exploration of therapeutic modalities. Regarding the patient's follow-up, we have carefully considered several factors. The presence of multiple fibroadenomas in both breasts raises concerns about recurrence. Does this heightened recurrence risk correlate with an increased susceptibility to breast cancer? While the malignant transformation of juvenile fibroadenomas is exceedingly rare [ 26 ], a study published in the New England Journal of Medicine posits adult breast fibroadenomas as potential long-term risk factors for breast cancer. The study indicates a 2.17-fold higher risk of fibroadenoma progression to breast cancer in the study group compared to the control group (95% CI 1.5–3.2). Moreover, the risk escalates in individuals with complex fibroadenomas, proliferative diseases, or a familial history of breast cancer [ 7 ]. In this case, the absence of a family history of breast tumor-related ailments excludes genetic predisposition. To delve deeper, we conducted a genetic analysis, revealing a PIK3CA gene mutation in this patient. Such mutations, while rare in breast fibroadenoma patients, were initially reported by Panagiotis A Vorkas et al. in 2010 [ 16 ]. The PIK3CA gene ranks among the commonly mutated genes in solid tumors, frequently implicated in colorectal cancer, breast cancer, brain cancer, and lung cancer[ 27 ]. However, a study by Nur Diyana Md Nasir found no significant disparity in mutation spectra between recurrent and non-recurrent fibroadenomas [ 28 ]. Whether PIK3CA gene mutation is related to the occurrence and recurrence of breast fibroadenoma still needs more experiments to confirm. Nonetheless, it is noteworthy that our patient harbors a history of fibroadenomas coupled with a PIK3CA gene mutation, heightening her breast cancer risk compared to the general populace. Hence, we advocate for vigilant patient monitoring. Prompt diagnosis and treatment are imperative should any malignant breast alterations transpire. Conclusion The etiology of giant fibroadenomas in the breast may be linked to sex hormones, yet precise causation remains elusive. In addition to surgical intervention, there is a compelling recommendation for actively seeking systemic medications to complement therapy. Although PIK3CA gene mutations are infrequent in individuals with breast fibroadenomas, their coexistence escalates the risk of breast cancer development. Consequently, diligent monitoring is imperative, with swift diagnosis and intervention mandated in the event of any malignant breast alterations. Declarations Acknowledgements Not applicable. Authors ’ contributions Yuemei Zhang collected data and wrote the paper. Yugui Xiao, Shengkai Huang, Wenhai Zhang and Wenhao Wang analyzed the data. Qixing Tan, Wei Wei and Qinguo Mo reviewed and verified all the raw data. All authors read and approved the final manuscript. Funding This work was supported by the National Natural Science Foundation of China (NSFC; Grant No. 82160481), the Natural Science Foundation of Guangxi， China (Grant No. 2021GXNSFBA196015, 2021GXNSFAA196013, 2024GXNSFAA010058) Data availability The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate Not applicable. Consent for publication Written consent for publication was obtained from the patient. We declare that the patient has been informed and agrees to publish identifiable information in open access journals. Competing interests The authors declare no competing interests. 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N Engl J Med, 1994. 331 (1): p. 10-5. Chen, Z., et al., Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets. Nat Commun, 2023. 14 (1): p. 3469. Li, X., et al., Gene Expression Profiling of Fibroepithelial Lesions of the Breast. Int J Mol Sci, 2023. 24 (10). Sosin, M., et al., Giant juvenile fibroadenoma: a systematic review with diagnostic and treatment recommendations. Gland Surg, 2015. 4 (4): p. 312-21. Reinhardt, K., et al., PIK3CA-mutations in breast cancer. Breast Cancer Res Treat, 2022. 196 (3): p. 483-493. Mei, Z.B., et al., Prognostic role of tumor PIK3CA mutation in colorectal cancer: a systematic review and meta-analysis. Ann Oncol, 2016. 27 (10): p. 1836-48. Harada, K., et al., Prognostic and clinical impact of PIK3CA mutation in gastric cancer: pyrosequencing technology and literature review. BMC Cancer, 2016. 16 : p. 400. Liu, W., et al., Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma. Mol Cancer, 2022. 21 (1): p. 72. Mosele, F., et al., Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer. Ann Oncol, 2020. 31 (3): p. 377-386. Vorkas, P.A., et al., PIK3CA hotspot mutation scanning by a novel and highly sensitive high-resolution small amplicon melting analysis method. J Mol Diagn, 2010. 12 (5): p. 697-704. Lee, E.J., et al., Breast Lesions in Children and Adolescents: Diagnosis and Management. Korean J Radiol, 2018. 19 (5): p. 978-991. Simmons, P.S., Diagnostic considerations in breast disorders of children and adolescents. Obstet Gynecol Clin North Am, 1992. 19 (1): p. 91-102. Tochika, N., et al., Rapid growing fibroadenoma in an adolescent. Breast Cancer, 1998. 5 (3): p. 321-4. Rao, B.R., J.S. Meyer, and C.G. Fry, Most cystosarcoma phyllodes and fibroadenomas have progesterone receptor but lack estrogen receptor: stromal localization of progesterone receptor. Cancer, 1981. 47 (8): p. 2016-21. Neville, M.C., T.B. McFadden, and I. Forsyth, Hormonal regulation of mammary differentiation and milk secretion. J Mammary Gland Biol Neoplasia, 2002. 7 (1): p. 49-66. Pötsch, N., et al., Contrast-enhanced Mammography versus Contrast-enhanced Breast MRI: A Systematic Review and Meta-Analysis. Radiology, 2022. 305 (1): p. 94-103. Gnerlich, J.L., et al., Utilization of radiotherapy for malignant phyllodes tumors: analysis of the National Cancer Data Base, 1998-2009. Ann Surg Oncol, 2014. 21 (4): p. 1222-30. Bernardes, J.R., Jr., et al., The effect of tamoxifen on PCNA expression in fibroadenomas. Breast J, 2003. 9 (4): p. 302-6. Bogorad, R.L., et al., Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors. 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Supplementary Files Supplementalfiles1.docx Cite Share Download PDF Status: Published Journal Publication published 21 Oct, 2025 Read the published version in BMC Women's Health → Version 1 posted Editorial decision: Revision requested 18 Jul, 2025 Reviews received at journal 25 Jun, 2025 Reviews received at journal 23 Jun, 2025 Reviewers agreed at journal 23 Jun, 2025 Reviewers agreed at journal 21 Jun, 2025 Reviewers agreed at journal 18 Jun, 2025 Reviews received at journal 18 Jun, 2025 Reviewers agreed at journal 18 Jun, 2025 Reviewers invited by journal 16 Jun, 2025 Editor invited by journal 20 May, 2025 Editor assigned by journal 20 May, 2025 Submission checks completed at journal 20 May, 2025 First submitted to journal 19 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6695035","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":471930110,"identity":"bd875ac8-c3a6-4ddc-b4a0-0a668fefaa53","order_by":0,"name":"Yuemei Zhang","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuemei","middleName":"","lastName":"Zhang","suffix":""},{"id":471930111,"identity":"578e8262-9afc-4f96-ad54-97b4952123f0","order_by":1,"name":"Qixing Tan","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qixing","middleName":"","lastName":"Tan","suffix":""},{"id":471930112,"identity":"5afb908f-2b8d-42f2-a481-97b5cbfecea9","order_by":2,"name":"Yugui Xiao","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yugui","middleName":"","lastName":"Xiao","suffix":""},{"id":471930113,"identity":"1747c4b1-28fe-43c4-94f0-0d2e23e33026","order_by":3,"name":"Wenhao Wang","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wenhao","middleName":"","lastName":"Wang","suffix":""},{"id":471930114,"identity":"f1d53db9-0226-44f9-840c-7c62e869d899","order_by":4,"name":"Shengkai Huang","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shengkai","middleName":"","lastName":"Huang","suffix":""},{"id":471930115,"identity":"45b98f1e-0c0b-4f00-8649-d6a32b787b3a","order_by":5,"name":"Qinguo Mo","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qinguo","middleName":"","lastName":"Mo","suffix":""},{"id":471930116,"identity":"846ffdbd-6aef-448e-95a2-b96ea64aa414","order_by":6,"name":"Wenhai Zhang","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wenhai","middleName":"","lastName":"Zhang","suffix":""},{"id":471930117,"identity":"02aa584f-0279-483f-b74a-20e3ea050352","order_by":7,"name":"Wei Wei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBACfmb+xw8k//2Ts29vIFKLZHsPm4EF2wFjA54DRGox6DnDIFHBdiDRQCKBWC0SuQcMbvDcSTCXfLzxBkONTTRBLeYSeQkPZ0g8y7OcnVZswXAsLbeBkBbLGQkGxhIGzMUMt3PMJBgbDhPWYnAjwUD6TwJzYsPNM8RqOXPGQELiwOHEDTd4iNQi2d6WZiDZkGYs2QP0SwIxfuFnZj78QLLBRo6f/fDGGx9qbAhrQXEk0VGDpIVUHaNgFIyCUTAyAACG2UJlz1bNYgAAAABJRU5ErkJggg==","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":true,"prefix":"","firstName":"Wei","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2025-05-19 04:53:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6695035/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6695035/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12905-025-04032-3","type":"published","date":"2025-10-21T16:17:09+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":85069704,"identity":"94e703ca-6d72-4888-9e9b-9d831f90a9fd","added_by":"auto","created_at":"2025-06-20 15:31:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":392490,"visible":true,"origin":"","legend":"\u003cp\u003ePreoperative photographs of the patient taken in January 2024.\u003c/p\u003e\n\u003cp\u003e(a) Frontal view showing severe deformation and ptosis of the breasts due to tumor traction. (b) Preoperative surgical markings. (c) Right lateral view. (d) Left lateral view.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6695035/v1/104b61bb274e4129373eb89e.png"},{"id":85071312,"identity":"2ae6f2cf-f049-4692-97ac-4a8a12ae28a4","added_by":"auto","created_at":"2025-06-20 15:39:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":141006,"visible":true,"origin":"","legend":"\u003cp\u003eBreast MRI performed in January 2024 showing diffuse multiple nodules and mass shadows of varying sizes in all quadrants of both breasts, with the largest lesion measuring approximately 10.7cm x 8.1cm x 7.0cm in the left breast. Some nodules and masses exhibit lobulated margins, with multiple non-enhancing linear septations, some of which are closely related to the adjacent skin, without evident thickening. (a) T1-weighted imaging shows slightly low signal intensity, (b) T2-weighted imaging with fat suppression shows slightly high to low signal intensity, (c) and (d) Time-signal intensity curve is plateau-shaped.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6695035/v1/43086c4c2b637e464a8d2928.png"},{"id":85069708,"identity":"de028dc6-6fb3-4d49-8dfa-36d0c83bf4f5","added_by":"auto","created_at":"2025-06-20 15:31:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":182054,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Intraoperative observation, showing dissection of breast gland tissue until reaching the tumor, which appears gray-white in color. (b): Intraoperative excision of bilateral breast masses, approximately 70 masses in the left breast, with the largest measuring approximately 12x8cm, and approximately 80 masses in the right breast, with the largest measuring approximately 6x6cm. The masses appear gray-white in color, firm in consistency, with clear margins, smooth surfaces, and intact capsules. The cut surface is gray-white.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6695035/v1/1dbc725561daf85aaaeb6bbe.png"},{"id":85071313,"identity":"835785d7-7c0e-4b12-9993-d6b009e258e8","added_by":"auto","created_at":"2025-06-20 15:39:31","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":302938,"visible":true,"origin":"","legend":"\u003cp\u003ePathological results indicate multiple fibroadenomas in both breasts.\u003c/p\u003e\n\u003cp\u003e(a) Microscopic examination reveals fibroadenomas with irregular ductal dilation, ordinary-type epithelial hyperplasia, focal interstitial cellularity, and scattered calcifications. (b) CK5/6 (patchy +). (c) ER (moderate to strong, \u0026gt;90%). (d) PR expression status.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6695035/v1/942f0b9bbaa82478b3e413ed.png"},{"id":85069709,"identity":"47e56c12-9e78-479e-ab7b-6654b9a4c71a","added_by":"auto","created_at":"2025-06-20 15:31:31","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":310846,"visible":true,"origin":"","legend":"\u003cp\u003eIGV software showing PIK3CA p. G106v mutation.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6695035/v1/565dd6f835a5c2fc1a1422de.png"},{"id":94490444,"identity":"eebb78a5-6363-42f7-9b42-a2b0a5c2e6fb","added_by":"auto","created_at":"2025-10-27 17:10:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1788264,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6695035/v1/1f47e5c5-e24e-4bce-8907-2a8e1ec93a8e.pdf"},{"id":85069706,"identity":"47a73860-cae1-4e92-8a0a-5de152fedc50","added_by":"auto","created_at":"2025-06-20 15:31:31","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":147926,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementalfiles1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6695035/v1/398778f39ce9a0771f2ba5a4.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Case Report of Recurrent Bilateral Giant Fibroadenomas in a Young Woman with PIK3CA Mutation","fulltext":[{"header":"Background","content":"\u003cp\u003eFibroadenomas stand as the most prevalent benign breast tumors in women [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], boasting an incidence rate of 27.6%, notably affecting young women aged 20\u0026ndash;30 years [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Giant fibroadenomas, characterized by their size exceeding 5cm and weight surpassing 500g [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], occupying over 4/5 of breast volume, constitute approximately 0.5-2% of all breast fibroadenomas [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Certain variants, particularly those hormonally influenced, such as juvenile fibroadenomas and lactating adenomas, may manifest rapid growth [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Hormonal factors are believed to contribute to the pathogenesis of fibroadenomas [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough the likelihood of fibroadenomas undergoing malignant transformation is rare, with rates ranging between 0.002\u0026ndash;0.124% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], studies suggest that their growth can profoundly affect patients' physical and psychological well-being, potentially elevating the risk of breast cancer [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Presently, the primary diagnostic and therapeutic strategy for giant fibroadenomas revolves around complete surgical excision, which boasts high safety and low recurrence rates [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePIK3CA is involved in numerous physiological processes within cells, including the promotion of cell transformation, tumor occurrence and proliferation, and resistance to apoptosis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. While PIK3CA mutations are commonly found in solid tumors such as gastric cancer, colorectal cancer, liver cancer, and breast cancer, they are relatively rare in breast fibroadenomas [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The presence of PIK3CA mutations in breast fibroadenomas was initially reported by Panagiotis A. Vorkas and colleagues [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe present the case of a 23-year-old woman who presented with bilateral multiple giant fibroadenomas. Despite undergoing surgical treatment, the patient experienced postoperative recurrence, the cause of which remains unknown. This recurrence has significantly impacted her quality of life and was accompanied by a PIK3CA gene mutation. This case is rare and complex, prompting further exploration and analysis of its etiology, treatment options, and follow-up recommendations.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 23-year-old female patient presented at our hospital in January 2024, approximately four years post-bilateral breast lump excision surgery, with a recurrence of bilateral breast lumps persisting for over two years. In 2019, the patient noticed multiple palpable breast lumps, each approximately 4.0\u0026times;4.0cm in size. Subsequently, in July of the same year, the patient underwent excision surgery for multiple bilateral breast masses, with over 40 masses removed from each breast. Pathological examination indicated multiple fibroadenomas with intraductal papillomas and adenosis. The largest nodules measured 0.8-4.0cm and 0.7-5.5cm in diameter in the left and right breasts, respectively, accompanied by local calcifications and ductal hyperplasia.\u003c/p\u003e \u003cp\u003eTwo years later, the patient noticed recurrent breast lumps that progressively increased in size, prompting medical consultation. Her past, personal, and family medical history was unremarkable. On examination, a firm, non-tender mass approximately 7.5\u0026times;3.5cm in size was palpable at the 11 o'clock position of the right breast, while a mass approximately 9.5\u0026times;8.2cm in size was palpable at the 4 o'clock position of the left breast. Both breasts exhibited significant ptosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Preoperative investigations revealed prolactin levels of 52.5ng/ml, estradiol of 71pg/ml, and progesterone of 0.16ng/ml. Ultrasound showed multiple solid lesions in both breasts, while breast MRI revealed diffuse multiple nodules and mass shadows of varying sizes in all quadrants of both breasts, with the largest lesion measuring approximately 10.7 \u0026times; 8.1\u0026times; 7.0cm in the left breast. Histologically, the lesion exhibited slightly low signal intensity on TIWI and slightly high to low signal intensity on T2WI fat suppression, with progressive and sustained enhancement on dynamic contrast-enhanced scans. Diffusion-weighted imaging and apparent diffusion coefficient maps showed low signal intensity, and the time-signal intensity curve was plateau-shaped. Some nodules and masses exhibited lobulated margins, with multiple non-enhancing linear septations, some of which were closely related to the adjacent skin, without evident thickening (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). To rule out neurological conditions, a cranial MRI was performed, revealing no abnormalities.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eConsidering the patient's presentation of multiple bilateral giant breast masses with significant ptosis, she underwent bilateral breast mass excision surgery, bilateral reduction mammoplasty, breast suspension surgery, and nipple-areola reconstruction surgery on the sixth day of hospitalization. Intraoperatively, multiple masses were observed in both breasts, with approximately 70 masses in the left breast, the largest measuring approximately 12.0\u0026times;8.0cm, and approximately 80 masses in the right breast, the largest measuring approximately 6.0\u0026times;6.0cm. The masses were gray-white, firm in consistency, with clear margins, smooth surfaces, and intact capsules (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Postoperative pathological examination confirmed multiple fibroadenomas in both breasts, with the largest lesions measuring approximately 17\u0026times;7.0\u0026times;2.8cm and 16.0\u0026times;11.2\u0026times;4.5cm in the left and right breasts, respectively. Microscopically, some ducts exhibited irregular dilation, with ordinary-type epithelial hyperplasia focal interstitial cellularity, and scattered calcifications. The margins of the specimens were negative for tumor invasion. Immunohistochemical analysis revealed cytokeratin 5/6 positivity (patchy+), estrogen receptor positivity (moderate to strong, \u0026gt;\u0026thinsp;90%), and Ki-67 positivity (5\u0026ndash;10%) in areas of ductal epithelial hyperplasia (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). High-throughput sequencing (NGS) covered 437 genes with a total of 1.53Mb base sites, including exons, fusion-related introns, alternative splicing regions and specific microsatellite (MS) sites. Analysis of point mutations, small indels, gene fusions, copy number variations, microsatellite analysis, and tumor mutation burden (TMB) revealed a missense mutation c.317G\u0026thinsp;\u0026gt;\u0026thinsp;T (p.G106V) in PIK3CA, p.G106V (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).The patient recovered uneventfully postoperatively, with good symmetry of the breasts (SI).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBreast fibroma is a common benign lesion of the breast, often presented as a unilateral, painless mass of 1-2cm in size in young women [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Breast fibroadenomas that exceed 5cm, weigh more than 500mg, or occupy more than 4/5 of the breast are called giant fibroadenomas [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Michael Sosin et al reported that the average age of onset of giant juvenile fibroadenomas was 16.7 years old, and the average diameter of the tumors was 11.2cm [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. While the etiology of fibroadenomas remains elusive, genetic factors may contribute [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Additionally, Simmons, P. S., posits that fibroadenomas are influenced by estrogen and may undergo rapid growth during puberty and pregnancy [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The stimulation of reproductive hormones, breast tissue hypersensitivity to estrogen, and a relative deficiency in estrogen antagonists are also postulated as potential causative factors [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In this case review, the patient first presented symptoms at age 15, experiencing continued rapid tumor growth into late adolescence despite normal hormone levels. Given the pivotal role of prolactin in breast development [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], central nervous system involvement was considered, prompting prolactin and estrogen testing, along with cranial MRI, which revealed no abnormalities. The precise etiology of the patient's condition remains unresolved.\u003c/p\u003e \u003cp\u003eThe diagnosis of breast fibroadenomas predominantly relies on the patient's medical history, physical examination, and imaging studies. Ultrasound serves as the preferred modality due to the high breast tissue density in young women, limiting the diagnostic efficacy of mammography. CBBCT offers a more comprehensive three-dimensional assessment of breast lesions compared to mammography and demonstrates a good correlation with pathological diagnoses. For young women presenting with breast masses, CBBCT may be recommended to assess lesion characteristics. Breast MRI boasts a sensitivity of 97% and specificity of 69% for detecting breast lesions [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In this particular case, breast MRI revealed multiple nodules, suggesting the primary diagnosis of multiple fibroadenomas, with the potential of phyllodes tumors not entirely excluded. Phyllodes tumors can manifest at any age in women but are more prevalent in the 35\u0026ndash;55 age demographic [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], aiding in the initial differentiation from fibroadenomas. A definitive diagnosis hinges on histopathological examination. Given the patient's previous histological assessment following mass excision, the preoperative diagnosis remained consistent with fibroadenomas.\u003c/p\u003e \u003cp\u003eIn terms of treatment, clinical investigations have illuminated the limited efficacy of the hormone receptor antagonist tamoxifen in managing breast fibroadenomas [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], potentially attributable to endocrine resistance. The research underscores that beyond hormone-sensitive pathways, fibroadenomas activate endocrine resistance pathways [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], elucidating the suboptimal response to tamoxifen therapy. Notably, certain patients harboring multiple breast fibroadenomas exhibit heterozygous single-nucleotide polymorphisms in exon 6 of the prolactin receptor (prlr) gene, encoding an Ile146\u0026rarr;Leu substitution in the extracellular region[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], offering a novel therapeutic avenue.\u003c/p\u003e \u003cp\u003eCompared to their adult counterparts, fibroadenomas in adolescents display rapid growth and are conventionally addressed through surgical excision [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In the present case, the patient underwent surgical tumor removal without systemic pharmacotherapy. However, despite surgical intervention, recurrence ensued, necessitating a subsequent surgical procedure that culminated in favorable symmetry and recovery. The prospect of future recurrence looms, underscoring the imperative for ongoing surveillance. Consequently, adjunctive systemic pharmacotherapy assumes importance, albeit hindered by the dearth of reliable drug options. Hence, there is a pressing need for further exploration of therapeutic modalities.\u003c/p\u003e \u003cp\u003eRegarding the patient's follow-up, we have carefully considered several factors. The presence of multiple fibroadenomas in both breasts raises concerns about recurrence. Does this heightened recurrence risk correlate with an increased susceptibility to breast cancer? While the malignant transformation of juvenile fibroadenomas is exceedingly rare [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], a study published in the New England Journal of Medicine posits adult breast fibroadenomas as potential long-term risk factors for breast cancer. The study indicates a 2.17-fold higher risk of fibroadenoma progression to breast cancer in the study group compared to the control group (95% CI 1.5\u0026ndash;3.2). Moreover, the risk escalates in individuals with complex fibroadenomas, proliferative diseases, or a familial history of breast cancer [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In this case, the absence of a family history of breast tumor-related ailments excludes genetic predisposition. To delve deeper, we conducted a genetic analysis, revealing a PIK3CA gene mutation in this patient. Such mutations, while rare in breast fibroadenoma patients, were initially reported by Panagiotis A Vorkas et al. in 2010 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The PIK3CA gene ranks among the commonly mutated genes in solid tumors, frequently implicated in colorectal cancer, breast cancer, brain cancer, and lung cancer[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, a study by Nur Diyana Md Nasir found no significant disparity in mutation spectra between recurrent and non-recurrent fibroadenomas [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Whether PIK3CA gene mutation is related to the occurrence and recurrence of breast fibroadenoma still needs more experiments to confirm. Nonetheless, it is noteworthy that our patient harbors a history of fibroadenomas coupled with a PIK3CA gene mutation, heightening her breast cancer risk compared to the general populace. Hence, we advocate for vigilant patient monitoring. Prompt diagnosis and treatment are imperative should any malignant breast alterations transpire.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe etiology of giant fibroadenomas in the breast may be linked to sex hormones, yet precise causation remains elusive. In addition to surgical intervention, there is a compelling recommendation for actively seeking systemic medications to complement therapy. Although PIK3CA gene mutations are infrequent in individuals with breast fibroadenomas, their coexistence escalates the risk of breast cancer development. Consequently, diligent monitoring is imperative, with swift diagnosis and intervention mandated in the event of any malignant breast alterations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003e contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYuemei Zhang collected data and wrote the paper. Yugui Xiao, Shengkai Huang, Wenhai Zhang and Wenhao Wang analyzed the data. Qixing Tan, Wei Wei and Qinguo Mo reviewed and verified all the raw data. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (NSFC; Grant No. 82160481), the Natural Science Foundation of Guangxi， China (Grant No. 2021GXNSFBA196015, 2021GXNSFAA196013, 2024GXNSFAA010058)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent for publication was obtained from the patient. We declare that the patient has been informed and agrees to publish identifiable information in open access journals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTan, P.H., \u003cem\u003eFibroepithelial lesions revisited: implications for diagnosis and management.\u003c/em\u003e Mod Pathol, 2021. \u003cstrong\u003e34\u003c/strong\u003e(Suppl 1): p. 15-37.\u003c/li\u003e\n\u003cli\u003eZhang, M., et al., \u003cem\u003eImaging and Management of Fibroepithelial Lesions of the Breast: Radiologic-Pathologic Correlation.\u003c/em\u003e Radiographics, 2023. \u003cstrong\u003e43\u003c/strong\u003e(11): p. e230051.\u003c/li\u003e\n\u003cli\u003eGobbi, D., et al., \u003cem\u003eGiant fibroadenoma of the breast in adolescents: report of 2 cases.\u003c/em\u003e J Pediatr Surg, 2009. \u003cstrong\u003e44\u003c/strong\u003e(2): p. e39-41.\u003c/li\u003e\n\u003cli\u003eSong, B.S., et al., \u003cem\u003eGiant juvenile fibroadenoma of the breast: a case report and brief literature review.\u003c/em\u003e Ann Pediatr Endocrinol Metab, 2014. \u003cstrong\u003e19\u003c/strong\u003e(1): p. 45-8.\u003c/li\u003e\n\u003cli\u003eYu, J.H., et al., \u003cem\u003eBreast diseases during pregnancy and lactation.\u003c/em\u003e Obstet Gynecol Sci, 2013. \u003cstrong\u003e56\u003c/strong\u003e(3): p. 143-59.\u003c/li\u003e\n\u003cli\u003eWu, Y.T., et al., \u003cem\u003eBreast cancer arising within fibroadenoma: collective analysis of case reports in the literature and hints on treatment policy.\u003c/em\u003e World J Surg Oncol, 2014. \u003cstrong\u003e12\u003c/strong\u003e: p. 335.\u003c/li\u003e\n\u003cli\u003eDupont, W.D., et al., \u003cem\u003eLong-term risk of breast cancer in women with fibroadenoma.\u003c/em\u003e N Engl J Med, 1994. \u003cstrong\u003e331\u003c/strong\u003e(1): p. 10-5.\u003c/li\u003e\n\u003cli\u003eChen, Z., et al., \u003cem\u003eSingle cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets.\u003c/em\u003e Nat Commun, 2023. \u003cstrong\u003e14\u003c/strong\u003e(1): p. 3469.\u003c/li\u003e\n\u003cli\u003eLi, X., et al., \u003cem\u003eGene Expression Profiling of Fibroepithelial Lesions of the Breast.\u003c/em\u003e Int J Mol Sci, 2023. \u003cstrong\u003e24\u003c/strong\u003e(10).\u003c/li\u003e\n\u003cli\u003eSosin, M., et al., \u003cem\u003eGiant juvenile fibroadenoma: a systematic review with diagnostic and treatment recommendations.\u003c/em\u003e Gland Surg, 2015. \u003cstrong\u003e4\u003c/strong\u003e(4): p. 312-21.\u003c/li\u003e\n\u003cli\u003eReinhardt, K., et al., \u003cem\u003ePIK3CA-mutations in breast cancer.\u003c/em\u003e Breast Cancer Res Treat, 2022. \u003cstrong\u003e196\u003c/strong\u003e(3): p. 483-493.\u003c/li\u003e\n\u003cli\u003eMei, Z.B., et al., \u003cem\u003ePrognostic role of tumor PIK3CA mutation in colorectal cancer: a systematic review and meta-analysis.\u003c/em\u003e Ann Oncol, 2016. \u003cstrong\u003e27\u003c/strong\u003e(10): p. 1836-48.\u003c/li\u003e\n\u003cli\u003eHarada, K., et al., \u003cem\u003ePrognostic and clinical impact of PIK3CA mutation in gastric cancer: pyrosequencing technology and literature review.\u003c/em\u003e BMC Cancer, 2016. \u003cstrong\u003e16\u003c/strong\u003e: p. 400.\u003c/li\u003e\n\u003cli\u003eLiu, W., et al., \u003cem\u003eCirc-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma.\u003c/em\u003e Mol Cancer, 2022. \u003cstrong\u003e21\u003c/strong\u003e(1): p. 72.\u003c/li\u003e\n\u003cli\u003eMosele, F., et al., \u003cem\u003eOutcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer.\u003c/em\u003e Ann Oncol, 2020. \u003cstrong\u003e31\u003c/strong\u003e(3): p. 377-386.\u003c/li\u003e\n\u003cli\u003eVorkas, P.A., et al., \u003cem\u003ePIK3CA hotspot mutation scanning by a novel and highly sensitive high-resolution small amplicon melting analysis method.\u003c/em\u003e J Mol Diagn, 2010. \u003cstrong\u003e12\u003c/strong\u003e(5): p. 697-704.\u003c/li\u003e\n\u003cli\u003eLee, E.J., et al., \u003cem\u003eBreast Lesions in Children and Adolescents: Diagnosis and Management.\u003c/em\u003e Korean J Radiol, 2018. \u003cstrong\u003e19\u003c/strong\u003e(5): p. 978-991.\u003c/li\u003e\n\u003cli\u003eSimmons, P.S., \u003cem\u003eDiagnostic considerations in breast disorders of children and adolescents.\u003c/em\u003e Obstet Gynecol Clin North Am, 1992. \u003cstrong\u003e19\u003c/strong\u003e(1): p. 91-102.\u003c/li\u003e\n\u003cli\u003eTochika, N., et al., \u003cem\u003eRapid growing fibroadenoma in an adolescent.\u003c/em\u003e Breast Cancer, 1998. \u003cstrong\u003e5\u003c/strong\u003e(3): p. 321-4.\u003c/li\u003e\n\u003cli\u003eRao, B.R., J.S. Meyer, and C.G. Fry, \u003cem\u003eMost cystosarcoma phyllodes and fibroadenomas have progesterone receptor but lack estrogen receptor: stromal localization of progesterone receptor.\u003c/em\u003e Cancer, 1981. \u003cstrong\u003e47\u003c/strong\u003e(8): p. 2016-21.\u003c/li\u003e\n\u003cli\u003eNeville, M.C., T.B. McFadden, and I. Forsyth, \u003cem\u003eHormonal regulation of mammary differentiation and milk secretion.\u003c/em\u003e J Mammary Gland Biol Neoplasia, 2002. \u003cstrong\u003e7\u003c/strong\u003e(1): p. 49-66.\u003c/li\u003e\n\u003cli\u003eP\u0026ouml;tsch, N., et al., \u003cem\u003eContrast-enhanced Mammography versus Contrast-enhanced Breast MRI: A Systematic Review and Meta-Analysis.\u003c/em\u003e Radiology, 2022. \u003cstrong\u003e305\u003c/strong\u003e(1): p. 94-103.\u003c/li\u003e\n\u003cli\u003eGnerlich, J.L., et al., \u003cem\u003eUtilization of radiotherapy for malignant phyllodes tumors: analysis of the National Cancer Data Base, 1998-2009.\u003c/em\u003e Ann Surg Oncol, 2014. \u003cstrong\u003e21\u003c/strong\u003e(4): p. 1222-30.\u003c/li\u003e\n\u003cli\u003eBernardes, J.R., Jr., et al., \u003cem\u003eThe effect of tamoxifen on PCNA expression in fibroadenomas.\u003c/em\u003e Breast J, 2003. \u003cstrong\u003e9\u003c/strong\u003e(4): p. 302-6.\u003c/li\u003e\n\u003cli\u003eBogorad, R.L., et al., \u003cem\u003eIdentification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors.\u003c/em\u003e Proc Natl Acad Sci U S A, 2008. \u003cstrong\u003e105\u003c/strong\u003e(38): p. 14533-8.\u003c/li\u003e\n\u003cli\u003eTea, M.K., et al., \u003cem\u003eSurgical breast lesions in adolescent females.\u003c/em\u003e Pediatr Surg Int, 2009. \u003cstrong\u003e25\u003c/strong\u003e(1): p. 73-5.\u003c/li\u003e\n\u003cli\u003eSamuels, Y. and V.E. Velculescu, \u003cem\u003eOncogenic mutations of PIK3CA in human cancers.\u003c/em\u003e Cell Cycle, 2004. \u003cstrong\u003e3\u003c/strong\u003e(10): p. 1221-4.\u003c/li\u003e\n\u003cli\u003eMd Nasir, N.D., et al., \u003cem\u003eGenomic characterisation of breast fibroepithelial lesions in an international cohort.\u003c/em\u003e J Pathol, 2019. \u003cstrong\u003e249\u003c/strong\u003e(4): p. 447-460\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Recurrent Bilateral Giant Fibroadenomas, Young Woman, PIK3CA Mutation","lastPublishedDoi":"10.21203/rs.3.rs-6695035/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6695035/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBreast fibroadenoma is a common benign tumor of the breast. Giant fibroadenoma accounts for about 0.5-2.0% of all breast fibroadenomas, the cause of which remains unclear. PIK3CA mediates various cellular processes and is frequently mutated in solid malignancies. However, the association between breast fibroma and gene mutations remains unclear.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase report\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article reviews a case involving recurrent bilateral giant fibroadenomas with a PIK3CA mutation, exploring causative factors, treatment modalities, and post-treatment recommendations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe etiology of giant fibroadenoma of the breast may be related to sex hormones, and in addition to surgical intervention, the recommendation is to actively seek systemic drugs as complementary treatment. Although PIK3CA mutations are rare in patients with breast fibroadenoma, their coexistence increases the risk of breast cancer. Therefore, close monitoring is essential, and once malignant breast lesions occur, rapid diagnosis and intervention are necessary.\u003c/p\u003e","manuscriptTitle":"A Case Report of Recurrent Bilateral Giant Fibroadenomas in a Young Woman with PIK3CA Mutation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-20 15:31:27","doi":"10.21203/rs.3.rs-6695035/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-18T23:32:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-25T19:38:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-23T15:52:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"311201417771901685387141862855033574466","date":"2025-06-23T13:08:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"318502903878798760316176075701566933597","date":"2025-06-21T07:03:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"306622716250262871493024307586282144863","date":"2025-06-18T12:36:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-18T05:57:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"295583717392059836293722041557821364135","date":"2025-06-18T05:15:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-16T04:56:10+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-20T11:48:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-20T08:11:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-20T08:03:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2025-05-19T04:50:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"706b4baa-f016-43c6-aca4-216a82dd92d2","owner":[],"postedDate":"June 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T16:38:37+00:00","versionOfRecord":{"articleIdentity":"rs-6695035","link":"https://doi.org/10.1186/s12905-025-04032-3","journal":{"identity":"bmc-womens-health","isVorOnly":false,"title":"BMC Women's Health"},"publishedOn":"2025-10-21 16:17:09","publishedOnDateReadable":"October 21st, 2025"},"versionCreatedAt":"2025-06-20 15:31:27","video":"","vorDoi":"10.1186/s12905-025-04032-3","vorDoiUrl":"https://doi.org/10.1186/s12905-025-04032-3","workflowStages":[]},"version":"v1","identity":"rs-6695035","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6695035","identity":"rs-6695035","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}