Materiały źródłowe

• #1 Breast Fibroadenoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK535345/

  A fibroadenoma is a painless, unilateral, benign (non-cancerous) breast tumor that is a solid, not fluid-filled, lump. […] The causes of fibroadenoma are debatable, but professionals believe that the lesion has a hormonal etiology related to the increased sensitivity of breast tissue to the female reproductive hormone estrogen. […] Fibroadenoma arises from stromal and epithelial connective tissue cells that are functionally and mechanically important in the breast. These tissues contain receptors for both estrogen and progesterone. For this reason, fibroadenomas tend to proliferate during pregnancy because of excessive production of female reproductive hormones. Hormone sensitivity causes excessive proliferation of breast connective tissues. […] Mediator complex subunit 12 (MED12) gene is also important in the pathophysiology of fibroadenomas.

• #1 Understanding Fibroadenoma of the Breast: A Comprehensive Review of Pre-operative and Post-operative Clinicopathological Correlations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10823311/

  Several factors contribute to the development of fibroadenomas, reflecting the complex interplay of hormonal, genetic, and environmental influences. Firstly, hormonal influences, particularly estrogen and progesterone, play a pivotal role in the growth and maintenance of breast tissue. Fibroadenomas exhibit hormonal responsiveness, with their development or enlargement often coinciding with periods of hormonal fluctuations, such as puberty, pregnancy, and the menstrual cycle. The presence of hormone receptors in fibroadenoma cells underscores their sensitivity to hormonal cues, suggesting a driving force behind their growth. […] Moreover, research indicates a genetic predisposition to fibroadenoma development, supported by the identification of specific genetic mutations or variations in some studies. For instance, it may be valuable to consider suggesting a particular mutation that has been associated with an increased susceptibility to fibroadenomas. Although the genetic basis of fibroadenomas remains intricate and not entirely understood, these findings underscore the complexity of the condition, suggesting that multiple genes and factors likely interact to influence their occurrence.

• #1 Estrogen receptor-β is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast | Modern Pathology

  https://www.nature.com/articles/3800574

  An estrogen dependency has been suggested for the growth of fibroadenomas: however, thus far, none of the steroid hormone receptors acting on breast tissues has been demonstrated in the stroma of breast fibroepithelial lesions. […] In conclusion, (i) only ER- is detected in the stroma of fibroadenomas and phyllodes tumors; (ii) its expression correlates with the expression of smooth muscle markers and suggests a role of ER- in myofibroblastic differentiation of stromal cells. These two results, together with the young age of patients carrying fibroadenomas with highly ER- positive stroma cells, may further indicate a hormone-receptor mechanism involved in regulating the growth of fibroadenomas. Conversely, the older age of patients with ER- rich phyllodes tumors suggests that mechanisms, probably independent from estrogen stimulation, act on the growth of these tumors.

• #1 Breast fibroadenomas: a review in the light of current…

  https://ppch.pl/seo/article/01.3001.0014.5676/en

  Lim W.K. et al. undertook exome sequencing of eight fibroadenomas with matching whole-blood samples and found recurrent somatic mutations solely in MED12, which encodes a Mediator complex subunit and thereby concluded that the fibroadenomas and the benign tumors of uterus, both of which are key target tissues of estrogen, may share a common genetic basis underpinned by highly frequent and specific MED12 mutations. […] Multiple fibroadenomas has also been associated to a strong history of breast lesions in the family and it has been suggested that the physiologic level of estrogen in such patients did not increase, but instead, the number of estrogen receptor increased leading to hypersensitivity of local breast tissue to estrogen.

• #1 Fibroadenoma – Wikipedia

  https://en.wikipedia.org/wiki/Fibroadenoma

  Fibroadenomas are benign breast tumours characterized by an admixture of stromal and epithelial tissue. […] The cause of fibroadenoma is unknown (idiopathic). A connection between fibroadenomas and reproductive hormones has been suggested which may explain why they present themselves during reproductive years, increase in size during pregnancy, and regress post-menopause. […] Up to 66% of fibroadenomas harbor mutations in the exon (exon 2) of the mediator complex subunit 12 (MED12) gene. In particular, these mutations are restricted to the stromal component.

• #1 MED 12 gene mutation in a case of bilateral giant juvenile fibroadenoma – IJPO

  https://www.ijpo.co.in/html-article/17932

  Giant juvenile fibroadenoma is a rare variant of more common benign lesion, fibro adenoma observed in younger population. […] Somatic mutation in exon 2 of the MED12 gene is identified in 60% of breast fibroadenomas. […] The genetic basis of fibroadenoma has not been studied as widely as done for breast carcinoma. Recent studies have shown association of somatic mutations of Exon 2 of the MED 12 gene with benign fibro epithelial lesions of breast. […] The MED 12 somatic mutation is said to be tumorigenic as it leads to loss of mediator associated CDK activity and overexpression of RAD51B by decreased interaction between MED12 and Cyclin C-CDK8/CDK19. […] The MED12 somatic mutation also has an influence on estrogen signaling as Mediator complex interacts with and receptors of estrogen, evidenced by association of MED12 with other estrogen stimulated tumours like uterine leiomyomas and stromal tumours.

• #1 Pulsenotes | Fibroadenoma notes

  https://app.pulsenotes.com/surgery/breast-surgery/notes/fibroadenoma

  Fibroadenomas are fibroepithelial tumours arising from stromal and epithelial tissue. […] There is clear evidence of a hormonal link. They tend to develop after menarche and regress after menopause. They may be triggered or increase in size during pregnancy or when taking hormone replacement therapy (HRT). […] A genetic basis has also been identified with a mutation to MED12 found in around 60% of tumours. MED12 has been implicated in many other conditions including uterine fibroids.

• #1 Fibroadenoma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Fibroadenoma_pathophysiology

  Fibroadenoma is a common benign tumor of the breast. The pathogenesis is not completely understood. […] Fibroadenoma is a proliferation of stromal and epithelial connective tissue cells (biphasic) originating from the terminal duct-lobular unit. Analysis of the stromal and epithelial cells showed that both are polyclonal, which supports the theory that fibroadenomas are hyperplastic lesions associated with a deviation from the normal maturation of the breast, rather than a true neoplasm. […] In some patients, fibroadenomas may express estrogen and progesterone receptors. These hormones stimulate the fibroadenomas via hormone-receptor mechanism leading to excessive proliferation of epithelial and stromal cells. They undergo atrophy during menopause. […] Some fibroadenomas may express epidermal growth factor (EGF) receptors.

• #1 Fibroadenoma overview – wikidoc

  https://www.wikidoc.org/index.php/Fibroadenoma_overview

  Fibroadenoma is a common benign tumor of the breast. Fibroadenoma arises from connective tissue cells, which are cells that are normally involved in the functional and mechanical support of the surrounding tissues. Fibroadenoma demonstrate estrogen and progesterone sensitivity and may grow during pregnancy. The mediator complex subunit 12 (MED12) gene is the most common gene involved in the pathogenesis of fibroadenoma. […] On microscopic pathology, charectersitic findings of fibroadenoma include a biphasic proliferation of both stromal and epithelial components that can be arranged in two growth patterns; a pericanalicular growth pattern and an intracanalicular growth pattern.

• #1 Fibroadenoma of the breast

  https://www.pathologyatlas.ro/fibroadenoma-breast-pathology.php

  Fibroadenoma is the most common benign breast tumor, mostly in young women. It consists in two components (epithelial and fibroblastic), estrogen-dependent, slowly growing. […] Until recently, traditionally, fibroadenoma was considered to be a benign mixed tumor, but recent studies showed that only the fibroblastic component is neoplastic (being monoclonal), while the epithelial one is only reactive, non-neoplastic (being policlonal). […] The epithelial proliferation appears in a single terminal ductal unit and describes duct-like spaces surrounded by a fibroblastic stroma. Depending on the proportion and the relationship between these two components, there are two main histological features: intracanalicular and pericanalicular. Often, both types are found in the same tumor.

• #1 Fibroadenoma | Basicmedical Key

  https://basicmedicalkey.com/fibroadenoma/

  Fibroadenomas are due to proliferation of lobular stroma and may be polyclonal or monoclonal […] Most FAs are polyclonal hyperplasias of lobular stroma […] Some stromal cells have estrogen receptor /or progesterone receptors […] FAs occur most commonly in young premenopausal women […] Some FAs are monoclonal stromal tumors […] Clonal genetic changes may be present in stromal cells […] As stromal proliferation becomes more pronounced and autonomous, spectrum of changes seen in FAs overlaps with low-grade phyllodes tumors […] Some phyllodes tumors likely arise from FAs.

• #1 Understanding Fibroadenoma of the Breast: A Comprehensive Review of Pre-operative and Post-operative Clinicopathological Correlations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10823311/

  Reproductive factors are significant contributors to the risk of fibroadenoma development. Factors such as early onset of menstruation (menarche) and nulliparity (not having given birth) have been associated with an elevated likelihood of developing fibroadenomas. These reproductive factors are frequently linked to hormonal changes that contribute to the growth and development of these benign breast lesions. […] Additionally, while trauma or injury to the breast tissue is not a direct cause of fibroadenomas, it may serve as a triggering event for their development or growth. Trauma can disrupt the standard tissue architecture within the breast, creating an environment conducive to the formation of fibroadenomas. It’s noteworthy, however, that fibroadenomas can also develop spontaneously without any preceding injury, highlighting the multifaceted nature of their etiology.

• #1 Fibroadenoma of the breast: what it is, its types, symptoms, diagnosis and treatment

  https://medconsonline.com/en/blog/fibroadenoma-of-the-breast

  This is a benign tumor resulting from the overgrowth of connective (stromal) and glandular (epithelial) tissue, so it belongs to the group of fibroepithelial neoplasms. […] The exact causes of these breast tumors are unknown, but several factors are thought to contribute to their development. […] Reproductive hormone imbalance: abnormal estradiol and progesterone ratio with increased levels of the former. The hormone dependence of fibrous glandular overgrowths is proved, in particular, by the fact that their size partially changes during the menstrual cycle and increases during pregnancy, while regression symptoms (reduction in size, calcification, etc.) often occur in postmenopause. […] Familial predisposition: it is known that if fibroadenomas or other benign breast disorders are present in close relatives, the risk of developing these conditions is increased.

• #1 Rare findings in a common tumor: A case of complex fibroadenoma with secondary changes in a young female – IJPO

  https://www.ijpo.co.in/html-article/11356

  Fibroadenoma (FA) is one the most common breast tumours seen in adolescent and young women. […] Complex FA is defined as FAs with cysts, sclerosing adenosis, epithelial calcifications or papillary apocrine changes. […] Despite these unusual findings, recent large cohort studies concluded that complex FA is not an independent risk factor for carcinoma breast. […] The stroma of FA in postmenopausal women shows regressive changes and tends to be hypocellular and hyalinized and it frequently harbours coarse dystrophic calcifications. […] Extensive literature search did not reveal any similar case as ours. […] Dupont et al. in their retrospective cohort study of 1,835 women with FA emphasized upon the significance of complex FA. […] They found that the risk of invasive breast cancer in these patients was 3.1 times higher than in women of the general population as compared to relative risk of 1.89 in FAs not associated with complex features.

• #1 Fibroadenoma | Breast Cancer Now

  https://breastcancernow.org/about-breast-cancer/breast-lumps-and-benign-not-cancer-breast-conditions/fibroadenoma/

  Fibroadenomas develop from a lobule. Tissue and ducts grow over the lobule and form a solid lump. […] Its not known what causes fibroadenomas, but its thought they may occur because of the effects of the hormone oestrogen. […] Having a complex fibroadenoma can very slightly increase the risk of developing breast cancer in the future. […] For most people, having a fibroadenoma does not increase the risk of developing breast cancer.

• #1 Rare findings in a common tumor: A case of complex fibroadenoma with secondary changes in a young female – IJPO

  https://www.ijpo.co.in/html-article/11356

  Awareness of complex FA is vital because, USG finding of complex FA e.g. presence of internal cysts, small punctuate echogenicities or heterogeneous echotexture inside a solid nodule are encountered in a nodule which is otherwise classified as BIRADS 3 on sonography, a biopsy may be taken instead of routine follow-up. […] Recently Nassar et al. studied a cohort of 9076 women aged 18 to 85 years who underwent surgical excision of a benign breast lesion. […] They concluded that complex FA does not confer increased risk of invasive breast carcinoma beyond that of other recognized histologic features such as proliferative disease without atypia and atypical hyperplasia. […] Hyalinization of FA suggesting regressive change, is an exceptional phenomenon in younger patients which makes our case a unique one.

• #1 Pathogenesis and progression of fibroepithelial breast tumors

  https://dspace.library.uu.nl/handle/1874/10374

  Fibroadenoma and phyllodes tumor are fibroepithelial breast tumors. The behavior of fibroadenomas is benign, whereas phyllodes tumors can recur and even metastasize. Further, morphological observations have suggested that fibroadenoma may progress to phyllodes tumor. The aim of this thesis can be summarized as a study of tumorigenesis and progression in fibroepithelial tumors, i.e. progression in fibroadenomas and progression in grade of phyllodes tumors. We therefore demonstrated that fibroadenoma may show both epithelial (to carcinoma) and stromal (to phyllodes tumor) progression. The molecular mechanisms underlying development of fibroepithelial tumors are largely unknown. We showed that, in phyllodes tumors, stromal progression is driven by cell cycle deregulation and EGFR overexpression.

• #1 Pathogenesis and progression of fibroepithelial breast tumors

  https://dspace.library.uu.nl/handle/1874/10374

  Although not related to grade, it seems that genomic instability plays a role in development of phyllodes tumors. […] In this thesis we demonstrated that benign fibroadenoma may progress to the unpredictable phyllodes tumor. Further, we studied several major carcinogenic phenomena and found important roles for cell cycle deregulation, EGFR overexpression, angiogenic factors and genomic instability in phyllodes tumor genesis and progression. Although fibroadenoma and phyllodes tumor share morphological similarities, both tumors are different molecular entities.

• #1 Estrogen receptor-β is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast | Modern Pathology

  https://www.nature.com/articles/3800574

  The role of ER- in the mammary gland epithelium has been widely studied, but, to our knowledge, no function for ER- in stroma has been reported. Our results suggest that, in addition to a well established antiproliferative effect on epithelial cells, the expression of ER- in the breast is probably related to a prodifferentiative function on stromal cells. […] In fibroadenomas, ER–related myofibroblastic differentiation of fibroblasts may act on remodelling of the matrix and inhibition of the sclerotic involution. […] In contrast to these data, ER- expression was directly correlated to the age of patients in phyllodes tumors, suggesting an estrogen-independent tumor growth, possibly mediated by cytokines. […] In conclusion, the present work suggests that a heterogeneous fibroblast population with different lifespan is activated and recruited through ER- in the stroma of fibroadenomas and phyllodes tumors.

• #1 Fibroadenoma of the Breast: Types, Causes, Symptoms & Treatment

  https://www.ganeshdiagnostic.com/blog/fibroadenoma-of-the-breast-types-causes-symptoms-and-treatment

  The foremost vital of these hormones incorporate estrogen, progesterone, and prolactin. […] Chronic hormonal changes, in the long run, create little blisters and/or ranges of thick or fibrotic tissue over a long time. […] Over time, probably driven by abnormal development signals, such injuries may gather epigenetic, hereditary, and karyotypic changes such as altered expression of hormone receptors and loss of heterozygosity. […] There’s proof that iodine insufficiency contributes to fibrocystic breast changes by improving breast tissue’s affectability to estrogen.

• #1 Fibroadenoma (breast) | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/fibroadenoma-breast?lang=us

  Fibroadenoma is a common benign breast lesion resulting from the excess proliferation of connective tissue. Fibroadenomas characteristically contain both stromal and epithelial cells. […] They are assumed to be aberrations of normal breast development (ANDI) or the product of hyperplastic processes, rather than true neoplasms. Fibroadenomas can be stimulated by estrogen and progesterone. Some fibroadenomas also have receptors and respond to growth hormone and epidermal growth factor.

• #1 iBreastBook: Fibroadenoma

  https://www.ibreastbook.com/fibroadenoma

  Fibroadenomas are part of ANDI (Aberration of Normal Development and Involution). It usually arises from the terminal ductal-lobular Unit and is composed of epithelial and connective tissue components. They are influenced by hormonal variation. […] Between the ages of 15 and 25, under the influence of cyclic exposure to sex hormones, the breast develops lobules in addition to the ducts which develop during puberty. Commonly hyperplastic lobules develop at this stage in development. Fibroadenoma occur in a single breast lobule, histologically they are identical to hyperplastic lobules. They contain both epithelial and stromal cells. Like normal breast lobules fibroadenoma are responsive to hormones, demonstrating growth when exposed to sex hormones and involution following menopause.

• #2 Fibroadenoma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Fibroadenoma_pathophysiology

  Fibroadenoma is a common benign tumor of the breast. The pathogenesis is not completely understood. […] Fibroadenoma is a proliferation of stromal and epithelial connective tissue cells (biphasic) originating from the terminal duct-lobular unit. Analysis of the stromal and epithelial cells showed that both are polyclonal, which supports the theory that fibroadenomas are hyperplastic lesions associated with a deviation from the normal maturation of the breast, rather than a true neoplasm. […] In some patients, fibroadenomas may express estrogen and progesterone receptors. These hormones stimulate the fibroadenomas via hormone-receptor mechanism leading to excessive proliferation of epithelial and stromal cells. They undergo atrophy during menopause. […] Some fibroadenomas may express epidermal growth factor (EGF) receptors.

• #2 Estrogen receptor-β is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast | Modern Pathology

  https://www.nature.com/articles/3800574

  An estrogen dependency has been suggested for the growth of fibroadenomas: however, thus far, none of the steroid hormone receptors acting on breast tissues has been demonstrated in the stroma of breast fibroepithelial lesions. […] In conclusion, (i) only ER- is detected in the stroma of fibroadenomas and phyllodes tumors; (ii) its expression correlates with the expression of smooth muscle markers and suggests a role of ER- in myofibroblastic differentiation of stromal cells. These two results, together with the young age of patients carrying fibroadenomas with highly ER- positive stroma cells, may further indicate a hormone-receptor mechanism involved in regulating the growth of fibroadenomas. Conversely, the older age of patients with ER- rich phyllodes tumors suggests that mechanisms, probably independent from estrogen stimulation, act on the growth of these tumors.

• #2 Fibroadenoma (breast) | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/fibroadenoma-breast?lang=us

  Fibroadenoma is a common benign breast lesion resulting from the excess proliferation of connective tissue. Fibroadenomas characteristically contain both stromal and epithelial cells. […] They are assumed to be aberrations of normal breast development (ANDI) or the product of hyperplastic processes, rather than true neoplasms. Fibroadenomas can be stimulated by estrogen and progesterone. Some fibroadenomas also have receptors and respond to growth hormone and epidermal growth factor.

• #2 Estrogen receptor-β is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast | Modern Pathology

  https://www.nature.com/articles/3800574

  The role of ER- in the mammary gland epithelium has been widely studied, but, to our knowledge, no function for ER- in stroma has been reported. Our results suggest that, in addition to a well established antiproliferative effect on epithelial cells, the expression of ER- in the breast is probably related to a prodifferentiative function on stromal cells. […] In fibroadenomas, ER–related myofibroblastic differentiation of fibroblasts may act on remodelling of the matrix and inhibition of the sclerotic involution. […] In contrast to these data, ER- expression was directly correlated to the age of patients in phyllodes tumors, suggesting an estrogen-independent tumor growth, possibly mediated by cytokines. […] In conclusion, the present work suggests that a heterogeneous fibroblast population with different lifespan is activated and recruited through ER- in the stroma of fibroadenomas and phyllodes tumors.

• #2 Giant juvenile fibroadenoma of the breast: a case report and brief literature review

  https://www.e-apem.org/journal/view.php?doi=10.6065/apem.2014.19.1.45

  A girl (age, 12 years 11 months) consulted the pediatric endocrinology clinic because of a rapidly growing right breast mass over 13 cm observed during the preceding 3 months. […] The etiology is believed to be an end-organ hypersensitivity to normal levels of estrogen. […] Giant juvenile fibroadenoma is a rare variant of fibroadenoma (0.5%-2% of all fibroadenomas) and is characterized by rapid growth. […] Hormonal influences are thought to be a contributing factor. Excessive endogenous or exogenous estrogen stimulation, hypersensitivity of mammary gland tissue to local estrogen, and relative deficiency of estrogen antagonists such as progesterone, have been implicated in the pathogenesis because giant juvenile fibroadenomas increase in frequency during puberty or pregnancy and in response to oral contraceptives. […] The exact etiology is unknown.

• #2 MED 12 gene mutation in a case of bilateral giant juvenile fibroadenoma – IJPO

  https://www.ijpo.co.in/html-article/17932

  Giant juvenile fibroadenoma is a rare variant of more common benign lesion, fibro adenoma observed in younger population. […] Somatic mutation in exon 2 of the MED12 gene is identified in 60% of breast fibroadenomas. […] The genetic basis of fibroadenoma has not been studied as widely as done for breast carcinoma. Recent studies have shown association of somatic mutations of Exon 2 of the MED 12 gene with benign fibro epithelial lesions of breast. […] The MED 12 somatic mutation is said to be tumorigenic as it leads to loss of mediator associated CDK activity and overexpression of RAD51B by decreased interaction between MED12 and Cyclin C-CDK8/CDK19. […] The MED12 somatic mutation also has an influence on estrogen signaling as Mediator complex interacts with and receptors of estrogen, evidenced by association of MED12 with other estrogen stimulated tumours like uterine leiomyomas and stromal tumours.

• #2 MED 12 gene mutation in a case of bilateral giant juvenile fibroadenoma – IJPO

  https://www.ijpo.co.in/html-article/17932

  c122_ 139 deletion in MED 12 Exon 2 has been reported in this case. […] Identifying MED12 gene in fibroadenomas opens the door of understanding the lesser-known genetic basis and genetic abnormalities of highly common lesions such as fibroadenoma and thus leading to development of novel treatment strategies with an aim to target the causative gene mutation and spare the patient of surgical intervention.

• #2 Breast fibroadenomas: a review in the light of current…

  https://ppch.pl/seo/article/01.3001.0014.5676/en

  Lim W.K. et al. undertook exome sequencing of eight fibroadenomas with matching whole-blood samples and found recurrent somatic mutations solely in MED12, which encodes a Mediator complex subunit and thereby concluded that the fibroadenomas and the benign tumors of uterus, both of which are key target tissues of estrogen, may share a common genetic basis underpinned by highly frequent and specific MED12 mutations. […] Multiple fibroadenomas has also been associated to a strong history of breast lesions in the family and it has been suggested that the physiologic level of estrogen in such patients did not increase, but instead, the number of estrogen receptor increased leading to hypersensitivity of local breast tissue to estrogen.

• #2 Fibroadenoma of the breast

  https://www.pathologyatlas.ro/fibroadenoma-breast-pathology.php

  Fibroadenoma is the most common benign breast tumor, mostly in young women. It consists in two components (epithelial and fibroblastic), estrogen-dependent, slowly growing. […] Until recently, traditionally, fibroadenoma was considered to be a benign mixed tumor, but recent studies showed that only the fibroblastic component is neoplastic (being monoclonal), while the epithelial one is only reactive, non-neoplastic (being policlonal). […] The epithelial proliferation appears in a single terminal ductal unit and describes duct-like spaces surrounded by a fibroblastic stroma. Depending on the proportion and the relationship between these two components, there are two main histological features: intracanalicular and pericanalicular. Often, both types are found in the same tumor.

• #2 Fibroadenoma | Basicmedical Key

  https://basicmedicalkey.com/fibroadenoma/

  Fibroadenomas are due to proliferation of lobular stroma and may be polyclonal or monoclonal […] Most FAs are polyclonal hyperplasias of lobular stroma […] Some stromal cells have estrogen receptor /or progesterone receptors […] FAs occur most commonly in young premenopausal women […] Some FAs are monoclonal stromal tumors […] Clonal genetic changes may be present in stromal cells […] As stromal proliferation becomes more pronounced and autonomous, spectrum of changes seen in FAs overlaps with low-grade phyllodes tumors […] Some phyllodes tumors likely arise from FAs.

• #2 Fibroadenoma of Breast: Causes, Symptoms, and Diagnosis

  https://www.healthline.com/health/fibroadenoma-breast

  Its unknown exactly what causes fibroadenomas. Hormones such as estrogen may play a part in the growth and development of the tumors. […] Taking oral contraceptives before the age of 20 has been associated with a higher risk of developing fibroadenomas as well. […] These tumors may grow larger in size, particularly during pregnancy. During menopause, they often shrink. […] Complex fibroadenomas can slightly increase your risk of breast cancer. The American Cancer Society states that women with complex fibroadenomas have approximately one and a half times greater risk of developing breast cancer than women with no breast lumps.

• #2 Fibroadenoma of the breast: what it is, its types, symptoms, diagnosis and treatment

  https://medconsonline.com/en/blog/fibroadenoma-of-the-breast

  Local growth factors: by promoting the proliferation of stromal tissue and glandular components, local growth factors can stimulate the growth of breast lumps. […] Injury: it is hypothesized that damage to the organ can induce local tissue changes leading to the development of benign lesions. […] Diet and lifestyle: although there is no direct link, some studies suggest that certain dietary and lifestyle factors, such as a high-fat diet, can affect hormone levels and, consequently, stimulate the development of breast nodules. […] Other possible causes that are still being debated include certain immunosuppressant drugs and viral infections such as the Eppstein-Barr virus.

• #2 The surgeon’s guide to fibroadenomas – Kopkash – Annals of Breast Surgery

  https://abs.amegroups.org/article/view/6448/html

  Fibroadenomas (FA) are the most common benign breast lesion. […] The exact etiology of FA is unknown. There is likely a hormonal component because FA are most common during the reproductive years and they also often enlarge during pregnancy or with estrogen therapies. […] FA are characterized as proliferative breast lesions without atypia and they are associated with a slight increased risk of developing breast cancer in the future, however there is some variation in risk based on subtype. […] Complex FA are FA with associated cysts, sclerosing adenosis, epithelial calcifications, or papillary apocrine changes and they represent approximately 14% of FA. Breast cancer risk in patients with complex FA is increased if there are proliferative changes in the surrounding breast tissue and complex FA alone is not considered an independent risk factor. […] The ideal approach for a patient with a breast mass suggestive of FA is to image with US +/ mammogram, confirm the lesion is an FA using percutaneous core biopsy, and conservative follow-up in the future.

• #2 How Are Fibroadenomas Formed?: Trevan Fischer, MD: Surgical Oncologist

  https://www.drtrevanfischer.com/blog/how-are-fibroadenomas-formed

  No one knows what causes the creation of a fibroadenoma. Since it usually occurs in women between the ages of 15-35 and those who are pregnant or breastfeeding, experts speculate it may occur due to changing hormone levels. […] A fibroadenoma begins as an excess lobule that then gets overgrown by glandular tissue and ducts, ultimately resulting in a solid lump.

• #2 Fibroadenoma: Symptoms, Causes, Diagnosis, and Treatment

  https://www.webmd.com/breast-cancer/what-are-fibroadenomas

  Doctors don’t know what causes fibroadenomas. They may be related to changing levels of the hormone estrogen. They often grow during pregnancy when your estrogen levels are high, and shrink when your estrogen levels drop after menopause. […] Fibroadenomas and other benign breast lumps won’t turn into cancer. But it is possible that complex fibroadenomas could slightly increase your risk of breast cancer in the future. […] Having a simple fibroadenoma may raise your risk of breast cancer, compared with women without fibroadenomas. But if you had a fibroadenoma that was complex, it might mean a slightly higher risk of breast cancer later on.

• #2 iBreastBook: Fibroadenoma

  https://www.ibreastbook.com/fibroadenoma

  Fibroadenomas are part of ANDI (Aberration of Normal Development and Involution). It usually arises from the terminal ductal-lobular Unit and is composed of epithelial and connective tissue components. They are influenced by hormonal variation. […] Between the ages of 15 and 25, under the influence of cyclic exposure to sex hormones, the breast develops lobules in addition to the ducts which develop during puberty. Commonly hyperplastic lobules develop at this stage in development. Fibroadenoma occur in a single breast lobule, histologically they are identical to hyperplastic lobules. They contain both epithelial and stromal cells. Like normal breast lobules fibroadenoma are responsive to hormones, demonstrating growth when exposed to sex hormones and involution following menopause.

• #3 Fibroadenoma overview – wikidoc

  https://www.wikidoc.org/index.php/Fibroadenoma_overview

  Fibroadenoma is a common benign tumor of the breast. Fibroadenoma arises from connective tissue cells, which are cells that are normally involved in the functional and mechanical support of the surrounding tissues. Fibroadenoma demonstrate estrogen and progesterone sensitivity and may grow during pregnancy. The mediator complex subunit 12 (MED12) gene is the most common gene involved in the pathogenesis of fibroadenoma. […] On microscopic pathology, charectersitic findings of fibroadenoma include a biphasic proliferation of both stromal and epithelial components that can be arranged in two growth patterns; a pericanalicular growth pattern and an intracanalicular growth pattern.

• #3 Pulsenotes | Fibroadenoma notes

  https://app.pulsenotes.com/surgery/breast-surgery/notes/fibroadenoma

  Fibroadenomas are fibroepithelial tumours arising from stromal and epithelial tissue. […] There is clear evidence of a hormonal link. They tend to develop after menarche and regress after menopause. They may be triggered or increase in size during pregnancy or when taking hormone replacement therapy (HRT). […] A genetic basis has also been identified with a mutation to MED12 found in around 60% of tumours. MED12 has been implicated in many other conditions including uterine fibroids.

• #3 Genetics and genomics of breast fibroadenomas | Journal of Clinical Pathology

  https://jcp.bmj.com/content/71/5/381.abstract

  Fibroadenomas of the breast are benign fibroepithelial tumours most frequently encountered in women of reproductive age, although they may be diagnosed at any age. The mechanisms underlying fibroadenoma pathogenesis remain incompletely understood. […] Recent sequencing studies have demonstrated the presence of highly recurrent mutations in fibroadenomas, and also delineated the genomic landscapes of fibroadenomas and the closely related phyllodes tumours, revealing differences at the gene level, which may be of potential adjunctive diagnostic use. The present article provides an overview of key studies uncovering genetic and genomic abnormalities in fibroadenomas, from initial karyotype reports revealing myriad cytogenetic aberrations to next-generation sequencing-based approaches that led to the discovery of highly recurrent MED12 mutations. A thorough understanding of these abnormalities is important to further elucidate the mechanisms by which fibroadenomas arise and to refine diagnostic assessment of this very common tumour.

• #3 Giant Juvenile Fibroadenoma: Case Report and Review of the Literature

  https://www.mdpi.com/2077-0383/12/5/1855

  Fibroadenomas are benign masses that consist of estrogen-sensitive epithelial and stromal tissue. Malignancy in a pre-existing juvenile fibroadenoma is very rare. Fibroadenomas are not linked to an increased risk of breast cancer in the general population. However, in women with a significant family history of breast cancer and in cases of proliferative changes in the histopathologic examination of the mass, an increase in breast cancer risk has been reported. […] The precise etiology of juvenile fibroadenomas remains unknown. Reproductive hormones could play a role, since estrogen and progesterone receptors are expressed in fibroadenomas, and these lesions occur more frequently in puberty, pregnancy, and in individuals who take oral contraceptives. Genetic predisposition also plays a role, since fibroadenomas appear more commonly in African-American females, and occasionally patients report positive family history of breast fibroadenomas, as was the case in our patient.

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