Fibroadenoma

Last updated

Fibroadenoma
Other namesBreast mice, breast mouse
Breast fibradenoma (1).jpg
Histopathologic image of breast fibroadenoma. Core needle biopsy. H&E stain.
Specialty Gynecology

Fibroadenomas are benign breast tumours characterized by an admixture of stromal and epithelial tissue. Breasts are made of lobules (milk producing glands) and ducts (tubes that carry the milk to the nipple). These are surrounded by glandular, fibrous and fatty tissues. Fibroadenomas develop from the lobules. The glandular tissue and ducts grow over the lobule to form a solid lump.

Contents

Since both fibroadenomas and breast lumps as a sign of breast cancer can appear similar, it is recommended to perform ultrasound analyses and possibly tissue sampling with subsequent histopathologic analysis in order to make a proper diagnosis. Unlike typical lumps from breast cancer, fibroadenomas are easy to move, with clearly defined edges. [1] [2]

Fibroadenomas are sometimes called breast mice or a breast mouse owing to their high mobility in the breast. [3]

Signs and symptoms

Fibroadenomas are benign tumours of the breast, most often present in women in their 20s and 30s. [4] Clinically, fibroadenomas are usually solid breast lumps that are:

People who have a simple fibroadenoma likely do not have an increased risk of developing malignant (harmful) breast cancer compared to the general population. [4] Complex fibroadenomas may increase the risk of breast cancer slightly. [4]

In the male breast, fibroepithelial tumors are very rare, and are mostly phyllodes tumors. Exceptionally rare case reports exist of fibroadenomas in the male breast; however, these cases may be associated with antiandrogen treatment. [5]

Cause

The cause of fibroadenoma is unknown (idiopathic). [6] 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. [6]

Higher intake of fruits and vegetables, higher number of live births, lower use of oral contraceptives and moderate exercise are associated with lower frequency of fibroadenomas. [7]

Pathology

Macroscopic view of fibroadenoma of the breast FibroAdenoma of the breast.JPG
Macroscopic view of fibroadenoma of the breast
Closeup of a fibroadenoma of the breast Fibroadenoma of breast.jpg
Closeup of a fibroadenoma of the breast

Cytology

The diagnostic findings on needle biopsy consist of abundant stromal cells, which appear as bare bipolar nuclei, throughout the aspirate; sheets of fairly uniform-size epithelial cells that are typically arranged in either an antler-like pattern or a honeycomb pattern. These epithelial sheets tend to show typical metachromatic blue on Diff-Quik staining. Foam cells and apocrine cells may also be seen, although these are less diagnostic features. [8] [9] The gallery images below demonstrate these features.

Cellular fibroadenoma, also known as juvenile fibroadenoma, is a variant type of fibroadenoma with increased stromal cellularity. [10] [11]

Macroscopic

Approximately 90% of fibroadenomas are less than 3 cm in diameter. However, these tumors have the potential to grow reaching a remarkable size, particularly in young individuals. The tumor is round or ovoid, elastic, and nodular, and has a smooth surface. The cut surface usually appears homogenous and firm, and is grey-white or tan in colour. The pericanalicular type (hard) has a whorly appearance with a complete capsule, while the intracanalicular type (soft) has an incomplete capsule. [9]

Microscopic

Fibroadenoma of the breast is a benign tumor composed of a biplastic proliferation of both stromal and epithelial components. [12] [13] This biplasia can be arranged in two growth patterns: pericanalicular (stromal proliferation around epithelial structures) and intracanalicular (stromal proliferation compressing the epithelial structures into slit-like spaces).

These tumors characteristically display hypovascular stroma compared to malignant neoplasms. [2] [14] [9] Furthermore, the epithelial proliferation appears in a single terminal ductal unit and describes duct-like spaces surrounded by a fibroblastic stroma. The basement membrane is intact. [15]

Molecular pathology

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. [16] [17]

Diagnosis

A fibroadenoma is usually diagnosed through clinical examination, ultrasound or mammography, and often a biopsy sample of the lump. [8] Suspicious findings on imaging may result in a person needing a biopsy in order to gain a definitive diagnosis. There are three types of biopsies: fine-needle aspiration, core-needle biopsy and surgical biopsy. The method of biopsy depends on the appearance, size and location of the breast mass. [18]

Treatment

Fibroadenomas can be expected to shrink naturally, so most are simply monitored. [19] Monitoring fibroadenomas involves regular check-ups to make sure that the breast mass is not growing and is not potentially cancerous. [19] Check-ups involve physical examinations performed every 3–6 months and optional diagnostic imaging performed every 6–12 months for 1–2 years. [19] Generally, surgery is only recommended if the fibroadenoma gets larger or causes increased symptoms. [20] They are removed with a small margin of normal breast tissue if the preoperative clinical investigations are suggestive of the necessity of this procedure. A small amount of normal tissue must be removed in case the lesion turns out to be a phyllodes tumour on microscopic examination. [9] [21]

Because needle biopsy is often a reliable diagnostic investigation, some doctors may decide not to operate to remove the lesion, and instead opt for clinical follow-up to observe the lesion over time using clinical examination and mammography to determine the rate of growth, if any, of the lesion. A growth rate of less than sixteen percent per month in women under fifty years of age, and a growth rate of less than thirteen percent per month in women over fifty years of age have been published as safe growth rates for continued non-operative treatment and clinical observation. [22]

Some fibroadenomas respond to treatment with ormeloxifene. [23]

Fibroadenomas have not been shown to recur following complete excision or transform into phyllodes tumours following partial or incomplete excision. [9]

Non-invasive surgical interventions

There are several non-invasive options for the treatment of fibroadenomas, including percutaneous radiofrequency ablation (RFA), cryoablation, and percutaneous microwave ablation. [24] With the use of advanced medical imaging, these procedures do not require invasive surgery and have the potential for enhanced cosmetic results compared with conventional surgery. [24]

Cryoablation

The FDA approved cryoablation of a fibroadenoma as a safe, effective, and minimally-invasive alternative to open surgical removal in 2001. [25] During cryoablation, ultrasound imaging is used to guide a probe into the mass of breast tissue. Extremely cold temperatures are then used to destroy the abnormal cells, and over time the cells are reabsorbed into the body. [26] The procedure can be performed as an outpatient surgery using local anesthesia, and leaves substantially less scarring than open surgical procedures and no breast tissue deformation.[ citation needed ]

The American Society of Breast Surgeons recommends the following criteria to establish a patient as a candidate for cryoablation of a fibroadenoma: [25]

  1. The lesion must be sonographically visible.
  2. The diagnosis of a fibroadenoma must be confirmed histologically.
  3. The lesion should be less than 4 cm in diameter.

High-intensity focused ultrasound

High-intensity focused ultrasound (HIFU) is a newer technique for the treatment of malignant and benign tumors of the breast and has shown promising results in the form of complete radiological removal of tumors. [27] An ultrasound beam is focused on a target in the breast and leads to tissue death and protein degradation by raising the temperature in that area. [27] Currently, the use of radiation is recommended in some cases, but HIFU in particular is not part of treatment guidelines. [28] Further research into the usefulness of HIFU, specifically in fibroadenoma, is required before more widespread use of the technique in fibroadenoma. [27]

Epidemiology

Of all breast tissue samples taken, fibroadenomas comprise about 50%, and this rate rises to 75% for tissue sample in women under the age of 20 years. [29] Fibroadenomas are more frequent among women in higher socioeconomic classes and darker-skinned people. [29] Body mass index and the number of full-term pregnancies were found to have a negative correlation with the risk of fibroadenomas. [29] There are no known genetic factors that influence the rate of fibroadenomas. [29] The rate of occurrence of fibroadenomas in women has been reported in literature to range from 7% to 13%. [29]

Related Research Articles

<span class="mw-page-title-main">Bone tumor</span> Medical condition

A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, thyroid, kidney and prostate. There may be a lump, pain, or neurological signs from pressure. A bone tumor might present with a pathologic fracture. Other symptoms may include fatigue, fever, weight loss, anemia and nausea. Sometimes there are no symptoms and the tumour is found when investigating another problem.

<span class="mw-page-title-main">Biopsy</span> Medical test involving extraction of sample cells or tissues for examination

A biopsy is a medical test commonly performed by a surgeon, an interventional radiologist, or an interventional cardiologist. The process involves the extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is then fixed, dehydrated, embedded, sectioned, stained and mounted before it is generally examined under a microscope by a pathologist; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous or inflammatory conditions.

<span class="mw-page-title-main">Adenoma</span> Type of benign tumor

An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenomas grow from epithelial tissue in nonglandular areas but express glandular tissue structure. Although adenomas are benign, they should be treated as pre-cancerous. Over time adenomas may transform to become malignant, at which point they are called adenocarcinomas. Most adenomas do not transform. However, even though benign, they have the potential to cause serious health complications by compressing other structures and by producing large amounts of hormones in an unregulated, non-feedback-dependent manner. Some adenomas are too small to be seen macroscopically but can still cause clinical symptoms.

<span class="mw-page-title-main">Sex cord–gonadal stromal tumour</span> Medical condition

Sex cord–gonadal stromal tumour is a group of tumours derived from the stromal component of the ovary and testis, which comprises the granulosa, thecal cells and fibrocytes. In contrast, the epithelial cells originate from the outer epithelial lining surrounding the gonad while the germ cell tumors arise from the precursor cells of the gametes, hence the name germ cell. In humans, this group accounts for 8% of ovarian cancers and under 5% of testicular cancers. Their diagnosis is histological: only a biopsy of the tumour can make an exact diagnosis. They are often suspected of being malignant prior to operation, being solid ovarian tumours that tend to occur most commonly in post menopausal women.

<span class="mw-page-title-main">Fine-needle aspiration</span> Diagnostic medical procedure

Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin, hollow needle is inserted into the mass for sampling of cells that, after being stained, are examined under a microscope (biopsy). The sampling and biopsy considered together are called fine-needle aspiration biopsy (FNAB) or fine-needle aspiration cytology (FNAC). Fine-needle aspiration biopsies are very safe minor surgical procedures. Often, a major surgical biopsy can be avoided by performing a needle aspiration biopsy instead, eliminating the need for hospitalization. In 1981, the first fine-needle aspiration biopsy in the United States was done at Maimonides Medical Center. Today, this procedure is widely used in the diagnosis of cancer and inflammatory conditions. Fine needle aspiration is generally considered a safe procedure. Complications are infrequent.

<span class="mw-page-title-main">Phyllodes tumor</span> Medical condition

Phyllodes tumors, are a rare type of biphasic fibroepithelial mass that form from the periductal stromal and epithelial cells of the breast. They account for less than 1% of all breast neoplasms. They were previously termed cystosarcoma phyllodes, coined by Johannes Müller in 1838, before being renamed to phyllodes tumor by the World Health Organization in 2003. Phullon, which means 'leaf' in Greek, describes the unique papillary projections characteristic of phyllodes tumors on histology. Diagnosis is made via a core-needle biopsy and treatment is typically surgical resection with wide margins (>1 cm), due to their propensity to recur.

<span class="mw-page-title-main">Pleomorphic adenoma</span> Medical condition

Pleomorphic adenoma is a common benign salivary gland neoplasm characterised by neoplastic proliferation of epithelial (ductal) cells along with myoepithelial components, having a malignant potentiality. It is the most common type of salivary gland tumor and the most common tumor of the parotid gland. It derives its name from the architectural Pleomorphism seen by light microscopy. It is also known as "Mixed tumor, salivary gland type", which refers to its dual origin from epithelial and myoepithelial elements as opposed to its pleomorphic appearance.

<span class="mw-page-title-main">Fibroepithelial neoplasm</span> Medical condition

A fibroepithelial neoplasm is a biphasic tumor. They consist of epithelial tissue, and stromal or mesenchymal tissue. They may be benign or malignant.

<span class="mw-page-title-main">Cryoablation</span> Process using extreme cold to destroy tissue

Cryoablation is a process that uses extreme cold to destroy tissue. Cryoablation is performed using hollow needles (cryoprobes) through which cooled, thermally conductive, fluids are circulated. Cryoprobes are positioned adjacent to the target in such a way that the freezing process will destroy the diseased tissue. Once the probes are in place, the attached cryogenic freezing unit removes heat from ("cools") the tip of the probe and by extension from the surrounding tissues.

<span class="mw-page-title-main">Fibrocystic breast changes</span> Medical condition

Fibrocystic breast changes is a condition of the breasts where there may be pain, breast cysts, and breast masses. The breasts may be described as "lumpy" or "doughy". Symptoms may worsen during certain parts of the menstrual cycle due to hormonal stimulation. These are normal breast changes, not associated with cancer.

Breast diseases make up a number of conditions. The most common symptoms are a breast mass, breast pain, and nipple discharge.

<span class="mw-page-title-main">Surgical pathology</span> Area of practice for anatomical pathologists

Surgical pathology is the most significant and time-consuming area of practice for most anatomical pathologists. Surgical pathology involves gross and microscopic examination of surgical specimens, as well as biopsies submitted by surgeons and non-surgeons such as general internists, medical subspecialists, dermatologists, and interventional radiologists.

<span class="mw-page-title-main">Breast cyst</span> Medical condition

A breast cyst is a cyst, a fluid-filled sac, within the breast. One breast can have one or more cysts. They are often described as round or oval lumps with distinct edges. In texture, a breast cyst usually feels like a soft grape or a water-filled balloon, but sometimes a breast cyst feels firm.

<span class="mw-page-title-main">Thyroid nodule</span> Medical condition

Thyroid nodules are nodules which commonly arise within an otherwise normal thyroid gland. They may be hyperplastic or tumorous, but only a small percentage of thyroid tumors are malignant. Small, asymptomatic nodules are common, and often go unnoticed. Nodules that grow larger or produce symptoms may eventually need medical care. A goitre may have one nodule – uninodular, multiple nodules – multinodular, or be diffuse.

<span class="mw-page-title-main">Salivary gland tumour</span> Medical condition

Salivary gland tumours, also known as mucous gland adenomas or neoplasms, are tumours that form in the tissues of salivary glands. The salivary glands are classified as major or minor. The major salivary glands consist of the parotid, submandibular, and sublingual glands. The minor salivary glands consist of 800 to 1000 small mucus-secreting glands located throughout the lining of the oral cavity. Patients with these types of tumours may be asymptomatic.

<span class="mw-page-title-main">Leydig cell tumour</span> Medical condition

Leydig cell tumour, also Leydig cell tumor, (testicular) interstitial cell tumour and (testicular) interstitial cell tumor, is a member of the sex cord-stromal tumour group of ovarian and testicular cancers. It arises from Leydig cells. While the tumour can occur at any age, it occurs most often in young adults.

<span class="mw-page-title-main">Breast mass</span> Localized swellings that feel different from the surrounding tissue

A breast mass, also known as a breast lump, is a localized swelling that feels different from the surrounding tissue. Breast pain, nipple discharge, or skin changes may be present. Concerning findings include masses that are hard, do not move easily, are of an irregular shape, or are firmly attached to surrounding tissue.

<span class="mw-page-title-main">Breast biopsy</span> Surgical diagnostic procedure for breast tumours

A breast biopsy is usually done after a suspicious lesion is discovered on either mammography or ultrasound to get tissue for pathological diagnosis. Several methods for a breast biopsy now exist. The most appropriate method of biopsy for a patient depends upon a variety of factors, including the size, location, appearance and characteristics of the abnormality. The different types of breast biopsies include fine-needle aspiration (FNA), vacuum-assisted biopsy, core needle biopsy, and surgical excision biopsy. Breast biopsies can be done utilizing ultrasound, MRI or a stereotactic biopsy imaging guidance. Vacuum assisted biopsies are typically done using stereotactic techniques when the suspicious lesion can only be seen on mammography. On average, 5–10 biopsies of a suspicious breast lesion will lead to the diagnosis of one case of breast cancer. Needle biopsies have largely replaced open surgical biopsies in the initial assessment of imaging as well as palpable abnormalities in the breast.

<span class="mw-page-title-main">Mammary-type myofibroblastoma</span> Medical condition

Mammary-type myofibroblastoma (MFB), also named mammary and extramammary myofibroblastoma, was first termed myofibrolastoma of the breast, or, more simply, either mammary myofibroblastoma (MMFB) or just myofibroblastoma. The change in this terminology occurred because the initial 1987 study and many subsequent studies found this tumor only in breast tissue. However, a 2001 study followed by numerous reports found tumors with the microscopic histopathology and other key features of mammary MFB in a wide range of organs and tissues. Further complicating the issue, early studies on MFB classified it as one of various types of spindle cell tumors that, except for MFB, were ill-defined. These other tumors, which have often been named interchangeably in different reports, are: myelofibroblastoma, benign spindle cell tumor, fibroma, spindle cell lipoma, myogenic stromal tumor, and solitary stromal tumor. Finally, studies suggest that spindle cell lipoma and cellular angiofibroma are variants of MFB. Here, the latter two tumors are tentatively classified as MFB variants but otherwise MFB is described as it is more strictly defined in most recent publications. The World Health Organization in 2020 classified mammary type myofibroblastoma tumors and myofibroblastoma tumors as separate tumor forms within the category of fibroblastic and myofibroblastic tumors.

Interventional oncology is a subspecialty field of interventional radiology that deals with the diagnosis and treatment of cancer and cancer-related problems using targeted minimally invasive procedures performed under image guidance. Interventional oncology has developed to a separate pillar of modern oncology and it employs X-ray, ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) to help guide miniaturized instruments to allow targeted and precise treatment of solid tumours located in various organs of the human body, including but not limited to the liver, kidneys, lungs, and bones. Interventional oncology treatments are routinely carried out by interventional radiologists in appropriate settings and facilities.

References

  1. 22-251c.Fibroadenomas at Merck Manual of Diagnosis and Therapy Home Edition
  2. 1 2 Tavassoli, F.A.; Devilee, P., eds. (2003). World Health Organization Classification of Tumours: Pathology & Genetics: Tumours of the breast and female genital organs. Lyon: IARC Press. ISBN   978-92-832-2412-9.[ page needed ]
  3. Dirbas, Fredrick M.; Scott-Conner, Carol E.H., eds. (2010). Breast surgery office management and surgical techniques. New York: Springer. p. 71. ISBN   978-1-4419-6075-7.
  4. 1 2 3 4 5 6 7 "Fibroadenomas of the Breast". cancer.org. Retrieved 13 November 2018.
  5. Shin SJ, Rosen PP (July 2007). "Bilateral presentation of fibroadenoma with digital fibroma-like inclusions in the male breast". Archives of Pathology & Laboratory Medicine. 131 (7): 1126–9. doi:10.5858/2007-131-1126-BPOFWD. PMID   17617003.
  6. 1 2 Pruthi S, Jones KN (February 2013). "Nonsurgical management of fibroadenoma and virginal breast hypertrophy". Seminars in Plastic Surgery. 27 (1): 62–6. doi:10.1055/s-0033-1343997. PMC   3706058 . PMID   24872742.
  7. Nelson ZC, Ray RM, Wu C, Stalsberg H, Porter P, Lampe JW, Shannon J, Horner N, Li W, Wang W, Hu Y, Gao D, Thomas DB (July 2010). "Fruit and vegetable intakes are associated with lower risk of breast fibroadenomas in Chinese women". The Journal of Nutrition. 140 (7): 1294–301. doi:10.3945/jn.109.119719. PMC   2884330 . PMID   20484549.
  8. 1 2 DeMay, M. (2007). Practical Principles of Cytopathology (Revised ed.). ASCP Press. p. 2007. ISBN   978-0-89189-549-7.[ page needed ]
  9. 1 2 3 4 5 Rosen, PP. (2009). Rosen's Breast Pathology (3rd ed.). ISBN   978-0-7817-7137-5.[ page needed ]
  10. Fekete P, Petrek J, Majmudar B, Someren A, Sandberg W (May 1987). "Fibroadenomas with stromal cellularity. A clinicopathologic study of 21 patients". Archives of Pathology & Laboratory Medicine. 111 (5): 427–32. PMID   3032124.
  11. Nassar, Hind. "Cellular fibroadenoma of breast" . Retrieved 14 January 2013.
  12. Salati SA (2020). "Breast fibroadenomas: a review in the light of current literature". Pol Przegl Chir. 93 (1): 40–48. doi:10.5604/01.3001.0014.5676. PMID   33729177.
  13. Yang, Xiaofang; Kandil, Dina; Cosar, Ediz F.; Khan, Ashraf (2014). "Fibroepithelial Tumors of the Breast: Pathologic and Immunohistochemical Features and Molecular Mechanisms". Archives of Pathology & Laboratory Medicine. 138 (1): 25–36. doi: 10.5858/arpa.2012-0443-RA . ISSN   0003-9985. PMID   24377809.
  14. Pathology Outlines Website. Accessed 12 February 2009.
  15. "Fibroadenoma of the breast" . Retrieved 15 December 2007.
  16. Lim WK, Ong CK, Tan J, Thike AA, Ng CC, Rajasegaran V, Myint SS, Nagarajan S, Nasir ND, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VK, Hartman M, Ong KW, Tan BK, Rozen SG, Tan PH, Tan P, Teh BT (August 2014). "Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma". Nature Genetics. 46 (8): 877–80. doi:10.1038/ng.3037. PMID   25038752. S2CID   7623650.
  17. Piscuoglio S, Murray M, Fusco N, Marchiò C, Loo FL, Martelotto LG, Schultheis AM, Akram M, Weigelt B, Brogi E, Reis-Filho JS (November 2015). "MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast". Histopathology. 67 (5): 719–29. doi:10.1111/his.12712. PMC   4996373 . PMID   25855048.
  18. Tasoulis, MK. "Evaluation of breast mass". BMJ Best Practice. Retrieved 13 November 2018.
  19. 1 2 3 American College of Obstetricians Gynecologists' Committee on Practice Bulletins—Gynecology (June 2016). "Practice Bulletin No. 164: Diagnosis and Management of Benign Breast Disorders". Obstetrics and Gynecology. 127 (6): e141-56. doi:10.1097/aog.0000000000001482. PMID   27214189. S2CID   37836506.
  20. "Fibroadenoma – Diagnosis and treatment – Mayo Clinic". mayoclinic.org. Retrieved 13 November 2018.
  21. Rosai, J. (2004). Rosai and Ackerman's Surgical Pathology (9th ed.). ISBN   978-0-323-01342-0.[ page needed ]
  22. Gordon PB, Gagnon FA, Lanzkowsky L (October 2003). "Solid breast masses diagnosed as fibroadenoma at fine-needle aspiration biopsy: acceptable rates of growth at long-term follow-up". Radiology. 229 (1): 233–8. doi:10.1148/radiol.2291010282. PMID   14519878.
  23. Dhar A, Srivastava A (June 2007). "Role of centchroman in regression of mastalgia and fibroadenoma". World Journal of Surgery. 31 (6): 1178–84. doi:10.1007/s00268-007-9040-4. PMID   17431715. S2CID   22828570.
  24. 1 2 Sag AA, Maybody M, Comstock C, Solomon SB (June 2014). "Percutaneous image-guided ablation of breast tumors: an overview". Seminars in Interventional Radiology. 31 (2): 193–202. doi:10.1055/s-0034-1376159. PMC   4078155 . PMID   25049447.
  25. 1 2 "Management of Fibroadenomas of the Breast : Official Statement" (PDF). American Society of Breast Surgeons. 29 April 2008. Retrieved 23 June 2020.
  26. "WebMD – Cryotherapy Shrinks Benign Breast Lumps". Archived from the original on 8 February 2014. Retrieved 18 September 2009.
  27. 1 2 3 Peek MC, Wu F (2018). "High-intensity focused ultrasound in the treatment of breast tumours". ecancermedicalscience. 12: 794. doi:10.3332/ecancer.2018.794. PMC   5804717 . PMID   29434660.
  28. "BMJ Best Practice". bestpractice.bmj.com. Retrieved 13 November 2018.
  29. 1 2 3 4 5 Greenberg R, Skornick Y, Kaplan O (September 1998). "Management of breast fibroadenomas". Journal of General Internal Medicine. 13 (9): 640–5. doi:10.1046/j.1525-1497.1998.cr188.x. PMC   1497021 . PMID   9754521.