National Cancer Institute
Post Date: Feb 22, 2022
This evidence-based, expert-reviewed summary discusses the incidence, outcome, risk factors, and treatment of pediatric fibroadenoma and breast cancer.
Childhood Breast Cancer Treatment
Fibroadenoma is the most common breast tumor seen in children aged 18 years or younger. More than 95% of patients are female. Types of fibroadenoma in this age range include simple fibroadenoma (70%–90% of cases) and giant juvenile fibroadenoma (0.5%–2% of cases). Giant juvenile fibroadenomas have been variably defined as any rapidly enlarging encapsulated fibroadenoma with a diameter greater than 5 cm, a weight more than 500 g, or displacement of at least four-fifths of the breast. Other benign breast masses include tubular adenomas, benign phyllodes tumors, and benign fibroepithelial neoplasms.
Incidence and Clinical Presentation
The prevalence of fibroadenoma is 2.2% in females aged 10 to 30 years. Fibroadenoma usually presents as an asymptomatic mass that can vary in size with a woman's menstrual cycle. However, they can cause localized pain or breast asymmetry. Giant fibroadenomas can be associated with skin ulceration and venous engorgement. In one retrospective series of 80 girls aged 12 to 18 years with fibroadenomas, 10% of patients had bilateral disease and 2.5% of patients had unilateral disease but more than one nodule (multicentric fibroadenoma).
The prevalence of fibroadenoma increases with age, although girls aged 12 to 16 years tend to have larger lesions than women aged 17 years and older. Fibroadenomas have been associated with Beckwith-Wiedemann, Maffucci, and Cowden syndromes.
Fibroadenomas are benign biphasic tumors with epithelial and stromal components that have variable mitotic activity. These tumors can be difficult to distinguish from phyllodes tumors when a tumor sample is obtained using fine needle aspiration or core needle biopsy.
Treatment of Fibroadenoma
Treatment options for fibroadenoma include the following:
- Observation. A study of 29 patients with presumed fibroadenomas were diagnosed prospectively over a 13-month period via physical examination; 9 presumed fibroadenomas (31%) resolved during the follow-up period of 1 to 12 months, and 4 presumed fibroadenomas (14%) became smaller. Twelve teenagers underwent ultrasonography and had solid masses. None of these masses resolved after a year of observation. In addition, resection determined that all of these masses were fibroadenomas. There is no evidence that childhood or adolescent fibroadenomas have carcinomatous potential.
- Core needle biopsy. Fine needle aspiration is not considered to be adequate for diagnosis. Indications for core needle biopsy or excision of a suspected fibroadenoma in children and adolescents are not evidence-based. Indications have included tumor size at presentation of 2 cm to 5 cm (or larger); tumor enlargement during 2 to 12 months of observation; and multiple breast masses or bilateral breast masses. One single-institution retrospective review conducted between 1999 and 2018 aimed to characterize the breast masses of 70 females aged 19 years or younger with fibroadenomas who underwent excision of masses between 2 cm and 16 cm. Histological evaluation found that 87% of the breast masses were benign, 10% of the masses were benign phyllodes tumors that were aggressive in nature (n = 7), one mass was a malignant phyllodes tumor, and one mass was a metastatic sarcoma. Pathological examination of the core needle biopsy specimen may either underestimate or overestimate the aggressiveness of lesions when compared with what is found on excision in about 13% of patients.
- Resection. Indications for resection, in addition to those listed above, include patient, parental, or provider anxiety. In one series of 39 patients who had follow-up after resection, 6 patients experienced recurrences between 2 years and 7.5 years (median, 4.9 years) later. Tumor size, mitotic index, and mesenchymal cellularity did not predict recurrences, and all recurrent tumors were benign. Surgical complications have included breast hypoplasia, acute pain, and chronic pain. While recurrence is rare, careful follow-up monitoring is important. Recurrent tumors can be resected successfully using conservative techniques.
Treatment options for phyllodes tumors include the following:
- Wide local excision without mastectomy. Phyllodes tumors can be very large, and hence, they can be challenging to treat surgically in women with smaller breasts. Complete excision of the phyllodes tumor with grossly negative margins and a small amount of normal tissue circumferentially is necessary. Radical mastectomy or modified radical mastectomy should be avoided. Lymph node evaluation is not necessary.
Phyllodes tumors present a small risk of recurrence, as they fall into the intermediate-grade sarcoma category. These tumors do not metastasize, but they can recur locally.
- Jayasinghe Y, Simmons PS: Fibroadenomas in adolescence. Curr Opin Obstet Gynecol 21 (5): 402-6, 2009.
- Lee M, Soltanian HT: Breast fibroadenomas in adolescents: current perspectives. Adolesc Health Med Ther 6: 159-63, 2015.
- McLaughlin CM, Gonzalez-Hernandez J, Bennett M, et al.: Pediatric breast masses: an argument for observation. J Surg Res 228: 247-252, 2018.
- Sun C, Zhang W, Ma H, et al.: Main Traits of Breast Fibroadenoma Among Adolescent Girls. Cancer Biother Radiopharm 35 (4): 271-276, 2020.
- Neinstein LS, Atkinson J, Diament M: Prevalence and longitudinal study of breast masses in adolescents. J Adolesc Health 14 (4): 277-81, 1993.
- Zmora O, Klin B, Iacob C, et al.: Characterizing excised breast masses in children and adolescents-Can a more aggressive pathology be predicted? J Pediatr Surg 55 (10): 2197-2200, 2020.
- Javed A, Jenkins SM, Labow B, et al.: Intermediate and long-term outcomes of fibroadenoma excision in adolescent and young adult patients. Breast J 25 (1): 91-95, 2019.
- Valdes EK, Boolbol SK, Cohen JM, et al.: Malignant transformation of a breast fibroadenoma to cystosarcoma phyllodes: case report and review of the literature. Am Surg 71 (4): 348-53, 2005.
Special Considerations for the Treatment of Children With Cancer
Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975. Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
- Primary care physicians.
- Pediatric surgeons.
- Radiation oncologists.
- Pediatric medical oncologists/hematologists.
- Rehabilitation specialists.
- Pediatric nurse specialists.
- Social workers.
- Child-life professionals.
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer. At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years. The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people. Therefore, all pediatric cancers are considered rare.
The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States. Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:
- A consensus effort between the European Union Joint Action on Rare Cancers and the European Cooperative Study Group for Rare Pediatric Cancers estimated that 11% of all cancers in patients younger than 20 years could be categorized as very rare. This consensus group defined very rare cancers as those with annual incidences of fewer than 2 cases per 1 million people. However, three additional histologies (thyroid carcinoma, melanoma, and testicular cancer) with incidences of more than 2 cases per 1 million people were also included in the very rare group because there is a lack of knowledge and expertise in the management of these tumors.
- The Children's Oncology Group defines rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancer, melanoma and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinoma, nasopharyngeal carcinoma, and most adult-type carcinomas such as breast cancer, colorectal cancer, etc.). These diagnoses account for about 4% of cancers diagnosed in children aged 0 to 14 years, compared with about 20% of cancers diagnosed in adolescents aged 15 to 19 years.
Most cancers in subgroup XI are either melanomas or thyroid cancer, with other types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Information about these tumors may also be found in sources relevant to adults with cancer, such as the PDQ summary on Breast Cancer Treatment (Adult).
- Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.
- American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 1, 2022.
- Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.
- Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr.
- Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017.
- DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017.
- Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019.
- Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010.
- Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2012. National Cancer Institute, 2015. Also available online. Last accessed June 22, 2021.
Childhood Breast Cancer
Incidence and Outcome
Breast cancer has been reported in both males and females younger than 21 years. A review of the Surveillance, Epidemiology, and End Results (SEER) Program database of the National Cancer Institute shows that 75 cases of malignant breast tumors in females aged 19 years or younger were identified from 1973 to 2004. Fifteen percent of these patients had in situ disease, 85% had invasive disease, 55% of the tumors were carcinomas, and 45% of the tumors were sarcomas—most of which were phyllodes tumors. Only three patients in the carcinoma group presented with metastatic disease, while 11 patients (27%) had regionally advanced disease. All patients with sarcomas presented with localized disease. Of the carcinoma patients, 85% underwent surgical resection, and 10% received adjuvant radiation therapy. Of the sarcoma patients, 97% had surgical resection, and 9% received radiation. The 5- and 10-year survival rates for patients with sarcomatous tumors were both 90%; for patients with carcinomas, the 5-year survival rate was 63% and the 10-year survival rate was 54%.
A National Cancer Database report described 181 cases of breast malignancy in patients aged 21 years and younger; 65% of patients had invasive carcinoma and the remaining patients had sarcoma or malignant phyllodes. In this study, the authors compared the pediatric patients with the adult patients and found that pediatric patients were more likely to have an undifferentiated malignancy, more advanced disease at presentation, and more variable management. Outcomes between children and adults were similar.
A subsequent report from the SEER database (1973–2009) discovered 91 girls aged 10 to 20 years with breast cancer, predominantly carcinomas (57% invasive, 5.5% in situ) and sarcomas (37%, mostly phyllodes tumors). The mortality rate was 46.6% for patients with regional disease and 18.7% for patients with localized disease. The mortality rates for the patients in this study were higher than the rates for premenopausal and postmenopausal women, although the sample size was small.[Level of evidence: 3iiA]
While rare, breast cancer has also been described in males. In a review of the National Cancer Database, 677 male adolescents and young adults were diagnosed with breast cancer during the period of 1998 to 2010; most patients (82%) had invasive disease. Age younger than 25 years and absence of nodal evaluation at the time of surgery were associated with worse outcomes.
Breast tumors may also occur as metastatic deposits from leukemia, rhabdomyosarcoma, other sarcomas, or lymphoma (particularly in patients who are infected with HIV).
Risk factors for breast cancer in adolescents and young adults (AYA) include the following:
- Previous malignancy. A retrospective review of the American College of Surgeons National Cancer Database from 1998 to 2010 identified 106,771 patients aged 15 to 39 years with breast cancer. Of these patients, 6,241 (5.8%) had experienced a previous histologically distinct malignancy. Patients with breast cancer as a subsequent neoplasm had a significantly decreased 3-year overall survival rate (79% vs. 88.5%, P< .001), with subsequent neoplasm status identified as an independent risk factor for increased mortality (hazard ratio, 1.58; 95% confidence interval, 1.41–1.77).
- Chest irradiation. There is an increased lifetime risk of breast cancer in female survivors of
Hodgkin lymphoma who were treated with radiation to the chest area; however, breast cancer is also seen in patients who were treated with chest irradiation for any cancer.[Level of evidence: 1A] Carcinomas are more frequent than sarcomas.
Mammograms with adjunctive breast magnetic resonance imaging (MRI) start at age 25 years or 10 years postexposure to radiation therapy (whichever came last). (Refer to the PDQ summary on the Late Effects of Treatment for Childhood Cancer for more information about secondary breast cancers.)
Homologous recombination deficiency (HRD) is a prevalent phenotype of breast cancer in AYA patients (aged 15–39 years). HRD influences the efficacy of PARP inhibitor–based therapy and platinum agent–based therapy. An analysis of 46 Japanese AYA patients with breast cancer and two existing breast cancer cohorts of U.S. and European patients identified an HRD-high phenotype that was associated with germline BRCA1 and BRCA2 mutations, somatic TP53 mutations, triple-negative subtype, and higher tumor grade. A model based on three of these factors, excluding germline BRCA1 and BRCA2 mutations, yielded high predictive power of death in cases from these two cohorts without germline BRCA1 or BRCA2 mutations; the area under the receiver operating characteristic curve was 0.92 and 0.90, respectively.
Treatment of Breast Cancer in Adolescents and Young Adults (AYA)
Breast cancer is the most frequently diagnosed cancer among AYA women aged 15 to 39 years, accounting for about 14% of all AYA cancer diagnoses. Breast cancer in this age group has a more aggressive course and worse outcome than in older women. Expression of hormone receptors for estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) on breast cancer in the AYA group is also different from that in older women and correlates with a worse prognosis. In a review of data from the National Cancer Database, AYA patients (aged 15–39 years) had more triple-negative breast cancer (TNBC) or HER2-positive (HER2+) cancer than did adult patients (TNBC: 21.2% vs. 13.8%, respectively; HER2+: 26.0% vs. 18.6%, respectively; both P< .001). In addition, AYA patients aged 15 to 29 years had more advanced disease and TNBC or HER2+ disease than did AYA patients aged 30 to 39 years.[Level of evidence: 3iA]
Treatment of the AYA group is similar to that of older women. However, unique aspects of management must include attention to genetic implications (i.e., familial breast cancer syndromes) and fertility.
(Refer to the PDQ summary on Breast Cancer Treatment [Adult] or the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information.)
Treatment Options Under Clinical Evaluation for Childhood and AYA Breast Cancer
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
- APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified in a patient's tumor (refractory or recurrent). Children and adolescents aged 1 to 21 years are eligible for the trial.
Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
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- Murphy BL, Day CN, Hoskin TL, et al.: Adolescents and Young Adults with Breast Cancer have More Aggressive Disease and Treatment Than Patients in Their Forties. Ann Surg Oncol 26 (12): 3920-3930, 2019.
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Changes to This Summary (02/23/2022)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
About This PDQ Summary
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood breast cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
- be discussed at a meeting,
- be cited with text, or
- replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Breast Cancer Treatment are:
- Denise Adams, MD (Children's Hospital Boston)
- Karen J. Marcus, MD, FACR (Dana-Farber Cancer Institute/Boston Children's Hospital)
- Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
- Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
- Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
- Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
- Carlos Rodriguez-Galindo, MD (St. Jude Children's Research Hospital)
- Stephen J. Shochat, MD (St. Jude Children's Research Hospital)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Breast Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated
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