Fibrocystic Change

Fibrocystic change of the breast is a non-specific term referring to several types of benign breast conditions Benign breast conditions Benign breast epithelial lesions are grouped histologically as nonproliferative, proliferative without atypia, and atypical hyperplasia. The classifications are based on subsequent cancer risk in either breast. Benign Breast Conditions. These are non-proliferative lesions, which include cystic and fibrous tissue formation. Fibrocystic changes are seen in up to 50–60% of women, most commonly between 30–50 years of age. Changes are stimulated by both estrogen and progesterone, and often diminish or resolve with menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause. Patients typically present with a breast mass, “lumpy” or firm breasts Breasts The breasts are found on the anterior thoracic wall and consist of mammary glands surrounded by connective tissue. The mammary glands are modified apocrine sweat glands that produce milk, which serves as nutrition for infants. Breasts are rudimentary and usually nonfunctioning in men. Breasts, and/or cyclic breast pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. The work-up involves imaging, with mammogram or ultrasound, and biopsy (if needed) to exclude malignancy. Management includes observation, supportive measures, and altering hormone therapy, as needed. These changes do not appear to significantly increase the risk for breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

  • A non-specific term without a universally agreed upon definition
  • Refers to benign changes in the breasts Breasts The breasts are found on the anterior thoracic wall and consist of mammary glands surrounded by connective tissue. The mammary glands are modified apocrine sweat glands that produce milk, which serves as nutrition for infants. Breasts are rudimentary and usually nonfunctioning in men. Breasts, particularly fibrosis and cysts
  • Not associated with an increased risk of breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer

Classification of benign breast lesions

  • Non-proliferative lesions 
    • Classic fibrocystic changes
    • Examples:
      • Fibrosis
      • Cysts
      • Adenosis (↑ number of acini per lobule)
  • Proliferative lesions without atypia 
    • Generally not included in the term fibrocystic changes
    • Associated with a slight ↑ risk for cancer
    • Examples: 
      • Sclerosing adenosis
      • Epithelial hyperplasia
  • Atypical hyperplasias
    • Not considered fibrocystic changes
    • Associated with an ↑↑ risk for cancer 
    • Often incidental findings on mammogram
    • Histologically similar to carcinoma in situ
    • Examples: 
      • Atypical ductal hyperplasia
      • Atypical lobular hyperplasia

Epidemiology

  • Most frequent benign breast lesion
  • Affects up to 50–60% of women
  • Most common in women reproductive-age women, 30–50 years of age 
  • Changes decrease (or resolve) with menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause.

Etiology

  • Tied to estrogen and progesterone levels
  • Risk factors:
    • Nulliparity
    • First live birth at age > 30 years old
    • Early menarche

Pathophysiology

Anatomy

  • Breast tissue consists of: 
    • Epithelial components → glands and ducts
    • Stroma → adipose and fibrous connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue
  • Lobules are functional units (milk-producing sacs), separated by Cooper ligaments
    • Each contains multiple acini (tubuloalveolar glands) and adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or "brite" adipose tissue, which is a transitional form. Adipose Tissue.
    • Acini empty into the lactiferous ducts.

Pathophysiology

  • The pathogenesis is incompletely understood, but appears to be associated with hormone levels.
    • Estrogen stimulates ductal elements (including adenosis).
    • Progesterone stimulates stromal elements.
  • Classic fibrocystic changes:
    • Cystic lesions: 
      • Derived from the terminal duct lobular unit
      • Form by dilation and obstruction of the efferent duct
      • Often associated with apocrine metaplasia
      • Grow and shrink cyclically as estrogen levels fluctuate → cyclic mastalgia
      • Blue-dome cysts: fluid-filled blue-brown unopened breast cysts
    • Fibrosis:
      • Ruptured cysts → chronic stromal inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → ↑ stromal fibrosis
      • Results in palpable firmness on exam
  • Comparison with proliferative lesions without atypia:
    • Sclerosing adenosis
      • ↑ acini and intralobular fibrosis → enlarged and distorted lobules
      • Associated stromal fibrosis and interspersed glandular cells
    • Epithelial hyperplasia:↑ in number of epithelial cell layers in the ductal space or lobule

Clinical Presentation

Fibrocystic changes typically present in reproductive-aged women as either “lumpy breasts Breasts The breasts are found on the anterior thoracic wall and consist of mammary glands surrounded by connective tissue. The mammary glands are modified apocrine sweat glands that produce milk, which serves as nutrition for infants. Breasts are rudimentary and usually nonfunctioning in men. Breasts,” a discrete breast mass, or mammographic abnormalities found on routine screening. 

  • Ill-defined, diffuse ↑ in breast consistency (firmness)
  • Palpable breast lumps
    • Single mass or multifocal (more common)
    • Discrete, well-circumscribed, mobile, and compressible
    • May be tender or nontender
    • Size and number of lesions can fluctuate throughout the menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle
  • Cyclic breast pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Generally mid-cycle
    • Fullness or heaviness
  • Findings are often similar in both breasts Breasts The breasts are found on the anterior thoracic wall and consist of mammary glands surrounded by connective tissue. The mammary glands are modified apocrine sweat glands that produce milk, which serves as nutrition for infants. Breasts are rudimentary and usually nonfunctioning in men. Breasts.

Diagnosis and Management

Diagnosis

The most important thing is to differentiate benign fibrocystic changes from malignant conditions. 

  • Mammography:
    • Recommended for all women ≥ 30 years old with a breast mass
    • Reveals round or oval-shaped masses with defined boundaries 
    • May contain densities or dispersed calcifications
  • Breast ultrasound:
    • Recommended for all women with a breast mass (including those < 30 years old)
    • Findings: 
      • Anechoic, well circumscribed, compressible lesions
      • Posterior wall enhancement
      • Thickened parenchyma
      • Increased echongenicity
    • Findings suspicious for cancer (these would be lacking in fibrocystic changes):
      • Thickened walls
      • Septa
      • Vascular flow
      • Solid or other echogenic components
      • Absence of posterior wall enhancement
  • Core needle biopsy (CNB): 
    • Histologic evaluation of suspicious imaging findings
    • Possible benign findings include:
      • Cystic structures
      • Fibrosis of stromal tissue
      • Epithelial hyperplasia
      • Apocrine metaplasia

Management

  • Observation:
    • For patients without significant discomfort 
    • Provide reassurance.
    • Routine breast screening based on age
  • Treat pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain:
    • Supportive bra
    • Warm compresses
    • Avoid caffeine (limited evidence)
    • Non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen
  • Hormonal issues:
    • ↓ or discontinue postmenopausal hormone replacement therapy
    • Oral contraceptive pills (OCPs)
      • Can help with cyclic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
      • Produces negative feedback for endogenous estrogen production
      • May need to ↓ estrogen component in some patients
  • For severe symptoms:
    • Danazol (androgen)
    • Tamoxifen (estrogen receptor antagonist)
    • Bromocriptine (dopamine agonist)
    • Fine needle aspiration of cysts

Differential Diagnosis

  • Fibroadenoma Fibroadenoma Fibroadenomas are the most common benign tumor of the female breast and the most common breast tumor in adolescent and young women. The tumors are well-circumscribed, mobile, and unencapsulated, with a rubbery or firm consistency. Fibroadenoma: a benign, solid breast mass composed of fibrous and glandular tissue. This presents as a small, well-defined, mobile mass with a rubbery or firm consistency. The exact etiology is unknown. Diagnosis is confirmed with a CNB. Management is either excision or observation.
  • Phyllodes tumor: a fibroepithelial tumor similar to fibroadenomas, usually characterized by rapid growth. They may behave like benign fibroadenomas, or they may become malignant and metastasize. Phyllodes tumors are associated with Li-Fraumeni syndrome. Diagnosis is by CNB and management involves complete resection, with adjuvant radiation in malignant cases.
  • Galactocele: a cystic collection of fluid usually caused by an obstructed milk duct. They present as a palpable, firm mass in the subareolar region, and may show a classic fat-fluid level on imaging. Diagnosis is based on history and aspiration, yielding milky fluid. These lesions do not require excision, but this may be considered for significant discomfort.
  • Mastitis Mastitis Mastitis is inflammation of the breast tissue with or without infection. The most common form of mastitis is associated with lactation in the first few weeks after birth. Non-lactational mastitis includes periductal mastitis and idiopathic granulomatous mastitis (IGM). Mastitis or breast abscess: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the breast tissue, most commonly due to infection with skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin or oral flora introduced during breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding. A purulent abscess may form. Occasionally non-lactational mastitis and abscess are also possible. Cases usually present with a fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, breast pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, erythema, edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, and a possible tender, fluctuant abscess. The diagnosis is clinical. Management involves antibiotics, continued expression of breast milk if lactating, and incision and drainage of an abscess.
  • Fat necrosis of the breast Fat necrosis of the breast Fat necrosis of the breast is an inflammatory, benign condition resulting from injury to the breast tissue. Forms of injury include blunt traumatic injury as well as trauma from surgical procedures, biopsies, and radiation therapy. Fat Necrosis of the Breast: usually due to breast injury resulting in liquefactive necrosis of the adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or "brite" adipose tissue, which is a transitional form. Adipose Tissue. As the damaged breast tissue is repaired, there is progressive fibroblastic proliferation resulting in scar tissue. Calcifications may appear and can be difficult to distinguish from a malignant mass. Management involves supportive measures for pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain control, but this condition is usually self-limited and does require further treatment.
  • Malignant breast lesions: the most common types of breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer are invasive ductal carcinoma and lobular carcinoma. Most patients are asymptomatic, and a breast mass may be picked up on standard cancer screening (mammography). Diagnosis is made with a core needle biopsy. Management may involve surgery, chemotherapy, radiation, and hormonal treatment.

References

  1. Sabel, M.S. (2020). Overview of benign breast disease. In Chen, W. (Ed.), Uptodate. Retrieved January 31, 2021, from https://www.uptodate.com/contents/overview-of-benign-breast-disease
  2. Sabel, M.S. (2020). Clinical manifestations, differential diagnosis, and clinical evaluation of a palpable breast mass. In Chen, W. (Ed.), Uptodate. Retrieved January 31, 2021, from https://www.uptodate.com/contents/clinical-manifestations-differential-diagnosis-and-clinical-evaluation-of-a-palpable-breast-mass
  3. Laronga, C., Tollin, S., and Mooney, B. (2019). Breast cysts: clinical manifestations, diagnosis, and management. In Chen, W. (Ed.), Uptodate. Retrieved January 31, 2021, from https://www.uptodate.com/contents/breast-cysts-clinical-manifestations-diagnosis-and-management
  4. Beckmann C.R.B., Ling, F.W., et al. (Eds.). Obstetric and Gynecology (6th Ed., pp. 283-294).
  5. Lester, S.C. (2005). The breast. In Kumar, V., Abbas, A.K., and Fausto, N. (Eds). Robbins and Cotran Pathologic Basis of Disease (7th ed., pp. 1126-1128).
  6. Pearlman, M.D., and Griffin, J.L. (2010). Benign breast disease. Obstet Gynecol. Vol 116, pp. 747-58.
  7. Golshan, M. (2020). Breast pain. In Chen, W. (Ed.), Uptodate. Retrieved January 31, 2021, from https://www.uptodate.com/contents/breast-pain
  8. Kosir, M.A. (2020). Breast masses (breast lumps). [online] MSD Manual Professional Version. Retrieved February 4, 2021, from https://www.merckmanuals.com/professional/gynecology-and-obstetrics/breast-disorders/breast-masses-breast-lumps
  9. Malherbe, K., and Fatima, S. (2020). Fibrocystic breast disease. [online] StatPearls. Retrieved February 4, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK551609/

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