Ductal Carcinoma In Situ

Basics

Description

  • Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions that have the presence of a clonal proliferation of neoplastic, noninvasive epithelial cells confined to ducts and lobules.
  • Considered a premalignant lesion
  • Can be classified as low, intermediate, or high grade
  • Mortality from DCIS with subsequent progression to invasive breast carcinoma (IBC) is low, regardless of histologic type or type of treatment.

Epidemiology

Incidence

  • Average annual percentage increase of 1%
  • Estimated 62,738 new diagnoses of DCIS in 2019
  • Estimated 49,290 new diagnoses of DCIS in 2021
  • DCIS accounts for approximately 80–85% of in situ breast carcinomas (lobular carcinoma in situ [LCIS] accounts for approximately 15–20%).
  • Represents ~26% of all new breast cancers
  • Incidence rate comparable in different ethnicities
  • More stable incidence in women 50 to 69 years old
  • Increasing incidence in women <50 and >70 years old

Etiology and Pathophysiology

  • A nonobligate precursor to IBC
  • Poorly understood spectrum of polyclonal and clonal epithelial proliferative lesions—final step prior to IBC
    • The changes necessary for transition to IBC are poorly understood.
  • Molecular evidence suggests that low- and high-grade DCIS are genetically distinct lesions.
    • High-grade DCIS associated with a higher likelihood of progression to invasive disease

Genetics

  • Low-grade DCIS typically expresses estrogen receptor (ER) and progesterone receptor (PR), without HER2 protein overexpression or amplification.
  • High-grade DCIS not consistently ER+ or PR+
    • Frequent HER2 protein overexpression and amplification (even more frequent compared to IBC)
    • Commonly associated with p53 gene mutations
  • BRCA1 and BRCA2 associations observed
  • Consider genetic counseling in high-risk DCIS patients.

Risk Factors

  • Similar to IBC, although not as strongly associated
  • Female gender, nulliparity, late age at first birth or menopause, first-degree relative with breast cancer, long-term use of postmenopausal combined estrogen and progestin therapy, history of atypical ductal hyperplasia (ADH), dense breast tissue are all risk factors.
  • Association with age, body mass index, smoking, lactation, early menarche, alcohol consumption, and oral contraceptive use is less clear.

General Prevention

  • Screening may result in overdiagnosis with little or no reduction in the incidence of advanced cancers.
  • Women with increased risk should have more aggressive screening (risk assessment tool available at http://bcrisktool.cancer.gov).
  • General screening guidelines—U.S. Preventive Services Task Force (USPSTF):
    • Biennial mammography for women aged 50 to 74 years (B recommendation)
    • The decision to start screening mammography in women <50 years should be an individual one.
    • Insufficient evidence regarding benefits and harms of screening mammography if ≥75 years old
    • Insufficient evidence to assess the benefits and harms of digital breast tomosynthesis (DBT) as a primary screening method (I statement)
    • Insufficient evidence to assess the balance of benefits and harms of adjunctive screening using breast ultrasonography (US), magnetic resonance imaging (MRI), DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram (I statement)
  • General screening guidelines—National Comprehensive Cancer Network (NCCN):
    • Women should be familiar with their breasts and promptly report changes; periodic consistent breast self-exam (BSE) may facilitate breast self-awareness.
    • Clinical breast exam (CBE):
      • USPSTF states evidence is insufficient to assess benefits and harms when added to mammography screening for women ≥40 years.
      • WHO states CBE may be beneficial in settings with weak health settings (mammography not accessible) for women 50 to 69 years old.
      • NCCE recommends annual CBE in women starting at age 40 years, and from age 25 to 39 years, perform BSE with CBE every 1 to 3 years.
  • Risk reduction:
    • Assess familial/genetic history.
    • Lifestyle modifications: Limit alcohol intake to <1 drink per day, exercise, maintain a healthy diet, and weight control.
    • Hormonal risk reduction agent recommended in certain high-risk women ≥35 years old; tamoxifen for premenopausal women and raloxifene for postmenopausal women
    • Benefits of aromatase inhibitors are less clear.

There's more to see -- the rest of this topic is available only to subscribers.