Ductal Carcinoma In Situ

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Basics

Description

  • Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions that have in common the presence of a clonal proliferation of neoplastic, noninvasive epithelial cells confined to ducts and lobules.
  • Considered a premalignant lesion
  • 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 62,117 new diagnoses of DCIS in 2018
  • Estimated 62,738 new diagnoses of DCIS in 2019
  • DCIS accounts for approximately 80–85% of in situ breast carcinomas (lobular carcinoma in situ [LCIS] accounts for approximately 15–20%).
  • More stable incidence in women 50 to 69 years old
  • Increasing incidence in women <50 and >70 years old
  • Represents ~26% of all new IBC
  • Incidence rate comparable in different ethnicities

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, with high-grade DCIS associated with more aggressive 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, high breast density, history of atypical ductal hyperplasia (ADH)
  • Association with age, body mass index, smoking, lactation, early menarche, alcohol consumption, and oral contraceptive use is less clear.

General Prevention

  • Controversy exists because studies have suggested that screening may result in overdiagnosis with little or no reduction in the incidence of advanced cancers.
  • General screening guidelines suggested for asymptomatic women with an average risk
  • Women with increased risk should have more aggressive screening (risk assessment tool available at http://www.cancer.gov/bcrisktool/Default.aspx).
  • 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.
    • If a higher value is placed on potential benefit, consider beginning biennial screening between 40 and 49 years of age (C recommendation).
    • 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, 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 BSE may facilitate breast self-awareness.
    • Age 25 to 39 years: breast awareness, CBE every 1 to 3 years
    • Age ≥40 years: breast awareness, annual CBE, annual screening mammography
  • Clinical judgment when applying screening guidelines
  • Mammography screening should be individualized.
  • If no intervention would occur based on screening findings, patient should not undergo screening.
  • Risk reduction:
    • Assess familial/genetic history.
    • Lifestyle modifications: Limit alcohol intake to <1 drink per day, exercise, maintain healthy diet, and weight control.
    • Risk reduction surgery supported for carefully selected women at high risk of breast cancer
    • Hormonal risk reduction agents (i.e., tamoxifen) recommended in certain high-risk women ≥35 years old
    • Benefits of aromatase inhibitors are less clear.
    • Recent clinical trial with anastrozole (an aromatase inhibitor) significantly decreased incidence of DCIS in postmenopausal women.

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