Ductal Carcinoma In Situ
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- Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions that have in common the presence of a clonal proliferation of neoplastic epithelial cells confined to ducts and lobules.
- Considered a premalignant lesion—the neoplastic cells are not invasive (pure DCIS)
- 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.
- Based on an observed average annual percentage increase of 1%, there were an estimated 61,500 new diagnoses of DCIS in 2017, and there will be an estimated 62,117 new diagnoses of DCIS in 2018.
- 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 of age over the last several years
- Increasing incidence in women <50 years of age and >70 years of age over the last several years
- Represents ~26% of all new IBC
- Incidence rate of DCIS is comparable among women of different ethnicities.
Etiology and Pathophysiology
- A nonobligate precursor to IBC
- Presumed to be the final step prior to IBC, part of a poorly understood spectrum of polyclonal and clonal epithelial proliferative lesions
- Either low- or high-grade DCIS has the potential for subsequent invasion into the surrounding stroma; however, 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.
- Low-grade DCIS typically shows diffuse and strong expression of 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; commonly associated with p53 gene mutations
- HER2 overexpression is even more frequent in high-grade DCIS compared to IBC.
- BRCA1 and BRCA2 associations observed; only screen those at high risk.
- Female gender, nulliparity, late age at first birth, late age at menopause, family history of a first-degree relative with breast cancer, long-term use of postmenopausal hormone replacement therapy (combined estrogen/progestin), high breast density, history of atypical ductal hyperplasia (ADH)
- Association with age, body mass index, smoking, lactation, early menarche, increased alcohol consumption, and oral contraceptive use is less clear.
- Screening increases 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://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)
- Mammography prior to age 50 years should be patient centered.
- Biennial screening of ages 40 and 49 years without evidence of benefit (C recommendation)
- Insufficient evidence to support screening mammography in women aged 75 years or older
- There is insufficient evidence to assess the benefits and harms of digital breast tomosynthesis (DBT) as a primary screening method for breast cancer (I statement).
- Insufficient evidence to support adjunctive screening for breast cancer using breast ultrasonography, magnetic resonance imaging (MRI), DBT, or other methods in women with dense breasts on an otherwise negative screening mammogram (I statement)
- General screening guidelines—National Comprehensive Cancer Network (NCCN):
- NCCN recommends that women should be familiar with their breast; promptly report changes to their health care provider; and that periodic, consistent BSE may facilitate breast self-awareness.
- Ages 25 to 39 years: breast awareness, CBE every 1 to 3 years
- Age 40 years and older: breast awareness, annual CBE, annual screening mammography
- If no intervention would occur based on screening findings, patient should not undergo screening.
- Risk reduction:
- Lifestyle modifications: Limit alcohol to <1 drink/day, exercise, maintain healthy diet, BMI <30.
- Hormonal agents (i.e., tamoxifen) are recommended in certain high-risk women ≥35 years of age; benefits of aromatase inhibitors are less clear.
- A recent clinical trial with anastrozole (an aromatase inhibitor) showed a significantly decreased incidence of DCIS in postmenopausal women.