DCIS

Pre-invasive breast malignancy, remaining confined within the ductal system

Epidemiology

• Accounts for 25% of all newly-diagnosed breast cancers

Risk factors

• Essentially the same as for invasive breast cancer

Pathophysiology

• Discrete spaces filled with malignant cells, usually with a recognisable basal cell layer composed of presumably normal myoepithelial cells
• Spreads along the 'galactophoric tree' and often is continuous along the branching ductal network
• The malignant cells can invade across the basement membrane, usually recapitulating the morphology of the cells inside the duct
• Microinvasion - breach of the myoepithelial duct boundary by malignant cells, but measuring <=1mm
  • It is possible to mistake various structures for microinvasion, including lobules, crush artefacts, and branching ducts
• 90% of DCIS expresses ER and 40% expresses HER2
  • Low-grade lesions have higher ER expression
  • Progesterone expression tends to correlate with ER
• Timelines for progression to invasion are not fully understood

Classification

• Grade
  • Classify by highest grade present
  • Key factors
    • nuclear pleomorphism
    • Nuclear size
    • Nuclear polarity
    • mitotic rate
    • presence of necrosis/calcification
    • solid architecture
  • Not as simple as for IDC - can use the NHS Breast Screening Programme (NHS BSP)
    • Low: monomorphic cells, small nuclei, few mitoses, rare necrosis, retained polarity, cribriform or micropapillary architecture
    • Intermediate: moderate pleomorphism, mildly enlarged muclei, polarity largely maintained, solid, cribriform or micropapillary
    • High (60%): nuclear pleomorphism, large nuclei, frequent mitoses, comedo-type necrosis, loss of polarity, frequently solid
• Morphology
  • Solid - malignant cells fill extended duct spaces
  • Micropapillary - tufts of cells project into the duct lumen perpendicular to the basement membrane
  • Papillary - projecting tufts are larger than the microvascular type and contain a fibrovascular core
  • Cribriform - the arrangement of malignant cells takes on a fenestrated/sieve-like appearance
  • 'Clinging' - single-layered, atypical epithelial cells lining the duct
  • Rarer subtypes also exist
• Comedo necrosis presence or absence
  • Central necrosis associated with DCIS, although exact definitions vary
  • This leads to the microcalcifications
  • Central necrosis has a tendency to appear as the cells inside the ductal membrane grow, which coagulates and eventually calcifies, causing the tiny, pleomorphic and frequently linear forms of microcalcifications seen on mammograms

Presentation

• Mostly presents as suspicious calcifications on mammography, often screen-detected
• 80% is impalpable
• Rarely as palpable mass, single-duct nipple discharge or Paget's disease of the nipple
• <1% have metastatic disease
• Multicentric if separate foci of tumours are found in >1 quadrant
• Multifocal if there are separate tumour foci in the same quadrant
• Assessment
  • Examine - signs of invasive disease

Diagnosis

• Requires tissue
• Try for core biopsy
• Usually stereotactic, unless there is an associated density
• Clip at same time to aid future localisation
• If impossible, as per breast lump workup, can do surgical excisional biopsy

Imaging

• Mammogram
  • Calcifications from necrosis and debris in the involved duct. Tend to cluster together and are pleomorphic.
    • Linear
    • Segmental - branching calcifications extending posteriorly from the nipple into the interior of the breast
  • Pleomorphic in size and shape
  • 75% have clustered calcifications without an associated density, 15% calcifications and density, and 10% have a density alone
• MRI
  • Probably no role if DCIS has already been diagnosed
  • Controversial if DCIS has already been diagnosed
  • Can be useful in patients where you can't define the extent of disease with standard imaging alone
  • Concerns that it overestimates the extent of disease, leading to wider than necessary excisions

Treatment

• Approach
  • Prevent development of breast cancer
  • Minimise treatment-associated morbidity
  • Treatment recommendations based on perceived risk of local recurrence, patient's comorbidities and patient preference
  • Lumpectomy + radiotherapy +/- tamoxifen is the optimal strategy based on RCTs
    • All individually improve recurrence rate
    • About one third of DCIS excisions are found to contain cancer

Treatment options

• Mastectomy
  • Indications
    • Patient preference
    • Contraindication to radiotherapy
    • Multicentric or extensive DCIS, or suspected extensive based on mammogram
    • Inability to obtain clear margins with BCS
    • Likelihood of a poor cosmetic result with BCS
    • Unwilling or unable to have follow-up surveillance
    • Recurrence of DCIS after prior treatment with lumpectomy and radiation
  • Overtreatment for the majority of patients
  • Can be performed in skin-sparing or nipple-sparing fashion if desired
  • Does not improve overall survival compared to breast-conserving therapy, but does improve recurrence rate from 1-2% per year to 1-2% lifetime
• Breast-conserving therapy with radiotherapy
  • Will require localisation
  • Specimen oriented and x-rayed
  • Radiation significantly decreases local recurrence risk but does not improve survival
    • Decreased recurrence rate from 30.8% to 14.9%
    • Decreased ipsilateral invasive cancer rate from 16.4% to 7.1%
• Breast-conserving therapy without radiotherapy
  • Best for lower-risk cohorts or patient preference
  • Proposed low-risk cohort: (however, these results were not validated, and probably still would have a lower risk of recurrence if they had radiotherapy; the effect size is just lower) - note this is low-grade on the Van Nuys prognostic index
    • Low DCIS nuclear grade
    • Small lesion (<1.4cm)
    • Age >60
    • Surgical margins >1cm

Other treatment considerations

• Margins
  • Controversial
  • >2mm is often considered adequate to declare negative margin - does not significantly increase recurrence rate compared to bigger margins
  • <2mm should be considered for re-excision, although >1mm is acceptable in the UK
• SLNB
  • Not typically performed with DCIS unless doing a mastectomy
  • Indications
    • Microinvasion on core biopsy
    • Otherwise concerning for invasive disease
    • Mastectomy for DCIS (since won't be able to do it later if it's upstaged to invasive on pathology specimen)
    • High-grade, large (>5cm) or palpable DCIS (since there may be a subsequent upstaging based on pathological specimen, which happens about 15% of the time in this cohort)
• Hormone therapy
  • If DCIS is ER/PR positive, can give adjuvant hormone therapy for 5 years (either anastrazole or tamoxifen are ok)
  • Benefit only seen with ER-positive DCIS
  • Especially important in high-risk patients
  • Probably not necessary after mastectomy
  • Improves local control after breast-conserving therapy and prevents new tumours
  • After 7 years, reduced ipsilateral breast cancer from 9% to 6% and reduced the risk of new contralateral breast cancer by 47%
• Chemotherapy
  • Not indicated, as the rate of metastatic disease is so low

Prognosis

• Van Nuys Prognostic Index
  • Predicts likelihood of recurrence after BCS for DCIS
  • Factors: DCIS size, margin width, pathological assessment (high grade, non-high grade with and without necrosis), age
  • Each criterion scored 1-3 and combined
  • 4-6 is low, 7-9 is moderate and 10-12 is high risk for 5-year recurrence
  • May be able to omit radiotherapy for low-risk disease

• 10 year survival >95%
• Total cancer recurrence rate at 7 years
  • 30% with excision alone
  • 17% for excision with radiation therapy
  • 10% for excision, irradiation, and tamoxifen
• Risk factors for recurrence
  • Margins <1mm
  • High-grade
  • Comedo necrosis
  • Age <40yo
  • Symptomatic
  • ER/PR negative, bcl-2 negative, HER2 positive, p21/p53 positive, high Ki-67