DCIS

Things you should know about DCIS

  • Malignant cells within basal membrane
    • No invasion of basal membrane
  • Most likely presentation sign :
    • Microcalcification in mammogram
      • vs LCIS which is mostly accidentally finding
  • Siza can be underestimated in mammogram 1-2cm comparing to pathology
  • Progression of DCIS —> Invasive Ca
    • No therapy: 30%
    • After BCS only(Breast Conserving Therapy): ~15%
    • After BCS+RT: ~8%

DCIS in mammogram

  • Microcalcification
    • Linear
      • High grade, comedo necrosis
    • Heterogenous granular
      • Intermediate grade
    • Fine granular
      • Low grade, non-comedo
  • Non-Calcified irregularity
    • Circumscribed nodule
    • Poorly defined mass
    • Asymmetry
    • Architectural distortion

DCIS and Pathology

  • Features:
    • Nuclear grade
    • Necrosis
    • Polarization
    • Architectural pattern
      • Comedo
      • Solid
      • Cribriform
      • Papillary
      • Micro-papillary
      • RARE patterns:
        • apocrine
        • neuro-endocrine
        • signet cell cystic
        • hypersecretory ca
        • clinging
    • margin
    • size
    • micro-calcification

Treatment

  • Mastectomy
  • BCS+RT

Margin

  • We know that with closer and positive margin chance of breast event is higher
    • ~15% and ~20%
  • The benefit is bigger with close and positive margin from Rt but still the chance of recurrence is higher

What about positive or close margin after mastectomy?

  • Some evidence that it's more than expected
    • ~ 7-10% after 10years
    • All data retrospective
  • In one Swedish retrospective study RT given after mastectomy for pos and close margins
      • 100% LR after 10 years

Role of RT after BCS in DCIS

  • No randomized study comparing Mastectomy vs BCS+RT
  • NSABP B17
    • DCIS with negative margins
      • XRT vs No XRT
    • F/U 8 years
    • Recurrence of DCIS→ XRT makes it HALF
      • 8.4% vs 13.4%
        • IBTR recurrence rate is ~4% per year
  • Predictors of recurrence:
    • Moderate to marked comedo-necrosis
    • Positive margins
  • Cancer-specific survival for DCIS → 95%
Options of Local Therapy
  • Mastectomy→ 98% cure regardless of age, size and grade
  • Indications
    • If lesion is too large for clear margin
    • Multicentric
    • Best measure: magnification mammogram; MRI over and underestimates
  • Partial Mastx + RT
  • Partial Mastx alone

How to choose the therapy?!

  • extent of the DCIS (size)
  • Consider risk of local recurrence with each form of treatment

How do we know XRT is beneficial after excision of DCIS?

There are 4 trials :
Risk of recurrence : no RT → with RT

  • European ( EORTC)
    • 26% → 15%
  • UK-Australia-New Zealand
    • 14% → 6%
  • Swedish
    • 22% → 7%
  • NSABP
    • 32% → 16%
What is important to know about these four trials?
  • All decreased the risk by half
  • Half of local recurrence were INVASIVE
  • Median time to LR —>3years
  • 50 Gy to the whole breast /25 fractions
    • No boost dose
      • Only 9% in NSABP and 5% in EORTC got boost
    • But in young patients it is generally recommended just based on data of invasive ca
  • No difference in OS
  • Risk of axillary recurrence regardless of use of Tamoxifen is , 0.1%
  • No Tamoxifen except UK/ANZ
  • Risk reduction in both invasive and in situ

What about Tamoxifen?

  • 80% of DCIS → ER+
  • In UK/ANZ → two-by-two randomization
    • RT versus none and tamoxifen versus none
  • No benefit invasive recurrence ( ipsi or contra )
  • But risk reduction 34% in in situ recurrence
    • So why do we recommend TAMOXIFEN in DCIS?
  • NSABP B24 trial
    • 1,804 patients → RT + Sx
    • Tamoxifen 20 mg daily vs placebo
    • 5 years
    • Breast Ca event → 13.4% vs 8.2%
      • Ipsilateral Breast Event
        • 11% vs 8%
      • Contralateral Breast Event
        • 5% vs 2.5%
    • What factors affect risk of recurrence?
      • Age
      • 40 and younger; 60 and older
      • Grade
      • Palpable ( Clinical presentations of DCIS)

Who may not require RT?

  • Some advise omitting RT if negative margin > 1 cm
Eastern Cooperative Oncology Group (ECOG)
  • A prospective trial attempt to prove this —> BUT 12% rate of recurrence (30% invasive ) ==> study closed early
        • A prospective, single-arm study
        • 670 patients
          • Low or intermediate grade DCIS 2.5 cm or less
          • High grade DCIS 1 cm or less
            • Include comedo necrosis as well
          • Surgical margins 3 mm or greater
          • No residual calcifications on postoperative mammography
          • About 30% of pts received Tamoxifen
          • 5-yr ipsilateral breast events
            • 6.1% (low/int)
            • 15.3% (high)
          • 7-yr rate
            • 10.5% (low/int)
            • 18.0% (high)

Hence there is significant risk to dictate give RT post-op.