Carcinoma In-situ

DCIS

INTRODUCTION

DCIS is intraductal carcinoma with malignant cells within the ductal system and no evidence of invasion through the basement membrane.

EPIDEMIOLOGY

  • 5% of all breast biopsy specimens.
  • 25-35% of all breast cancers.
  • DCIS is more common than LCIS with ratio of 5:1.
  • 36,000 new cases and 12-15% of all breast cases a year.
  • Typically women are 10 years younger than those with invasive disease. Average age is 54-68 years.

PRESENTATION AND NATURAL HISTORY

  • Typically, patients present with suspicious microcalcifications (calcium is deposited in areas of rapid growth and necrosis) on mammograms. They are granular, linear, or clustered.
  • Also, they present with painless mass or nipple discharge, Paget’s disease of the nipple.
  • Multicentricity is about 25-40%
    • Low-grade is more multicentric, histologically
    • High-grade is more continuous, histologically
  • Bilaterality occurs in 10-20%.
  • Incidence of axillary metastasis is 1-2% (probably from microinvasion).
  • Malignant potential is 35% (35% will go on to become invasive if not treated).
  • Incidence of contralateral invasive cancer is 10-15% over 20 years.

WORK-UP

  • H (family hx) &P (with breast exam), bilateral mammo,
  • Biopsy
  • FNA – no architecture (invasive v. in situ), need palpable mass
  • Stereotactic core bx – can be used with no palpable mass, does get some architecture, can distort tumor bed.
  • Excisional bx – can be therapeutic (lumpectomy), provides architecture, can be used without palpable mass (needle localized).

DIFFERENTIAL

  • Benign – adenoma, fibrocystic changes, atypical ductal hyperplasia, abscess
  • Malignant – DCIS, LCIS, invasive breast cancer.

PATHOLOGY

Subtypes

  • Comedo type (comedocarcinoma): large cells obliterating all spaces and have central necrosis correlating with microcalcifications. High correlation of histological extent of lesion with extent of microcalcifications. Associated with aneuploidy, increased p53, amplification of HER/2NEU, rapid proliferation rates, high grade (90%), multicentricity (37%), and microinvasion(63%).
  • Cribiform: cells growing on fenestrated pattern.
  • Micropapillary: tufts of cells growing perpendicularly from BM.
  • Papillary: tufts of cells with fibrovascular core.
  • Solid type

Markers

  • DCIS tumors are ER-positive in 70%.
  • HER-2/neu is positive in 55% of cases

PROGNOSTIC INDICATORS

  • Patient: young age is bad.
  • Tumor characteristics: nuclear grade, margin width, tumor size, and presence of necrosis, HER-2/NEU , erb-C

TREATMENT/RESULTS

  • Mastectomy (Simple mastectomy without axillary dissection)
  • Local control rates about 95-100%.
  • Survival about 95-99%.
  • Disadvantage: deforming
  • Indications for mastectomy: 1)high risk of recurrence – close/positive margins if can’t re-excise, diffuse disease, personal choice to remove breast due to risk/family hx of invasive disease,
  • 2)contraindication to treating with RT – prior RT, CVD, or difficult treatment set-up,
  • 3)cosmesis cannot be preserved with lumpectomy/RT.

Excision +RT: Recurrence rates are ~12%

  • Hiramatsu: 76 patients with 9% LR (57% invasive).
  • Solin: 172 patients with LR of 17% (44% invasive).
  • Fisher (B06): 27 patients with LR 7% (50% invasive).
  • Fisher (B17) 1998: 399 patients with LR 12% (33% invasive). Showed that there was a decrease of both DCIS (13.4% to 8.2%) and invasive disease (13.4% to 3.9%) with the addition of EBRT.

Excision alone: Recurrence rates are about 15-30% with half of them being invasive.

  • Schwartz: 70 patients with <2.5cm and negative margins. 15% recurrence.
  • Fisher(B06): 21 patients with LR of 43% (56% invasive)
  • Fisher (B17) 1998: 391 patients with LR in 26.8% (50% invasive).

Silverstein 1996: 333 patients in retrospective review were treated either with excision alone versus excision + RT and an index was used to determine outcome (the Van Nuys Prognostic Index or VNPI):

VNPI: 1) size (< 15mm, 16-40mm, > 41mm), scored 1-3
2) margin (>10mm, 1-9mm, <1mm), scored 1-3
3) pathology (high grade, non-high grade (+) necrosis, non-high grade (-) necrosis), scored 1-3
Scores 3 or 4 : no benefit from EBRT, local recurrence free survival (100% vs. 97%), so recommend excision only.
Scores 5,6,or 7: the patients with EBRT benefited by 17% in LRFS (85% vs. 68%), so recommended excision + RT
Scores 8 or 9: experienced high rates of recurrence even with RT in excess of 60% so recommend mastectomy.

Problems: the study was retrospective and may need longer follow-up, the VNPI is difficult to reproduce without spending lots of time and money, some patients with the same VNPI should be treated differently.

NSABP B06: 76 patients found to have DCIS (initially thought to have invasive disease) randomized to mastectomy, lumpectomy + RT, and lumpectomy alone. None of patients undergoing mastectomy had recurrence, 7% for combined and 43% for excision alone. No overall survival difference (96%).

NSABP B17: randomized 818 DCIS patients to excision alone versus excision + RT. LR was 26.8% for excision alone and 13% for RT + excision. Event free survival was better for combined treatment. Most recurrences occur at the or near the primary site.

There are 3 versions of NSABP 17:
1) 1993 version had problems of short 43 median month follow-up, no note of tumor size or histological type and definition of positive margin having cells at margin.
2) 1995 version focused on pathological specimen and stated that comedo necrosis and margin status (+ or -) were significant prognostic indicators on MVA. All subgroups of patients benefited from RT (goes against VNPI).
3) 1998 version updated f/u with results shown above.

EORTC 10853
* 50 Gy to whole breast (no boost)
* showed equivalent reductions in invasive and non-invasive breast cancer
* No event-free survival advantage to RT arm due to higher contra-lateral breast events

RANDOMIZED TRIALS OF DCIS

LCIS (Lobular carcinoma in situ)

Presentation

  • 1-6% in mammographically screened
  • Usually found as incidental finding
  • LCIS is bilateral in 50-70% of women when both breasts are examined in contrast 10-20% of DCIS present as bilateral.
  • Median age is 40 to 50 years

Risk of Invasive Cancer

  • marker for development of invasive disease
  • 25-30% risk of invasive carcinoma in 20 years (9-12 times normal)
  • 20 year follow-up is required to see the increase in risk

Treatment

The treatment of choice is careful observation and TAM for 5-years

  • Close Follow-up
    • monthly breast self-examination
    • physical examination by MD once or twice a year
    • yearly bilateral screening mammography.
  • Tamoxifen reduces the risk of sequent disease by 56% at 5-years (NSABP P-1)

Bilateral mastectomy is the alternative. Unilateral treatment (ie. mastectomy) is inadequate as this is a bilateral disease.

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