Breast Conservative Therapy

When not to preserve Breast?

First step for me when proposing breast conservative therapy is make sure there is no contraindications:

  1. Pregnancy; BCS in 3rd trimester is possible with XRT after delivery
  2. Multicentric
  3. Prior XRT
  4. Persistent positive margin
  5. Collagen Vascular Disease → scleroderma or active lupus erythematous,
  6. Big tumour in small breast

Risk Factors for local recurrence

So! If we preserve the breast, who has a higher risk to recur?

PATIENT FACTORS

1. AGE

How do we know that age is important?

  • EORTC boost vs no boost trial showed age is an independent factor
    • At age of <35-40:
      • Tumour was significantly larger
      • More often ER/PR negative.
      • Invasive & CIS : often high grade.
      • CIS : more frequently incompletely resected
      • More often re-excisions
      • Age was the only independent prognostic factor for local control (P=0.0001).
      • Boost dose significantly reduced the 5-year LR rate from 7 to 4% for patients with a complete excision (P<0.001).
          • =<40year : The boost dose ==> LR 20 to 10% (P=0.002).

2. GENETICS

  • germ-line mutations in BRCA1 and BRCA2⇒ An inherited susceptibility to breast & ovarian Ca
  • substantial risk of contralateral and late ipsilateral breast cancers.

What's the evidence?

  • A retrospective study
    • Lumpectomy+RT
    • 160 pts stage I or II
    • BRCA1 or BRCA2 +
    • 445 age and stage-matched control patients without a mutation
      • F/U : 7 years
    • Results:
      • no radiosensitivity
      • actuarial rates of ipsilateral breast cancer recurrence and survival were similar at 10 years.
      • BRCA + → higher risk of contralateral breast ca.
        • 26% vs 3%!!!
      • TAMOXIFEN reduces the risk
  • Another Study:
    • 10-year risk of a contralateral breast cancer
      • 43% BRCA1 +
      • 35% BRCA2 +
      • Tamoxifen and bilateral oophorectomy (especially prior to age 49) was associated with reduced risk of contralateral breast cancer→ about 90%
TUMOR FACTORS

1. Margins

The single most important

  • Amount of disease is important
    • Focal vs extensive
      • Focal→ disease should be encompassed by 3 or less low power microscopic field

How do we know margin is important?
JCRT study: extensive LR 27% vs focal LR 14%

  • Marseille (France) study
    • Single margin vs multiple
    • LR: 14% vs 36%
    • Chemo will reduce this risk

2. EIC ( extensive intraductal component )

More than 25% of mass is intraductal Ca.

  • Intraductal Ca clearly extending beyond the margin or present in sections of grossly normal breast tissue
  • Predominantly non-invasive tumour + focal area of invasion = EIC

3. Palpable/Non Palpable → no effect on LR

4. Size → more difficult to get clear margin

  • If margin NEG→ no effect
  • Size is risk factor for distant metastasis

5. Location→ no effect

  • A risk factor for distant metastasis (?)

6. Multiple ipsilateral tumor

  • No effect if margin NEG

7. Markers :

  • Luminal A tumors (ER or PR positive, HER2 negative, Ki-67 < 1%) → best prognosis and the lowest rate of local or regional relapse.
  • After Lumpectomy: HER2+ and basal subtypes → increased risk of LR
  • After mastectomy, luminal B, luminal-HER2, HER2-enriched, and basal subtypes ⇒ increased risk of local and regional relapse on multivariable analysis
TREATMENT RISK FACTORS
  • Extent of resection
  • Adjuvant Therapy
  • Use of Boost

KATZ (2006)

  • 4 or more involved axillary nodes is positively associated
  • increased tumor size
  • lobular histology
  • LVI
  • increased number of involved SLNs
  • decreased number of uninvolved SLNs
  • increased size of SLN metastasis.