XRT Post Mastectomy

How do we know RT is necessary after Mastectomy?

The story behind why we give RT post-Mastectomy starts with Cuzick study which didn't show any benefit for RT as Cancer Specific Death (CSS) was less with RT but non-Ca death were higher. That shows detrimental effect of post-mastectomy RT in old days specially on heart. That's specially true in old ages when techniques were not as sophisticated as today.

  • Meta-analysis Cuzick 1987
    • Mastx + XRT
      • ⇒ lower death due to breast ca
      • ⇒higher non breast ca death
  • EBCT meta-analysis 2004
    • Mastx +/- XRT
      • If LN + ⇒ LR 9% vs 24%
      • Breast Ca specific survival 53.4% vs 48.6%
      • Cardio Vascular Disease (CVD) death increased in XRT group

Van de Steene meta-analysis
* Excluded old, out of date and small series
* Mastx +/- XRT
* ==> OS increased by 12.4%

Danish Trial 82b

  • 1708 patients ; premenopausal , stage II & III
  • Arms:
    • Mastx + 9cycles of CMF (Cyclophosphamide, Methotrexate, and Fluorouracil)
    • Mastx + 8cycles of CMF + XRT ( Chest Wall + Regional LN )
  • Results:
    • Loco-regional Recurrence with/without DM :
      • RT group—> 9%
      • noRT group —> 32%
    • 10yr OS:
      • RT group —> 54%
      • noRT gourp —> 45%

Danish Trial 82c

  • 1300 patients, postmenopausal, stage II & III
  • Arms:
    • Mstx + Tamoxifen ( 30mg OD )
    • Mstx + Tamoxifen + RT ( Chest Wall + LN )
  • Results:
    • Loco-regional Recurrence:
      • RT group —> 8%
      • no-RT group —> 35%
    • 10yr OS:
      • RT —> 45%
      • no-RT —> 36%

Vancouver Trial
* 318 patients, premenopausal, LN +
* Mastx + CMF
* If XRT ⇒ 20yr LR less and OS better, less DM

What do we learn from Danish and Vancouver Trials:

  • Reducing LR, post-Mastx XRT in stage II and III(node + or T>2cm) ⇒ improve OS
  • The risk of LR despite systemic therapy is substantial ( about 15% in LN 1-3 and 30% in LN >4 ⇒ we understand that systemic therapy is predominantly to lower distant metastases⇒ LR control even more important.

An important question: whether post-Mastx XRT is indicated for patients with stage II (1-3) LN +?

  • Most of patients in these trials were N1 Stage II→ Many say that means all Node + patients need post-Mastx XRT.
  • The problem/answer is:
      • Low number of LN removed ( median 7 in Danish and 11 in BC )
      • So if there was standard axillary dissecti/on the number of LN + would be higher ( >4 maybe? )
      • Also such patients with remained disease in axilla have higher risk of SCN and chest wall recurrence which could be avoided by a more complete axillary dissection
  • Danish trial→ 43% of all LR is in axilla
    • Comparing with series in which patients had standard axillary dissection these trials show higher LR.
      • However one serie showed that 3% of pts with post-Mastx XRT had LR vs 13% of those who didn’t have XRT.(Woodward)

Who are at higher risk for LR recurrence mastectomy?

  • Thigs to consider!
    • Adequecy of LN dissection
    • Multifocal pattern of disease
    • Margin
    • In one series just in younger age
    • age <40 years
    • tumor ≥2 cm
    • ER NEG
    • LVI
    • Grade II; III
  • Postmenopausal with grade III and >2cm ⇒ LR risk 24% ; grade I & II and <2cm ⇒ LR risk <15%

International Breast Cancer Study Group Trials

  • 1-3 LN + grade II; III ⇒ LR risk : 19-27%; grade I ⇒ <15%
  • Cofactors Associated with a Greater Than 15% Local-Regional Recurrence after Mastectomy and Chemotherapy in Patients with One to Three Positive Lymph Nodes
  • Tumor size >4 cm
  • Extracapsular extension >2 mm <10 lymph nodes removed 20% of lymph nodes involved
  • Invasion of skin/nipple
  • Invasion of pectoralis fascia
  • Close or positive margins

//Taghian et al //
2,957 Age <50, T2 disease

When do we give XRT post-Mastx in Node NEG patients?

Jagsi 2004…… retrospective analysis of 877 pts from 1980-2000……… median F/U→ 100m

  • 10yr LR as first event was 6
    • 80% of these were chest wall
  • Risk factors:
    • Size > 2 cm
    • Margin < 2 mm
    • Premenopausal
    • LVI
  • 10year LR:
    • NO risk factor → 1.2%
    • 1 risk factor → 10.0%
    • 2 risk factors → 17.9%
    • 3 risk factors → 40.6%

A meta-analysis from UK
→patients with two or more risk factors should be treated with PMRT, since their LRR risk is >= 15%

  • LVI
  • Grade 3
  • T2+
  • Close SM
  • Age <50/premenopausal

LR in Patients Not Treated with RT after Mstx in Randomized Trials

Patterns-of-Failure Studies LN+ ~ Number of Patients LR Rates at 10 Years(%)
ECOG LN+(1–3) 1,018 13%
LN+ (≥4) 998 29%
M.D. Anderson LN+ (1–3) 466 12%
LN+ (≥4) 419 27%
NSABP LN+ (1–3) 2,957 6–11%
LN+ (≥4) 2,784 14–25%
IBCSG LN+ (1–3) 2,408 14–27%
LN+ (≥4) 1,659 24–35%

XRT post Mastx – What if patient had chemo upfront? ( neoadjuvant )

a. We know that the correlations between pathological extent of disease and LR after mastectomy are different for those who had neoadj. chemo with those who didn’t.
b. The risk of LR is determined by both the pretreatment stage and the residual disease after chemo.
c. One of the only published studies:
o 579 patients; neoadj. Chemo + Mastx + XRT vs 136 patients with neoadj. chemo + Mastx.
• A prospective trial but XRT was not a randomized variable in any of the trials ⇒ significant imbalances in the prognostic factors were present between the two groups.
a. Patients with worse disease were often offered XRT
b. Despite this, lower LR in XRT group.
c. 10-year LR rates 8% vs 22%
d. Those who have extensive dis. After chemo→ clearly they benefit from XRT post-OP → better OS and lower LR
o What about those who achieve pCR
• LR rate 7%( with XRT ) versus 33% ( no XRT )
• Also better OS
e. What about those with stage II
o 132 patients with no XRT ( same study as above)
• if T3N0 or LN > 4 ⇒ High risk of LR
• if Ln 1-3 → 8% LR