Risk Factors for Local Failure

Rule of Thumb

Local Recurrence with Surgery

Tumor Treatment Local Recurrence/ year Study
DCIS Lumpectomy 2.6% B-17
< 1 cm Lumpectomy 3.1% B-06
< 4 cm Lumpectomy 5.2% EBCTCG
< 4 cm MRM 0.7% B-06
Locally advanced MRM + CT 3.5% 82c
  • Chemotherapy: Systemic therapy can approximately halve the 5-year risks of both local and distant recurrence.[2]
  • Tamoxifen: annual recurrence (overall not just local, I think local is more like 1/3 reduction) rate was almost halved (recurrence rate ratio 0·59 [SE 0·03]) and the breast cancer mortality rate was reduced by a third.[3]
  • Radiation reduces local recurrence rate by 70%. [3]
  • Mortality general finding that a 20% absolute reduction in 5-year local recurrence risk leads to about a 5% absolute reduction in 15-year breast cancer mortality (ie, a four-to-one ratio of absolute effects). [3]

Local-Regional Recurrence after Mastectomy

  • After Mastectomy
  • Most commonly occur under the skin of chest wall.
  • Occasionally form a erythematous, often pruritic skin rash
  • 80-90% of local recurrence appear by 5 years.

Prognosis

  • Despite aggressive local treatment almost all fail distantly
  • Three factors important in prognosis
    • Prolonged DFS interval
    • Tumor excision
    • Local control
  • When all factors were favorable 5-year relapse free survival is 59% and overall survival is 61%

Reirradiation

  • 2 series showed lower local control in patient who previously had RT (36% vs 68%)
  • With 40 to 60 Gy a series of 13 patients had no soft tissue necrosis
  • Another series of 7 patients treated to 40-50 Gy with 10-15 Gy boost had 1 osteomyelitis and 1 superficial necrosis which healed in 8 weeks.

Multivariate analysis of locoregional recurrence [4]
from retrospectively reviewed of 542 patients using neoadjuvant chemotherapy and postmastectomy radiotherapy.

Factor Hazard ratio 95% Confidence interval p-value
Skin or nipple involvement 2.8 1.5–5.2 0.001
Supraclavicular nodal involvement 2.7 1.3–5.6 0.009
No tamoxifen use 2.7 1.2–6.0 0.019
Extracapsular extension 2.1 1.1–4.0 0.020
Estrogen receptor negative disease 2.1 1.2–3.7 0.013

Factors associated with increased risk of LRF after mastectomy and chemotherapy without radiation [1]

Nodal Status Pre-menopausal Post-menopausal
negative VI+, T > 2 cm VI+
positive VI+, high-grade, 4+ nodes T > 2 cm, high-grade, 4+ nodes
  • VI: vascular invasion
  • T > 2 cm: tumor size greater than 2 cm
  • high-grade: high-grade tumor histology
  • 4+ nodes: 4 or more positive nodes on dissection

T3 N0 M0[5]

  • NSABP data-base, the other a combined study from the Massachusetts General Hospital, Yale, and the M.D. Anderson Cancer Center) — both studies found that long-term LRF rates were less than 10% in patients receiving systemic therapy.
  • However, several points should be made.
  1. both studies included many tumors that were “exactly” 5 cm
    1. 144 patients in the Taghian study, or 46% of the study population, and 24 in the Floyd study, or 34%).
    2. these are classified as T2 by the AJCC staging system, rather than T3.
  2. The LRF rate was higher for tumors larger than 5 cm than for those exactly 5 cm in the Floyd study (none versus 12.4%, respectively), although not in the NSABP study. The latter study contains more patients, so this discrepancy may be statistical noise.
  3. Floyd and colleagues found that the LRF rate was 21% when LVI was present, compared to 4% when it was not. However, only 14 patients had LVI. Such information was apparently not available in the NSABP data-base.
  4. Neither study examined the impact of tumor grade, margin width, or young age (40 years old or less) on the risk of LRF.
Bibliography
1. A. Wallgren, M. Bonetti, R.D. Gelber, A. Goldhirsch, M. Castiglione-Gertsch, S.B. Holmberg, J. Lindtner, B. Thürlimann, M. Fey, I.D. Werner, J.F. Forbes, K. Price, A.S. Coates, J. Collins. Risk Factors for Locoregional Recurrence Among Breast Cancer Patients: Results From International Breast Cancer Study Group Trials I Through VII. Journal of Clinical Oncology, Vol 21, Issue 7 (April), 2003: 1205-1213.
2. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687–717.
3. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials Lancet 2005; 366: 2087–2106
4. Eugene H. Huang, Susan L. Tucker, Eric A. Strom, Marsha D. McNeese, Henry M. Kuerer, Gabriel N. Hortobagyi, Aman U. Buzdar, Vicente Valero, George H. Perkins, Naomi R. Schechter, et al. Predictors of locoregional recurrence in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiotherapy International Journal of Radiation Oncology*Biology*Physics, Volume 62, Issue 2, 1 June 2005, Pages 351-357.
5. Floyd SR, Buchholz TA, Haffty BG, Goldberg S, NIEMIERKO A, RAAD RA, OSWALD MJ, Sullivan T, STROM EA, Powell SN, Katz A, Taghian AG. Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger. Int J Radiat Oncol Biol Phys. 2006 Oct 1;66(2): 358-64.
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