Radiotherapy following breast conserving surgery Breast surgery by benbenzhou


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Discussion                                                                        2. Greenhalgh DG. The role of growth factors in wound healing. J Trauma
                                                                                     1996; 41: 159–167.
Wound healing is a complex and coordinated process beginning                      3. Tokumaru S, Higashiyama S, Endo T et al. Ectodomain shedding of epi-
with tissue injury [2–4]. After tissue injury, a coagulation cascade                 dermal growth factor receptor ligands is required for keratinocyte migra-
is activated to stop bleeding. Inflammatory mediators are then                       tion in cutaneous wound healing. J Cell Biol 2000; 151: 209–220.
activated, resulting in an outpouring of cytokines and growth fac-                4. Yamaguchi Y, Yoshikawa K. Cutaneous wound healing: an update.
tors that initiate collagen repair and granulation tissue formation.                 J Dermatol 2001; 28: 521–534.
The final process, which completes the healing process, involves                  5. Nakamura Y, Sotozono C, Kinoshita S. The epidermal growth factor
                                                                                     receptor (EGFR): role in corneal wound healing and homeostasis. Exp
extracellular tissue remodeling, angiogenesis and reproduction of
                                                                                     Eye Res 2001; 72: 511–517.
the original tissue.
                                                                                 DOI: 10.1093/annonc/mdg352
   Keratinocytes play a key role in skin healing in response to
injury. Keratinocytes not only proliferate to complete tissue heal-
ing, but they also serve as a source of several cytokines. EGFR
ligands are among the most prominent cytokines secreted by the
keratinocytes [2]. EGFR ligands include epidermal growth factor                  Radiotherapy following breast-
(EGF), transforming growth factor-α, amphiregulin, heparin                       conserving surgery
binding EGF-like growth factor (HB-EGF), betacellulin and
epiregulin [5]. These secreted cytokines stimulate adjacent keratino-            I read Chung and Cady’s letter urging caution with repeat sentinel

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cytes. There appears to be a biphasic production of EGFR ligands                 node biopsy [1] with some alarm. Surely the other pertinent point
during the wound healing process. The first phase of production                  that this case illustrates is the imperative to irradiate the breast
of EGFR ligands is secondary to local induction in response to                   following breast-conserving surgery, a procedure now accepted as
injury; the second wave of production is secondary to autocrine                  standard, to reduce local recurrence in the remaining breast tissue
activation of the keratinocytes. Some evidence suggests that                     [2]. The patient reported in this case did not receive radiotherapy
HB-EGF is the most important of the ligands. The activation of                   to the breast following wide local excision, despite this being a
EGFR and vascular endothelial growth factor receptor promotes                    standard procedure, and 20 months after diagnosis she presented
wound healing. Consequently, agents that inhibit EGFR could                      with local recurrence. As the authors themselves state, local recur-
potentially interfere with wound healing. Topical application of                 rence is an indication that the patient is at risk of systemic disease
OSU 8-1, an inhibitor of EGFR ligand shedding, has been shown                    [3, 4], and indeed 10 months later, this 48-year-old patient with a
to decrease keratinocyte migration and delay cutaneous wound                     T1a tumour presented with lung and liver metastases. This is
healing [3]. In addition, systemic administration of gefitinib has               clearly a very poor outcome for all concerned. Whilst the role of
been shown to decrease epithelial proliferation and stratification               radiotherapy following mastectomy for histologically high-grade
in response to corneal injury [5].                                               but node-negative breast cancer remains controversial, its use
   Gefitinib is absorbed orally and inhibits skin EGFR phos-                     following breast-conserving surgery, even in seemingly low-risk
phorylation. Gefitinib accumulates in the skin, which means                      women such as the patient described, is clear, and this unfortunate
theoretically that patients treated with this agent could have prob-             case clearly illustrates this point.
lems with wound healing. Preclinical studies have shown that                     A. L. Appleton
gefitinib can delay and inhibit corneal wound healing [5]. Gefit-
inib has not been shown to impair skin wound healing in our small                Unité de Sénologie, Clinique de Genolier, near Geneva, Switzerland,
series reported here. This data suggests that the role of EGFR in                CH-1272 (E-mail:

wound healing needs to be re-evaluated.
                                                                                  1. Chung MA, Cady B. Caution urged with repeat sentinel lymph node
R. G. has received honoraria from Astra Zeneca for speaking                          biopsies. Ann Oncol 2002; 13: 1951.
engagements.                                                                      2. Morris AD, Morris RD, Wilson JF et al. Breast-conserving therapy vs
                                                                                     mastectomy in early-stage breast cancer: a meta-analysis of 10-year
R. Govindan1,2*, D. Behnken1,2, W. Read1,2 & H. McLeod1,2                            survival. Cancer J Sci Am 1997; 3: 6–12.
1                                                                                 3. Vicini FA, Kestin L, Huang R, Martinez A. Does local recurrence affect
Washington University School of Medicine, St Louis, MO; 2Alvin J Siteman
                                                                                     the rate of distant metastases and survival in patients with early-stage
Cancer Center, St Louis, MO, USA (*E-mail:
                                                                                     breast carcinoma treated with breast-conserving therapy? Cancer 2003;
                                                                                     97: 910–919.
                                                                                  4. Meric F, Mirza NQ, Vlastos G et al. Positive surgical margins and ipsi-
                                                                                     lateral breast tumour recurrence predict disease-specific survival after
    1. de Bono JS, Rowinsky EK. The ErbB receptor family: a therapeutic target       breast-conserving therapy. Cancer 2003; 97: 926–933.
       for cancer. Trends Mol Med 2002; 8 (4 Suppl): S19–S26.                    DOI: 10.1093/annonc/mdg355

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