Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome.
BACKGROUND
There are no specific recommendations for the management of breast cancer patients with germ-line p53 mutations, an exceptional genetic condition, particularly regarding postoperative radiotherapy. Preclinical data suggested that p53 mutations conferred enhanced radiosensitivity in vitro and in vivo and the few clinical observations showed that Li-Fraumeni families were at a higher risk of secondary radio-induced malignancies.


METHODS
We reviewed a cohort of patients with germ-line p53 mutations who had been treated for breast cancer as the first tumor event. We assessed their outcome and the incidence of secondary radio-induced malignancies.


RESULTS
Among 47 documented Li-Fraumeni families treated from 1997 to 2007 at the Institut Gustave Roussy, 8 patients had been diagnosed with breast cancer as the first tumor event. Three patients had undergone conservative breast surgery followed by postoperative radiotherapy and five patients had undergone a mastectomy (3 with postoperative radiotherapy). Thus, 6/8 patients had received postoperative radiotherapy. Median follow-up was 6 years. Median age at the diagnosis of the primary breast cancer was 30 years. The histological characteristics were as follows: intraductal carcinoma in situ (n = 3), invasive ductal carcinoma (n = 4) and a phyllodes tumor (n = 1). Among the 6 patients who had received adjuvant radiotherapy, the following events had occurred: 3 ipsilateral breast recurrences, 3 contralateral breast cancers, 2 radio-induced cancers, and 3 new primaries (1 of which was an in-field thyroid cancer with atypical histology). In contrast, only one event had occurred (a contralateral breast cancer) among patients who had not received radiation therapy.


CONCLUSIONS
These observations could argue in favor of bilateral mastectomy and the avoidance of radiotherapy.
Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France. steve.heymann@igr.fr
Steve
S
Heymann
Suzette
S
Delaloge
Arslane
A
Rahal
Olivier
O
Caron
Thierry
T
Frebourg
Lise
L
Barreau
Corinne
C
Pachet
Marie-Christine
MC
Mathieu
Hugo
H
Marsiglia
Céline
C
Bourgier
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics / Q000532:radiotherapy / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D016158:Genes, p53; D006801:Humans; D015994:Incidence; D016864:Li-Fraumeni Syndrome / Q000150:complications* / Q000235:genetics; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D055815:Young Adult