Post radiation changes following breast carcinoma treatment include arm edema, brachial plexopathy, decreased arm mobility, soft tissue necrosis, rib fractures, radiation pneumonitis, radiation related heart disease and carcinogenesis [3
Primary malignant fibrous histiocytoma of the female breast are rare. Clinically, radiation associated sarcomas present as cutaneous lumps within the previously irradiated area of the chest wall (parasternal area, supraclavicular fossa, shoulder girdle and conserved breast). Mammography is typically negative [3
] and the mean latency period approximately 11 years (4 to 44 years).
Patients who developed RIS were young [6
] when diagnosed with breast cancer (range 26 – 54 ; median 43 years) compared to patients with lymphangiosarcoma (range 39 to 69 years, median 51 years) and the general breast cancer population. The median age in a separate study carried out at Institut Gustave Roussy (France) in comparison were 65.8 years (49 – 83 years) and the mean latent period was 9.5 years (4–24 years). The cumulative incidence of sarcoma following irradiation of breast cancer was 0.2% (range 0.09 to 0.47) at 10 years. In a separate retrospective analysis of RIS following XRT for breast cancer at Henri Mondor Hospital, France (1983 – 1997) [7
] RIS appeared with a latency period of 5 to 18 years (mean 10.3 years) and the mean age being 57.6 years (range 39 to 88 years).
Few studies have addressed the risk of contralateral breast cancer after post operative RT. In a large cohort study of 41,109 patients diagnosed with breast cancer (1935 – 1982). RT was associated with a small but marginally significant elevation in the risk of the contralateral breast cancer [8
] Patients aged 45 years or younger the risk of contralateral breast cancer within 15 years was found to be 11% without RT and increased to about 12–13% with the addition of RT. The quantitative risk of Radiation induced sarcoma following breast conserving radiotherapy was no greater than that following mastectomy. Patients receiving both XRT and chemotherapy was noted to be at highest risk for secondary malignancies, including sarcomas and leukaemias.
Radiation induced neoplastic transformation is thought to be related to irreversible DNA damage [9
]. Several years following radiotherapy, dominant gene mutations and gene deletions accumulate in the genome, making carcinogenesis a multistage process. Cells in G2 and M phases of the cell cycle [10
] are radiosensitive in terms of both killing and induction of neoplastic transformation compared with mid G1 phase. The exact molecular mechanisms of tumor promotion by ionizing radiation are unknown. Proto-oncogene c-jun expression [11
] and inactivation of tumor suppressor genes p53 and Rb are commonly discussed theories. The retinoblastoma locus may be important in the pathogenesis of soft tissue sarcomas. Retinoblastoma gene alterations have been detected in de novo leiomyosarcomas as well as RIS.
It is difficult to analyze the exact relationship between the total irradiation dose and RIS. Minimum total doses of 10 Gy in conventional doses per fraction appear necessary to result in RIS, most cases of RIS occur in association with total radiation doses in the range of 40 – 50 Gy [12
]. The risk of carcinogenesis increases linearly with doses up to 10 Gy. Pierce et al [13
] suggested a relationship between radiation technique, potential overlapping of fields, and the development of secondary tumors.
Current radiation therapy regimens consist of delivery of 5000 cGy to the whole breast at a dosage of 200 c Gy/day, additional 1000–1500 cGy to the tumor bed. Postmastectomy radiation is mainly reserved for patients with T3 or T4 primary tumours or multiple positive lymph nodes.
Radiation associated sarcomas are usually high grade tumors [6
] reflected by the advanced stage at the time of diagnosis. Pathological diagnosis is often delayed due to lack of symptoms, distortion of histological architecture and long latency period after diagnosis of the original tumor.