The increased incidence of breast cancer in women after previous radiotherapy for Hodgkin’s disease is well described and is attributed to the incidental inclusion of portions of the breast in the portals used to irradiate the mediastinum with or without infraclavicular/axillary regions. 1–6 For such patients, there are published opinions suggesting mastectomy as the preferred treatment based on concern about the high total cumulative dose of radiotherapy that would be delivered to at least portions of the treated breasts and the possible sequelae thereof, such as skin pigmentation changes, soft-tissue and bone necrosis, and a poor cosmetic outcome. 6–9
In 1996, a report by two of the authors (M.D. and K.G.) detailed six women treated with breast irradiation for carcinomas developing after previous radiotherapy for Hodgkin’s disease or non-Hodgkin’s lymphoma. 10 Since that time, six additional patients have been treated, and further follow-up of the initial six patients is presented.
MATERIALS AND METHODS
Presentation of Lymphoma
The age at examination for lymphoma was 19 to 41 years (median: 23 years). Eleven women had Hodgkin’s disease and one, a 38-year-old white woman, had non-Hodgkin’s lymphoma (Table 1). The patient with non-Hodgkin’s lymphoma had stage II-B disease involving the mediastinum and right part of the neck. Of the 11 women with Hodgkin’s disease, 7 had stage I disease and 4 had stage II disease. Eleven women were white and one was black.
All the women with Hodgkin’s disease had radiotherapy directed to at least the mantle with doses ranging from 23 Gy to 44 Gy. Four women had radiotherapy also to the paraaortic nodal areas. The patient with non-Hodgkin’s lymphoma had radiotherapy to the mediastinum and right part of the neck (30–36 Gy). This patient also received chemotherapy using the cyclophosphamide/doxorubicin/vincristine/prednisone regimen. Of the 11 women with Hodgkin’s disease, 5 were treated with radiotherapy alone, 3 had radiotherapy alone initially with nitrogen mustard/vincristine, procarbazine/prednisone for recurrence and 3 had radiotherapy and nitrogen mustard/vincristine, procarbazine/prednisone initially.
Presentation of Breast Cancer
The interval from completion of radiotherapy for lymphoma or Hodgkin’s disease to diagnosis of breast cancer ranged from 10 to 29 years (median: 22 years) (Table 2).
Breast cancer was located in the upper outer quadrants in five patients and in inner quadrants of the breast in six patients. One patient had presented with metastatic adenocarcinoma in the axilla without an obvious primary in the ipsilateral breast. She underwent axillary dissection alone, whereas 10 women underwent lumpectomy and axillary dissection and 1 had lumpectomy and sentinel node biopsy with three negative nodes. Three women had pathologically positive nodes and nine had pathologically negative nodes. Nine patients were treated with 5,000 cGy in 25 fractions to the entire breast. Three women were treated with 5,020 cGy to 5,100 cGy/27 to 30 fractions. Eleven received an additional boost of 1,000 cGy in five fractions to the operative area in the breast. One patient was treated with an additional 900 cGy in five-fraction boost to the operative area. Four women received adjuvant chemotherapy with cyclophosphamide/methotrexate/5-fluorouracil, one with cyclophosphamide/doxorubicin (Adriamycin)/5-fluorouracil, one with cyclophosphamide/methotrexate/5-fluorouracil and tamoxifen, five with tamoxifen, and one had no adjuvant systemic therapy.
The course of radiotherapy was well tolerated in all women without any unusual acute reactions. In one woman (patient 9), breast cancer, T2N1, subsequently developed in the opposite breast 4 years after treatment of her first breast cancer; she elected to undergo bilateral mastectomies. There was no evidence of residual tumor in the ipsilateral irradiated breast. Ten women are alive and well 1 to 174 months from completion of radiotherapy to the breast (median: 46 months). Two women died of distant metastasis at 44 and 78 months, respectively, without local recurrence.
There have been no severe late sequelae, and all women have a good to excellent cosmetic result.
Several reports have suggested mastectomy as the treatment of choice for breast cancer arising after previous radiotherapy for Hodgkin’s disease. 6–9 This is based on concern about possible severe sequelae arising after a high total cumulative dose to portions of the breast. In this series, the interval between radiotherapy for lymphoma and subsequent breast cancer was at least 10 years. Because no patient had skin changes from the previously administered radiotherapy, it was considered feasible to proceed with breast conservation surgery and breast irradiation, which was well tolerated despite the previously administered mantle irradiation. Thus, it is appropriate to consider lumpectomy and breast irradiation for those women in whom breast cancer develops many years after radiotherapy for Hodgkin’s disease.
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