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Breast Cancer After Hodgkin's Lymphoma

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    Breast Cancer After Hodgkin's Lymphoma

    Silvana Martino, M.D.
    The Angeles Clinic Foundation

    Radiation exposure, even many years previously, is known to increase the risk of many cancers, including breast cancer. Women previously treated for Hodgkin’s
    lymphoma, particularly if radiation was part of their treatment have been recognized as being at higher risk for the subsequent development of breast cancer. An article, published in the June 2012 issue of The Oncologist, adds detail to our understanding of these women.

    The data used was obtained from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. It encompassed the dates 1973-2007. Included were 9,620 women with a diagnosis of Hodgkin’s lymphoma (HL). Among them, 316 subsequent breast cancers occurred. During this same period, 450,413 women without Hodgkin’s lymphoma were diagnosed with breast cancer and were used for comparison. Several important observations were made in this comparison.

    As a group, the women with a prior diagnosis of HL were 2.4 times more likely to develop breast cancer. The risk was highest among patients who were 19 years of age or younger at time of their treatment. The risk decreased progressively as the age of diagnosis of HL increased and approached that of the general population as the women were diagnosed with lymphoma at age 50 or later. This confirms prior observations demonstrating that the female breast is most vulnerable to the damaging effects of radiation during the teenage years when the breasts are developing. The increased risk for breast cancer was noted from 5 years post HL treatment onward. Those whose treatment included radiation had a higher risk of breast cancer than those whose treatment did not include radiation. The difference between these two groups persisted for at least 30 years.

    Women with breast cancer developing after treatment for HL were younger at diagnosis, were more likely to have breast cancer in the external portions of the breast, were more likely to have tumors that did not express hormone receptors, and were more likely to be diagnosed at a somewhat lower stage. The lower stage at diagnosis is possibly a reflection that these women were being watched and screened more closely. In spite of this, their prognosis is not better, but is somewhat worse. Their breast cancer tends to be more aggressive and they are also more prone to develop a second breast cancer of the opposite breast as well.

    I found this article to be one of the more informative on this topic in part because of its level of detail. We previously thought that these women were more prone to breast cancer on the inner half of the breast, but as radiation techniques have changed in the treatment of Hodgkin’s lymphoma, so has the location of breast cancer.

    The incidence of Hodgkin’s lymphoma is increasing among both children and young adults. More intensive therapy has resulted in a cure rate of approximately 75%. This reflects clear therapeutic success. However, we need to recognize that young women with this diagnosis, especially if they received radiation, must be watched closely for the subsequent development of bilateral breast cancer.

    Reference: Risk, Characteristics, and Prognosis of Breast Cancer after Hodgkin’s Lymphoma, Veit-Rubin N, Rapiti E, Usel M, Benhamou S, VinhHung V, Vlastos G, Bouchardy C, The Oncologist 2012:17: 783-791.
    Gregory D. Pawelski

    Risk, Characteristics, and Prognosis of Breast Cancer after Hodgkin's Lymphoma

    Risk, Characteristics, and Prognosis of Breast Cancer after Hodgkin's Lymphoma

    Nikolaus Veit-Rubin, a, Elisabetta Rapiti, c, Massimo Usel, c, Simone Benhamou, c,d,e, Vincent Vinh-Hung, b, Georges Vlastos, a and Christine Bouchardy, c

    a. Unit of Senology, Department of Gynaecology and Obstetrics, Geneva University Hospitals, Geneva
    b. Division of Radiation Oncology, Geneva University Hospitals, Geneva, Switzerland
    c. Geneva Cancer Registry, Institute for Social and Preventive Medicine, University of Geneva, Geneva, Switzerland
    d. INSERM, U946, Fondation Jean Dausset - CEPH, Paris, France
    e. CNRS, UMR 8200, Gustave-Roussy Institute, Villejuif, France

    Correspondence: Christine Bouchardy, M.D., M.P.H., Ph.D., Geneva Cancer Registry, 55 Boulevard de la Cluse, 1205 Geneva, Switzerland; [email]



    To assess breast cancer (BC) risk after Hodgkin's lymphoma (HL) and compare characteristics, risk of second BC, and prognosis of patients with these BCs with patients with first primary BC.

    Patients and Methods:

    We considered all 9,620 women with HL recorded in the Surveillance, Epidemiology and End Results dataset in 1973–2007. We calculated age-period standardized incidence ratios of BC. We compared patient, tumor, and treatment characteristics, risk of second BC, and prognosis between patients with BC after HL (n = 316) and patients with other BCs occurring during the same period (n = 450,413) using logistic regression and Cox models adjusted for confounders.


    HL patients had a 2.4-fold higher risk for developing BC (95% confidence interval [CI], 2.2–2.7) than the general population. Age at HL diagnosis and radiation therapy influenced this risk. Compared with first primary BCs, BCs after HL were diagnosed at a younger age, at an earlier stage, were less frequently hormone receptor positive, were located more frequently in external quadrants, and were less frequently treated using radiotherapy. These patients had a higher risk (adjusted hazard ratio [HR], 2.85; 95% CI, 1.79–4.53) for developing a second BC and had a higher BC mortality risk (adjusted HR, 1.36; 95% CI, 1.05–1.76). The higher mortality risk was only partly explained by the higher occurrence rate of a second BC.


    HL survivors have a higher risk for developing BC, their BCs are more aggressive, they have a higher risk for a second BC occurrence, and they have a poorer prognosis. Guidelines of care should be adapted to decrease the impact of BC in these high-risk patients.

    The Oncologist June 2012 vol. 17 no. 6 783-791
    Gregory D. Pawelski


      Late Leukemia Risk Rises after Breast Cancer Therapy

      Antonio C. Wolff, M.D.
      Johns Hopkins University, Baltimore

      The 10-year incidence of leukemia after adjuvant chemotherapy for breast cancer appears to hover around 0.5%, twice as high as previously reported.

      A review of more 20,000 patient records included in the National Comprehensive Cancer Network (NCCN) database found 51 cases of leukemia that developed within 10 years of treatment. Women who had only chemotherapy were at the greatest risk – almost six times more likely to develop the disease than the surgery-only control group, Dr. Antonio Wolff said at that annual San Antonio Breast Cancer Symposium.

      "We know that the observed survival benefit with adjuvant therapy does take into account the potential mortality associated with leukemia," said Dr. Wolff of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore. "But often we are in the situation where we make the decision to give chemotherapy ‘just because.’ We need to be very careful here, because some of those patients will potentially derive none of the benefits of chemo, and be at risk of its toxicities."

      Dr. Wolff examined the 1997-2008 data from eight facilities in the NCCN database – a total of 20,533 women with a first diagnosis of breast cancer. The median follow-up was 5 years, but some data were available for up to 15 years after treatment.

      About half of the cohort had stage I disease; in most, the cancer was invasive ductal. Slightly more than half had hormone receptor–positive/HER2 negative disease.

      The only baseline characteristic significantly different between the groups was age. Women who developed leukemia were significantly older at the time of their cancer treatment (60 vs. 54 years; P = .02); 78% of those with leukemia were older than 50 years.

      Of the 51 cases, 44 were acute myeloid leukemia (AML), with a median onset time of 3.5 years after treatment. One-third of these occurred in women with a family history of breast or ovarian cancer. The median time to onset in the AML cases was 2 years.

      None of the tumor characteristics were significantly associated with the development of leukemia. There were no significant differences among those who had breast-conserving surgery, mastectomy, or no surgery; or between those who had no radiation therapy, radiation without surgery, radiation after breast-conserving surgery, or radiation after mastectomy, though larger numbers of patients are needed for some of these smaller subset analyses.

      The overall rate of leukemia per 1,000 patient/years was 0.46; in the surgery-only group, the rate was 0.16 per 1,000 patient-years. "Of interest is that the rates in each of the treatment groups were similar to the overall rate," – 0.43 in the radiation-only group, 0.52 in the chemotherapy-only group, and 0.54 in the combination therapy group.

      At 5 years, the cumulative incidence of leukemia was 0.05% in the surgery-only group; 0.19% in the radiation-only group; 0.30% in the chemotherapy-only group; and 0.32% in the combination therapy group.

      But the onset accelerated over the study period, Dr. Wolff noted, with the bulk of cases developing from years 6 to 10. .By the end of the 10-year period, the incidence was 0.2% in the surgery-only group; 0.44% in the radiation-only group; 0.52% in the chemotherapy group; and 0.51% in the combination group.

      In a risk analysis using surgery as the control, the overall hazard ratio of leukemia was 2.7 in the radiation-only group; 5.68 in the chemotherapy only group; and 5.64 in the combination group.

      Radiation appeared to confer no significant additional risk when it was combined with chemotherapy, Dr. Wolff added.

      The findings are strikingly different than previously identified. The largest study of the association was published in 2003, when researchers from the National Surgical Adjuvant Breast and Bowel Project Operations Center reviewed six trials that examined rates of acute myeloid leukemia and myelodysplastic syndrome after doxorubicin and cyclophosphamide therapy (Clin. Breast Cancer 2003;4:273-9).

      The subgroup that received anthracycline/cyclophosphamide in that review had a cumulative 8-year incidence of 0.24%. In Dr. Wolff’s chemotherapy subgroup, the cumulative 8-year incidence was 0.52%.

      "It’s very important to keep in mind that the known leukemia latency period for anthracycline is 1-3 years, but that of alkylating drugs like cyclophosphamide is 4-6 years and there are case reports of it developing after 10 years," he said. "We need to be very careful when we talk about survival at 5 years vs. 10 years in exposed patients, because they could be at risk for a decade and, potentially, even longer."

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      Gregory D. Pawelski