The UK national breast cancer screening programme for survivors of Hodgkin lymphoma detects breast cancer at an early stage.
AuthorsHowell, Sacha J
Linton, Kim M
Cowan, Richard A
Harris, Maggie A
Wardley, Andrew M
Radford, John A
AffiliationDepartment of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK. Showell@picr.man.ac.uk
MetadataShow full item record
AbstractBACKGROUND: Supradiaphragmatic radiotherapy (SRT) to treat Hodgkin's lymphoma (HL) at a young age increases the risk of breast cancer (BC). A national notification risk assessment and screening programme (NRASP) for women who were treated with SRT before the age of 36 years was instituted in the United Kingdom in 2003. In this study, we report the implementation and screening results from the largest English Cancer Network. METHODS: A total of 417 eligible women were identified through cancer registry/hospital databases and from follow-up (FU) clinics. Screening results were collated retrospectively, and registry searches were used to capture BC cases. RESULTS: Of the 417 women invited for clinical review, 243 (58%) attended. Of these 417 women, 23 (5.5%) have been diagnosed with BC, a standardised incidence ratio of 2.9 compared with the age-matched general population. Of five invasive BCs diagnosed within the NRASP, none involved axillary lymph nodes compared with 7 of 13 (54%) diagnosed outside the programme (P<0.10). The mean latency for BC cases was 19.5+/-8.35 years and the mean FU duration for those unaffected by BC was 14.6+/-9.11 years (P<0.01), suggesting that those unaffected by BC remain at high risk. Recall and negative biopsy rates were acceptable (10.5 and 0.8%, respectively). CONCLUSIONS: The NRASP appears to detect BC at an early stage with acceptable biopsy rates, although numbers are small. Determination of NRASP results on a national basis is required for the accurate evaluation of screening efficacy in women previously treated with SRT.
CitationThe UK national breast cancer screening programme for survivors of Hodgkin lymphoma detects breast cancer at an early stage. 2009, 101 (4):582-8 Br. J. Cancer
JournalBritish Journal of Cancer
- Screening mammography for young women treated with supradiaphragmatic radiation for Hodgkin's lymphoma.
- Authors: Lee L, Pintilie M, Hodgson DC, Goss PE, Crump M
- Issue date: 2008 Jan
- Breast Imaging in Women Previously Irradiated for Hodgkin Lymphoma.
- Authors: Horst KC, Fero KE, Hancock SL, Advani RH, Ikeda DM, Daniel B, Rosenberg SA, Donaldson SS, Hoppe RT
- Issue date: 2016 Apr
- Risk of breast cancer and breast cancer characteristics in women treated with supradiaphragmatic radiation for Hodgkin lymphoma: Mayo Clinic experience.
- Authors: Wahner-Roedler DL, Nelson DF, Croghan IT, Achenbach SJ, Crowson CS, Hartmann LC, O'Fallon WM
- Issue date: 2003 Jun
- Breast cancer risk in female survivors of Hodgkin's lymphoma: lower risk after smaller radiation volumes.
- Authors: De Bruin ML, Sparidans J, van't Veer MB, Noordijk EM, Louwman MW, Zijlstra JM, van den Berg H, Russell NS, Broeks A, Baaijens MH, Aleman BM, van Leeuwen FE
- Issue date: 2009 Sep 10
- Management of breast cancer after Hodgkin's lymphoma and paediatric cancer.
- Authors: Terenziani M, Massimino M, Magazzù D, Gandola L, Capri G, Carcangiu ML, Catania S, Di Russo A, Gennaro M, Meazza C, Podda M, Schiavello E, Valagussa P
- Issue date: 2015 Sep
Showing items related by title, author, creator and subject.
AZD8186 study 1: phase I study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumour activity of AZD8186 in patients with advanced castration-resistant prostate cancer (CRPC), squamous non-small cell lung cancer, triple negative breast cancer and with PTEN-deficient/mutated or PIK3CB mutated/amplified malignancies, as monotherapy and in combination with vistusertib (AZD2014) or abiraterone acetate.Lillian, S; De Bono, J; Higano, C; Shapiro, G; Brugger, W; Mitchell, P; Colebrook, S; Klinowska, T; Barry, S; Dean, Emma J; et al. (2016-12)
Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth: understanding the aging and cancer connection.Balliet, R M; Capparelli, C; Guido, C; Pestell, T G; Martinez-Outschoorn, U E; Lin, Z; Whitaker-Menezes, D; Chiavarina, B; Pestell, R G; Howell, Anthony; et al. (2011-12-01)Increasing chronological age is the most significant risk factor for cancer. Recently, we proposed a new paradigm for understanding the role of the aging and the tumor microenvironment in cancer onset. In this model, cancer cells induce oxidative stress in adjacent stromal fibroblasts. This, in turn, causes several changes in the phenotype of the fibroblast including mitochondrial dysfunction, hydrogen peroxide production, and aerobic glycolysis, resulting in high levels of L-lactate production. L-lactate is then transferred from these glycolytic fibroblasts to adjacent epithelial cancer cells and used as "fuel" for oxidative mitochondrial metabolism. Here, we created a new pre-clinical model system to directly test this hypothesis experimentally. To synthetically generate glycolytic fibroblasts, we genetically-induced mitochondrial dysfunction by knocking down TFAM using an sh-RNA approach. TFAM is mitochondrial transcription factor A, which is important in functionally maintaining the mitochondrial respiratory chain. Interestingly, TFAM-deficient fibroblasts showed evidence of mitochondrial dysfunction and oxidative stress, with the loss of certain mitochondrial respiratory chain components, and the over-production of hydrogen peroxide and L-lactate. Thus, TFAM-deficient fibroblasts underwent metabolic reprogramming towards aerobic glycolysis. Most importantly, TFAM-deficient fibroblasts significantly promoted tumor growth, as assayed using a human breast cancer (MDA-MB-231) xenograft model. These increases in glycolytic fibroblast driven tumor growth were independent of tumor angiogenesis. Mechanistically, TFAM-deficient fibroblasts increased the mitochondrial activity of adjacent epithelial cancer cells in a co-culture system, as seen using MitoTracker. Finally, TFAM-deficient fibroblasts also showed a loss of caveolin-1 (Cav-1), a known breast cancer stromal biomarker. Loss of stromal fibroblast Cav-1 is associated with early tumor recurrence, metastasis, and treatment failure, resulting in poor clinical outcome in breast cancer patients. Thus, this new experimental model system, employing glycolytic fibroblasts, may be highly clinically relevant. These studies also have implications for understanding the role of hydrogen peroxide production in oxidative damage and "host cell aging," in providing a permissive metabolic microenvironment for promoting and sustaining tumor growth.
Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family.Evans, D Gareth R; Shenton, Andrew; Woodward, Emma; Lalloo, Fiona; Howell, Anthony; Maher, Eamonn R; Academic Unit of Medical Genetics and Regional Genetics Service, St Mary's Hospital Manchester M13 0JH, UK. email@example.com (2008)BACKGROUND: The identification of a BRCA1 or BRCA2 mutation in familial breast cancer kindreds allows genetic testing of at risk relatives. However, considerable controversy exists regarding the cancer risks in women who test positive for the family mutation. METHODS: We reviewed 385 unrelated families (223 with BRCA1 and 162 with BRCA2 mutations) ascertained through two regional cancer genetics services. We estimated the penetrance for both breast and ovarian cancer in female mutation carriers (904 proven mutation carriers - 1442 females in total assumed to carry the mutation) and also assessed the effect on penetrance of mutation position and birth cohort. RESULTS: Breast cancer penetrance to 70 and to 80 years was 68% (95%CI 64.7-71.3%) and 79.5% (95%CI 75.5-83.5%) respectively for BRCA1 and 75% (95%CI 71.7-78.3%) and 88% (95%CI 85.3-91.7%) for BRCA2. Ovarian cancer risk to 70 and to 80 years was 60% (95%CI 65-71%) and 65% (95%CI 75-84%) for BRCA1 and 30% (95%CI 25.5-34.5%) and 37% (95%CI 31.5-42.5%) for BRCA2. These risks were borne out by a prospective study of cancer in the families and genetic testing of unaffected relatives. We also found evidence of a strong cohort effect with women born after 1940 having a cumulative risk of 22% for breast cancer by 40 years of age compared to 8% in women born before 1930 (p = 0.0005). CONCLUSION: In high-risk families, selected in a genetics service setting, women who test positive for the familial BRCA1/BRCA2 mutation are likely to have cumulative breast cancer risks in keeping with the estimates obtained originally from large families. This is particularly true for women born after 1940.