Breast cancer and radiotherapy in ataxia-telangiectasia heterozygote

Ramsay, Jonathan; Birrell, Geoff W.; Lavin, Martin F.

doi:10.1016/s0140-6736(96)91114-9

Cited by 23 publications

(9 citation statements)

References 5 publications

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“…19,20 Much is known about radiotherapy-related factors that increase risks, and ovarian-toxic treatments that decrease them, 1,3 but it is unknown whether genetic factors affect these risks further. It has been suggested that radiotherapy might constitute a particular hazard for ataxiatelangiectasia carriers, 21 but studies have been small and not shown any clear association. 22,23 Family history of breast or ovarian cancer has not been found associated with risk, based on small numbers.…”

Section: Resultsmentioning

confidence: 99%

FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma

Yussanne

Leeuwen

Cooke

et al. 2012

Blood

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Section: Resultsmentioning

confidence: 99%

FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma

Yussanne

Leeuwen

Cooke

et al. 2012

Blood

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“…Ramsay et al (1996) reported on a case with bilateral disease whose fibroblasts and lymphoblastoid cells showed elevated radiosensitivity compared with controls in clonogenic assays. The patient received radiotherapy and developed only a mild skin reaction and minimal late effects.…”

Section: Resultsmentioning

confidence: 99%

Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy

Appleby

Barber²,

Levine³

et al. 1997

Br J Cancer

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The effectiveness of cancer radiotherapy is compromised by the small proportion (approximately 5%) of patients who sustain severe normal tissue damage after standard radiotherapy treatments. Predictive tests are required to identify these highly radiosensitive cases. Patients with the rare, recessively inherited, cancer-prone syndrome ataxia-telangiectasia (A-T) sustain extremely severe normal tissue necrosis after radiotherapy and their cultured cells are also highly radiosensitive. Clinically normal carriers (heterozygotes) of the A-T gene have an increased risk of breast cancer, account for approximately 4% of all breast cancer cases and show a modest increase in cellular radiosensitivity in vitro. It has been suggested that a substantial proportion of highly radiosensitive (HR) breast cancer patients may be A-T heterozygotes, and that screening for mutations in the A-T gene could be used as a predictive test. We have tested this hypothesis in a group of cancer patients who showed adverse reactions to radiotherapy. Sixteen HR breast cancer patients showing mainly acute reactions (and seven HR patients with other cancers) were tested for ATM mutations using the restriction endonuclease fingerprinting assay. No mutations typical of those found in obligate A-T heterozygotes were detected. If the estimate that 4% of breast cancer cases are A-T gene carriers is correct, then ATM mutations do not confer clinical radiosensitivity. These early results suggest that screening for ATM mutations in cancer patients may not be of value in predicting adverse reactions.

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“…Bhatia et al (1997) found no excess of breast cancer in relatives of patients with breast cancer after Hodgkin's disease, but this was based on small numbers. Because carriers of the ataxia telangiectasia (AT) gene have increased in vitro sensitivity to radiation, and have been found to have raised risk of breast cancer (Ramsey et al, 1996), they might be a group for whom radiotherapy constitutes a particular hazard. Genetic analyses of 32 patients developing breast cancer more than 10 years after radiotherapy for Hodgkin's disease did not reveal evidence of truncating mutations (Broeks et al, 2000).…”

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confidence: 99%

Second primary breast cancer after Hodgkin's disease

Horwich

Swerdlow

2004

Br J Cancer

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Although the potential carcinogenic risk of radiotherapy is well known, it has become clear that there is a particularly high risk of radiation-induced breast cancer in women treated for Hodgkin's disease at young ages. Thankfully, death from breast cancer in this population is uncommon, but it is important to understand factors contributing to the risk, including treatment parameters, and to develop a logical and efficient method for medical management of those at risk. In this minireview, we examine the evidence which should inform such a management policy. The prognosis of patients with Hodgkin's disease has been improved dramatically over the last 40 years by the development of extended field radiotherapy techniques and then by combination chemotherapy (DeVita et al, 1980;Rosenberg and Kaplan, 1985). However, long-term follow-up of survivors has demonstrated that a price of this success has been an increased risk of second cancers. Acute leukaemia frequently occurs in the first decade after treatment, mainly as a consequence of chemotherapy regimens that included an alkylating agent (Tucker et al, 1988;Kaldor et al, 1990;Swerdlow et al, 2000). In the long term, however, the absolute excess risks of a second solid cancer are higher (Swerdlow et al, 2000;Ng et al, 2002b; and are linked mainly with radiotherapy, although for some sites, such as lung cancer, there may be a substantial risk also from chemotherapy (Swerdlow et al, 2000;Travis et al, 2002). Recent reports from The Netherlands and from an international consortium of cancer registries have refined our understanding of how therapy may affect breast cancer risk.The relative risks of many cancers are higher if patients have been treated for Hodgkin's disease at a younger age (Swerdlow et al, 2000;van Leeuwen et al, 2000;Dores et al, 2002). Thus, although the risk of breast cancer is only about 50% increased in most all-age studies of women with Hodgkin's disease (van Leeuwen et al, 1999), relative risks are far larger than this in patients treated at young ages, especially those treated in childhood and adolescence (Hancock et al, 1993;Bhatia et al, 1996b); for them this is one of the main long-term sequelae of radiotherapy. This effect of age is unsurprising, as similar gradients are seen in other cohorts of radiation-exposed women (United Nations Scientific Committee on the Effects of Atomic Radiation, 1994).The size of risk of breast cancer found in Hodgkin's disease patients has varied between studies. For patients treated under age 21 years relative risks have generally been around 15 -25 (Hancock et al, 1993;Sankila et al, 1996;Wolden et al, 1998;Metayer et al, 2000;van Leeuwen et al, 2000;Dores et al, 2002), although they have been less raised (Neglia et al, 2001) or more raised (Mauch et al, 1996;Bhatia et al, 1996b;Aisenberg et al, 1997;Ng et al, 2002b) than this in a few studies; absolute excess risks have generally been of the order of 20 -40 per 10 000 per annum. Relative risks have been greater for patients treated at ages 10 -16 than at...

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Breast cancer and radiotherapy in ataxia-telangiectasia heterozygote

Cited by 23 publications

References 5 publications

FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma

FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma

Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy

Second primary breast cancer after Hodgkin's disease

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