Background Limiting thoracic radiation burden is a driving force for development of diagnostics, with the use of childhood CT scans particularly linked to increased cancer incidence [1]. Imaging of children with known or suspected hereditary haemorrhagic telangiectasia (HHT) has been performed for more than 30 years, in order to diagnose and/or treat pulmonary arteriovenous malformations (PAVMs). Childhood screening thoracic CT scans are currently recommended international practice [2]. Our aim was to explore if breast cancer rates differed in HHT patients compared to controls.

Methods To provide sufficient power to compare breast cancer rates in HHT patients and controls, we developed a questionnaire capturing data on multiple relatives per respondent, powered to detect differences in breast cancer rates. Blinded to cancer responses, reports of HHT-specific features allowed assignment of participants and relatives as HHT-subject, unknown, or control.

Results By data download on 30.6.2012, 1,307 participants (including 1,012 HHT-subjects, 142 controls) had completed the international questionnaire, with the majority of respondents residing in North America. Ages (medians 55/53 ys), gender (65/65% female) and general demographics were similar between the groups. Combining data of participants and relatives resulted in a control-arm of 2,817 (52% female), and HHT-arm of 2,166 (58% female). Median ages were 77ys [IQR 65–82] and 66ys [IQR 53–77] respectively. Rates of breast cancer in the control group matched the age standardised frequency reported by Globocan for the general population, with a ratio of observed/expected incidence of 1.22. As expected, cancer rates increased with age (p < 0.0001, all cancers). Following age-adjustment, breast cancer was reported significantly more frequently for the HHT group than controls (quadratic regression age-adjusted OR 1.52 (1.07, 2.14, p = 0.018).

Conclusions Individuals with HHT may be more likely to develop breast cancer. Further study is required to validate, and to assess if any excess is related to radiation exposure, or other factors. Nevertheless, given the rationale for PAVM screening programmes relates to risk reductions in adult life, the data support the widespread view that PAVM screening CT scans should be postponed until after puberty.

References

1. Matthews et al, BMJ. 2013 May 21;346:f2360.

2. Faughnan et al, J Med Genet. 2011 Feb;48(2):73–87.