Search

Genes have been identified for which germline mutations are associated with high lifetime risks of breast, colorectal and other cancers. Identification of mutation carriers through genetic testing is important as it could help lower cancer incidence and mortality. The translation of genetic information into better health outcomes is expensive because of the costs of genetic counselling as well as laboratory testing. Approaches to triage for mutation screening of known genes which rely on cancer family history are not necessarily sensitive and specific or the most cost-effective. Recent population-based research has shown that the cancers and precancerous lesions arising in mutation carriers have specific molecular and morphological characteristics. People with colorectal cancer, especially those diagnosed atayoung age, whose tumours exhibit microsatellite instability and some specific pathology and immunohistochemi-cally-defined features are more likely to carry a germline mutation in one of four mismatch repair genes. Some morphological and immunohistochemically-defined features are associated with breast cancers arising in women who carry BRCA1or BRCA2germline mutations, especially if atayoung age. Screening paradigms based on molecular and morphological features that predict mutation status, especially if focused on early-onset disease, have the potential to identify mutation carriers with greater sensitivity and specificity, and in a more cost-effective way, than those based on family history alone. Genetic testing results could help inform treatment if those affected are tested soon after diagnosis using pathologyled selection strategies to identify cases most likely to carry germline mutations. We propose how this new approach could be undertaken by having genetic testing and counselling prioritised to those with the greatest probability of carrying a germline mutation in these known cancer predisposition genes.

Population-based women (n=1049) with breast cancer diagnosed mainly between 1996 and 1998, when aged 20–59 years, were mailed a questionnaire seeking information about self-reported shoulder stiffness and swelling, numbness and pain/ache in the arm following treatment (excluding 6 months from diagnosis). Of the 809 who completed the survey, approximately seven in eight experienced at least one symptom, one in six reported all four symptoms, and one in three considered that their arm morbidity interfered substantially with activities of daily living. Arm swelling occurred at some time in 39% of women, was present in 20% 1 year, and in 29% 4 years, after diagnosis. The prevalence of arm swelling was higher in women with axillary node dissection (OR=2.4; 95% Cl 1.0–5.6), and was increased in a women with a higher body mass index (P=0.02) and less education (P=0.01), but was not related to age, number of nodes excised or self-reports of radiation or type of surgery.