Abstract P6-06-06: Family history and young breast cancer patients in the UK: The POSH study
Authors: Copson ER , Cutress RI , Eccles BK , Maishman T , Stanton L , Eccles DM 
Published: August 2014

Abstract
Background
Approximately 4% of breast cancer cases occur in women under 40 years. Young age at diagnosis is associated with inferior survival compared to older patients. It is unclear whether an increased incidence of adverse biological features fully explains this. An underlying genetic pre-disposition to breast cancer is characterised by young age of disease onset, yet even at a very young age of diagnosis most individuals do not have an identifiable mutation in a known high risk breast cancer gene. Genome wide association studies have identified low penetrance genetic variants which may account for unexplained family histories of breast cancer. The effect of a BRCA 1/2 mutation on breast cancer prognosis remains controversial with retrospective studies reporting inconsistent outcomes for mutation carriers compared to sporadic tumours. The prognostic effect of low penetrance breast cancer susceptibility genes is under investigation.
POSH is a prospective observational cohort study designed to investigate prognostic factors in young breast cancer patients. Here we report pathology, treatment and outcome of these patients according to their family history of breast cancer.
Methods
2956 patients aged ≤40 at breast cancer diagnosis were recruited from 126 UK hospitals between 2001 and 2007. Details of personal characteristics, tumour pathology and treatment were collected. Family history details were collected using a questionnaire completed by participants at recruitment. BRCA mutation testing is in progress. Follow-up data were collected at 6 and 12 months and then annually.
Results
Family history data were available for 2850 patients. 1878 (65.9%) reported no family history of breast/ ovarian malignancies and 972 (34.1%) reported breast/ ovarian cancer in one or more 1st or 2nd degree relative. Patients with a positive family history were significantly more likely to have a surveillance detected breast cancer than those without a family history (3.0% vs. 0.1% p&lt;0.001) and patients with an affected 1st degree relative had a higher incidence of surveillance detected tumours than those with an affected 2nd degree relative (6.0% vs. 0.7% p&lt;0.001). Patients with a positive family history were significantly more likely to have a grade 3 tumour than patients with a negative family history (63.3% vs. 58.9% p = 0.04). There were no significant differences in median tumour diameter, incidence of nodal involvement or presence of metastases between the positive and negative family history groups. The frequency of ER and PR overexpressing tumours did not vary significantly between family history groups. Patients with a negative family history were significantly more likely to have a HER2 positive tumour than those with a positive family history (28.8% vs.24.7% p = 0.031). There were no significant differences in tumour grade, size, nodal status, and ER, PR or HER2 status between patients with 1st degree or 2nd degree affected relatives.
Conclusions
Our data indicates that having a first or second degree relative with a breast/ ovarian cancer is associated with an increased frequency of grade 3 and HER2 negative breast tumours but not with other pathological features. Further analyses will investigate the independent effect of family history on breast cancer survival and recurrence rates.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-06.