Impact of familial risk and mammography screening on prognostic indicators of breast disease among women from the Ontario site of the Breast Cancer Family Registry.

Although several studies have found screen-detected cancers in women with familial breast cancer risk have favorable prognostic features compared with symptomatic cancers, the impact of level of familial risk is unknown. A cohort of 899 first-degree female relatives of cases of breast cancer from the Ontario site of the Breast Cancer Family Registry was followed for 2 years. Logistic regression analyses compared diagnoses of breast cancer or benign breast disease (BBD) between women at high (n = 258, 28.7 %) versus low/moderate (n = 641, 71.3 %) familial risk. Similar analyses compared prognostic features of invasive cancers and BBD by level of familial risk and mammography screening status. Among 899 women, 44 (4.9 %) were diagnosed with invasive breast cancer and/or ductal carcinoma in situ, and 56 (6.2 %) with BBD. Women with high familial risk were significantly more likely to be diagnosed with breast cancer [odds ratio (OR) = 2.84, 95 % confidence interval (CI) 1.50-5.38] than low/moderate risk women, particularly if diagnosed at age ≥50 (OR = 2.99, 95 % CI 1.37-6.56) or screened with mammography (OR = 3.33, 95 % CI 1.54-7.18). High risk women were more likely to be diagnosed with BBD (OR = 1.94, 95 % CI 1.03-3.66). Level of familial risk was not associated with prognostic features. Cancers among unscreened women were larger (OR = 9.72, 95 % CI 1.01-93.61) and diagnosed at stage II or above (OR = 7.80, 95 % CI 1.18-51.50) compared with screen-detected cancers. Screening mammography may be effective for women with a first-degree family history of breast cancer, irrespective of level of familial risk.

Detection of PIK3CA Mutations in Breast Cancer Bone Metastases.

Background. An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of individual patients. However, whole genome sequencing studies have shown that the mutational profiles of cancers evolve over time and often differ between primary and metastatic sites. Activating point mutations in the PIK3CA gene are common in primary breast cancer tumors, but their presence in breast cancer bone metastases has not been assessed previously. Results. Fourteen patients with breast cancer bone metastases were biopsied by three methods: CT-guided bone biopsies; bone marrow trephine biopsies; and bone marrow aspiration. Samples that were positive for cancer cells were obtained from six patients. Three of these patients had detectable PIK3CA mutations in bone marrow cancer cells. Primary tumor samples were available for four of the six patients assessed for PIK3CA status in their bone metastases. For each of these, the PIK3CA mutation status was the same in the primary and metastatic sites. Conclusions. PIK3CA mutations occur frequently in breast cancer bone metastases. The PIK3CA mutation status in bone metastases samples appears to reflect the PIK3CA mutation status in the primary tumour. Breast cancer patients with bone metastases may be candidates for treatment with selective PIK3CA inhibitors.