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Background Breast cancer survival has been shown to be associated among relatives. In this study, we used a population-based cohort of Swedish sisters, both diagnosed with breast cancer, to determine whether prognostic information of a previously diagnosed sibling is useful for the clinical management of a newly diagnosed sibling. Patients and methods The population-based cohort included all sister pairs, 1617 sisters, diagnosed with breast cancer in Sweden, from 1 January 1992, through 31 December 2006, with complete follow-up. All information was collected manually from original pathology reports and patient records. The Kappa statistic was used to measure the agreement of primary tumor characteristics between the sisters. We modeled the breast cancer-specific survival using multivariate (Cox) proportional hazard analyses in two steps categorizing the older sister's survival. Results Estrogen receptor status was the only tumor characteristic significantly associated between the sisters [κ 0.18 (95% confidence interval (CI) 0.089–0.27)]. Younger sisters with poor older sister survival showed significantly worse survival compared with patients with good older sister survival (log rank, P = 0.017). A twofold increased hazard ratio (HR) for death from breast cancer was found in younger sisters with poor older sister survival compared with patients with good sister survival [HR 2.56 (95% CI 1.16–5.65)], adjusting for age and calendar period of diagnosis, socioeconomic factors, number of children and hospital of primary tumor diagnosis. When further adjusting for primary tumor characteristics and adjuvant therapy, the risk for death from breast cancer in younger sisters with poor older sister survival became more pronounced [HR 3.35 (1.34–8.34)]. Conclusions Our findings derived from a population-based cohort of Swedish sister pairs suggest that breast cancer-specific survival is inherited independent of tumor characteristics and treatment in the sibling later diagnosed with the disease. Prognostic information of a previously diagnosed sibling with breast cancer could be important in the clinical management.

Today, the diagnosis of metastatic breast cancer is usually based on radiological findings, and therapeutic decisions are made by considering the pathological characteristics and predictive markers of the primary tumour. Accumulating evidence suggests that tumour characteristics, including estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), are unstable through tumour progression. Several retrospective studies and, recently, two prospective studies have investigated the discrepancies in receptor status between primary tumours and the corresponding metastases in a total of 1773 patients (for ER) and 2845 patients (for HER2). Changes in ER and HER2 status in these studies range from 14.5% to 40% and from 0% to 37.5%, respectively. In the two prospective studies, a different diagnosis, usually non-malignant, was obtained in 3% and 9% of the cases, and the biopsy led to a treatment modification in about one out of seven patients. Here, we review and discuss the currently available data and provide our recommendations on when a metastatic biopsy should be obtained.

This is a report looking into the genetic differences between screen-detected and interval cancers. It is an affirmation that screen-detected and interval cancers may have unique underlying biology. Genetic risk discrimination has potential relevance in clinical care where interval cancers, which are usually rapidly growing and aggressive, do not currently benefit from mammography screening. Background Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. Patients and methods A 77 single-nucleotide polymorphism polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term. Results PRS weighted by breast cancer overall estimates was found to be differentially associated with 1865 screen-detected and 782 interval cancers in the LIBRO-1 study {age-adjusted odds ratio (OR)perSD [95% confidence interval (CI)] 0.91 [0.83–0.99],P = 0.023}. The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates [ORperSD = 0.90 (0.82–0.98),P = 0.011]. This result was corroborated by two independent studies [combined ORperSD = 0.87 (0.76–1.00),P = 0.058] with no evidence of heterogeneity. When enriched for ‘true’ interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced [ORperSD = 0.74 (0.62–0.89),P = 0.001], with a significant interaction effect between PRS and mammographic density (Pinteraction = 0.017). Conclusion To our knowledge, this is the first report looking into the genetic differences between screen-detected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology.