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Patients with advanced-stage ovarian cancer are widely believed to have a dismal prognosis; however, around 20% of women with this disease survive beyond 12 years after treatment and are effectively cured. In this Perspectives, Steven Narod presents the case that this proportion could be substantially increased through the combination of maximal debulking surgery and intraperitoneal chemotherapy.

Hormone replacement therapy (HRT) has been linked by several reports to an increased risk of breast cancer. The precipitous decrease in breast cancer incidence shortly after the cessation of HRT is well established. In this Review, Steven Narod summarizes the evidence and asks the question, where do the breast cancers go?

Breast cancers in young women are typically aggressive and so young age can correlate with a poorer outcome. In this Review article, Steven Narod discusses the risk factors, risks of recurrence and secondary cancer, treatment, prevention and awareness of very-early onset breast cancer.

Genetic testing for breast cancer susceptibility is widely available in North America and in Europe. The optimum treatment of women with breast (or ovarian) cancer and aBRCA1 or BRCA2 mutation may be different from that of non-carriers. Thus, identifying the BRCAmutation status in patients could assist appropriate decision making for individualized cancer prevention, screening and treatment.

The results of three recent studies demand that more attention be placed on defining the most-appropriate approach to population-based breast-cancer screening, in particular regarding the potential harms of increasing overdiagnosis. Two of these studies report that more-sensitive detection of breast neoplasms is possible by 3D tomography and by MRI, but the third paper raises the question of whether this increased sensitivity is desirable.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

A genome-wide association study for lung cancer finds that genetic sequences in the nicotinic acetylcholine receptor subunit gene cluster contribute susceptibility. Interestingly, this susceptibility is not related to smoking status or frequency, and seems to come from a change in an amino acid in the receptor itself.

The diagnostic utility of tumor size in breast cancer is dependent on multiple factors. In this Perspective, Foulkes and coauthors recommend that tumor size should not be automatically considered in treatment decisions for all breast cancer subtypes. The authors discuss how the correlation between size and survival is disrupted in triple-negative and basal-like breast cancers and propose two specific mechanisms that might be responsible for this disrupted relationship.

The paradigm of precision medicine implies that breast cancer treatment should be tailored based on inherent risk of recurrence and/or individual sensitivity to various chemotherapies. A recent trial of olaparib in women with a BRCA1/2 mutation provides supporting evidence for this paradigm and suggests that the identification of genetic variants at the time of diagnosis might benefit an increasing number of patients.

Paul Brennan and colleagues report a genome-wide association study for lung cancer susceptibility. In addition to a previously reported variant at 15q25, they detect and replicate a new association at 5p15.33.

HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.

Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

Bilateral mastectomy is used to treat an increased percentage of women with unilateral breast cancer in order to prevent a second primary cancer in the unaffected breast. Although this surgical approach has been proposed to benefit women at high risk of contralateral cancer, the decision to remove the contralateral breast is controversial and requires a careful evaluation on an individual basis. This Review discusses the risk factors for contralateral breast cancer, and the evidence that bilateral mastectomy might in fact reduce breast-cancer associated mortality.