Patients with advanced breast cancer who are treated with a combination of drugs that target specific molecules important for cancer development and also the hormones that are driving it are at increased risk of suffering adverse side effects.

In new research presented at the Advanced Breast Cancer Fourth International Consensus Conference (ABC 4), researchers have shown that combining targeted drugs with hormone therapy results in a significant increase in the risk of severe or life threatening adverse events (grades 3 and 4). 

However, the researchers, Dr Matteo Lambertini, a medical oncologist at the Institut Jules Bordet (Brussels, Belgium) and Professor Samuel Martel, a medical oncologist at CISSS Montérégie Centre/Hôpital Charles-Lemoyne, Université de Sherbrooke (Québec, Canada), say that most of these side effects are treatable and potentially preventable, and that the information gained from their research will enable doctors and patients to make more informed choices, as well as providing the basis for further research.

Previous studies have shown that patients with advanced breast cancer live longer without their disease progressing if they are treated with combination therapy, but, until now, it was not known to what extent these combined treatments could lead to more and worse adverse side effects.

Breast cancers that are described as "hormone receptor-positive" have receptors that receive signals from hormones such as oestrogen and progesterone that tell the cancer cells to proliferate. Drugs such as tamoxifen, which blocks the oestrogen receptors, interrupt these hormonal messages. Nowadays, in patients with advanced disease, they are often given in combination with other drugs that target specific molecules important for cancer development; for instance, trastuzumab is a monoclonal antibody targeting breast cancers that produce the protein HER2.

In the study presented today, the researchers analysed data from 8,529 patients who had taken part in 16 randomised controlled clinical trials up to July 2017. The patients all had advanced hormone receptor-positive breast cancer that had spread away from the site of the original tumour (metastatic or advanced breast cancer), and the trials investigated hormonal therapies given in combination with targeted drugs, such as CDK4/6, PI3K or mTOR inhibitors, and anti-HER2 agents. The patients had been randomised to receive either the combination therapy or the hormonal therapy alone.

Alterations in four main genes are responsible for how long patients survive with pancreatic cancer, according to a new study in JAMA Oncology. Before now, the presence and patterns between the genes and disease progression was not clearly established. One key difference in this study is the relatively large size: it involved 356 patients who all had pancreatic adenocarcinoma that could be surgically removed.

Adenocarcinoma is by far the most common type of pancreas  tumor. Ninety of the patients were treated at the University of Rochester Medical Center's Wilmot Cancer Institute; the others at Dana Farber/Brigham and Women's Cancer Center in Boston and Stanford Cancer Institute. In all cases after the tumors were removed, scientists extracted DNA from the cancerous tissue and nearby normal tissue, and conducted next-generation DNA sequencing on the specimens.
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The analysis centered on the activity of the KRAS, CDKN2A, SMAD4, and TP53 genes. Results showed that patients who had three or four of the altered genes had worse disease-free survival (the time between surgery and when the cancer returns), and overall survival (from surgery to death), compared to patients with a single or two altered genes. A more detailed breakdown of survival and specific gene activity is available in the full study.