Imagine having to counsel a patient who has been diagnosed with breast cancer about the possibility she may need to have her stomach removed. That’s what happened to Marc Tischkowitz, MD, Ph.D., an oncologist affiliated with Cambridge University Hospitals National Health Service (NHS) Trust in the United Kingdom. The patient with breast cancer was referred to him after the treating physician received the results from a multigene panel. The test showed that she carried a gene tied to increased risk for a certain type of stomach cancer, the treatment of which includes prophylactic removal of the stomach.
We were in the situation in which this woman asked one question: is my breast cancer hereditary?” he said. We didn’t answer that question. Instead, we gave her a completely different problem to worry about.” The gene in this patient was CDH1, which has been linked to up to 70% increased risk for diffuse stomach cancer, a rare but very aggressive type of cancer. Carrying a CDH1 mutation may also increase the risk for lobular breast cancer by up to 50%. Multiple factors complicated this case. The patient’s CDH1 mutation was a variant of uncertain significance (VUS). Evidence is inconclusive about whether this patient’s genetic variant causes diffuse gastric cancer. Also, she had ductal breast cancer, which has not been linked to the CDH1 gene. And she had no family history of gastric cancer, so her risk for gastric cancer would probably be lower than that of someone with a CDH1 genetic mutation who also had a family history of gastric cancer. But it’s unclear how much lower her risk would be.
All of this made it difficult to discuss the risks that she was facing.
For Tischkowitz, this patient’s experience illustrates one reason to question the use of large, multigene panels in breast cancer. Together with colleague Amy Taylor, Ph.D., they wrote a letter to the editor of the Journal of Clinical Oncology in response to a recent study published in the journal. That study has added fire to an already heated debate. The study found that nearly half of breast cancer patients with a pathogenic or likely pathogenic variant are missed by current testing guidelines.
The authors, led by Peter Beitsch, MD, from the Dallas Surgical Group–TME/Breast Care Network in Texas, recommended that all patients who have been diagnosed with breast cancer undergo expanded panel testing. A flurry of letters to the editor in response to this conclusion shows that many in this field disagree and think this is not a good idea. At the heart of the controversy is a much larger, longer-running debate: who should make complex medical decisions, the patient or the medical establishment?
Let’s backtrack to 2013 when the US Supreme Court made a landmark decision in a case concerning the tumor suppressor genes BRCA1 and BRCA2, the most important genes involved in breast cancer.
Up to 10% of all female breast cancers are thought to be due to mutations in BRCA1 or BRCA2.
The Supreme Court’s decision effectively barred patents on naturally occurring genes. That, along with next-generation sequencing, which enables testing for multiple genes in one assay, contributed to a large drop in the price of genetic testing. The net effect has been a considerable expansion in the use of multigene panels for breast cancer.