A new study, published in the journal Cancer Discovery, revealed that genetic variations could be a key indicator of which women are likely and which are unlikely to benefit from tamoxifen or raloxifene for breast cancer prevention.

James Ingle, M.D., an oncologist at the Mayo Clinic, who was part of the study, said that the findings are important “because we identified genetic factors that could eventually be used to select women who should be offered the drugs for prevention.”

The genome-wide association study included a total of 592 patients with breast cancer while receiving preventative therapy, as well as 1,171 matched controls. The researchers selected women who were part of the NSABP breast cancer prevention trials.

By analyzing the participants’ DNA the investigators were able to identify two variations in their genetic mutations, called single nucleotide polymorphisms (SNPs), in ZNF423 and CTSO.

Tamoxifen Raloxifen nci-vol-2738-300
Tamoxifen and Raloxifen can significantly reduce the risk of developing breast cancer.
Women who responded best to the preventative therapy with drugs tended to have more favorable variations in these two genes, whereas women who had unfavorable variations didn’t respond so well, these women were at a significantly higher risk of developing breast cancer as well (by a factor of five).

Current guidelines set by the U.S. Preventitive Services Task Force state that selective estrogen receptor modulators (SERM) therapy with tamoxifen and raloxifene can help reduce the risk of breast cancer. However, it is difficult to know who will benefit the most from this form of therapy.

Dr. Ingle, said:

“This is a major step toward truly individualized prevention of breast cancer. Our findings provide clear direction as to which women are likely and which are unlikely to benefit from tamoxifen or raloxifene.”

He added that the discovery could drive a reinvigoration of research efforts in breast cancer prevention.

In addition, the investigators analyzed which breast cancer cells had the most common variation of the SNPs.

They found that estrogen increased the expression of cells with the most common variation of the SNPs (ZNF423 and CTSO and the expression of BRCA). However, cell expression wasn’t increased with the least common forms of the SNPs.

When the researchers added tamoxifen or raloxifene to estrogen in cells with the less common ZNF423 SNP, ZNF423 and BRCA1 expression significantly increased.

The finding has huge potential in explaining why women undergoing SERM therapy who carry this SNP are at a decreased risk of developing breast cancer.

Research led by the University of Manchester, identified a biomarker in women diagnosed with breast cancer who do not respond to treatment with the hormone drug tamoxifen. The finding helps doctors know which breast cancer patients are likely to respond well to therapy with tamoxifen.

Dr. Richard Gray of the University of Oxford said that the evidence that tamoxifen can prevent breast cancer is overwhelming.

Breast cancer survivors who take tamoxifen for ten years reduce their risk of dying from estrogen receptor positive breast cancer by 50 percent, according to researchers from Cancer Research UK reported at the ASCO Annual Meeting in Chicago, Illinois, USA.

Written by Joseph Nordqvist