Gene Testing May Identify Effective Cancer Treatments

Triple negative breast cancer patients may have genetic mutations that can show doctors what treatments might work best

/ Author:  / Reviewed by: Joseph V. Madia, MD Beth Bolt, RPh

(RxWiki News) The term "genetic mutation" may sound a little scary, but some gene mutations may reveal lifesaving alternative cancer treatments — and show who is at risk for cancer in the future.

A new Mayo Clinic-led study recommended that triple-negative breast cancer patients undergo genetic testing. This testing may reveal gene mutations that determine the risk of cancer returning after treatment and the risk of it affecting a family member.

This genetic testing may also find mutations that make patients more likely to respond to some new treatments, the authors of this study said.

“Clinicians need to think hard about screening all their triple-negative patients for mutations because there is a lot of value in learning that information, both in terms of the risk of recurrence to the individual and the risk to family members,” said Fergus J. Couch, PhD, laboratory medicine and pathology expert at the Mayo Clinic in Rochester, MN, in a press release. “In addition, there may be very specific therapeutic benefits of knowing if you have a mutation in a particular gene.”

About 15 percent of all breast cancers are triple-negative, according to the Triple Negative Breast Cancer Foundation. Triple-negative tumors lack three receptors: estrogen, progesterone and HER2. These are proteins found inside or on the surface of breast cells. Some effective cancer therapies target these receptors and prevent cancer growth. Commonly used breast cancer treatments — such as hormone therapy or therapies that focus on HER2 receptors — don’t work for triple-negative breast cancer.

Dr. Couch and colleagues analyzed DNA (genetic material) from 1,824 triple-negative breast cancer patients seen at 12 cancer clinics in the US and Europe. They found harmful mutations in almost 15 percent of these patients.

Of these, 11 percent had mutations in the BRCA1 and BRCA2 genes. These genes suppress cancer tumors, and mutations can stop them from functioning. These mutations can be inherited and may increase family members’ risk of breast cancer.

The other triple-negative breast cancer patients had harmful mutations in 15 other genes that could raise cancer risk. Some of these other genes included ones that repair DNA.

Many types of breast cancer respond to hormonal therapy — such as tamoxifen (brand names Soltamox or Nolvadex) or aromatase inhibitors (Arimidex or Femara) — or therapies that target HER2 receptors, such as trastuzumab (Herceptin). Dr. Couch and colleagues said triple-negative breast cancer patients might have gene mutations that make them more likely to respond to alternative treatments.

Cisplatin (Platinol) may be one such alternative treatment. Platinum-based agents, such as cisplatin, have emerged as possible treatments for triple-negative breast cancer, according to the National Cancer Institute.

PARP inhibitors — cancer-fighting agents that inhibit the poly ADP-ribose polymerase (PARP) family of enzymes — have also shown potential in fighting cancer. Several forms of cancer depend on PARP enzymes to survive. Some studies have found that inhibiting these enzymes may make chemotherapy more effective and could stop cancer growth, according to Chemotherapy refers to cancer treatment with multiple powerful medications.

Dr. Couch and team noted that patients with gene mutations that may cause cancer were diagnosed at an earlier age and had higher-grade tumors than those without mutations. Higher-grade cancers tend to grow and spread faster than lower-grade tumors, according to the National Cancer Institute.

Obtaining information about patients' gene mutations through testing could help doctors determine the best course of cancer treatment, Dr. Couch and colleagues noted.

These researchers said that their study offers additional support for the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing of triple-negative breast cancer patients. These guidelines call for genetic screening when a patient has a family history of cancer or a diagnosis under age 60.

“Other studies have suggested that [triple-negative breast cancer] might be associated with some defect in DNA repair, and our study verifies that,” Dr. Couch said. “Our findings generate a whole new set of hypotheses about how triple-negative breast cancer might be arising, which could give us better ideas for prevention or new therapies for this disease.”

This study was published online Dec. 1 in the Journal of Clinical Oncology.

The research was funded by the National Institutes of Health, the Breast Cancer Research Foundation and the David F. and Margaret T. Grohne Family Foundation. Conflict of interest information was not available at the time of publication.

Review Date: 
December 3, 2014
Last Updated:
December 7, 2014