BRCA mutation incidence comparable between ER-negative, ER-low–positive breast tumors

SAN FRANCISCO — The rate of deleterious BRCA1 or BRCA2 germline mutations detected in patients with ER-low–positive breast cancer is similar to that observed in patients with ER-negative breast cancer, according to study results presented at the Breast Cancer Symposium.

The findings suggest the potential for underutilization of BRCA testing among appropriate patients, researchers wrote.

“In light of the life-saving interventions that may be offered to a patient once he or she has been identified to carry a deleterious BRCA mutation, we strongly recommend patients younger than age 60 with ER-low–positive tumors be referred for genetic counseling and consideration of BRCA testing,” Rachel A. Sanford, MD, a fellow in cancer medicine at The University of Texas MD Anderson Cancer Center, said during a presentation.

National Comprehensive Cancer Network guidelines recommend patients aged younger than 60 years who have triple-negative breast cancer be referred for genetic counseling and be considered for BRCA mutation testing.

However, the manner in which ER-negative tumors — those with staining of 0% on immunohistochemistry — and ER-positive tumors are distinguished in practice varies considerably.

That is due, in part, to guidelines ASCO and the College of American Pathologists (CAP) released in 2010. The guidelines recommend breast tumors with ER staining ≥1% on immunohistochemistry be classified as ER-positive.

This has led to the creation of a new subclass of tumors — ER-low–positive, defined as those with staining between 1% and 9% — that traditionally had been considered ER-negative. Consequently, patients determined to have ER-low–positive disease do not consistently receive referrals for genetic counseling or BRCA testing.

The incidence of BRCA mutations among patients with ER-low–positive disease as it compares to that observed among patients with ER-negative disease is not known.

In the current study, Sanford and colleagues compared BRCA mutation incidence among patients with ER-negative, PR-negative, HER-2–negative disease and those with ER-low–positive, PR-negative, HER-2–negative disease.

They reviewed a prospectively maintained database that included patients who received referrals for genetic risk assessment and BRCA mutation testing at MD Anderson. All patients had HER-2–negative breast cancer with ER staining <10% and PR staining of 0%.

The researchers identified 144 patients who underwent BRCA mutation testing. Of these patients, 122 (85%) had ER-negative tumors and 22 (15%) had ER-low–positive tumors.

Among those who underwent testing, BRCA mutations were found in 33 (27%) of those with ER-negative tumors and seven (31.8%) of those with ER-low–positive tumors. The difference in incidence of BRCA mutations between groups was not statistically significant (P=.64).

“Limitations of our study include our relatively small sample size … [and the fact that] as an academic cancer center, our patient population may not be representative of patients in all practice locations across the United States,” Sanford said.

Further studies with greater numbers of patients and multiple collaborative partners are warranted, she said.

For more information:

Sanford RA. Abstract #2. Presented at: Breast Cancer Symposium; Sept. 4-6, 2014; San Francisco.

Disclosure: The researchers report a consultant/advisory role with Bayer, as well as research funding from Avon, NCI and Susan G. Komen for the Cure.