Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study.

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study.:

Study
Breast Cancer Res Treat. 2012 Mar 21;

Abstract

In spite the close association of the triple-negative breast cancer immunophenotype with hereditary breast cancers and the BRCA1 pathway, there is a lack of population studies that determine the frequency of BRCA1 mutations among triple-negative breast cancer patients. To address this, we have screened a large sample of 403 women diagnosed with triple-negative invasive breast cancer, independently of their age or family history, for germline BRCA1 mutations.

Median age at diagnosis was 50 years (range 20-83). The overall prevalence of triple-negative cases among the initial patient group with invasive breast cancer was 8 %. BRCA1 was screened by direct DNA sequencing in all patients, including all exons where a mutation was previously found in the Greek population (exons 5, 11, 12, 16, 20, 21, 22, 23, 24-77 % of the BRCA1 coding region), including diagnostic PCRs to detect the three Greek founder large genomic rearrangements. Sixty-five deleterious BRCA1 mutations were identified among the 403 triple-negative breast cancer patients (16 %).

Median age of onset for mutation carriers was 39 years. (?? Blogger's Note: screening guidelines...)  Among a total of 106 women with early-onset triple-negative breast cancer (<40 years), 38 (36 %) had a BRCA1 mutation, while 27 % of women with triple-negative breast cancer diagnosed before 50 years (56/208) had a BRCA1 mutation. A mutation was found in 48 % (50/105) of the triple-negative breast cancer patients with family history of breast or ovarian cancer.

It is noteworthy, however, that of the 65 carriers, 15 (23 %) had no reported family history of related cancers. All but one of the carriers had grade III tumors (98 %). These results indicate that women with early-onset triple-negative breast cancer, and ideally all triple-negative breast cancer patients, are candidates for BRCA1 genetic testing even in the absence of a family history of breast or ovarian cancer.

MBCC: PARP Inhibitors for Breast Cancer—Which Subpopulation to Target? - Cancer Network (BRCA, triple-negative breast...)

MBCC: PARP Inhibitors for Breast Cancer—Which Subpopulation to Target? - Cancer Network

"Speaking at the 29th Annual Miami Breast Cancer Conference, Jorge S. Reis-Filho, PhD, MD, professor of medical pathology at the Institute of Cancer Research in London, England, described the rationale of applying poly (ADP-ribose) polymerase inhibitors (PARP) to breast cancer patients.

Tumors that have a loss of function in DNA-repair genes such as BRCA1 and BRCA2, and homologous recombination, as Dr. Joyce O'Shaughnessy described during her session on emerging triple-negative breast cancer therapies, may be particularly sensitive to PARP inhibitors.

Reis-Filho highlighted that sequencing tumors may not be enough to characterize whether tumors have intact DNA-repair pathways—tumors also have epigenetic changes that regulate homologous recombination......"

abstract: A Phase I Study of Veliparib in Combination with Metronomic Cyclophosphamide in Adults with Refractory Solid Tumors and Lymphomas (brca/triple negative bc)

CONCLUSIONS:

The combination of veliparib with metronomic cyclophosphamide is well tolerated and shows promising activity in a subset of patients with BRCA mutations. A phase II trial of the combination compared to single-agent cyclophosphamide is ongoing in BRCA-positive ovarian cancer, triple-negative breast cancer, and low-grade lymphoma.

Clinical Oncology News - Triple-Negative Breast Cancers Associated With Ashkenazi Origin

(free) Registration page: Triple-Negative Breast Cancer: Genetic Risk and Treatment Updates - U of Michigan/Sunnybrook Toronto

April teleconference on triple-negative breast cancer risk and updates

Triple-Negative Breast Cancer: Genetic Risk and Treatment Updates

Join Living Beyond Breast Cancer and The Triple Negative Breast Cancer Foundation for our next free teleconference, Triple-Negative Breast Cancer: Genetic Risk and Treatment Updates, from 12:00 p.m. to 1:15 p.m. Eastern Daylight Time (EDT) on Thursday, April 15.