Prognosis in BRCA1, BRCA2 associated breast cancer (BC): a prospective Breast Cancer Family Registry (BCFR) international population-based cohort study.

Abstract

#2072 Hereditary BC occurs at a younger age and is associated with more adverse tumor-related features than sporadic breast cancer (BC) (defined here as BC in those with no 1st or 2nd degree family history of breast or ovarian cancer). Using pre-specified criteria, we assembled a population-based cohort of newly diagnosed BC at 3 centers: Ontario, Canada (1996-98), San Francisco Bay area, USA (1995-2000), Melbourne/Sydney, Australia (1991-1998). Medical information was obtained from medical records; women were followed prospectively for recurrence, new cancers and death. Pathology data were obtained from central review or pathology reports. BRCA1 and BRCA2 mutation testing was performed on 77% and 70% of cases, respectively (sporadic BC cases were not tested at 2 centers). Hereditary and sporadic BC cases were compared using Cox proportional hazards (stratified by center). 3215 eligible cases were enrolled in the BCFR, with a mean age at diagnosis of 46.9 years. Median follow-up was 7.61 years; 565 women had distant recurrences and 547 died. There were 92 cases with BRCA1 and 72 with BRCA2 mutations; 1549 (48.2%) had sporadic BC; the remainder had familial BC as defined above. BRCA1 mutations were associated with young age, estrogen and progesterone receptor (ER and PgR) negativity and high grade; BRCA2 mutations were associated with node positivity and high grade. Distant disease-free survival (DDFS) and overall survival (OS) did not differ significantly between BRCA1 carriers and sporadic cases in univariate or multivariate analyses. DDFS and OS were worse in BRCA2 carriers than in sporadic cases (HR 1.6, p=0.04 and HR 1.8, p=0.01, respectively) in univariate analyses but not in multivariate analyses (DDFS HR 1.0, p=0.98; OS HR 1.13, p=0.61). The small group of BRCA2 carriers who did not receive adjuvant chemotherapy had a significantly worse OS (multivariate HR 3.63, p = 0.005). Furthermore, BRCA2 carriers who received adjuvant tamoxifen had significantly worse OS than women with sporadic BC (HR=2.0, p=0.03). We conclude that BRCA1 and BRCA2 mutations do not independently impact DDFS or OS. Significantly worse outcomes were seen in BRCA2 carrier subgroups defined by adjuvant treatment; this requires further investigation and may have implications for clinical practice. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2072.

Twenty‐one–gene recurrence score assay in BRCA‐associated versus sporadic breast cancers: Differences based on germline mutation status

“…8 It has previously been suggested that the increased chemosensitivity of BRCA-related breast cancers might explain an observed prognosis similar to that of patients with sporadic cancers despite more aggressive tumor phenotypic features. 8,10,14 Goodwin et al 8 found that outcomes were similar for BRCA1 mutation carriers and noncarriers with stage I breast cancer.…”

“…8 It has previously been suggested that the increased chemosensitivity of BRCA-related breast cancers might explain an observed prognosis similar to that of patients with sporadic cancers despite more aggressive tumor phenotypic features. 8,10,14 Goodwin et al 8 found that outcomes were similar for BRCA1 mutation carriers and noncarriers with stage I breast cancer. In their study, as in the current report, a significantly higher proportion of BRCA mutation carriers received adjuvant systemic therapy in comparison with noncarriers, and the authors concluded that "BRCA mutation carriers who receive standard adjuvant treatment may fare as well as noncarriers of the same age who present with similar cancers."…”

“…[8][9][10] BRCA-associated cancers have distinct pathological features 8,11,12 and gene expression profiles 13 in comparison with sporadic cancers. These biological differences may translate into treatment responses different from those for sporadic cancers.…”

“…Indeed, multiple reports indicate that BRCA-associated tumors demonstrate an enhanced response to chemotherapy, 9,10,[14][15][16] which may, in these patients, abrogate otherwise inferior outcomes. 8,10 Accordingly, different recommendations for adjuvant treatment may be warranted for BRCA mutation carriers and noncarriers with phenotypically similar cancers.…”

Improving mutation notification when new genetic information is identified in research: a trial of two strategies in familial breast cancer

“…For newly diagnosed breast cancer patients, for example, identification of a BRCA1 and/or BRCA2 mutation may improve prognosis by allowing tailoring of their surgical, radiotherapy, and chemotherapeutic treatment to their mutation status. 2 Genetic testing also allows more accurate prognostic information to be provided to both breast 4 and ovarian 5 cancer patients identified as BRCA1 and/ or BRCA2 mutation carriers, as well as those found to be noncarriers. 6 For unaffected female mutation carriers, the striking effect of risk reducing salpingo-oophorectomy on all-cause, breast cancer-specific, and ovarian cancer-specific mortality can no longer be ignored.…”