Increased centrosome number in BRCA-related breast cancer specimens determined by immunofluorescence analysis.

BRCA-related breast carcinoma can be prevented through prophylactic surgery and an intensive follow-up regimen. However, BRCA genetic tests cannot be routinely performed, and some BRCA mutations could not be defined as deleterious mutations or normal variants. Therefore, an easy functional assay of BRCA will be useful to evaluate BRCA status. As it has been reported that BRCA functions in the regulation of centrosome number, we focused on centrosome number in cancer tissues. Here, 70 breast cancer specimens with known BRCA status were analyzed using immunofluorescence of γ-tubulin (a marker of centrosome) foci. The number of foci per cell was higher in cases with BRCA mutation compared to wild-type cases, that is, 1.9 (95% confidence interval [CI], 1.5-2.3) vs 0.5 (95% CI, 0.2-0.8) (P < .001). Specifically, foci numbers per cell in BRCA1 and BRCA2 mutation cases were 1.2 (95% CI, 0.6-1.8) and 2.2 (95% CI, 1.7-2.6), respectively, both higher than those in wild-type cases (P = .042 and P < .0001, respectively). The predictive value of γ-tubulin foci as determined by area under the curve (AUC = 0.86) for BRCA status was superior to BRCAPRO (AUC = 0.69), Myriad Table (AUC = 0.61), and KOHBRA BRCA risk calculator (AUC = 0.65) pretest values. The use of γ-tubulin foci to predict BRCA status had sensitivity = 83% (19/23), specificity = 89% (42/47), and positive predictive value = 77% (20/26). Thus, γ-tubulin immunofluorescence, a functional assessment of BRCA, can be used as a new prospective test of BRCA status.

Prognostic significance of the progesterone receptor status in Ki67-high and -low Luminal B-like HER2-negative breast cancers.

BACKGROUND: Breast cancer is a heterogeneous disease, and immunohistochemical evaluation is a surrogate marker that is widely used in clinical settings to identify the intrinsic subtypes. The definition of the Luminal B-like breast cancer was changed at the 2013 St. Gallen meeting; therefore, we investigated the clinicopathological features of the new Luminal B-like breast cancer categorized in the latest definition. We also compared the conventional PgR-high Luminal B-like breast cancer with the conventional PgR-low or -negative Luminal B-like breast cancer. PATIENTS: We investigated 118 Luminal HER2-negative breast cancer patients who were operated in 2005-2008 at a single institution. Data on each patient's medical history were retrieved. RESULTS: A subset of patients (14.4 %) was categorized as the new Luminal B-like due to low or negative PgR: 58.8 % were histological grade I, 65 % were T1 in tumor size, and half had node involvement. Chemotherapy was performed in half of the cases. Breast cancer-related events were more frequent for the new Luminal B-like breast cancer than for the Luminal A-like breast cancer and were less frequent than for the conventional Luminal B-like breast cancer. Based on multivariate analysis, low or negative expression of PgR and the absence of hormonal therapy were worse prognostic factors. When categorized into two groups by the PgR status, 48.1 % of the conventional Luminal B-like breast cancer was PgR-high; tumor size was smaller, and nodal involvement was less in this group. The rate of adjuvant chemotherapy of the conventional PgR-high Luminal B-like breast cancer was less than that of the conventional PgR-low or -negative Luminal B-like breast cancer. Breast cancer-related events were significantly lower in the conventional PgR-high Luminal B-like breast cancer. CONCLUSIONS: Our results show the possibility that PgR status has some influence on the prognosis for Luminal HER2-negative breast cancers. Therefore, attention should be paid to the PgR status as well as Ki-67.