BRCAness predicts resistance to taxane-containing regimens in triple negative breast cancer during neoadjuvant chemotherapy.

To provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response. We retrospectively investigated BRCAness in 73 patients with breast cancer who had been treated with taxane- and/or anthracycline-based neoadjuvant chemotherapy (NAC). Using multiplex, ligation-dependent probe amplification on formalin-fixed core needle biopsy (CNB) specimens before NAC and surgical specimens after NAC. BRCAness status was assessed with the assessor unaware of the clinical information. We obtained 45 CNB and 60 surgical specimens from the 73 patients. Of the 45 CNB specimens, 17 had BRCAness (38.6% of all subtypes). Of the 23 TNBC CNB specimens, 14 had BRCAness (61% of TNBC cases). The clinical response rates were significantly lower for BRCAness than for non-BRCAness tumors, both for all tumors (58.8% vs. 89.3%, P = .03) and for TNBC (50% vs. 100%, P = .02). All tumors that progressed with taxane therapy had BRCAness. Of the patients with TNBC, those with non-BRCAness cancer had pathologic complete responses significantly more often than did those with BRCAness tumors (77.8% vs. 14.3%, P = .007). After NAC, the clinical response rates were significant lower for BRCAness than for non-BRCAness tumors in all subtypes (P = .002) and in TNBC cases (P = .008). After a median follow-up of 26.4 months, 6 patients-all with BRCAness-had developed recurrence. Patients with BRCAness had shorter progression-free survival than did those with non- BRCAness (P = .049). Identifying BRCAness can help predict the response to taxane, and changing regimens for BRCAness TNBC might improve patient survival. A larger prospective study is needed to further clarify this issue.

Akashi-Tanaka S ，Watanabe C ，Takamaru T ，Kuwayama T ，Ikeda M ，Ohyama H ，Mori M ，Yoshida R ，Hashimoto R ，Terumasa S ，Enokido K ，Hirota Y ，Okuyama H ，Nakamura S ... -  《-》

BRCAness is beneficial for indicating triple negative breast cancer patients resistant to taxane.

Triple negative breast cancer (TNBC) is a heterogeneous disease and is associated with the cancer stem cell (CSC), basal-like, and BRCA1 function deficient (BRCAness) subtypes. We examined these 3 subtypes in TNBC and compared their chemosensitivity against anthracycline or taxane with a special attention to BRCAness. Sixty-six TNBC cases were obtained from a randomized phase II trial comparing TCx6 (TC6) with FEC-Docetaxel (FEC-D) as neoadjuvant chemotherapy. The core needle specimens before chemotherapy were used for subtyping. The basal-like and CSC subtypes were identified by immunohistochemistry; CK5/6 and EGFR staining for the basal-like subtype and ALDH1 staining for the CSC subtype. The BRCAness subtype was examined by Multiplex Ligation-dependent Probe Amplification (MLPA). Correlations between subgroups and pCR rates according to each regimen and subtype were examined. The basal-like and BRCAness subtypes were significantly associated (p = 0.010) with the other subtypes, but not the CSC subtype. The pCR rates were higher with FEC-D than with TC6 in the basal-like (54.5% vs 14.3%, p = 0.081) and BRCAness (56.2% vs 16.7%, p = 0.030) subtypes. Both were not effective in the CSC subtype (18.2% vs 11.8%, p = 1.00). BRCAness identified by MLPA was practically useful for treatment selection for avoiding taxane. ALDH1 may be considered as a marker for the CSC subtype requiring novel agents.

Ishikawa T ，Narui K ，Tanabe M ，Kida K ，Oba MS ，Yamada A ，Ichikawa Y ，Endo I ... -  《-》

BRCAness and Prognosis in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

Tanino H ，Kosaka Y ，Nishimiya H ，Tanaka Y ，Minatani N ，Kikuchi M ，Shida A ，Waraya M ，Katoh H ，Enomoto T ，Sengoku N ，Kajita S ，Hoffman RM ，Watanabe M ... -  《PLoS One》

Evaluation with 3.0-T MR imaging: predicting the pathological response of triple-negative breast cancer treated with anthracycline and taxane neoadjuvant chemotherapy.

Triple-negative breast cancer (TNBC) which expresses neither hormonal receptors nor HER-2 is associated with poor prognosis and shorter survival. Several studies have suggested that TNBC patients attaining pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) show a longer survival than those without pCR. To assess the accuracy of 3.0-T breast magnetic resonance imaging (MRI) in predicting pCR and to evaluate the clinicoradiologic factors affecting the diagnostic accuracy of 3.0-T breast MRI in TNBC patients treated with anthracycline and taxane (ACD). This retrospective study was approved by the institutional review board; patient consent was not required. Between 2009 and 2012, 35 TNBC patients with 3.0-T breast MRI prior to (n = 26) or after (n = 35) NAC were included. MRI findings were reviewed according to pCR to chemotherapy. The diagnostic accuracy of 3.0-T breast MRI for predicting pCR and the clinicoradiological factors affecting MRI accuracy and response to NAC were analyzed. 3.0-T MRI following NAC with ACD accurately predicted pCR in 91.4% of TNBC patients. The residual tumor size between pathology and 3.0-T MRI in non-pCR cases showed a higher correlation in the Ki-67-positive TNBC group (r = 0.947) than in the Ki-67 negative group (r = 0.375) with statistical trends (P = 0.069). Pre-treatment MRI in the non-pCR group compared to the pCR group showed a larger tumor size (P = 0.030) and non-mass presentation (P = 0.015). 3.0-T MRI in TNBC patients following NAC with ACD showed a high accuracy for predicting pCR to NAC. Ki-67 can affect the diagnostic accuracy of 3.0-T MRI for pCR to NAC with ACD in TNBC patients.

Kim MJ ，Kim EK ，Park S ，Moon HJ ，Kim SI ，Park BW ... -  《-》

BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer.

Mori H ，Kubo M ，Nishimura R ，Osako T ，Arima N ，Okumura Y ，Okido M ，Yamada M ，Kai M ，Kishimoto J ，Miyazaki T ，Oda Y ，Otsuka T ，Nakamura M ... -  《PLoS One》