BRCAness Predicts Resistance to Taxane-Containing Regimens in Triple Negative Breast Cancer During Neoadjuvant Chemotherapy

AbstractBackgroundTo provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response.Patients and MethodsWe 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.ResultsWe 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).ConclusionIdentifying 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

BRCA1/2 Mutation Frequency is HIGH in Japanese Triple-Negative Breast Cancer Patients

Germline mutations of BRCA1/2 genes cause hereditary breast and/or ovarian cancer. However, whether guidelines like those of the National Comprehensive Cancer Network (NCCN) can suitably predict the likelihood of BRCA1/2 mutations in the Japanese population is unclear. Methods BRCA1/2 gene mutation frequencies were investigated in relation to parameters such as age, family history (FH), and breast cancer subtype using data collected from 922 Japanese breast cancer patients who underwent surgery between September 2010 and June 2013. BRCA1/2 mutations were present in 15 of 57 (26.3%) tested patients. The frequency of the mutations was not significantly related to age. Among the 180 patients who reported an FH of breast cancer, 11 of the 37 who were tested (29.7%) were positive for BRCA1/2 mutations. Of those with an FH of ovarian cancer (n = 34), seven of 12 patients tested (58.3%) were carriers of BRCA1/2 (P = 0.013). Six of these seven carriers were triple-negative breast cancer (TNBC) patients. In all, there were 97 TNBC patients, and the presence of the BRCA1/2 mutation in this subgroup was significantly greater than in non-TNBC patients, with 12 of 17 TNBC patients (70.5%) testing positive (P = 0.03). There were 59 TNBC patients < 60 years of age, and of the 16 (27.1%) who underwent BRCA1/2 genetic testing, 11 (68.8%) were found to have mutations in BRCA1/2. Among the TNBC patients, 29 also reported an FH of breast or ovarian cancer; of these, nine of the 13 tested (69.2%) were positive for a BRCA1/2 mutation. The data demonstrate that BRCA1/2 mutations are observed more frequently in TNBC patients, especially those < 60 years of age or in combination with an FH of breast and/or ovarian cancer, suggesting that some of the NCCN guidelines can adequately predict BRCA1/2 carriers in the Japanese population

A Case of Androgen Receptor-positive Triple Negative Breast Cancer with Good Response to Anti-androgen Therapy

Anti-androgen therapy has been proposed to be effective in the treatment of androgen receptor (AR)-positive triple negative breast cancer (TNBC). Herein, we report on the case of a 91-year-old female patient with AR-positive TNBC who underwent anti-androgen therapy and had a good response. Because of dementia, the patient lives in an aged care facility. It was here that a staff member noticed a mass with a rash on the patient\u27s breast. Consequently, the patient was sent for further examination. Ultrasonography revealed an irregularly shaped, indistinct hypoechoic mass measuring 19×18×9mm located in the upper outer quadrant of the left breast. Core needle biopsy (CNB) was performed and the mass was diagnosed as apocrine carcinoma. Further immunohistochemical analysis showed that the mass was AR-positive TNBC. Anti-androgen therapy was determined to be the optimal treatment option for this patient. The Institutional Review Board approval the off-label use of an anti-androgen for the treatment of this patient, who was subsequently treated with the anti-androgen flutamide. After 8 months, the size of the tumor had reduced to 15×9×5mm

Exploratory Study of Superparamagnetic Iron Oxide Dose Optimization in Breast Cancer Sentinel Lymph Node Identification Using a Handheld Magnetic Probe and Iron Quantitation

This exploratory study compared doses of ferucarbotran, a superparamagnetic iron oxide nanoparticle, in sentinel lymph nodes (SLNs) and quantified the SLN iron load by dose and localization. Eighteen females aged ≥20 years scheduled for an SLN biopsy with node-negative breast cancer were divided into two equal groups and administered either 1 mL or 0.5 mL ferucarbotran. Iron content was evaluated with a handheld magnetometer and quantification device. The average iron content was 42.8 µg (range, 1.3–95.0; 0.15% of the injected dose) and 21.9 µg (1.1–71.0; 0.16%) in the 1-mL and 0.5-mL groups, respectively (p = 0.131). The iron content of the closest SLN compared to the second SLN was 53.0 vs. 10.0 µg (19% of the injected dose) and 34.8 vs. 4.1 µg (11.1%) for the 1-mL and 0.5-mL groups, respectively (p = 0.001 for both). The magnetic field was high in both groups (average 7.30 µT and 6.00 µT in the 1-mL and 0.5-mL groups, respectively) but was not statistically significant (p = 0.918). The magnetic field and iron content were correlated (overall SLNs, p = 0.02; 1-mL, p = 0.014; 0.5-mL, p = 0.010). A 0.5-mL dose was sufficient for SLN identification. Primary and secondary SLNs could be differentiated based on iron content. Handheld magnetometers could be used to assess the SLN iron content