The Association between Angiotensin Receptor Blocker Usage and Breast Cancer Characteristics.

PURPOSE: To evaluate the association between angiotensin receptor blocker (ARB) usage and breast cancer characteristics and outcomes. METHODS: All patients who were treated in our institute for estrogen receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer between April 2005 and March 2012 and whose tumors were sent for Oncotype-DX analysis were included. Medical records were retrospectively reviewed. Data regarding ARB usage were retrieved. Usage of several prespecified medications for hypertension was also evaluated. Each medication group was compared with the rest of the cohort. RESULTS: A total of 671 patients were included. Forty-six (7%) patients were treated with ARB. ARB usage was associated with macroscopic nodal involvement (p < 0.001) and a more advanced stage at diagnosis (p < 0.001). These findings remained significant in the multivariate analysis. Patients treated with ARB also had a higher incidence of invasive lobular carcinoma subtype (p = 0.009), a worse 5-year breast cancer-specific survival (94.7 vs. 98.8%, p = 0.024) and a worse 5-year overall survival (94.6 vs. 98.8%, p = 0.015), but these differences were not demonstrated in the multivariate analysis. CONCLUSIONS: Patients treated with ARB presented with a more advanced breast cancer disease and some distinct histological features. Further research is required to elucidate the effect of ARB treatment on breast cancer.

Tailoring neoadjuvant chemotherapy for locally advanced breast cancer: a historical prospective study.

BACKGROUND: Despite the growing number of clinical trials assessing preoperative systemic chemotherapy (PST) for locally advanced breast cancer, the optimal regimen has still to be defined. PURPOSE: This was to evaluate the toxicity, operability rate, pathological response rate and disease-free and overall survival associated with a PST regimen consisting of the sequential administration of single agents according to the individual tumor response. METHODS: Medical files were reviewed of 102 consecutive patients with breast cancer treated in 2000-2007 with a neoadjuvant sequential regimen of doxorubicin followed by taxane. The number of cycles and the addition of taxane were based on tumor response. RESULTS: Seventy percent of the patients had inoperable disease at diagnosis and 29% were given preoperative therapy for breast conservation. All patients underwent surgery, 65% achieved breast conservation. An overall pathological complete response (breast and nodes) was achieved in 14% of the patients, and a complete nodal pathologic response in 34%. At a median follow-up of 54 months, the overall survival rate was 82% and the disease-free survival rate was 70%. There was no treatment-related mortality. Febrile neutropenia occurred in 19% of the patients. CONCLUSIONS: A neoadjuvant regimen of doxorubicin with or without a sequential taxane, in which the number of cycles and the sequential administration of taxane are determined according to clinical response, appears to be safe and effective for patients with locally advanced breast cancer and yields a high rate of breast conservation. Tailored PST can spare patients receiving unnecessary chemotherapy.

Hormone replacement therapy is more prevalent among Jewish BRCA1/2 mutation carriers.

The aim of this study was to compare reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) in consecutive Jewish Ashkenazi breast cancer patients, with and without BRCA1/BRCA2 mutations. Jewish Israeli women with breast cancer (n=385) were genotyped for the three predominant Jewish mutations in BRCA1 and BRCA2, and data on reproductive factors, OC and HRT use, were analyzed using logistic regression analyses. Overall, 28/385 (7.3%) of participants were mutation carriers, the majority of whom were Ashkenazi (n=22; 78.6%) and were diagnosed with breast cancer at or under age 49 years (n=18; 64.3%). Mutation carriers were more likely than non-carriers to ever use OC (39.3% vs. 20.2%; P=0.053), HRT (35.7% vs. 13.7%; P=0.007), and have first menarche at or below 12 years of age (71.4% vs. 40.6%; P=0.03). Multivariate analysis showed that Ashkenazi women diagnosed with breast cancer under 40 years of age, with a family history of breast/ovarian cancer, who ever used HRT were more likely to be mutation carriers. This study has shown that HRT use is more prevalent among Jewish Ashkenazi mutation carriers, but its role in modifying breast cancer risk in mutation carriers remains unknown.

BRCA1/2 mutations perturb telomere biology: characterization of structural and functional abnormalities in vitro and in vivo.

BRCA1 mutation is associated with carcinogenesis, especially of breast tissue. Telomere maintenance is crucial for malignant transformation. Being a part of the DNA repair machinery, BRCA1 may be implicated in telomere biology. We explored the role of BRCA1 in telomere maintenance in lymphocytes of BRCA1/2 mutation carriers and in in vitro system by knocking down its expression in non-malignant breast epithelial cells.The results in both systems were similar. BRCA1/2 mutation caused perturbation of telomere homeostasis, shortening of the single stranded telomere overhang and increased the intercellular telomere length variability as well as the number of telomere free chromosomal ends and telomeric circles. These changes resulted in an increased DNA damage status. Telomerase activity, inducibility and expression remained unchanged. BRCA1 mutation resulted also in changes in the binding of shelterin proteins to telomeres. DNMT-1 levels were markedly reduced both in the carriers and in in vitro system. The methylation pattern of the sub-telomeric regions in carriers suggested hypomethylation in chromosome 10. The expression of a distinct set of genes was also changed, some of which may relate to pre-disposition to malignancy.These results show that BRCA gene products have a role in telomere length homeostasis. It is plausible that these perturbations contribute to malignant transformation in BRCA mutants.

Association between standard clinical and pathologic characteristics and the 21-gene recurrence score in breast cancer patients: a population-based study.

BACKGROUND: The 21-gene recurrence score (RS) assay has been reported to accurately predict the risk of disease recurrence and chemotherapy benefit in women with estrogen receptor (ER)-positive, lymph node (LN)-negative breast cancer who are treated with tamoxifen. To the authors' knowledge, the association between the RS and clinicopathologic characteristics has been studied in randomized and case-control trials, but not in the general population. METHODS: The authors analyzed the correlation between clinicopathologic breast cancer characteristics and RS among 300 consecutive Israeli patients who were referred to undergo the test between October 2004 and October 2006. RESULTS: Low, intermediate, and high RS were noted in 109 patients (36%), 134 patients (45%), and 57 patients (19%), respectively. The median age of the patients was 54 years and the median tumor size was 1.6 cm. High tumor grade, low progesterone receptor expression, infiltrating ductal histology, and high HER-2 expression were found to be associated with a high RS, whereas patient age, tumor size, ER expression, and lymph node micrometastasis were found to correlate poorly with the RS. The ability of any of these variables, either alone or in combination, to predict the RS was limited. Similarly, neither commonly used guidelines nor the Adjuvant! Online software were found to be able to predict the RS. CONCLUSIONS: The results of the current study suggest that neither standard clinicopathologic features nor commonly used assessment tools can reliably predict the RS among referred breast cancer patients compared with a clinical trial population. These data also may indicate the need for additional studies regarding the role of the RS among certain subsets of breast cancer patients, including those with noninfiltrating ductal carcinoma histology and the presence of lymph node micrometastasis.

Breast conservation after neoadjuvant chemotherapy.

BACKGROUND: Tumor downstaging by preoperative neoadjuvant chemotherapy in patients with locally advanced breast tumors allows breast conservation in women who were previously candidates for mastectomy. Nevertheless, lumpectomy success in such cases cannot be fully achieved. The aim of this study was to create a quantitative tool for preoperative evaluation of the success of breast conservation in such patients. METHODS: The study population included 100 consecutive patients with stage II and III breast cancer who were designated for lumpectomy and 19 patients who were designated for mastectomy. All patients received neoadjuvant therapy. Breast-conserving surgery was offered in accordance with clinical and esthetic criteria. Demographic details and clinical, imaging, and pathologic information were collected from medical files. A decision protocol for classifying patients to lumpectomy or mastectomy was built by using the Classification and Regression Trees procedure based on preoperative characteristics. RESULTS: Three factors were found to be the main predictors for successful breast conservation: absence of diffuse microcalcifications as seen in the pretreatment mammogram, a postchemotherapy tumor size of < 25 mm, and the existence of a circumscribed lesion on mammography. CONCLUSIONS: The use of these criteria as a basis for decision on the type of surgery may decrease the performance of unnecessary procedures.