Treatment decisions in estrogen receptor-positive early breast cancer patients with intermediate oncotype DX recurrence score results

This retrospective study evaluated the impact of intermediate Recurrence Score(®) results on adjuvant treatment decisions in estrogen receptor-positive (ER+) early invasive breast cancer, comparing treatment recommendations pre-testing with actual treatments received post-testing. Of the 111 patients included in the analysis, 78 (70.3%) had hormonal therapy (HT) and 33 (29.7%) had chemohormonal therapy (CHT) recommendations pre-testing. The Recurrence Score was significantly higher in those with a pre-testing CHT recommendation compared with those with a pre-testing HT recommendation (median of 24 vs. 22; P = 0.047; Mann–Whitney–Wilcoxon [MWW] test). Post-testing, treatment of 24 patients (21.6%) was different from their pre-testing recommendation. The difference between CHT recommendation rate pre-testing and the rate of CHT received post-testing was nonsignificant for the entire cohort and for patients’ subgroups (by age, tumor size, and grade) (P >0.17; McNemar’s test). Following classification of the cohort into two Recurrence Score subcategories (low-intermediate, [18-25]; high-intermediate, [26-30]), changes in treatment decisions (pre-testing recommendations vs. actual treatments received post testing) were reported for 16.5% of low-intermediate and 34.4% of high-intermediate patients. Post-testing, the rate of CHT decreased (by 58%) in the low-intermediate subcategory and increased (by 64%) in the high-intermediate subcategory (P <0.01, both subcategories). In logistic regression analyses, the Recurrence Score subcategory was the only significant predictor of changes in treatment decisions (pre-testing recommendations vs. actual treatments received post testing; P <0.01). The only significant difference between the two subsets of patients with such a change (HT to CHT, 11 patients; CHT to HT, 13 patients) was the Recurrence Score (median of 28 vs. 20, respectively; P = 0.0014; MWW test). These findings demonstrate that intermediate Recurrence Score results provide clinically relevant information and impact treatment decisions in ER + early breast cancer

Biopsy of breast cancer metastases: patient characteristics and survival

Abstract Background Discordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival. Methods The medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival. Results Of 409 patients suspected of having MBC, 165 (40%) had a biopsy, and 34% of these had discordant HR or HER2 status when compared to the initial diagnosis. In multivariate analysis, having a biopsy was associated with: recurrence in years 2010–2014, disease-free interval of > =3 years, stage 0-IIA at presentation, suspected locoregional recurrence, being HR+/HER2-, or missing HR/HER2 at diagnosis. A similar multivariate analysis revealed that having a biopsy was associated with improved survival (HR = 0.67, p = 0.002). The association of biopsy and improved survival was noted in specific subgroups: patients with missing HR and HER2 data at initial diagnosis (p = 0.001), those without metastases in liver, lung or brain (p = 0.001), and being younger than 70 years old at recurrence (p < 0.001). Conclusions Specific clinical factors were associated with biopsy at the time of suspected recurrence. Having a biopsy was associated with reduced mortality

Oral bisphosphonates and improved survival of breast cancer

Abstract Purpose: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival. Experimental Design: A nested case–control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis. Results: In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41–0.96, P = 0.03; breast cancer–specific survival: OR = 0.28, 0.09–0.91, P = 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors. Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Clin Cancer Res; 23(7); 1684–9. ©2016 AACR.</jats:p

Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation

Purpose Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) -associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. Patients and Methods This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with >= three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. Results A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease >= 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade >= 3 AEs were reported for 54% of patients; anemia was the most common (17%). Conclusion Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations. Olaparib warrants further investigation in confirmatory studies. (C) 2014 by American Society of Clinical Oncolog

Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy.

The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCA1/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received ≥3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.govNCT01078662) have been reported previously