Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015.

Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the horizon.

SALL4 and NFATC2: two major actors of interstitial 20q13.2 duplication.

Interstitial duplication within the long arm of chromosome 20 is an uncommon chromosome structural abnormality. We report here the clinical and molecular characterization associated with pure 20q13.2 duplication in three unrelated patients. The most frequent clinical features were developmental delay, facial dysmorphism, cardiac malformation and skeletal anomalies. All DNA gains occurred de novo, ranging from 1.1 Mb to 11.5 Mb. Compared with previously reported conventional cytogenetic analyses, oligonucleotides array CGH allowed us to refine breakpoints and determine the genes of interest in the region. Involvement of SALL4 in cardiac malformations and NFATC2 gene disruption in both cardiac and skeletal anomalies are discussed.

Adjuvant chemotherapy in T1a/bN0 HER2-positive or triple-negative breast cancers: application and outcomes.

We assessed practice patterns and the impact of systemic adjuvant therapy on human epidermal growth factor receptor 2 (HER2)-positive or triple-negative, node-negative breast cancers up to 10 mm in size. Records of 161 patients identified among 1415 cases diagnosed in our institutions between 2000 and 2010 were assessed for factors associated with recommendation for chemotherapy and survival outcomes. Adjuvant chemotherapy was recommended in 53% of patients, more commonly in patients with younger age, stage T1b, high grade, HER2+/ER- status and diagnosis after 2006. With a median follow-up of 54 months, the 5-year cumulative incidence of recurrence was 5.3% and overall survival was 93.2%. Age less than 40 and presence of lymphovascular invasion (LVI) were associated with higher risk of recurrence. In a univariate analysis administration of adjuvant chemotherapy was not associated with a significantly better recurrence rate (P = 0.33).

Effects of adjuvant chemotherapy in HER2-positive or triple-negative pT1ab breast cancers: a multi-institutional retrospective study.

Previous studies have reported higher recurrence rates in T1a/b N0 breast cancers characterized by high-risk biology (HER2+ or triple-negative), but the benefits of adjuvant chemotherapy in these patients have not been established. This study was designed to determine whether recurrence risk is reduced with chemotherapy and to define a group of patients most appropriate for treatment based on retrospective data. We pooled cases from two multi-institutional databases spanning the period of 1996-2010. A propensity score model adjusted unbalanced confounders between the groups treated or untreated with adjuvant chemotherapy and, in case of HER2-positive disease, with trastuzumab. Competing risk analysis was utilized to study effects of chemotherapy on cancer recurrences in the matched populations. Among the 318 patients identified, 41 % received adjuvant chemotherapy and 54 % of HER2+ patients received it with trastuzumab. The cumulative risk of recurrence at 5 years was 7.3 %. Age less than 35 years and triple-negative status were the only significant prognostic factors. Overall, administration of chemotherapy was not associated with a significant decrease in the risk of recurrence (HR 0.93, p = 0.91). The rate of recurrence in HER2+ patients who received trastuzumab was lower but not statistically significant (HR 0.50, p = 0.63). Clinical characteristics are of limited prognostic value for stratifying risk of recurrence in very small, node-negative HER2+, or triple-negative cancers. While limited by the small number of events, our analysis does not support the increasingly prevalent practice of administering adjuvant chemotherapy in this population without more accurate prognostic and predictive factors.

Breast cancer: adjuvant modalities.

The mortality rate due to breast cancer has declined over the preceding decades to a great extent, secondary to the development and use of effective adjuvant therapy. Tamoxifen remains the standard of care in premenopausal women, whereas aromatase inhibitors have become standard therapy after menopause for women with hormone-sensitive disease. Tumor gene profiling assays are being increasingly used to identify women with hormone-sensitive disease, who would benefit from adjuvant chemotherapy. For those women with hormone negative cancer, systemic chemotherapy provides substantial reduction in the risk of disease recurrence and death.

Addressing clinical trials: can the multidisciplinary Tumor Board improve participation? A study from an academic women's cancer program.

OBJECTIVE: The Tumor Board (TB) allows for an interdisciplinary approach to cancer treatment designed to encourage evidence-based treatment. However, its role in facilitating clinical trial participation has not been reported. We aimed to determine whether a prospective TB is an effective strategy for trial recruitment and to identify steps within the TB process that facilitate discussion of trial eligibility and optimize accrual. METHODS: We conducted a retrospective cross-sectional analysis of women presented to Gynecologic Oncology TB between March and December 2008. Patient demographics, TB recommendations, and post-TB patient discussions were abstracted. These were compared to data derived from the Department of Oncology Research to determine research team awareness of eligible patients and confirm trial enrollment(s). Data analysis was completed with Chi-square test; risk ratios and confidence intervals were calculated as summary measures. RESULTS: We reviewed 1213 case presentations involving 916 women. Overall, 358 TB recommendations (30%) identified eligible patients, of which enrollment consisted of 87 (24%) trials (6% therapeutic trials and 18% non-therapeutic trials). Compared to other types of TB recommendations, those involving trials were discussed less frequently at post-TB patient visits (79% vs. 44%). Documentation of trial discussion at the post-TB visit was more likely to result in trial participation, versus solely relying on the research staff to communicate enrollment eligibility with the treating team (RR 2.5, p=0.006). CONCLUSIONS: Patients identified by the TB were 2.5-times as likely to enroll in a clinical trial, but trials were mentioned only 44% of the time. Interventions that facilitate trial discussions during post-TB meetings are needed to improve trial participation.