Jessica Sohl

Sites of Distant Recurrence and Clinical Outcomes in Patients With Metastatic Triple-negative Breast Cancer High Incidence of Central Nervous System Metastases

The purpose of the current study was to characterize the outcomes of patients with metastatic triple‐negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) recurrence.

Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era.

BACKGROUND Trastuzumab is associated with improvements in overall survival (OS) among patients with HER2-positive metastatic breast cancer (MBC); however disease course and patterns of care in individual patients are highly variable. METHODS 113 HER2-positive patients diagnosed with MBC from 1999 to 2005 who received trastuzumab-based therapy were retrospectively identified to allow for a minimum of 5 years of follow-up time. Median OS and median duration of therapy were determined using Kaplan-Meier methodology and group comparisons were based on the log-rank test. Hazard ratios (HR) were obtained using a Cox proportional hazards model. RESULTS Median OS was 3.5 years (95% CI 3.0-4.4) from time of initiation of first therapy in the metastatic setting. On univariate analysis, central nervous system (CNS) disease at first recurrence was associated with a shorter OS compared with liver and/or lung metastases or other sites (CNS: 1.9 years CI 0.1-5.9, liver/lung: 3.2 years CI 2.5-4.2, other: 4.6 years CI 2.7-8.0; p = 0.05), however, this was not predictive of survival outcome in multivariate analysis. CNS metastases developed in 62 (55%) patients by the time of death or last follow-up. Median duration of therapy was similar up to 6 lines of treatment, and ranged from 5.2 months to 7.2 months. CONCLUSIONS The natural history of HER2-positive MBC has evolved with trastuzumab-based therapy with median OS now exceeding 3 years. CNS disease is a major problem with continued risk of CNS progression over time. Patients demonstrate clinical benefit to multiple lines of HER2-directed therapy.

Clinicopathological features among patients with advanced human epidermal growth factor-2-positive breast cancer with prolonged clinical benefit to first-line trastuzumab-based therapy: a retrospective cohort study.

BACKGROUND The magnitude of benefit of trastuzumab for the treatment of advanced HER2-positive breast cancer varies widely. In this retrospective study, we investigated the clinicopathological features associated with prolonged first-line trastuzumab-based treatment duration. PATIENTS AND METHODS A total of 164 patients diagnosed with advanced HER2-positive breast cancer and treated with first-line trastuzumab-based therapy from 1999 to 2009 were identified. Duration of treatment was classified according to tertiles. Different logistic regression models including age, disease-free interval, number of metastatic sites, visceral disease, hormone receptor, and adjuvant trastuzumab were fitted to investigate associations with benefit of prolonged trastuzumab-based therapies. The predictive value of each model was assessed using C-statistics. RESULTS At a median follow-up of 5.8 years (range, 0.7-22.1 years), patients in the short-, intermediate-, and long-term treatment duration groups were given first-line trastuzumab-based therapy for < 7.2 months, 7.2 to 14 months, and > 14 months, respectively. In the multivariate analysis, patients with long-term clinical benefit had a higher likelihood of having hormone receptor-positive tumors (odds ratio [OR]positive vs. negative = 2.39 [95% confidence interval (CI), 1.08-5.31]; P = .032); and a lower likelihood of having received adjuvant trastuzumab (ORadjuvant trastuzumab vs. no adjuvant trastuzumab = 0.30 [95% CI, 0.10-0.96]; P = .043]. C-statistics varied between 0.634 and 0.699. CONCLUSION Long-term benefit of trastuzumab-based therapy is associated with hormone receptor positivity and the absence of previous adjuvant trastuzumab. Nevertheless, clinicopathological features had a low predictive value for prolonged treatment duration. The validation of the current findings and the identification of molecular features associated the magnitude of trastuzumab benefit should be encouraged.

Abstract P4-17-01: Attitudes of medical oncologists towards research breast biopsies in patients with newly diagnosed stage I-III breast cancer not enrolled in a clinical trial

Background: Patients (pts) with breast cancer treated with neo-adjuvant therapy on clinical trials are often asked to consent to pre-treatment and on-treatment research biopsies. There is increasing interest in obtaining tissue samples at similar time points in pts treated with neo-adjuvant therapy outside of clinical trials. However, medical oncologists’ (MOs) attitudes towards approaching pts about research biopsies in this setting are unknown. Methods: Three hundred and nine academic breast MOs identified from websites of the National Cancer Institute (NCI) – designated cancer centers were asked to complete a survey either by paper or online. Eligible MOs (MOs who saw breast cancer pts and who saw pts >4 hours/week.) were asked to predict what proportion of their pts with newly diagnosed, non-metastatic breast cancer would consent to research purposes only biopsies (RPOBs) i.e., biopsies with no clinical benefit to pt. Median values are reported. Two-sided Fisher’s exact test was used to compare categorical variables using a α level of .05. Results: Of 221 (101F,85M, 5 unknown) MOs who completed the survey, 30 MOs were ineligible (response rate=221/309,72%). Median age was 50 (Range 33-80). Median years of oncology experience was 15 (Range 1-45). MOs predicted that 14%, 63% and 21% of their pts would definitely/probably, maybe, probably not/definitely not consent to a RPOB of the breast. Forty-one percent, 34%, 19%, 3% of MOs were very comfortable, somewhat comfortable, somewhat uncomfortable, and very uncomfortable asking pts to consent to RPOBs respectively. The only factor associated with increased comfort discussing an RPOB was MOs’ years in practice. MOs with fewer years ( 15 years) (Adjusted RR=1.2, p =0.02). Gender, number of pts enrolled onto clinical trials, and MOs with pts who had research biopsies in the last 3 months was not associated with increased comfort. MOs who were more comfortable in approaching pts for RPOBs were associated with estimating a larger proportion of their pts as willing to undergo RPOB. For example, nearly one third of MOs who were very comfortable with approaching pts for RPOBs estimated that greater than 50% of their pts would consent to research biopsies. In contrast, nearly all the MOs who were very uncomfortable with approaching pts for RPOBs estimated that less than 25% of their pts would consent to research biopsies. The 3 most common reasons why MOs were reluctant to consent pts for a RPOB include pain/discomfort of a biopsy (59%), risk of a biopsy procedure complication, (44%), and inconvenience to the pt (33%). Conclusions: Academic breast MO’s predicted that fewer than 1 in 5 women with newly diagnosed, non-metastatic breast cancer would definitely or probably agree to a request for an RPOB outside of the context of a therapeutic trial, and approximately one-quarter of MOs expressed discomfort in approaching pts for such procedures. Our results have important implications regarding the feasibility of such research efforts, and identify potential barriers to target for intervention. Citation Format: Davinia SE Seah, Sarah Scott, Hao Guo, Julie Najita, Ruth Lederman, Elizabeth Frank, Jessica Sohl, Zsofia Stadler, Stuart G Silverman, Jeffrey Peppercorn, Eric P Winer, Steve E Come, Nancy U Lin. Attitudes of medical oncologists towards research breast biopsies in patients with newly diagnosed stage I-III breast cancer not enrolled in a clinical trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-17-01.