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Introduction: Caregivers of patients with breast cancer have demonstrated persistent unmet needs, including reduced physical and psychosocial well-being. This may be particularly acute in caregivers of patients with metastatic breast cancer (MBC), whose ongoing treatments and increasing disability with disease progression offer particular challenges. While prevalence of MBC is currently unknown, caregivers of women with MBC represent a sizable group. Objective: To explore the emotional, psychological, and social impact on caregivers of patients with MBC and to identify gaps in communications between patients and their caregivers and oncologists. Methods: The "Make Your Dialogue Count" survey was conducted online, by paper, and by telephone (June-August 2014) among caregivers in the United States (age ≥18 y) who attended ≥50% of doctor visits of women with MBC (age ≥21 y). Survey responses were single- or multiple-response, numeric text, or rated on a 4-point Likert scale. Caregiver data were unweighted and representative only of those responding. Statistically significant differences between groups were determined by standard t-test of column proportions and means at the 95% confidence level. Results: 234 caregivers responded; 73% were men, 44% were the patient's spouse/partner, and 27% were nonwhite. Median age was 44 y. The caregivers' loved ones had a median time from initial breast cancer diagnosis of 44 months prior, and 51% had recurred after early breast cancer. Most caregivers (76%) considered themselves to be extremely or very involved in treatment decisions, but a sizable fraction of caregivers were unaware of the HR (20%) or HER2 (29%) status of the patient's cancer, indicating a lack of basic information needed for informed decision-making. While most (93%) said they felt comfortable speaking with the treatment team about MBC treatment, 41% reported communication barriers. Over half of caregivers (53%) felt that nobody understands what they're going through, and most (86%) reported that their lives had been negatively affected in some way (such as sleep habits, relationships and social life, hobbies and personal time, and financial stability and employment). Most caregivers considered caregiving to be an emotional (77%) and physical (56%) burden and 36% felt unappreciated. At the time of initial MBC diagnosis, 69% of caregivers felt it was important/very important for their loved one's doctor to refer them to support services, but only 25% of caregivers reported receiving such a referral. Subgroup analysis of caregiver's gender revealed some differences in responses relating to communications with oncologists, treatment experience, and emotional impact. Conclusions: While committed to their roles, these caregivers often found their role to be a physical and emotional burden, and many reported feeling isolated and unappreciated for their caregiving. Our findings indicate a strong need for support services specifically tailored to caregivers, including outreach to address emotional, financial, and practical needs stemming from caring for a loved one with MBC. They also indicate a need for improved disease and treatment information exchange between caregivers, patients, and healthcare providers. Citation Format: Mayer M, Sampayo I, Bell Dickson R, Citron ML, Brufsky AM. The experience of caregivers of women with metastatic breast cancer: Insights from the Make Your Dialogue Count survey. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-11-06.

Background T-DM1 is an antibody-drug conjugate comprising the cytotoxic agent DM1 and trastuzumab, bound together with a stable linker. T-DM1 has demonstrated substantial activity in patients (pts) with HER2+ metastatic breast cancer (MBC) in the first-line and trastuzumab-refractory settings and was recently approved by the FDA for pts with HER2+ MBC previously treated with trastuzumab and a taxane. These findings have raised interest in evaluating T-DM1 in adjuvant studies. This phase 2 study assessed the safety and feasibility of approximately 1 year of T-DM1 therapy following anthracycline-based chemotherapy in the adjuvant or neoadjuvant setting for HER2+ EBC. Methods TDM4874g (NCT01196052) is a phase 2, single-arm, open-label study of T-DM1 (3.6 mg/kg q3w IV; up to 17 cycles) following completion of doxorubicin/cyclophosphamide (AC; q2w or q3w for 4 cycles), or 5-fluorouracil/epirubicin (100 mg/m2)/cyclophosphamide (FEC; q3w for 3-4 cycles) chemotherapy in pts with HER2+ EBC. Radiation therapy (RT) was administered after the first 4 cycles of T-DM1 to pts in whom it was indicated. Four cycles of trastuzumab/docetaxel (given after the first 4 cycles of T-DM1) were optional. Co-primary end points were safety and rate of prespecified cardiac events. Prechemotherapy LVEF by MUGA/ECHO ≥55% was required for enrollment. LVEF was evaluated at baseline, at the end of anthracycline treatment, after cycles 2 and 4 of T-DM1, and every 4 cycles of T-DM1 thereafter, as well as before and after the start of a new treatment (eg, optional docetaxel or RT). Results As of April 22, 2013, a total of 148 pts had received T-DM1. No prespecified cardiac events occurred (95% CI: 0.00%-2.45%), and there were no reports of symptomatic left ventricular systolic dysfunction or heart failure. One pt discontinued T-DM1 due to asymptomatic LVEF decline. Overall, 123 (83.1%) pts completed the planned course of T-DM1 treatment; 119 (80.4%) without dose reduction. Twenty pts (13.5%) had adverse events (AEs) leading to T-DM1 discontinuation. Eleven of these were laboratory abnormalities requiring discontinuation (none were grade 4), and 9 were due to symptomatic AEs (2 grade 3 [fatigue, joint crepitation]; no grade 4). Of the 148 pts, 32.4% had grade 3 T-DM1-related AEs and 2.7% had grade 4 T-DM1-related AEs (1 pt each: febrile neutropenia and pancytopenia; atrial fibrillation; decreased platelet count; hypokalemia); no deaths occurred. Of the 116 pts receiving RT, 39 received it concurrently with T-DM1 and 77 received it sequentially. The percentage of pts who completed the planned RT dose without delays was similar with concurrent or sequential treatment (90% and 92% respectively). Fifty pts (stage I, 8%; stage II, 56%; stage III, 36%) received neoadjuvant T-DM1 and underwent surgery. The pCR rate was 56.0% (95% CI, 41.3%-69.6%). Conclusions T-DM1 following anthracycline-based chemotherapy was feasible and was generally well tolerated in pts with HER2+ EBC. No symptomatic left ventricular dysfunction was observed. This favorable safety profile provides support for randomized trials of T-DM1 in pts with HER2+ EBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-15-03.

Background: Intrinsic breast cancer subtypes determined by the PAM50 assay are reported to be prognostic independent of standard clinicopathological variables. The CALGB (Alliance) 9741 adjuvant trial randomized treatment in a 2×2 factorial design to (i) 2-wk (dose dense; DD) vs 3-wk therapy and (ii) sequential vs concurrent doxorubicin, cyclophosphamide, paclitaxel (A>T>C vs AC>T). DD therapy improved disease-free survival and overall survival (OS) (Citron et al. JCO 2003.). A significant interaction between intrinsic breast cancer subtypes and the use of DD therapy was hypothesized. Methods: C9741 was conducted in collaboration with ECOG, NCCTG, and SWOG. Biospecimens were collected from 1652 of 2005 subjects. Multiplexed gene expression profiling (NanoString Technologies, Inc) generated PAM50 subtype calls (luminal A, luminal B, HER2-enriched, basal-like), risk of relapse (ROR) score, and proliferation score for 1321 cases (80%). Excluded samples were due to insufficient tumor (n = 181) or RNA (n = 150). The primary endpoint was relapse-free survival (RFS). The primary analysis to determine if the clinical benefit of DD therapy is dependent on intrinsic subtype was conducted as a test of interaction in a Cox proportional hazards model (3 degrees of freedom, df; alpha=0.05). Similar analyses were performed for ROR score and proliferation score as continuous measures of risk (1 df). PAM50 subtype, ROR score, and proliferation score were evaluated in separate multivariate models adjusting for number of positive nodes, menopausal status, dose density, and sequence of therapy. Results: Improved outcomes for DD therapy in the evaluable subset mirrored results from the complete dataset (HR = 1.20; 95%CI 0.99–1.44) with a median follow-up of 12.3 yrs. Subtype analysis identified 32% luminal A (n = 417), 26% luminal B (n = 341), 20% HER2-enriched (n = 267), and 22% basal-like (n = 296). Intrinsic subtypes were prognostic of RFS (p < 0.0001) irrespective of treatment assignment with HRs relative to the luminal A subgroup of 1.50 (luminal B), 1.70 (HER2-enriched) and 1.66 (basal-like). No subtype specific treatment effect on RFS was identified (p = 0.44). ROR scores (range 0–100, median 60) were also prognostic of RFS (HR = 1.12 for a 10-unit change; 95% CI 1.07–1.18; p < 0.0001), but no association with DD therapy benefit was seen (p = 0.58). Similar results were obtained for the proliferation score, for OS as a secondary endpoint, and from multivariate models with clinical covariates. Conclusion: The prognostic value of PAM50 subtype, ROR score, and proliferation score remains highly significant in patients treated with contemporary adjuvant anthracycline and taxane based chemotherapy. Intrinsic subtype did not predict for improved survival with the 2-wk DD vs 3-wk treatment schedule; we hypothesize that this is because the prognostic differences by subtype outweighed the modest but significant clinical benefit of DD chemotherapy administration for the overall population. Planned clinical validation studies will assess the ability of PAM50 and other gene signatures to stratify patients and individualize systemic therapy regimens based on the expected risk of distant recurrence. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-01.