Hwang, E. Shelley

AbstractBackground and objectivesPrevious studies have identified racial‐ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial‐ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT.MethodsWe performed an 11‐institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence‐free survival according to race‐ethnicity.ResultsWomen of non‐White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non‐Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence‐free survival in our cohort.ConclusionsDifferences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race‐ethnicity. These conclusions are supported by our finding that there were no differences in recurrence‐free survival.

Breast cancer is a heterogenous disease with variability in tumor cells and in the surrounding tumor microenvironment (TME). Understanding the molecular diversity in breast cancer is critical for improving prediction of therapeutic response and prognostication. High-plex spatial profiling of tumors enables characterization of heterogeneity in the breast TME, which can holistically illuminate the biology of tumor growth, dissemination and, ultimately, response to therapy. The GeoMx Digital Spatial Profiler (DSP) enables researchers to spatially resolve and quantify proteins and RNA transcripts from tissue sections. The platform is compatible with both formalin-fixed paraffin-embedded and frozen tissues. RNA profiling was developed at the whole transcriptome level for human and mouse samples and protein profiling of 100-plex for human samples. Tissue can be optically segmented for analysis of regions of interest or cell populations to study biology-directed tissue characterization. The GeoMx Breast Cancer Consortium (GBCC) is composed of breast cancer researchers who are developing innovative approaches for spatial profiling to accelerate biomarker discovery. Here, the GBCC presents best practices for GeoMx profiling to promote the collection of high-quality data, optimization of data analysis and integration of datasets to advance collaboration and meta-analyses. Although the capabilities of the platform are presented in the context of breast cancer research, they can be generalized to a variety of other tumor types that are characterized by high heterogeneity.

PURPOSE: Contemporary breast cancer surgery often requires hospital stays of 1 day or less, presenting challenges to delivery of high-quality care. Without sufficient time for proper education and guidance, patients may delay seeking care, experience anxiety, or seek unnecessary care, leading to poorer outcomes and increased costs. To address this, we evaluated the feasibility of a planning-, outcomes-, and analytics-based mobile health application called Manage My Surgery (MMS) for patients undergoing elective breast cancer surgery. METHODS: Patients undergoing breast cancer surgery at an academic health center were invited to use MMS. Those who used the application received pre- and postoperative surveys, which recorded and reported patient satisfaction and outcomes related to the application. RESULTS: Thirty-three female patients undergoing elective breast cancer surgery used MMS. The median age was 58 years. Nineteen patients underwent lumpectomy, and 14 underwent mastectomy. Users logged on to the application an average of 3.5 times. The median number of questions viewed was 12 (range 2-35). Of 17 patients who completed the feedback survey, 100% said that MMS was helpful during preparation for surgery, 82.3% said that MMS was helpful postoperatively, and 94.1% would recommend MMS to others. Preliminary data on patient-reported outcomes collected by MMS suggest improvements in anxiety and depression over time. CONCLUSION: Implementation of a digital care navigation tool in breast cancer surgery patients is feasible. Patients found the tool helpful in both the pre- and postoperative period. Additional ongoing work will focus on patients' self-management skills, long-term outcomes, and health system costs.

BackgroundThe goal of this study was to assess the impact of trastuzumab on locoregional failure.METHODSThe analysis included 2763 patients with HER2‐positive (HER2+) breast cancer who were randomly assigned to adjuvant doxorubicin (A), cyclophosphamide (C), paclitaxel (T) and trastuzumab (H) (arm A, AC→T [n = 922]; arm B, AC→T→H [n = 988]; arm C, AC→T+H→H [n = 853]). Radiotherapy was given after AC→T concurrently with H. Radiotherapy was given after lumpectomy (L) or after mastectomy (M) with ≥4 positive lymph nodes but was optional for 1 to 3 positive lymph nodes. Locoregional failures at 10 years (LFR10) as first events were compared using competing risk analysis.ResultsThe median follow‐up was 13.0 years. The first site of failure was local‐only in 96 cases, locoregional in 16 cases, regional in 32 cases, and not specified in 2 cases; LFR10 was 4.8% (95% CI 4.1%‐5.7%). LFR10 was 5.5% (95% CI 4.3%‐7.2%), 4.9% (95% CI 3.7%‐6.4%), and 2.8% (95% CI 1.9%‐4.1%) in arms A, B, and C (B vs A: hazard ratio [HR] 0.91, P = .62; C vs A: HR 0.72, P = .12). For estrogen receptor–positive patients, LFR10 was 3.7% (95% CI 2.8%‐4.8%) and for estrogen receptor–negative patients, it was 6.1% (95% CI 5.0%‐7.4%; HR 0.61, P = .004). Local treatment included L+RT (n = 1044 [38%]), M+RT (n = 1025 [37%]), and M (n = 694 [25%]). LFR10 was 6.% (95% CI 5.0%‐7.8%), 3.0% (95% CI 2.1%‐4.3%), and 5.5% (95% CI 4.0%‐7.4%) for L+RT, M+RT, and M, respectively (M+RT vs L+RT: HR 0.43, P < .001; M vs L+RT: HR 0.88, P = .57). For 1 to 3 positive lymph nodes, LFR10 was 6.5% (95% CI 4.8%‐8.9%), 4.1% (95% CI 2.4%‐7.0%), and 4.3% (95% CI 2.9%‐6.5%) in L+RT, M+RT, and M, respectively (M vs L+RT: HR 0.68, P = .14; M vs M+RT: HR 1.2, P = .6).ConclusionLow 10‐year LFRs were seen regardless of trastuzumab use. Differences in local therapy in patients with 1 to 3 positive lymph nodes did not appear to improve local control. Local therapy studies for HER2+ and other tumor characteristics are important as the role of local therapies continues to evolve.

Abstract Background: Side effects of and adherence to aromatase inhibitors in women with ductal carcinoma in situ are not well described. Methods: Postmenopausal women in a prospective phase II study of neoadjuvant letrozole for estrogen receptor positive DCIS completed questionnaires on side effects [Menopause Specific Quality of Life Questionnaire (MENQOL), Brief Pain Inventory-short form (BPI-SF), Arthritis Impact Measurement Scales (AIMS2)], well-being (FACT-G), and adherence [Medication-Taking questionnaire] at baseline, 1, 3 and 6 months (mo), and study completion. We used descriptive statistics and paired t-tests to compare 1, 3 and 6 mo results to baseline. Hierarchical linear mixed modeling, controlling for baseline symptom or well-being level, was used to examine effect of symptoms and well-being on intentional and nonintentional nonadherence, based on the Medication-Taking Questionnaire. Results: Included were 84 women, mean age 63 (39-83) years. In univariate analyses, compared to baseline, menopausal symptoms increased [physical (p=0.001 at 3, p&lt;0.001 at 6 mo); vasomotor (p&lt;0.001 at 1, 3, 6 mo), psychosocial (p=0.006 at 6 mo) and sexual (p=0.01 at 6 mo)]. Joint pain and stiffness increased [BPI-SF pain subscale (p=0.048 at 3, p=0.01 at 6 mo); AIMS2 joint pain subscale (p=0.03 at 1, p&lt;0.001 at 3 and 6 mo); AIMS2 stiffness subscale (p=0.004 at 3, p=0.01 at 6 mo)]. Intentional and nonintentional adherence did not significantly change over time (p&gt;0.05). Lower emotional (p=0.049) and functional (p=0.002) well-being by FACT-G and higher joint pain (p=0.03) by AIMS2 were associated with higher nonintentional nonadherence; higher physical side effects of menopause (p=0.001) by MENQOL were associated with lower intentional nonadherence. Conclusions: Among women taking letrozole for DCIS, menopausal symptoms and joint pain/stiffness increased over time with most differences noted at 3 and 6 mo. Lower well-being and higher symptom levels were associated with higher nonintentional nonadherence. NCT01439711.U10CA180821, U10CA180882, UG1CA189823, Breast Cancer Research Foundation, https://acknowledgments.alliancefound.org. Citation Format: Gretchen Kimmick, Amylou C Dueck, Rebecca Shelby, Michelle Naughton, Abigail Caudle, Briant Fruth, E. Shelley Hwang. Musculoskeletal side effects over time and association with adherence in women taking neoadjuvant letrozole for estrogen receptor positive DCIS: CALGB 40903 (Alliance) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-17.

PURPOSE Primary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in measurable radiographic and biologic changes in estrogen receptor (ER)–positive DCIS. PATIENTS AND METHODS A phase II single-arm multicenter cooperative-group trial was conducted in postmenopausal patients diagnosed with ER-positive DCIS without invasion. Patients were treated with letrozole 2.5 mg per day for 6 months before surgery. Breast magnetic resonance imaging (MRI) was obtained at baseline, 3 months, and 6 months. The primary end point was change in 6-month MRI enhancement volume compared with baseline. RESULTS Overall, 79 patients were enrolled and 70 completed 6 months of letrozole. Of these, 67 patients had MRI data available for each timepoint. Baseline MRI volumes ranged from 0.004 to 26.3 cm 3 . Median reductions from baseline MRI volume (1.4 cm 3 ) were 0.6 cm 3 (61.0%) at 3 months ( P < .001) and 0.8 cm 3 (71.7%) at 6 months ( P < .001). Consistent reductions were seen in median baseline ER H-score (228; median reduction, 15.0; P = .005), progesterone receptor H-score (15; median reduction, 85.0; P < .001), and Ki67 score (12%; median reduction, 6.3%; P = .007). Of the 59 patients who underwent surgery per study protocol, persistent DCIS remained in 50 patients (85%), invasive cancer was detected in six patients (10%), and no residual DCIS or invasive cancer was seen in nine patients (15%). CONCLUSIONS In a cohort of postmenopausal women with ER-positive DCIS, preoperative letrozole resulted in significant imaging and biomarker changes. These findings support future trials of extended endocrine therapy as primary nonoperative treatment of some DCIS.

Objective: To determine whether the association between overall survival (OS) and response to neoadjuvant chemotherapy (NACT) in breast cancer patients varies with tumor subtype and anatomic extent of pathologic complete response (pCR). Background: pCR after NACT predicts improved OS in breast cancer, but it is unclear whether pCR limited to the breast or axilla is also associated with OS. Methods: Women with cT1-3/cN0-1 breast cancer diagnosed in 2010 to 2014 who underwent surgery following NACT were identified in the NCDB and divided into 4 subtypes based on reported hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Kaplan-Meier curves and Cox proportional hazards models were used to estimate OS. Multivariate logistic regression was used to identify factors associated with post-NACT response, defined as upstage (yp stage>clinical stage); no change (clinical stage = yp stage); overall (breast+axilla, ypT0N0), breast-only (ypT0N1/N1mic), or node-only (ypT1-3N0) pCR. Results: Of 33,162 identified patients, 20,265 experienced overall pCR (n = 6370, 19.2%), breast-only pCR (n = 494, 1.5%), node-only pCR (n = 1133, 3.4%), no stage change (n = 9641, 29.1%), or upstage (n = 2627, 7.9%). Compared with no stage change, breast-only pCR was associated with improved OS in triple-negative disease [hazard ratio = 0.58, 95% confidence interval (95% CI) = 0.37–0.89], and node-only pCR was associated with improved OS in both triple-negative (hazard ratio = 0.55,95% CI = 0.39–0.76) and HR+/HER2− disease (hazard ratio = 0.54, 95% CI = 0.33–0.89). For patients achieving overall (breast+axilla) pCR, unadjusted 5-year OS was 0.94 (95% CI = 0.93–0.95), with no difference between patients who were cN0 (hazard ratio = 0.95, 95% CI = 0.93–0.96) or cN1 (hazard ratio = 0.94, 95% CI = 0.92–0.96) at diagnosis. Conclusions: In node-positive patients, pCR limited to either the breast or axilla predicts survival for select receptor subtypes. In patients achieving pCR in both the breast and axilla, survival is driven by response to NACT rather than presenting cN stage.