Clinicopathologic features of breast cancers diagnosed in females treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort.

567 Background: Childhood and young adult survivors of Hodgkin Lymphoma are at an increased risk of developing breast cancer, although little data exist on the characteristics and biologic subtype of breast cancers that develop in this high-risk population. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all histologically confirmed breast cancers diagnosed between 1990-2016 in women treated with prior radiation therapy for Hodgkin Lymphoma ≤ 30 years of age. Clinicopathologic features of subsequent breast cancers (BC-HL) were examined and compared to breast cancers diagnosed in women with no prior malignancy (BC-NPM). The association between prior chemotherapy use and biologic subtype of BC-HL was evaluated. Results: We identified 321 breast cancers diagnosed in 257 women with a history of radiation therapy for Hodgkin Lymphoma. The median age at Hodgkin Lymphoma diagnosis was 22 years (range, 12-30 years), and nearly all BC-HL (97.9%) were diagnosed 8 or more years after radiation therapy. Overall, 56 (21.8%) BC-HL patients developed bilateral breast cancer, of which 28 (50%) were synchronous. When compared to women with BC-NPM, women with BC-HL were significantly younger at time of diagnosis (median age, 43 years vs. 60 years, p<0.001) and less likely to present with ductal carcinoma in situ (8.4% vs. 14.9%, p=0.001). Patients with invasive BC-HL were more likely to have high grade (43.8% vs. 32.9%, p<0.001), estrogen receptor (ER) negative breast cancer (27.7% vs. 18.2%, p<0.001), although pathologic tumor size, nodal status, and stage were not significantly different from those with BC-NPM. Compared to women with BC-NPM, the majority of operable BC-HL patients underwent surgical management with mastectomy (86.5% vs. 42.5%, p<0.001). In subset analysis of 102 women for which HER2 status was available, BC-HL were HER2+ in 18.7% of patients. Distribution of biologic subtype between BC-HL and BC-NPM are shown in the table below. In BC-HL patients, prior chemotherapy exposure was not associated with substantial differences in the proportion of ER+HER2- breast cancers (65.8% vs. 63.5%, p=0.82). Conclusions: Breast cancers in women treated with radiation therapy for Hodgkin Lymphoma are characterized by earlier onset and more aggressive biologic features, although the majority remain estrogen sensitive and early stage at presentation. Further studies are warranted to evaluate the use of preventive strategies in this high-risk patient population.[Table: see text]

AML with Myelodysplasia-Related Changes: Development, Challenges, and Treatment Advances

Acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) is a distinct biologic subtype of AML that represents 25–34% of all AML diagnoses and associates with especially inferior outcomes compared to non-MRC AML. Typically, patients with AML-MRC experience low remission rates following intensive chemotherapy and a median overall survival of merely 9–12 months. In light of these discouraging outcomes, it has become evident that more effective therapies are needed for patients with AML-MRC. Liposomal daunorubicin–cytarabine (CPX-351) was approved in 2017 for adults with newly diagnosed AML-MRC and those with therapy-related AML (t-AML), and remains the only therapy specifically approved for this patient population. Other studies have also demonstrated the efficacy of the hypomethylating agent (HMA) azacitidine as upfront therapy for AML-MRC patients, which, to date, is the most common treatment employed for patients unable to tolerate the more intensive CPX-351. HMAs and venetoclax combinations have also been evaluated, but additional studies utilizing these agents in this specific subgroup are needed before conclusions regarding their role in the therapeutic armamentarium of AML-MRC patients can be reached. Currently, many studies are ongoing in attempts to further improve outcomes in this historically ill-fated patient group.

Breast cancer in women aged 80 years and older: Clinical characteristics and treatment patterns according to biologic subtype.

e12594 Background: Older age is associated with poorer breast cancer-specific survival (BCSS) outcomes, despite a higher prevalence of biologically favorable disease. We sought to evaluate differences in the clinical characteristics and management of older women according to biologic subtype of breast cancer. Methods: The Surveillance, Epidemiology, and End Results (SEER) treatment database was queried to identify all women aged 80 years or older with a first diagnosis of invasive breast cancer between 2010 and 2016. Patients were subgrouped according to biologic subtype and clinical and treatment-related variables were compared. Multivariable logistic regression was then performed to determine factors independently associated with receipt of breast-conserving surgery (BCS) and adjuvant radiation. Results: Overall, 27,375 women with a median age of 84 (range, 80-108 years) met inclusion criteria. The majority of older women were diagnosed with HR+HER2- breast cancer (78.9%), followed by HER2+ (11.0%) and triple-negative breast cancer (TNBC) (10.0%). In women with stage I-III disease, non-operative management was employed in 13.4% of HR+HER2- patients, compared to 16.7% of HER2+ patients and 11.0% of TNBC (p < 0.001). In those undergoing surgery, BCS was most common in HR+HER2- patients (80.9%), compared to HER2+ (68.9%) and TNBC (67.8%; p < 0.001). Axillary surgery was performed in 74.0% of early stage patients with HR+HER2- disease, compared to patients with HER2+ (77.8%) and TNBC (79.3%; p < 0.001). In adjusted analyses controlling for stage and clinical variables, women aged 80 years or older with HER2+ breast cancer and TNBC had a lower likelihood of BCS (ORHER2+ 0.72, 95% CI 0.65-0.80; ORTNBC 0.72, 95% CI 0.65-0.81), and an increased likelihood of adjuvant radiation (ORHER2+ 1.14, 95% CI 1.02-1.27; ORTNBC 1.40, 95% CI 1.25-1.57). Conclusions: One fifth of women with breast cancer over age 80 are diagnosed with HER2+ and triple-negative subtypes, which are associated with more aggressive local therapy. Further studies are warranted to determine if higher rates of adjuvant radiation optimize local control in older HER2+ and TNBC patients at increased risk for early locoregional recurrences.

RADI-29. BIOLOGIC SUBTYPES OF BREAST CANCER BRAIN METS AS A PREDICTOR OF LOCAL CONTROL AFTER STEREOTACTIC RADIOSURGERY

INTRODUCTION: Brain metastases (BM) are diagnosed in approximately 15% of breast cancer (BC) patients. Biologic subtype is predictive of loco-regional recurrence following breast conserving therapy and/or mastectomy with the highest risk in the ER-/PR-/HER2- (TN) subtype. The aim of this study is to determine whether biologic subtype is predictive of local control (LC) in BC patients with BM treated with Stereotactic Radiosurgery (SRS). MATERIALS/METHODS: All patients underwent LINAC-based SRS at our institution. Patients were subdivided into three biologic subtypes: ER+/Her2- (Luminal), Her2+, and TN (Basal). Kaplan Meier method was used to estimate the overall survival (OS). Cox proportional hazard model was used to analyze association of local failure (LF) with biologic subtypes. This is an IRB-approved single center retrospective study. RESULTS: 108 BC BM in 50 consecutive patients were included in this study with a median follow up of 11.1 months. The median disease-specific GPA was 2.0, and all patients received systemic chemotherapy and/or hormonal therapy. The 12 month LC rates for the entire cohort were 85%, 87%,49% for Luminal, Her2+ and Basal, respectively, with a significantly shorter LC for the basal sub-type (p=0.014). The 12 month OS rates were 83%, 88%, 80% for Luminal, Her2+ and Basal, respectively with a no significant difference in OS among the subgroups. 24% of the lesions were treated with salvage whole brain radiation therapy. CONCLUSIONS: This study shows that in BC patients with BM treated with SRS, biologic subtype impacts LC but not OS. Consideration of radiation treatment intensification or altered fractionation to improve LC may be indicated for the TN subtype. Further multi-center studies are necessary to corroborate our results.

National Cancer Institute Breast Cancer Steering Committee Working Group Report on Meaningful and Appropriate End Points for Clinical Trials in Metastatic Breast Cancer

Purpose To provide evidence-based consensus recommendations on choice of end points for clinical trials in metastatic breast cancer, with a focus on biologic subtype and line of therapy. Methods The National Cancer Institute Breast Cancer Steering Committee convened a working group of breast medical oncologists, patient advocates, biostatisticians, and liaisons from the Food and Drug Administration to conduct a detailed curated systematic review of the literature, including original reports, reviews, and meta-analyses, to determine the current landscape of therapeutic options, recent clinical trial data, and natural history of four biologic subtypes of breast cancer. Ongoing clinical trials for metastatic breast cancer in each subtype also were reviewed from ClinicalTrials.gov for planned primary end points. External input was obtained from the pharmaceutic/biotechnology industry, real-world clinical data specialists, experts in quality of life and patient-reported outcomes, and combined metrics for assessing magnitude of clinical benefit. Results The literature search yielded 146 publications to inform the recommendations from the working group. Conclusion Recommendations for appropriate end points for metastatic breast cancer clinical trials focus on biologic subtype and line of therapy and the magnitude of absolute and relative gains that would represent meaningful clinical benefit.

Breast Cancer Outcomes in a Racially and Ethnically Diverse Cohort of Insured Women

Background: It is unknown how subse­quent breast cancer outcomes vary by bio­logic subtype and race/ethnicity in a diverse cohort of breast cancer survivors.Methods: We conducted a prospective cohort study of 6,154 insured breast cancer survivors (AJCC TNM stages 0–IV) diagnosed between 1996-2007 and followed them through 1/1/2010 for subsequent breast cancer events (recurrence, contralateral breast cancer, metastasis, mortality). We compared subsequent breast cancer rates by race/ethnicity groups and biologic subtype (luminal A, luminal B, HER2-enriched, and triple negative). We calculated hazard ratios (HRs) with 95% CIs using multivariable Cox proportional hazards models, adjusted for sociodemographics, cancer treatments, and tumor characteristics.Results: The cohort was diverse: 62.4% non-Hispanic White, 13.2% Hispanic, 14.9% African American, and 9.5% Asian. We identified 1,456 subsequent breast cancer events over 22,830 person-years. Although certain Asian women had higher crude subsequent breast cancer rates com­pared with Whites, within each biologic subtype category, these disparities disap­peared in the multivariable analyses. After accounting for race/ethnicity, compared with women with luminal A tumors (refer­ence), women with luminal B (adjusted HR=3.65, 95% CI: 3.08-4.32), HER2- enriched (adjusted HR=2.81, 95% CI: 2.25-3.51) and triple negative (adjusted HR=1.25, 95% CI: 1.01-1.54) tumors had statistically increased risks of subsequent breast cancer. Factors that were statistically significantly associated with increased risk included higher stage, larger tumor size, positive lymph nodes, and no adjuvant endocrine or chemotherapy (all P<.025).Discussion: Our data suggest that dispari­ties in subsequent breast cancer outcomes were more strongly associated with tumor characteristics and non-use of adjuvant treatments than race/ethnicity. Ethn Dis. 2018;28(4):565-574; doi:10.18865/ed.28.4.565.

Outcomes Following Salvage Radiation and Systemic Therapy for Isolated Locoregional Recurrence of Breast Cancer after Mastectomy: Impact of Constructed Biologic Subtype

Purpose. This study examines factors associated with outcomes following salvage radiation and systemic therapy for breast cancer patients who developed isolated locoregional recurrence (ILRR) after mastectomy alone, while focusing on the prognostic significance of constructed biologic subtype in this setting. Methods and Materials. 269 postmastectomy patients in total treated for ILRR were included. Cumulative incidence of locoregional control (LRC), distant metastasis (DM)-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were calculated using Kaplan-Meier method. For statistical analysis, biologic subtypes were constructed from hormonal receptors (Rec) and HER2, consisting of Rec+/HER2-, Rec+/HER2+, Rec-/HER2+, and Rec-/HER2-. The association of clinic-pathological and treatment-related parameters with outcomes was evaluated using a Cox regression model. Results. At a median follow-up of 65 months, 56 (20.8%) patients failed to secure LRC after radiotherapy, and 165 patients (61.3%) developed DM. Overall, the actuarial 5-year LRC, DMFS, DFS, and OS rate was 77.3%, 45.6%, 43.9%, and 66.8%, respectively. Multivariate analysis revealed that constructed biologic subtype represented the most significant prognostic factor for any outcome. Compared to patients with Rec+/HER2- disease, those with Rec-/HER2- had significantly poorer 5-year LRC (84.2% versus 58.3%, HR = 4.36, P < 0.001) and worse survivals including 5-year DMFS (63.0% versus 15.8%, HR = 4.28, P < 0.001), DFS (59.7% versus 13.6%, HR=3.92, P < 0.001), and OS (87.8% versus 22.3%, HR = 8.55, P < 0.001). Other factors associated with reduced LRC were no radical surgery and involved field irradiation alone, whereas factors associated with poor survivals included positive nodes at primary diagnosis and regional recurrence. Conclusions. Constructed biologic subtypes remained to be predictive of both disease control and survivals after salvage radiation for postmastectomy ILRR. Notably, Rec-/HER2- patients were demonstrated to be at high risk of locoregional failure and subsequent DM and tended to have worse survivals despite salvage therapies.