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Abstract Background: Synchronous bilateral breast cancer is rare, with reported incidence from 0.3-12%; the incidence and pattern of bilateral breast cancer among younger women is unknown. Here we report the incidence and phenotypes of bilateral breast cancer in women ≤40 years of age enrolled in the Young Women's Study (YWS) cohort. Methods: The YWS is a multi-center, prospective cohort study that enrolled women with newly diagnosed breast cancer at age ≤40 years from 2006-2016. Those with synchronous bilateral breast cancer (in-situ and/or invasive) formed our study cohort. Disease characteristics and treatment were obtained by medical record review. Central pathology review was performed to capture histologic features and categorize the tumor phenotype as either luminal A (hormone receptor (HR)+, HER2-, grade 1 or 2), luminal B (HR+, HER2+, or HER2- and grade 3), HER2-type (HR-, HER2+), or triple negative (TNC; HR/HER2-). Tumor phenotypes of bilateral breast cancers were compared and evaluated for concordance. Results: Among 1302 patients enrolled in the YWS, 20 (1.5%) patients presented with bilateral disease, with median age of diagnosis of 38 years (range 18-40). The majority of patients (13 (65%)) presented with unilateral symptoms and contralateral disease was identified on subsequent imaging. 12 (60%) reported a positive family history of breast cancer and 17 (85%) underwent genetic testing; resulting in the identification of 6 mutation carriers (2 BRCA1, 3 BRCA2, 1 TP53). The majority of patients (15 (75%)) underwent bilateral mastectomy, 1 underwent unilateral mastectomy with contralateral lumpectomy, and 4 underwent bilateral lumpectomy. On pathology, 2 patients had bilateral in-situ disease, 5 had unilateral invasive and contralateral in-situ disease, and 13 had bilateral invasive disease. Of those with bilateral invasive disease, all had concordant tumor histology (92% ductal, 8% ductal and lobular), 10 (77%) patients had bilateral luminal tumors and when fully characterized 6 were of the same luminal type. Only one patient had bilateral basal-like breast cancer. Patient ID ERPRHer2 amplifiedGradePhenotype1Left++-2Luminal A Right++-3Luminal B3Left++-3Luminal B Right++-3Luminal B6Left++-3Luminal B Right++-3Luminal B9Left++-2Luminal A Right++-2Luminal A10Left+++3Luminal B Right++-2Luminal A12Left+--3Luminal B Right+--2Luminal A13Left---NABasal-like Right++-NALuminal A or B14Left+++2Luminal B Right++-3Luminal B15Left++-3Luminal B Right+++3Luminal B16Left+++3Luminal B Right--+NAHEr2-type17Left---3Basal-like Right---3Basal-like19Left++-2Luminal A Right++-3Luminal B20Left++-1Luminal A Right++-2Luminal A Conclusions: Among a large cohort of young women, only 20 (1.5%) had bilateral disease, and the majority of the invasive tumors were of the luminal phenotype, yet frequently differed by grade or HER2 status; supporting the need for thorough pathologic evaluation of bilateral disease to determine risk and tailor treatment. Overall the low incidence of bilateral disease and preponderance of the luminal phenotype in this population is reassuring. Citation Format: Pak LM, Rosenberg SM, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Snow C, Collins L, King TA, Partridge AH. Tumor phenotype and concordance in synchronous bilateral breast cancer in young women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-22-03.

Abstract Background: The live attenuated non-pathogenic Edmonston MV vaccine strain has advantages as an oncolytic platform given its tumor specificity, potent bystander effect, and ability to be engineered and retargeted. MV-NIS expresses the human thyroidal sodium-iodide symporter (NIS) and is selectively oncolytic, entering tumor cells through CD46 (overexpressed on many cancers, including breast cancer of all subtypes) and Nectin-4. NIS expression in MV-NIS infected cells permits noninvasive monitoring of virus spread by SPECT-CT imaging of Tc-99m pertechnetate or I-123 uptake. Methods: NCT01846091 is a standard 3+3 phase I trial of a single IT administration of MV-NIS in pts with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) or metastatic breast cancer (MBC). Primary objectives are (a) safety and tolerability and (b) maximally tolerated single dose. The secondary clinical objective is to preliminarily assess antitumor efficacy at and away from the MV injection site. Key eligibility criteria were: absence of standard therapy with life prolonging intent; at least one lesion >1 cm amenable to percutaneous injection; and no impending visceral crisis. MV-NIS was administered on D1 with mandatory SPECT-CT at baseline (BL) and on D3&D8; repeat SPECT-CT on D15&D21 if the prior result was positive; mandatory tumor biopsies on D3&D21; optional tumor biopsies on D8&D15; assessments for viremia and viral shedding at BL and on D3,D8,D15,D21; and standard imaging for restaging at BL,D21,W6,W12. Results: Accrual completed with 12 evaluable pts (6 SCCHN and 6 MBC) at 3 dose levels (108, 3x108, 109 TCID50). The MBC group included 5 HR+/HER2- pts and 1 pt with mixed HR+/HER2- and HR+/HER2+ disease. 5 pts had evidence of disease progression prior to study participation. No dose limiting toxicities were observed among the MBC pts; AEs possibly related to MV-NIS in this group were gr2 fatigue, gr1 flu-like illness, gr2 lymphopenia (all n=1). No SCCHN responses were observed. Best response for the MBC pts was: stable disease (SD) >6 wks, n=4; clinical response, n=1; progression, n=1. One MBC pt with SD for 12 wks had positive SPECT/CT imaging at and away from the injection site on D3&D8 and was the only pt seronegative for measles IgG antibodies prior to MV-NIS exposure. The MBC pt who responded after initial MV-NIS exposure was the only pt with low viral RNA in blood (D3); she received additional doses at W9&W13 without toxicity through an expanded access protocol exemption and had disease progression by W19. No viral shedding was detected from mouth rinse or urine in any pt. MV was detected in tumor samples from all pts treated at the highest dose level. Additional blood and tissue analyses are in progress. Conclusion: These results demonstrate the safety of IT MV-NIS administration, provide early evidence of biologic activity in MBC, and support the possibility of viral replication in tumors remote from the IT injection site. A MV strain encoding the immunomodulatory neutrophil activating protein transgene has been constructed (MV-s-NAP) with preclinical evidence of improved antitumor activity and immunogenicity. The phase I MV-s-NAP trial will start recruitment in Fall 2018. Citation Format: Liu MC, Peng K-W, Federspiel MJ, Russell SJ, Brunton BA, Zhou Y, Packiriswamy N, Hubbard JM, Loprinzi CL, Peethambaram PP, Ruddy KJ, Allred JB, Galanis E, Okuno SH. Phase I trial of intratumoral (IT) administration of a NIS-expressing derivative manufactured from a genetically engineered strain of measles virus (MV) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-03.

Abstract Background: Male breast cancer (MBC) is rare, and usually managed by extrapolation from female breast cancer. We report on the characteristics and survival outcomes of MBC patients from Mayo Clinic Rochester (MCR). Methods: Medical records of MBC patients treated at MCR during a 25-year period (1990-2015) were reviewed. Demographic variables, tumor characteristics, recurrences, and overall survival (OS) were collected. Progression free survival (PFS) and OS were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of OS. Results: One hundred sixty-seven patients were included in the final analysis, with a median follow-up of 58 months after diagnosis. Baseline characteristics are presented in Table 1. Eighty percent of patients with ER-positive tumors received endocrine therapy. Among men with stage I-III disease, approximately 90% underwent mastectomy, and 44% received adjuvant chemotherapy. The 5-year locoregional and distant recurrence rates for patients with stage I-III disease were 4.4% and 21.5%, respectively. The 5-year PFS and OS for patients with stage I-III disease were 65.5% and 80.1%, respectively. In a multivariate analysis assessing predictors of OS in patients with stage I-III disease, older age (HR 1.05; 95% CI: 1.02 – 1.09), stage II (HR 11.06; 95% CI: 3.84 – 31.85) or stage III disease (HR 14.74; 95% CI (3.99 – 54.45), and omission of surgery (HR 45.33; 95% CI: 3.97 – 517.32) were associated with poorer OS, while endocrine therapy (HR 0.21, 95% CI: 0.09 – 0.51) was associated with better OS. ER, PR, HER2 and grade were not independently prognostic. The median OS for stage IV patients was 10 months, though this 11-man cohort was too small to allow assessment of prognostic factors in advanced male breast cancer. Conclusions: MBC remains an understudied condition. Prognostic factors in this stage I-III disease are consistent with those identified in other MBC retrospective cohorts. Prospective studies are needed to better understand the unique clinical features of MBC, and to improve outcomes, particularly for advanced disease. Table 1:Baseline characteristics N=167 Median age at diagnosis (Years)64.4 Ethnicity/Race: Caucasian131 (78.4%)African American4 (2.4%)Other or unknown32 (19.2%) Overall AJCC 7th edition stage: Stage I39 (23.4%)Stage II80 (47.9%)Stage III32 (19.2%)Stage IV11 (6.6%)Unknown5 (3.0%) Grade: 18 (4.8%)247 (28.1%)3101 (60.5%)Unknown12 (7.1%) ER status: Negative8 (4.8%)Positive153 (91.6%)Unknown6 (3.6%) PR status: Negative17 (10.2%)Positive141 (84.4%)Unknown9 (5.4%) HER-2 status: Negative70 (41.9%)Positive12 (7.2%)Unknown85 (50.9%) Citation Format: Yadav S, Leon-Ferre RA, Jimenez RE, Hawse JR, Hieken TJ, Couch FJ, Boughey JC, Ruddy KJ. Clinical characteristics and survival of patients with male breast cancer: The Mayo Clinic experience [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-19-05.

Abstract Cyclin dependent kinase 4 and 6 inhibitors (CDK4/6i) are standard first line (1L) and second line (2L) treatments of ER+ MBC. However, the optimal treatment strategy after progression on a CDK 4/6i is unknown. Given concern for rapid disease progression after discontinuation of CDK4/6is (Bashour, J Cancer 2017), further data on responses to subsequent lines of therapy post CDK4/6i are needed. We performed a single institution retrospective review of patients (pts) with ER+ MBC who received 1L or 2L CDK4/6i to examine the prescribing patterns and clinical responses to post-CDK4/6i treatment. Methods: We identified 136 ER+ MBC pts prescribed a CDK4/6i at Mayo Clinic Rochester (from 12/2014 to 2/2018) on 1L or 2L who received at least 30 days of therapy and ≥ two clinic visits during treatment. For the 1L and 2L cohorts we assessed the time to treatment failure during (TTF-1) and after CDK4/6i therapy (TTF-2). TTF was defined as time from start of therapy to discontinuation for any cause. Additionally, we assessed overall survival (OS) post CDK4/6i discontinuation (defined as the date of TTF-1 to death or last follow up). Results: The study cohort included 81 and 55 pts treated with 1L and 2L CDK4/6is, respectively. In the 1L cohort, palbociclib/letrozole (82.3%) and palbociclib/fulvestrant (13.6%) were most commonly prescribed. Treatment was discontinued in 39/81 pts due to: progression (84.6%), intolerability (7.7%), and other (7.7%). The median TTF-1 was 19.7 mo (95% CI 11.2 – 25.4 mo). Subsequent treatment and response data were available in 37/39 pts that progressed on 1L CDK4/6i. The most commonly prescribed regimens included single-agent hormonal therapy (29.7%), everolimus/exemestane (27.0%), and single agent chemotherapy (21.7%). The overall median TTF-2 were as follows: everolimus/exemestane 13.2 mo [95%CI 0.33 mo – not reached (NR)]; single agent hormonal therapy 3.1 mo (95%CI 1.4 – 5.4 mo); and single agent chemotherapy 4.1 mo (95%CI 1.4 - 5.4 mo). With a median post-CDK4/6i follow up of 11.2 mo, we observed 8 deaths and the median OS-post CDK4/6i was NR. In the 2L cohort, common regimens were palbociclib/letrozole (63.6%) and palbociclib/fulvestrant (27.3%). Treatment was discontinued in 30/55 pts due to: progression (73.3%), intolerability (13.3%), and other (13.3%). The median TTF-1 in the 2L cohort was 8.3 mo (95%CI 4.6 – 12.7 mo). Subsequent treatment data were available in 24/30 pts and included single-agent hormonal therapy [n=7 (29.2%); median TTF-2 4.7 mo; 95%CI 1.9 – 14.0 mo], everolimus/exemestane [n=6 (25.0%); median TTF-2 3.2 mo, 95% CI 0.8-10.1 mo)] and single agent chemotherapy [n=6 (25.0%); median TTF-2 2.6 mo; 95%CI 1.7 mo – NR)]. With a median post-CDK4/6i follow up 18.7 mo in the 2L cohort, we observed 11 deaths, and the median OS-post CDK4/6i was 11.8 mo (95%CI 11.8 mo – NR). Conclusions: Single and combination-based endocrine strategies are commonly administered post-CDK4/6i without clinical evidence for rapid deterioration. The observation of a median treatment duration lasting >12 months in patients receiving everolimus/exemestane post-CDK4/6i supports ongoing studies evaluating drugs that target PI3K/mTOR pathway in combination and following progression on a CDK4/6i. Citation Format: Giridhar KV, Choong GM, Leon-Ferre RA, O'Sullivan CC, Ruddy KJ, Haddad TC, Hobday TJ, Peethambaram PP, Moynihan TJ, Loprinzi CL, Liu MC, Suman VJ, Goetz MP. Clinical management of metastatic breast cancer (MBC) after CDK 4/6 inhibitors: A retrospective single-institution study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-09.

Abstract Background: The 21-gene Recurrence Score (RS) assay is prognostic among women with early-stage estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC) and is used to select patients for chemotherapy (CT). Young women (age <40) have represented a minority in studies evaluating gene expression assays, including TAILORx, and additional data in young women are needed. Methods: In the Young Women's Breast Cancer Study, a prospective cohort study of women diagnosed with BC at age <40 enrolling between 2006-2016 (N=1302), we identified those with stage I-III ER+/HER2- BC. Disease and treatment information were obtained through serial surveys and medical record review. The RS was performed on banked specimens for those not tested clinically. Distant recurrence free interval (DRFI), defined as distant recurrence or BC specific death, by risk group was assessed using Cox regression and Kaplan-Meier survival estimates. Outcomes by receipt of CT were explored in the RS 11-25 group, and due to small number of events, reported descriptively. Results: Among eligible women (N=577), 189 (33%) had undergone RS testing and 320 (56%) had banked specimens sufficient for testing. Median follow-up was 6 years. Median age at diagnosis was 37, most had N0 BC (300/509, 59%), and the majority had RS 11-25 (306/509, 60%). RS result was significantly associated with DRFI in N0 BC, with hazard ratio (HR) (95% CI) of 0.29 (0.07,1.30) and 0.21 (0.09,0.50) for RS<11 and RS 11-25, respectively, relative to RS>26 (and trended towards significance in N1 BC). Results were similar using conventional RS groups. Among women with N0 BC and RS 11-25, 44% received CT, with two events in the 86 receiving CT (2.3%) and 6 events in the 109 without CT (5.5%); 5/8 (63%) occurred in those with RS 20-25. Table 1 N0N1Total Cohort N%N%N% 3005916332509100Median Age37.137.537.2Tumor Stage T120869694229358T28227784817635T3103159357T4001151Grade I4716855711II16555794926652III8829754618536Not assessed 1 1 PR status by IHC Negative (<1%)2071710398Positive (>=1%)280931469047092Chemotherapy No1414712715430Yes159531519335570Ovarian Suppression No263881499145289Yes37121495711TAILORx RS Groups RS <1133111495411RS 11-2519565885430660RS >=267224613714929Conventional RS Groups RS <1812742543319939RS 18-3012542694221142RS >=31481640259919 Table 2 6-year freedom from distant recurrence or breast cancer deathDRFI HR (95% CI) N0N1N0N1TAILORx RS Groups RS <1194.4%92.3%0.29 (0.07,1.30)0.21 (0.03,1.61)RS 11-2596.9%85.2%0.21 (0.09, 0.50)0.55 (0.27,1.12)RS >=2685.1%71.3%RefRefConventional RS Groups RS <1897.5%85.9%0.19 (0.06,0.59)0.31 (0.13,0.74)RS 18-3093.1%87.3%0.39 (0.16,1.00)0.32 (0.14,0.73)RS >=3186.4%62.8%RefRef Conclusions: The RS is prognostic among young women with node-negative and node-positive BC, and is a valuable tool for risk stratification. Disease outcomes among young women with N0 disease and RS 11-25, a minority of whom received CT, are very good. Evaluation of the effect of ovarian suppression/CT-induced amenorrhea by RS/treatment strata is ongoing. Citation Format: Poorvu PD, Gelber SI, Rosenberg SM, Ruddy KJ, Tamimi RM, Collins LC, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Jakubowski DM, Russell C, Winer EP, Partridge AH. Prognostic impact of the 21-gene recurrence score assay among young women with node-negative and node-positive ER+/HER2- breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-07.

Abstract Background: Chemotherapy can damage the ovaries and cause amenorrhea, a surrogate for infertility. Young women often wish to understand and minimize their risk of chemotherapy-related amenorrhea (CRA). However, the incidence of CRA with regimens that do not include either an anthracycline or cyclophosphamide is poorly studied. For patients with HER-2 positive disease, these anthracycline and cyclophosphamide-sparing regimens (e.g., docetaxel-carboplatin) are common (in combination with Her-2 directed therapy) in both the neoadjuvant and adjuvant settings. Methods: Women diagnosed with breast cancer under age 50 and within the past 10 years were recruited through a Dr. Susan Love Research Foundation Army of Women e-mail blast. Those who provided their contact information were mailed a consent form and medical record authorization form. Participants then received a web-based survey that inquired about receipt of and type of chemotherapy (including date of last dose) and date of last menstrual period (LMP). Patient-reported LMP was compared to date of final chemotherapy dose to determine if the LMP occurred before (defined as “CRA”) or after the last chemotherapy dose. When available, medical record data was used in place of survey data regarding type of chemotherapy used. Exclusion criteria included: LMP prior to diagnosis date, receipt of multiple chemotherapy regimens or no chemotherapy regimens, receipt of ovarian suppression medications (which interfere with interpretation of menstrual data), surgical menopause prior to or at the same time as diagnosis, a cancer diagnosis more than 10 years prior, incomplete menstrual data on the survey, report of an unknown chemotherapy regimen, and no date available for the last chemotherapy dose without an LMP within a month prior to survey completion. Fisher Exact test was used to compare CRA rates between regimens. Rates after two anthracycline-sparing regimens (taxane/cyclophosphamide; taxane/carboplatin) were compared to rates after anthracycline/cyclophosphamide/taxane. Results: 273 women consented to participate in this study, 258 of whom filled out the web survey. 151 of them were eligible for this analysis with a median age at diagnosis of 41 (range 24-49) and a median time from last chemotherapy dose to survey of 62.5 months (range 2-138). CRA occurred in 51.2% of the 86 participants who received an anthracycline, cyclophosphamide, and a taxane, in 41.9% of the 43 participants who received only a taxane and cyclophosphamide (p=0.35), and in 13.3% of the 15 participants who received carboplatin with a taxane (p=0.01). When the 11 patients who were <12 months since last chemotherapy were excluded, CRA rates changed minimally. Age did not differ by regimen, but median time since chemotherapy was shorter in the taxane/carboplatin group (35 months vs. 68 months). Trastuzumab with or without pertuzumab was administered in 100% of patients who received carboplatin/taxane, in 23.3% of patients who received taxane and cyclophosphamide, and in 22.1% of patients who received anthracycline/cyclophosphamide/taxane. Conclusions: This study suggests that carboplatin/taxane may be substantially less gonadotoxic than cyclophosphamide-based (neo)adjuvant regimens. Further research is necessary to confirm these findings. Citation Format: Gast KC, Cathcart-Rake EJ, Norman A, Eshragi L, Obidegwu N, Yost K, Nichols HB, Rosenberg S, Su HI, Stewart E, Couch F, Vachon C, Ruddy KJ. Regimen-specific rates of chemotherapy-related amenorrhea in breast cancer survivors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-10.

Abstract Background: HF occur in about 75% of midlife women and are associated with quality of life disruption and premature endocrine therapy discontinuation among breast cancer survivors. Estrogen therapy, effective for HF, is contraindicated in hormone receptor-positive breast cancer (BC). Previous studies have suggested that Oxy could be effective in managing HF. Methods: This randomized, placebo (P)-controlled trial enrolled women who had experienced HF ≥28 times per week over >30 days and of sufficient severity to seek treatment. Patients (pts) were randomized to receive oral Oxy at two doses: 2.5mg BID for 6 weeks (Oxy2.5), 2.5mg BID for a week with subsequent increase to 5mg BID (Oxy5), or matching P, in equal ratios. Baseline and monthly questionnaires were administered including a HF diary, the HF related daily interference scale (HFRDIS) and a symptom experience questionnaire. The primary endpoint was intra-patient change in weekly HF score and frequency from baseline to end of study compared using Kruskal-Wallis tests. Results: 150 pts were accrued between 2/23/2017-3/5/2018. 4 pts cancelled before starting treatment and were excluded from analyses. This interim report includes the first 104 pts for which at least one post-baseline evaluation was available. Baseline characteristics were well-balanced between the arms. Sixty-two percent were on tamoxifen or an aromatase inhibitor for the duration of the study. Pts on both Oxy doses had a significantly greater reduction in HF score and frequency compared to P. Pts on Oxy2.5 had a mean change in HF score of -10 (SD 7.4) vs -5.1 (SD 9.7) with P, p=0.003; and a mean change in average weekly number of HF of -4.6 (SD 3.1) vs -2.3 (SD 3.9), p=0.002. Pts on Oxy5 had a mean change in HF score of -16.2 (SD 5.1) vs -5.1 (SD 9.7) with P, p<0.001; and a mean change in average weekly number of HF of -7.0 (SD 4.0) vs -2.3 (SD 3.9), p<0.001. Repeated measures mixed models confirmed that, after adjusting for baseline values, both Oxy arms had significantly lower HF scores and frequency compared to P (p<0.001). HFRDIS revealed that pts in both Oxy arms experienced improvement in the following HF interference measures: work, social activities, leisure activities, sleep, relations, life enjoyment, and overall quality of life. Pts on Oxy5 also had improvement in HF interference with mood. Pts on Oxy2.5 experienced more stomach pain (p=0.031), diarrhea (p=0.007), nausea (p=0.04), headaches (0.032), episodes of confusion (0.012), dry mouth (p=0.003) and dry eyes (0.027) compared to P. Pts on Oxy5 experienced more constipation (0.004), dry mouth (0.001) and difficulty urinating (0.004) compared to P. There were no differences in study discontinuation due to adverse effects between either Oxy arm and P (Oxy2.5 vs P, p=0.653; Oxy5 vs P, p=0.483). Conclusions: Oxy is superior to P for management of HF. Oxy2.5 and 5 were both associated with significant improvements in HF scores and frequency as well as improvement in HF interference with several quality of life measures. While pts on Oxy experienced more side effects than pts on P, rates of discontinuation due to adverse events were low. This study was supported by the Breast Cancer Research Foundation. Citation Format: Leon-Ferre RA, Novotny PJ, Faubion SS, Ruddy KJ, Flora D, Dakhil C, Rowland KM, Graham ML, Le-Lindqwister N, Loprinzi CL. A randomized, double-blind, placebo-controlled trial of oxybutynin (Oxy) for hot flashes (HF): ACCRU study SC-1603 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-02.

Abstract Background: Young women with breast cancer (BC) are increasingly choosing contralateral prophylactic mastectomy (CPM), yet little is known about the impact of surgical choices on quality of life (QOL) and psychological health. Using a large, prospective cohort of young women with BC, we sought to evaluate psychosocial outcomes following surgery. Methods: Among participants of the Young Women's BC Study, a multi-center cohort of women dx'd with BC at age ≤40, we identified women with Stage 0-3 unilateral BC who had surgery and completed surveys that included measures of QOL (CARES) and psychological health (HADS). Linear mixed-effects models were fit to assess changes from 1 to 3 years (yrs) post-dx in anxiety, depression, psychosocial, body image, and sexual scores. Adjusted (stage, hormone receptor status, chemotherapy, age) means were estimated and differences compared (Bonferroni adjusted p-values) between CPM vs breast conserving surgery (BCS) and unilateral mastectomy (UM) at 1, 2, and 3 yrs. Results: Of 863 women, 30% had BCS, 24% UM, 46% CPM. Median age at dx was 37 (range: 22-40). Of women who had UM/CPM, 84% had reconstruction. Among women who had CPM, mean body image (p=.02), psychosocial (p<.0001), sexual (p<.0001), and depression p=.0007) scores decreased, indicating improvement, from yr 1 to 2 but remained stable from yr 2 to 3 (Table). Anxiety decreased from yr 1 to 2 for women who had BCS (p=.0007) and M (p=.03), and from yr 2 to 3 for women who had CPM (p=.003). Body image scores did not change significantly between any time points among women who had M or BCS. Overall change trajectories for sexual (p=.03) and anxiety scores (p=.008) differed by surgery. Compared to BCS and UM, psychosocial scores were higher in women who had CPM at 1 yr (p<.05) and remained higher compared to BCS at 2 yrs (p=.04). Anxiety was higher among women who had CPM vs UM at 1 and 2 yrs (p<.01), vs BCS at 2 yrs (p=.004). Depression was higher among women who had CPM vs UM in yr 1 (p=.05). By yr 3, there were no significant differences in anxiety, depression, and overall psychosocial scores between groups. Compared to BCS, women who had CPM had higher sexual and body image scores (p<.01), indicating worse QOL, at all timepoints. Compared to UM, women who had CPM had higher sexual scores at 1 and 3 yrs (p<.05) and body image scores at 3 yrs (p=.02). Conclusions: While psychosocial health improves over time, differences by surgery persist, with women who have CPM experiencing more sexual and body image issues compared to women who undergo BCS or M in the years following surgery. Given that surgical choices may be affected by distress experienced before or at dx, ensuring young women receive adequate support when making surgical decisions as well as after surgery is warranted. Mean CARES and HADS scores Year 123Psychosocial*CPM.89.78.76 UM.75.69.66 BCS.72.65.66 Sexual*CPM1.641.371.40 UM1.411.291.08 BCS1.181.071.04 Body image*CPM1.331.221.30 UM1.161.131.04 BCS.64.57.56 Anxiety**CPM7.657.406.79 UM6.505.916.39 BCS7.036.226.50 Depression**CPM3.723.213.25 UM3.022.802.70 BCS3.332.823.13**CARES range: 0-4;higher scores=worse QOL **HADS range 0-21;higher scores=more anxiety/depression Citation Format: Rosenberg SM, Hu J, Dominici LS, Poorvu PD, Ruddy KJ, Tamimi RM, Schapira L, Come S, Peppercorn JM, Borges VF, Partridge AH. Longitudinal changes in psychosocial health in young women following breast cancer surgery: Results from a multi-center cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-03.

Abstract Background: Breast cancer care imposes a significant financial burden to U.S. healthcare systems and has become a key focus in the health care debate. Therapies for breast cancer are expensive, and the economic burden of these therapies may be rising due to the rapid introduction of pricey new drugs and techniques. There are limited data on the health care costs of individuals with breast cancer after initial diagnosis and how these costs have changed over time. Methods: We conducted a retrospective analysis of commercially insured adult women with newly diagnosed non-metastatic breast cancer (identified via previously published claims-based algorithms) using 2007-2016 data from a large US health plan available in OptumLabs® Data Warehouse. We included patients with continuous health plan coverage for at least 2 years after initial diagnosis 2007-2014 and assessed how total health care spending and out-of-pocket costs (paid amounts) changed over this time. Costs were adjusted to 2016 US dollars using the general Consumer Price Index. Inpatient, outpatient, and outpatient pharmacy costs were evaluated. A multivariable logistic regression model was used to examine predictors of above average cost (cost > mean for that year of diagnosis). Results: A total of 12,446 newly diagnosed breast cancer patients were identified (mean age, 51.6 years). Forty percent had undergone mastectomy, 38% chemotherapy, and 63% radiation. After adjustment for inflation, total healthcare costs increased 29.7% from 2007 to 2014 (Table 1), with increases primarily observed during the first year after diagnosis. Out-of-pocket costs remained relatively stable, and accounted for 5.3% of the total spending. Approximately 80% of the total costs were related to care received in the outpatient setting. Factors independently associated with above average spending included treatment with mastectomy [OR 1.78 (95% CI 1.5-2.1)], reconstruction [OR 3.0 (95% CI 2.6-3.5)], radiation [OR 4.0 (95% CI 3.4-4.7)] and chemotherapy [OR 18.4 (95% CI 16.6-20.3]. Table 1.Average healthcare spending over time Mean cost during first year after diagnosisMean cost during second year after diagnosisYear of diagnosistotalout-of-pockettotalout-of-pocket2007$80,296.17$4,271.25$16,559.21$1,907.012008$84,126.70$4,445.78$16,785.43$2,205.982009$88,331.45$4,728.42$17,005.68$2,214.932010$91,502.58$5,067.78$17,243.91$2,126.192011$93,826.40$5,089.45$16,862.45$2,027.962012$96,690.06$5,449.91$17,814.09$2,179.262013$104,064.93$5,678.19$17,087.47$2,115.972014$104,169.74$5,620.51$16,714.12$1,590.67 Conclusions: Breast cancer care is increasingly expensive during the first year after diagnosis, and costs are greatest for the recipients of more aggressive treatments. Costs during the second year after diagnosis have remained relatively stable. Citation Format: Ruddy KJ, Sangaralingham LR, Freedman RA, Jemal A, Mougalian SS, Keegan T, Loprinzi CL, Gross CP, Henk HJ, Shah N. Trends in the cost of care for breast cancer among women with commercial insurance [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD6-07.

Abstract Background: In order to improve care and reduce costs of cancer treatment, attention has focused on reducing inpatient (IP) and emergency room (ED) utilization. The US Centers for Medicare and Medicaid Services (CMS) recently implemented an oncology outcome measure (OP-35) to assess the quality of care and determine outpatient hospital payment. It assesses 30-day post-chemotherapy rates of IP or ED events deemed “potentially avoidable” by CMS due to association with any of 10 CMS-defined toxicities: anemia, dehydration, diarrhea, fever, nausea, emesis, neutropenia, pain, pneumonia, or sepsis. Although CMS found that 20% of chemotherapy treatment resulted in such events, event rates with highly emetogenic chemotherapy (HEC) are understudied, particularly for breast cancer (bCA) patients treated with anthracycline + cyclophosphamide (AC), carboplatin, or cisplatin. Methods: In a large electronic health record database focused on US integrated delivery networks, HEC courses of therapy were identified from 4Q 2012 to 3Q 2017. IP/ED events within 30 days of chemotherapy administration were considered related to the OP-35 measure if they included a diagnosis code of any of the ten OP-35 toxicities, per CMS' definitions. HEC chemotherapy use, IP/ED events, bCA diagnosis, and toxicities were identified by ICD-9, ICD-10, and procedural codes. Subgroups were evaluated for 3 common HECs: AC, carboplatin (>14 days apart, as a proxy for AUC ≥4), and cisplatin. Results: 4128 courses of HEC in bCA were identified. Of these, 2304 involved AC (median 4 cycles), 1721 involved carboplatin (median 6 cycles), and 103 involved cisplatin (median 4 cycles), with median ages of 55, 59, and 64, respectively. 30-day IP/ED events were seen in 25% of these HEC bCA courses (22%, 30% and 23% for AC, carboplatin, and cisplatin, respectively). The 10 CMS-defined toxicities were associated with an IP/ED event for 73%, 72%, and 76% of events for these AC, carboplatin, and cisplatin courses respectively, confirming that these are principal contributors to 30-day IP/ED use for patients receiving HEC in bCA. The top five that were most commonly associated with IP/ED for bCA for patients receiving AC, carboplatin, or cisplatin were pain 53%/49%/63%, anemia 51%/51%/38%, fever 48%/31%/38%, neutropenia 46%/27%/31%, and nausea/emesis 30%/40%/25%; patients may have had ≥1 toxicity associated with each IP/ED event. The IP/ED rate may be understated because some events, particularly ED, may occur out of the network the EHR data covers. Conclusion: One quarter of patients receiving AC, carboplatin, or cisplatin for bCA visit the ED or are hospitalized within 30 days of at least one of their chemotherapy administrations. Most events involved ≥1 of 10 toxicities deemed avoidable causes of hospitalization by CMS and now tracked as an oncology outcome measure. Relative to patients receiving AC, acute care rates for patients receiving carboplatin were lower for fever and neutropenia and higher for nausea/emesis, perhaps because the study period largely precedes the 2017 addition of carboplatin AUC ≥4 to national guidelines as HEC requiring triplet antiemetic prophylaxis. Toxicity prevention and symptom monitoring are crucial to reduce acute care needs. Citation Format: Ruddy KJ, Roeland EJ, LeBlanc TW, Binder G, Sebastiani S, Potluri R, Schmerold LM, Papademetriou E, Navari RM. Avoidable acute care use associated with nausea and emesis among patients receiving AC, carboplatin, or cisplatin for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-05.