Ruddy, KJ

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.

Abstract Purpose: Prevention of chemotherapy-induced nausea and vomiting (CINV) is essential to preserve quality of life in cancer patients receiving highly emetogenic chemotherapy (HEC) such as doxorubicin-cyclophosphamide (AC) or cisplatin. Recently, new drugs (e.g. fosaprepitant and newer neurokinin 1 receptor antagonists [NK1RAs], rolapitant and netupitant) and updated guidelines for antiemetic use (e.g. adding olanzapine) have emerged. However, trends in real world antiemetic use are understudied. Methods: We performed a retrospective study using the OptumLabs Data Warehouse (OLDW), which includes administrative claims for privately insured and Medicare Advantage enrollees in the U.S. We identified 34,236 patients age 18 years or older treated with either AC or cisplatin between January 2006 and June 2016. Data collected included baseline demographics (age, gender, census region and race), chemotherapy administered, and presence/absence of a central intravenous access device. Trends of anti-emetic use were presented overall and separately for 5-HT receptor antagonists (5HT3RAs) and NK1RAs. Results: 23,030 patients (67.3%) received an anthracycline-based regimen (AC with or without docetaxel or paclitaxel), and 11,206 (32.7%) patients received cisplatin. Approximately two thirds of patients were female (n= 23,392). Dexamethasone use was stable over the decade (used by 85-90% in all years). Use of 5HT3RAs, primarily palonosetron and ondansetron, occurred in at least 95% of patients in all study years, consistent with guideline recommendations. NK1RAs were underutilized early on compared with guideline recommendations, but use increased to approximately 80% in the most recently evaluated year. Fosaprepitant use rose precipitously starting in 2009, preceding a sharp fall in aprepitant use beginning in 2011. The use of olanzapine, rolapitant and netupitant was minimal throughout the study period. Conclusions: Dexamethasone and 5-HT3RAs were used in the vast majority of patients receiving HEC, in accordance with guideline recommendations. Less compliance with guidelines was seen with NK1RA use. Citation Format: O'Sullivan CC, Van Houten HK, Sangaralingham L, Leal AD, Shinde S, Liu H, Ettinger D, Loprinzi CL, Ruddy KJ. Ten year trends in antiemetic prescribing in cancer patients receiving highly emetogenic chemotherapy (HEC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-11-18.

Abstract Background: HR+ breast cancer in younger vs older patients may have distinct biological features. The Breast Cancer Index (BCI) is a gene expression-based assay that includes two component biomarkers: the HoxB13/IL17BR (H/I ratio), an endocrine response biomarker; and the molecular grade index (MGI), a set of proliferation-related genes. The objective of this study was to assess age-related associations with endocrine sensitivity (H/I), proliferative status (MGI), and quantitative expression of ER and PR. Methods: Data were extracted from the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database containing clinicopathologic and molecular variables from clinical cases submitted for BCI testing. Molecular results from H/I, MGI, and quantitative (qPCR–based) ER and PR were analyzed across age groups. Chi-squared tests and ANOVA were used to compare the results between age groups (<40y, 40-49y, 50-59y, 60-69y, and ≥70y). Results: Analyses included 19,126 patients (median age at diagnosis 58.6y; 4.5% <40y, 20.6% 40-49y, 28.9% 50-59y, 32.5% 60-69y, and 13.6% ≥70y). Proliferation status (MGI) was significantly higher in patients <40y and 40-49y compared to older groups (P<.0001).H/I analysis indicated a similar distribution of high versus low endocrine responsiveness across all groups (P=.94), except the 40-49y group, in which fewer patients had high H/I (44.2% in <40y, 39.4% in 40-49y, 43.7% in 50-59y, 43.7% in 60-69y, and 43.1% in ≥70y; P=.0001). Median qER increased with age (P<0.0001), while qPR was similar across all age groups except for the 40-49y group (P=.57), in which expression was higher (P<.0001). Conclusion: Results from >19,000 patients with early-stage HR+ breast cancer and BCI testing showed a broad distribution in all variables. Tumors from the youngest patients (<40y) had the highest expression of proliferative genes and the lowest quantitative ER expression. However, endocrine response, according to the H/I biomarker, does not appear to be strongly linked to age. Citation Format: Melisko M, Chien AJ, Poage GM, Salganik M, Schnabel CA, Ruddy KJ, Blackwell K. Gene expression patterns in younger versus older HR+ breast cancer patients: An age-related analysis of HoxB13/IL17BR (H/I), proliferation status, and quantitative hormone receptor expression [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-03.

Abstract Introduction: Male BC is a rare disease (dx) for which management is extrapolated from trials in female BC. Comprehensive prospective data about QoL in men with BC could inform treatment. The international Male BC Consortium conducted a prospective registry of male BC patients of all stages who newly presented to a participating center between October 2013 and February 2017. A QoL substudy was conducted as part of this registry at most participating sites. Methods: Informed consent for participation in the QoL substudy was requested from new enrollees. Those who consented were asked to complete a survey including the EORTC QLQ-C30 and BR23 (breast cancer specific module), adapted by replacing female-specific items with male-specific sexual activity/function items from the prostate module (PR25). Outcomes were scored according to standard EORTC QLQ procedures on a 0-100 scale (with higher scores on QoL/functioning scales representing better QoL and functioning, and higher scores on symptom scales representing worse symptoms). Forms were analyzed centrally by EORTC. In order to compare to female BC, we used reference data from 2782 mixed age (62% under age 60) women with BC (of whom 1,147 had recurrent or metastatic dx, and 464 had stage 1-2 dx) reported in the EORTC QLQ-C30 Reference Values manual (2008). Results: A total of 557 men were enrolled in EORTC10085, 445 at sites participating in the QoL substudy. Consent forms were received from 422/445 (95%) for the substudy. Baseline survey (required to be completed within 30 days of enrollment) compliance was 85% (359/422). Median age at diagnosis was 67 years. There were 111 men (45%) with node-positive M0/MX dx and 27 men (8%) with M1 dx. Their median global health status score at baseline was 75 (IQR 67-83), higher than that documented historically in female BC (67, with IQR 50-83, in both the 2782 women with mixed stage and the subgroup of 464 with stage 1-2 tumors). The participating men's median social functioning score was 100 (IQR 67-100), also higher than the 83.3 (IQR 67-100) reported in mixed stage female BC patients, though no different than the 100 (IQR 67-100) found in women with stage 1-2 dx. Men's most commonly reported symptoms included fatigue (median score 13.9, IQR 0-33), insomnia (median score 0, IQR 0-33), and pain (median score 0, IQR 0-33), for which women's median scores were 33 (IQR 11-44), 33 (IQR 0-33), and 17 (IQR 0-50) with mixed stage dx, and 22 (IQR 0-33), 33 (IQR 0-33), and 17 (IQR 0-33) with stage 1-2 dx. Men's median sexual activity score was 33.3 (IQR 0-50), with less sexual activity reported by older patients and men with M1 dx. In those who were sexually active, median sexual function score was 83 (IQR 75-92), with no difference by age or stage. Conclusions: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses of 1- and 5-year surveys from this study will assess the impact of specific treatments on changes in symptoms and QoL over time. These data will be useful in future efforts to tailor treatments and target interventions for male BC. Funding: Breast Cancer Research Foundation, Dutch Pink Ribbon Foundation, Swedish BRO, and EBCC Council. Citation Format: Schroder C, Cardoso F, Dijkstra N, van Leeuwen-Stok E, Linderholm B, Morgenstern D, Van Poznak C, Wolff AC, Poncet C, Gomez HL, Aalders K, Bjelic-Radisic V, Werutsky G, Tryfonidis K, Coens C, Giordano SH, Ruddy KJ. Quality of life (QoL) in male breast cancer (BC): Prospective study of the EORTC10085/TBCRC029/BIG2-07/NABCG International male BC program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-02.

Abstract BACKGROUND: Arm morbidity, the most reported comorbidity following axillary surgery for breast cancer, is of particular importance in young patients given the longer survivorship period and detrimental effects of arm-morbidity on body image and social-, home- and personal care functions. We assessed the incidence of arm-morbidity stratified by local therapy strategies in young women enrolled in the Young Women's Breast Cancer Study (YWS). PATIENTS AND METHODS: The YWS, a multicenter prospective cohort study, established to explore biological, medical and psychosocial issues in young breast cancer patients, enrolled 1302 women with stage 0-4 breast cancer ≤40 years of age from October 2006 to June 2016. For this analysis, we examined incidence of patient reported arm-swelling or decreased range of motion (ROM) 1-year after diagnosis using relevant items of the CARES-SF. Patients with stage 4 disease (n = 60), those for whom no information on arm-morbidity was available (n=198) and those with bilateral cancer with different local therapy strategies on each side (n=7), were excluded. We performed logistic regression analyses to identify risk factors for arm morbidity. RESULTS: Among 1037 patients (median age 37 years), 13% and 40% reported arm-swelling or decreased ROM, respectively, in the ipsilateral arm at 1-year. 52% (n=539) of patients underwent SLNB and 39% (n=407) ALND. The incidence of arm-swelling was 4% (11/280) in patients who underwent SLNB without RT, 8% (21/252) in patients who underwent SLNB with RT, 20% (13/66) in patients who underwent ALND without RT and 24% (84/337) in patients who received ALND with RT. The incidence of decreased ROM was 21% (59) in patients who underwent SLNB without RT, 34% (86) in patients who underwent SLNB with RT, 33% (22) in patients who underwent ALND without RT and 44% (148) in patients who received ALND with RT. Being overweight, uncomfortable financial status, T4 tumors, ALND and RT were independently associated with an increased risk of arm-swelling. Overweight, mastectomy and RT were independently associated with an increased risk of a decreased ROM Table 1). Results of the logistic regression analyses. Arm swelling at 1 year (n=137)Decreased ROM at 1 year (n=335) ORpORpBMI <18.50.70.620.70.4018.5-24.9ref ref 25-29.91.70.031.50.05≥301.10.791.10.70Financial comfort Comfortableref ref Uncomfortable0.60.020.90.67pT stage pT1ref ref pT21.20.621.50.13pT31.20.701.30.63pT44.40.032.20.29pN stage pN0ref ref pN11.10.851.70.08pN23.00.111.90.27pN33.20.112.70.16Surgery BCSref ref Mastectomy1.20.611.80.02Bilateral mastectomy1.10.841.60.06Axillary surgery SLNBref ref SLNB + ALND3<0.011.30.33ALND3.6<0.011.00.90RT Noref ref Yes1.80.052.4<0.01Note. In these analysis we also corrected for age, incidence year, employment status, stage of disease, reconstructive surgery, and chemotherapy treatment. . CONCLUSION: Patient reported outcomes reveal high rates of arm-swelling and decreased ROM 1 year after breast cancer diagnosis in a large prospective cohort of young breast cancer survivors. These findings suggest an opportunity for pre-operative education and early intervention for arm impairment in this population. Citation Format: Kuijer A, Dominici LS, Rosenberg SM, Hu J, Gelber S, Di Lascio S, Ruddy KJ, Wong J, Tamimi RM, Schapira L, Borges VF, Come SE, Sprunck-Harrild K, Partridge AH, King TA. Risk of arm morbidity after local therapy in young breast cancer survivors [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS5-03.

Abstract Background: Despite the well-established survival benefit associated with adjuvant hormonal treatment, younger women with hormone receptor positive (HR+) breast cancer (BC) are less adherent to endocrine therapy (ET) as prescribed, compared to their older counterparts, and may have unique issues that contribute to ET non-adherence. In an effort to identify factors that can be targeted to improve ET uptake and adherence, we sought to evaluate ET initiation in young women with BC. Methods: As part of a multi-center, prospective cohort enrolling women with newly diagnosed BC at age ≤40 years between 2006-2016, we identified 657 women with HR+, Stage 0-III BC. Participants complete serial surveys that included questions about socio-demographics, fertility concerns, and treatment. Women who did not report taking tamoxifen or an aromatase inhibitor (AI) at least once in the 18 months after diagnosis (dx) were classified as non-initiators. Variables significant at p<0.20 in univariable models were entered into a multivariable logistic regression model to identify independent (p<0.05) predictors of non-initiation. Results: By 18 months post-dx, 15% (99/657) had not initiated ET; among women with Stage 0 BC, 77% (51/66) had not initiated vs 8% (48/591) with invasive BC (p<0.0001). Among initiators (N=558), 93% were on tamoxifen, with 7% reporting AI alone or in addition to tamoxifen; 97% started ET within 12 months of dx. Among women with invasive BC (Table), non-initiation was associated with having less than a college degree (OR: 2.49 95% CI: 1.25-4.94), non-Caucasian race (OR: 2.58 95% CI: 1.18-5.64) and non-receipt of radiation (OR: 0.40 95% CI: 0.21-0.75).Age at dx, marital status, having children, employment, perceived financial comfort, fertility concern, stage, surgery, and chemotherapy were not significantly associated with non-initiation. Conclusion: Most young women with HR+ DCIS do not take adjuvant ET despite the potential benefits (substantially reduced risk of local recurrence and contralateral BC) and very low risk of serious toxicity. Among young women with invasive HR+ BC, a significant minority fails to start ET within 18 months of dx. Adjuvant ET non-initiation may contribute in part to the racial and SES outcomes disparities that have been observed. Further study is needed to elucidate barriers to initiation with the goal of developing targeted interventions that will enhance ET initiation and adherence in general. Table. Predictors of ET non-initiation in women with invasive BC (N=577*) Univariable Multivariable Median (range)OR (95% CI)pOR (95% CI)ppAge at dx (years)36 (17-40)1.08 (0.99-1.18)0.07 N (%) Financial comfort300 (51)0.88 (0.49-1.60)0.68 Non-white59 (10)2.68 (1.25-5.71)0.012.58 (1.18-5.64)0.02Full employment282 (48)0.76 (0.42-1.39)0.38 Less than college graduate95 (16)2.61 (1.36-5.02)0.0042.49 (1.25-4.94)0.009Married/living as married452 (77)0.79 (0.41-1.55)0.50 Children pre-diagnosis369 (62)1.11 (0.60-2.05)0.75 Fertility concern234 (40)0.92 (0.50-1.70)0.80 Stage (ref=3) 1244 (41)1.22 (0.47-3.15)0.68 2259 (44)1.27 (0.50-3.24)0.62 Mastectomy vs lumpectomy335 (57)1.16 (0.64-2.12)0.63 Radiation therapy331 (56)0.40 (0.21-0.73)0.0030.40 (0.21-0.75)0.004Chemotherapy411 (70)0.66 (0.36-1.22)0.18 *multivariable analytic cohort Citation Format: Rosenberg SM, Gelber S, Ruddy KJ, Tamimi RM, Schapira L, Borges VF, Come S, Meyer ME, Partridge AH. Drugs don't work if people don't take them: Non-initiation of endocrine therapy in young women [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-09-07.

Abstract Background: Chemotherapy-related amenorrhea (CRA) impacts quality of life and reproductive options, and may play a role in treatment decision-making for young breast cancer patients. Although age, increasing doses of alkylating agents, and tamoxifen are known to increase the risk of chemotherapy-related amenorrhea (CRA), it is difficult to predict which women will develop CRA in order to inform fertility preservation and treatment decisions. We sought to investigate whether single nucleotide polymorphisms (SNPs) that have been associated with a younger age at natural menopause and ovarian reserve in non-oncologic populations were predictive of CRA in two large German clinical trials that administered gonadotoxic chemotherapy. Methods: A total of 1322 premenopausal participants under age 50 who enrolled in SUCCESS B (a phase 3 trial of FEC-docetaxel-trastuzumab +/- gemcitabine for high risk early stage breast cancer) or SUCCESS C (a phase 3 trial of FEC-docetaxel-cyclophosphamide vs. docetaxel-cyclophosphamide that also tested the efficacy of a weight loss intervention in early stage breast cancer patients) were eligible for this study. We excluded patients who were receiving ovarian suppression. On these trials, menstrual status was self-reported as amenorrheic or not every three months after chemotherapy. Bloods were stored and patients provided consent for DNA analysis. We genotyped nine candidate SNPs in six genes (rs2002555 and rs11170547 in AMHR2, rs6166 in FSHR, rs10852344 <60kb from TNFRSF17/RUNDC2A/ GSPT1, rs12461110 in NLRP11, rs1801133 in MTHFR, rs2066470 in MTHRF, rs3810682 in BMP15, and rs615942 in COASY), and examined their association with CRA at 12-month and 24-month time points using logistic regression adjusted for age, BMI, and tamoxifen. Results: Of the 554 eligible women with SNP data and menstrual data at 12 months, 70% reported CRA; of the 458 eligible women with SNP data and menstrual data at 24 months, 69% reported CRA. The two SNPs in AMHR2 showed suggestive associations with CRA at 12 and 24 months. [Final results pending]. Conclusions: Genetic variation in AMHR2 may be associated with CRA. Additional research will be needed to validate these findings in other breast cancer survivors and to identify additional SNPs that may be associated with CRA. Together with other clinical factors, genetic variation may improve our ability to predict who will experience CRA, and may inform reproductive and treatment decision-making in cancer patients. Citation Format: Ruddy KJ, Rack B, Schwitulla J, Lambrechts D, Haeberle L, Schramm A, Trapp E, Scholz C, Beutler AS, Ginsburg E, Couch F, Partridge AH, Wang L, Weinshilboum RM, Janni W, Vachon C, Fasching P. Genetic predictors of chemotherapy-related amenorrhea. [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 P4-10-07.