Rosenberg, Shoshana M.

Abstract Background: Extended adjuvant endocrine therapy (eET) beyond the first 5 years of ET improves long-term outcomes in breast cancer survivors. For women who remain premenopausal, evidence for benefit has only been demonstrated to date for 5 years of additional tamoxifen, after an initial 5 years of tamoxifen (from ATLAS, aTTom). There are no data available for eET among premenopausal women treated with initial adjuvant aromatase inhibition (AI) and ovarian functions suppression (OFS). Thus, there is uncertainty regarding the optimal eET regimen for young breast cancer survivors. Methods: The Young Women’s Breast Cancer Study (YWS) is a multicenter prospective cohort of women age ≤40 years newly diagnosed with breast cancer between 2006-2016. Women with stage I-III hormone receptor positive breast cancer, ≥6 years post-diagnosis without breast cancer recurrence were considered candidates for eET. Use of eET was elicited on surveys completed at 6, 7 and/or 8 years post-diagnosis, censoring for recurrence or death. Those completing ≥1 survey were eligible for analysis. Patient characteristics were compared by Chi-square test between eET users and non-users, and logistic regression applied to identify factors associated with eET use. Results: Of 667 potential eET candidates, 73.9% (493/667) returned ≥1 survey between year 6-8 and were eligible for analysis. Compared to those without a year 6-8 survey, the analytic cohort tended to be more non-Hispanic white (86.0% v. 77.6%), more financially comfortable (53.9% v. 39.5%) and more likely to have children pre-diagnosis (59.6% v. 41.4%); age and disease characteristics were similar. Overall, 59.6% (294/493) reported any eET use, with use declining over time from 56.9% (265/466) to 51.4% (219/426) to 46.8% (162/346) at years 6, 7 and 8 post-diagnosis, respectively. Among eET users (n=294), tamoxifen monotherapy was the most common approach (76.9%, 226/294), followed by AI monotherapy (22.1%, 65/294, presumably women who transitioned into menopause), AI-OFS (7.1%, 21/294) and tamoxifen-OFS (3.1%, 9/294). Women diagnosed after 2012 were as likely to receive eET as those diagnosed 2006-2011 (59.4%, 117/197 v. 59.8%, 177/296 p=0.928), however eET more often included AI, with or without OFS (41.0% v. 18.6%, p<0.001), or OFS (17.9% v. 7.3%, p=0.005) in later years. In multivariable analysis, increasing age (per year odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.15, p<0.001), higher stage (II v. I: OR: 2.85, 95% CI: 1.81-4.48, p<0.001; III v. I: OR: 3.73, 95% CI: 1.87-7.42, p<0.001) and receipt of chemotherapy (OR: 3.50, 95% CI: 2.08-5.91, p<0.001) were independently significantly associated with any eET use, while women not of white non-Hispanic race/ethnicity were less likely to report eET use (OR: 0.49, 95% CI: 0.28-0.87, p=0.014). Rates of pregnancy in years 1-5 did not differ between eET users and non-users (10.0%, 29/291 v. 8.7%, 17/195, p=0.645) Conclusion: The majority of eligible young breast cancer survivors in the YWS have received eET despite limited data regarding its utility in this population. Heterogeneity exists regarding strategies utilized, and while some factors associated with eET use appear to reflect appropriate risk-based care, such as stage and receipt of chemotherapy, others, including age and race, suggest disparate uptake. Clinical studies are needed in order to determine the optimal approach to eET for young women with a history of early stage hormone receptor-positive breast cancer who remain premenopausal following 5 years of ET. Ensuring risk and preference-based uptake of eET should be a priority. Citation Format: Tal Sella, Yue Zheng, Shoshana M Rosenberg, Kathryn J Ruddy, Shari I Gelber, Rulla M Tamimi, Jeffrey M Peppercorn, Lidia Schapira, Virgina F Borges, Steven E Come, Lisa A Carey, Eric P Winer, Ann H Partridge. Extended adjuvant endocrine therapy in a longitudinal cohort of young breast cancer survivors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD13-10.

Background Fear of cancer recurrence (FCR) is more intense in younger women. Because FCR is a powerful determinant of quality of life, identifying those at risk for persistently elevated FCR can inform timing of interventions. Methods A total of 965 women with stage 0 to stage III breast cancer enrolled in the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with breast cancer at age ≤40 years, completed the 3‐item Lasry Fear of Recurrence Index. Group‐based trajectory modeling was used to classify distinct FCR patterns from baseline through 5 years post‐diagnosis. Multinomial logistic regression was used to identify patient, disease, and treatment characteristics associated with each trajectory. Results Five FCR trajectories were identified with the majority of participants having moderate (33.1%) or high FCR (27.6%) that improved over time. A total of 6.9% participants had moderate FCR that worsened, whereas 21.7% had high FCR at baseline that remained high throughout. In the fully adjusted multinomial model, stages II and III (vs stage I) were associated with higher odds of being in the high/stable trajectory, whereas stage 0 (vs I), being financially comfortable (vs not comfortable), was associated with lower odds of being in the high/stable trajectory. White (vs non‐White) was associated with higher odds of being in a trajectory that improved over time. Conclusions Although FCR improves over time for many young women with breast cancer, approximately one‐third had FCR that was severe and did not improve or worsened over 5 years after diagnosis. Ongoing monitoring is warranted, with early referral to mental health professionals indicated for those at highest risk for unresolved FCR. Lay Summary Fear of recurrence is common among young women with breast cancer. The authors followed a large cohort of young women diagnosed with breast cancer when they were 40 years of age and younger, and found 5 distinct trajectories that show moderate and severe fears do not always improve over time and may require targeted mental health intervention.

PURPOSE The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2–positive (HER2+) breast cancer (BC). METHODS Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m 2 IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks). The co-primary objectives were to compare the incidence of clinically relevant toxicities (CRTs) in patients treated with T-DM1 versus TH and to evaluate iDFS in patients receiving T-DM1. RESULTS The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH). CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH ( P = .83). The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis ( P < .0001). Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH. CONCLUSION Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS, but was not associated with fewer CRT compared with TH.

12081 Background: Young women with breast cancer may be at increased risk for premature development of cardiovascular disease (CVD) in part due to their cancer treatment. Limited data are available on CVD risk among young breast cancer survivors. Methods: Women aged 30-40 years at diagnosis with stage 0-III breast cancer enrolled in a prospective cohort study of women diagnosed with breast cancer at ≤40 were eligible for inclusion in this analysis. Data were obtained from serial surveys and electronic medical records at breast cancer diagnosis and 5-year follow-up. We calculated “excess heart age,” which incorporates a CVD risk-based score (calculated using age, systolic blood pressure, blood pressure medication, diabetes, smoking, body mass index) to estimate the difference in years between an individual’s chronological age and their CVD-risk adjusted age. Multivariable logistic regression models (adjusting for age at diagnosis, stage, and race) were fitted to evaluate associations between treatment (radiation, endocrine therapy, anthracyclines, and trastuzumab) and having a change in excess heart age ≥2 years from baseline to 5 years. Results: Among 372 young breast cancer survivors, mean age at diagnosis was 36.6 (SD 2.89), 93% were white, and 79% were diagnosed with stage I or II breast cancer. Mean excess heart age was.32 (SD: 6.16) years at baseline, which declined to -.07 (SD 6.64) at 5-year follow-up (p=.17). At 5 years, 31% (n=114) of women experienced an increase of at least 2 years in their excess heart age since diagnosis, and their mean excess heart age was 4.34 years (range -9 to 30). In multivariable analyses, receipt of trastuzumab was associated with higher odds (OR: 1.68, 95% CI: 1.02-2.77) of experiencing an increase of ≥2 years in excess heart age between diagnosis and 5 years of follow-up. Endocrine therapy, anthracyclines, and radiation were not significantly associated with a change in excess heart age of ≥2 years at 5 years post-diagnosis. Conclusions: At 5 years post-diagnosis, approximately 1/3 of young breast cancer survivors experienced a change from baseline in their excess heart age of ≥2 years. Further research is warranted to confirm findings regarding trastuzumab and excess heart age, and potential effects on longer-term cardiac outcomes in this population. Extended follow-up of this cohort may further quantify CVD risk over time.[Table: see text]

e24108 Background: Clonal hematopoiesis of Indeterminate Potential (CHIP) is associated with adverse clinical outcomes including increased risk of hematologic malignancies and heart disease. Limited data suggest an increased prevalence of CHIP in patients treated for solid tumors, particularly after exposure to radiation and chemotherapy. CHIP testing may inform risk-reduction strategies for cancer survivors. Little is known about patient knowledge, attitudes, and preferences regarding CHIP testing. Methods: We surveyed survivors without history of recurrence participating in an ongoing prospective cohort study of young women with breast cancer (BC). The survey was sent by email and included an introduction to CHIP including risk factors and clinical associations. Respondents then reviewed a vignette and were asked about CHIP testing preferences (definitely/probably test vs. definitely/probably not test) considering sequentially: 1) population-based 10-year risk of BC recurrence, hematological malignancy and heart disease; 2) estimated increase in these risks with CHIP; 3) current CHIP management; 4) a dedicated CHIP clinic; and 5) a theoretical CHIP treatment. Changes in preferences from the prior scenario were evaluated with the McNemar's test using a type I error rate of 5%. Results: 528/642 (82.2%) eligible women responded to the survey, at a median age of 46 (range: 31-54) years (median time from diagnosis: 108 months (range: 60-168)), and 88% were white. Most had stage 1/2 BC (78.8%) and had received chemotherapy (73.1%) and/or radiation (61.9%). 93.6% had never heard of CHIP prior to survey. After initial patient vignette presentation, most women (87.1%,) recommended CHIP testing if offered. Preferences for testing decreased (p<0.05) when considering population-based risks, with 11.1% shifting their preference from CHIP testing to not testing. After considering increased risks associated with CHIP, interest in testing increased (p<0.05), with 10.1% shifting their preference to testing. Interest significantly (p<0.05) increased with the possibility of managing CHIP through a clinic or a hypothetical CHIP treatment, with 7.2% and 14.1% switching their preferences towards testing, respectively. Finally, 75.8% responded that they themselves, after learning about CHIP and reviewing the vignette, would want to have CHIP testing; 28.2% reported that learning about CHIP and the associated risks caused them at least moderate anxiety. Conclusion: Few young BC survivors were aware of CHIP yet most indicated an interest in testing after learning about it. Testing preferences were influenced by risks presented and potential management strategies. Findings highlight the importance of effective risk communication and the need for adequate psychosocial support when considering testing for CHIP and other potential clinical biomarkers predictive of cancer and other medical risks in cancer survivors.

e18561 Background: Young women with breast cancer (BC) have unique issues, including fertility, genetic, and emotional health concerns; these may sometimes be inadequately addressed by providers. Given documented disparities in BC care and outcomes, we sought to explore whether provider attention to these issues differs by race, as well as to examine racial differences in satisfaction with care among young patients with BC. Methods: The Young & Strong Study was a cluster randomized trial of an educational and supportive care intervention at 14 academic + 40 community oncology practices across the US enrolling women with newly diagnosed BC at age ≤45 and their providers. Patients completed surveys at baseline, 3, 6, and 12 months after enrollment. Race was self-reported at baseline. Provider attention to fertility, genetics, and emotional health was evaluated by medical record review. The proportions of patients with attention to these concerns by 3 months was compared by race (white, Black, Asian, multi-racial/other/unknown) using Fisher’s exact tests. Satisfaction with care was assessed with the Patient Satisfaction Questionnaire-18 (PSQ-18) at 3 months. Median scores for each of 7 PSQ-18 subscales (1-5 scale, higher scores=more satisfaction) were compared by race with the Kruskal-Wallis test. Results: 465/467 (99.6%) of enrolled patients had evaluable data. 77% were white, 12% Black, 4% Asian, and 7% multiracial/other/unk. Median age at diagnosis was 40 (range: 22-45) years. Provider attention to genetics (≥85%) and emotional health (≥90%) was high across groups, and there were no differences by race in attention to fertility, genetics, or emotional health (Table). Among 359/465 women (77%) who completed the PSQ-18, median subscale scores ranged from 3.5-4.5, indicating high levels of satisfaction with care. For the PSQ-18 technical quality domain, median scores were lower (p=.03), indicating less satisfaction, in Black and Asian women (4.0) and higher in white women (4.5). Median scores for other PSQ-18 domains (general satisfaction, interpersonal manner, communication, financial, time spent with doctor, accessibility) did not differ by race. Conclusions: Satisfaction with care was high and issues related to fertility, genetics and emotional health were addressed by providers in the majority of young women in our study, with minimal differences by race. These patients were all enrolled in a clinical trial and had access to high-quality care, limiting the generalizability of our findings. Larger, population-based studies in more diverse settings are warranted. Clinical trial information: NCT01647607. Attention to psychosocial concerns by race. [Table: see text]

BackgroundThe diagnosis and treatment of breast cancer can have profound effects on a young woman's family planning and fertility, particularly among women with hormone receptor–positive breast cancer.MethodsThe Young Women's Breast Cancer Study was a multicenter cohort of women aged 40 years or younger and newly diagnosed with breast cancer from 2006 to 2016. Surveys included assessments of fertility concerns, endocrine therapy (ET) preferences, and use. Characteristics were compared between women who reported that fertility concerns affected ET decisions and those who did not. Logistic regression was used to identify factors associated with having an ET decision affected by fertility concerns.ResultsOf 643 eligible women with hormone receptor–positive, stage I to III breast cancer, one‐third (213 of 643) indicated that fertility concerns affected ET decisions. In a multivariable analysis, only parity at diagnosis was significantly associated with fertility concerns affecting ET decisions (odds ratio for nulliparous vs ≥2 children, 6.96; 95% confidence interval, 4.09‐11.83; odds ratio for 1 vs ≥2 children, 5.30; 95% confidence interval, 3.03‐9.87). Noninitiation/nonpersistence was higher among women with fertility concerns versus those without fertility concerns (40% vs 20%; P < .0001). Among women with fertility‐related ET concerns, 7% (15 of 213) did not initiate ET, and 33% (70 of 213) were nonpersistent over 5 years of follow‐up. Of these women, 66% (56 of 85) reported 1 or more pregnancies or pregnancy attempts; 27% (15 of 56) had resumed ET at the last available follow‐up through 5 years.ConclusionsConcern about fertility is a contributor to adjuvant ET decisions among a substantial proportion of young breast cancer survivors. Ensuring family planning is addressed in the setting of ET recommendations should be a priority throughout the cancer care continuum.

Abstract BackgroundCancer diagnosis and early treatment may have wide-ranging consequences for a woman’spartner (ie. spouse or significant other). In general, younger caregivers have been found to havegreater unmet needs and higher levels of distress compared to those who are older. To date,there is little known about the unmet needs and experiences of partners who care for youngwomen with breast cancer during active treatment.Trial Design: Cross-sectional survey of partners of young women with breast cancer.Eligibility Criteria: The current analysis focuses on a subset of respondent partners of womenwith breast cancer participating in the Young Womens Breast Cancer Study (NCT01468246)who met the following criteria: diagnosed at age &lt; 40 years; time since diagnosis &lt;12 months;and/or Stage IV disease (at diagnosis or in metastatic setting); and/or local recurrent disease&lt; 12 months.Specific Aims: To explore the experience of partners of women in active treatment or havingvery recently completed treatment for breast cancer.Statistical Methods: We employed descriptive statistics to present sample characteristics,including means or medians for continuous variables and proportions for categorical variables.We assessed partners’ responses re: sociodemographics, perceived social support (MOS-Social Support Survey, Cancer Perceived Agents of Social Support), quality of life (QOL)(Caregiver QOL Index-Cancer), coping (Brief COPE), perceived financial security, perceivedparenting concerns (Parenting Concerns Questionnaire), anxiety and depression symptoms(Hospital Anxiety and Depression Scale), sexual satisfaction (Global Measure of SexualSatisfaction), posttraumatic growth (Posttraumatic Growth Inventory-Short Form), and an open-ended question to explore their experiences and needs.Accrual: 25 participants were included.Results: All partners were male (25/25; 100%), and most were white (n=23/25; 92%), workingfull-time (n=21/25; 91%); and college educated (n=19/25; 86%). Eighteen partners (n=18/25;72%) were parenting children &lt;18 years old and 40% (n=10/25) were partnered with womenwith Stage 4 breast cancer. At the time of the survey, the median age of partners was 44 years(range, 28-69) and of patients was 38 years (range, 25-40). Many partners (57%) reportedsymptoms of anxiety (&gt;8 on the HADS anxiety subscale), fewer (22%) were categorized ashaving symptoms of depression (&gt;8 on the HADS depression subscale). Additionally, 39%reported not being sexually active; 41% reported maladaptive coping; 30% reported financialstrain;30% reported relationship strain. Reported caregiver QOL ranged from 22-116, with amean score of 52.5 (SD, 23.9), similar to population norms, with higher scores indicating lowerquality of life. Parenting concerns scores were generally low indicating less concern, with arange of 12-35, and mean of 20.5 (SD, 7.6). Post-traumatic growth ranged from 4-33, with amean score of 20.7 (SD, 7.4), with higher scores indicating greater personal growthexperienced. 44% (11/25) responded to the open-ended experiences and needs question.Common responses included feeling a lack of support, need for tailored and titrated information,and desire to connect with other men who faced similar experiences. Partners also reportedtheir struggles with uncertainty about the future. Discussion: A subset of partners of young women in active treatment for breast cancerexpressed concerns related to relationship strain, sexuality, need for support, and finances.Future work designed to meet the needs of partners of breast cancer patients includinginformational and psychosocial supports may benefit them and the patients as they manage theprocess of ongoing treatment and challenges about the future. Citation Format: Tamryn F Gray, Nancy Borstelmann, Shoshana Rosenberg, Shari Gelber, Meghan E Meyer, Kathryn J. Ruddy, Lidia Schapira, Steven Come, Virginia Borges, Tamara Cadet, Peter Maramaldi, Ann H. Partridge. The psychosocial impact of caregiving on partners of young women with breast cancer in treatment [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-08.