Citations

Abstract Background: Young women with DCIS are at increased risk of recurrence and second BC compared to older women and may derive the greatest benefit from risk reduction strategies. Little is known about treatment decision-making, engagement in preventive behaviors, or fear of recurrence among young DCIS survivors. Thus, we sought to investigate treatment and prevention issues in this population. Methods: Using a multicenter prospective cohort that enrolled 1302 women with stage 0-IV BC at age ≤40, we identified participants with DCIS only who completed surveys in the year following diagnosis (dx). Surveys assessed treatment decisions, lifestyle factors (alcohol, smoking, physical activity [PA]), and fear of recurrence (Lasry Scale). Data was summarized with descriptive statistics and groups were compared with Fisher’s exact test. Results: Among 87 patients (median age 38, range 26-40), 75 had available treatment decision data, 19 (25%) of whom had breast-conserving surgery (BCS), 11 (15%) unilateral mastectomy (UM), and 45 (60%) bilateral mastectomy (BM). Most (77%) indicated their doctor said BCS was an option or recommended, including 34 (59%) who had BM. Of 40 patients who reported a patient-driven surgical decision, 73% had BM, 13% UM, and 15% BCS. Among 15 patients who reported the decision as doctor-driven, none had BM, 27% UM, and 73% BCS. Those who had BM were more likely to be extremely confident about the decision (80% vs. 73% UM vs. 53% BCS, p=0.022). Adjuvant tamoxifen was used by 10/27 (37%) patients with ER+ DCIS who had BCS/UM. Most who took tamoxifen reported this decision was shared with their doctor (90%); 1 reported the decision was made on her own. Of the 17 patients who did not take tamoxifen, 88% indicated their doctor said endocrine therapy was an option or recommended. Among all 87 patients, 31 (36%) were former and 3 (4%) were current smokers at baseline assessment (median 5 months post-dx); 51 (59%) never smoked. Overall, 4 quit within 1 year of dx. Most patients (83%) were current drinkers at baseline, though 79% consumed <5 alcoholic beverages/week; 8% reported lower consumption at 1 year. Regarding PA at 1 year, 73% (58/80) reported ≥150 minutes of moderate-intensity PA/week. Overall, 41% of young survivors were at least moderately concerned about their BC coming back, with concern varying numerically by surgery (65% post-BCS, 50% post-UM, 29% post-BM, p=0.053). Conclusions: BC recurrence concerns were frequent among young DCIS patients, particularly among those with remaining breast tissue. BM decisions were largely patient-driven and made with high confidence, reflecting preferences towards surgical prevention. While adherence to survivorship lifestyle guidelines was high, including not smoking, consumption of ≤7 drinks/week, and engaging in PA, tamoxifen use was low, even when offered by a provider. Young DCIS survivors appear motivated to lower future BC risk through surgery and maintenance of healthy behaviors, and less so with tamoxifen; such values should be considered during treatment and survivorship counseling. Citation Format: Megan E. Tesch, Julia S. Wong, Laura Dominici, Kathryn J. Ruddy, Rulla Tamini, Lidia Schapira, Virginia F. Borges, Ellen Warner, Steven E. Come, Karen Sepucha, Laura C. Collins, Ann H. Partridge, Shoshana M. Rosenberg. Breast cancer (BC) risk reduction in young women with ductal carcinoma in situ (DCIS) [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR009.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

The NCCN Guidelines for Survivorship are intended to help healthcare professionals who work with survivors to ensure that the survivors’ complex and varied needs are addressed. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for the consequences of adult-onset cancer and its treatment; recommendations to help promote physical activity, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes updates to the NCCN Guidelines pertaining to preventive health for cancer survivors, including recommendations about alcohol consumption and vaccinations.

Abstract Clonal hematopoiesis of indeterminate potential (CHIP), an emerging biomarker for personalized risk-directed interventions, is increased in cancer survivors. However, little is known about patient preferences for CHIP testing. We surveyed participants in a prospective cohort study of young women with breast cancer (BC). The emailed survey included an introduction to CHIP and a vignette eliciting participants’ preferences for CHIP testing, considering sequentially: population-based 10-year risk of BC recurrence, hematologic malignancy, and heart disease; increased CHIP-associated risks; current CHIP management; dedicated CHIP clinic; and hypothetical CHIP treatment. Preference changes were evaluated using the McNemar test. The survey response rate was 82.2% (528/642). Median age at time of survey was 46 years and median time from diagnosis was 108 months. Only 5.9% had prior knowledge of CHIP. After vignette presentation, most survivors (87.1%) recommended CHIP testing for the vignette patient. Presented next with CHIP-independent, population-based risks, 11.1% shifted their preference from testing to not testing. After receiving information about CHIP-associated risks, an additional 10.1% shifted their preference to testing. Preference for testing increased if vignette patient was offered a CHIP clinic or hypothetical CHIP treatment, with 7.2% and 14.1% switching preferences toward testing, respectively. Finally, 75.8% of participants desired CHIP testing for themselves. Among participants, 28.2% reported that learning about CHIP caused at least moderate anxiety. Most young survivors favored CHIP testing, with preferences influenced by risk presentation and potential management strategies. Our findings highlight the importance of risk communication and psychosocial support when considering biomarkers for future risk in cancer survivors. This trial has been registered at www.clinicaltrials.gov as #NCT01468246.

BackgroundWeight gain after a breast cancer diagnosis is common and is associated with inferior outcomes. Young survivors may be especially susceptible to weight changes given the impact of treatment on menopausal status.MethodsThe authors identified women who were diagnosed with stage 0 to III breast cancer at age 40 years or younger between 2006 and 2016 from a multicenter prospective cohort. Self‐reported weight was collected at diagnosis and at 1 year and 3 years postdiagnosis. Tumor and treatment data were obtained from medical records and patient surveys. Multinomial logistic regression was used to identify the factors associated with weight gain (≥5%) or weight loss (≥5%) versus stable weight at 1 year and 3 years postdiagnosis.ResultsThe cohort included 956 women with a median age of 37 years at diagnosis. Mean weight significantly increased over time from 66.54 ± 14.85 kg at baseline to 67.33 ± 15.53 and 67.77 ± 14.65 kg at 1 year and 3 years, respectively (p ≤ .001 for both comparisons). The proportion of women experiencing ≥5% weight gain increased from 24.8% at 1 year to 33.9% at 3 years. At 1 year, less self‐perceived financial comfort, Black race, and stage III disease were significantly associated with weight gain; at 3 years, only less self‐perceived financial comfort remained significant. Baseline overweight or obesity was significantly associated with weight loss at both time points. Chemotherapy, endocrine therapy, and treatment‐related menopause were not associated with weight change.ConclusionsOne third of young breast cancer survivors experienced clinically significant weight gain 3 years after diagnosis; however, treatment‐related associations were not observed. Age‐appropriate lifestyle interventions, including the reduction of financial barriers, are needed to prevent weight gain in this high‐risk population.

10607 Background: Young women with breast cancer who carry germline genetic pathogenic variants predisposing to breast and other cancers, including BRCA1 or BRCA2, may face unique challenges when making fertility decisions. Limited data exist on differences in fertility preferences, concerns, and preservation strategies between carriers and non-carriers. Methods: Participants in the Young Women’s Breast Cancer Study, a prospective cohort of women diagnosed with breast cancer at ≤ 40 yrs, who completed a baseline survey with a modified Fertility Issues Survey were included in this analysis. Genetic variant status was determined by medical record review complemented by survey self-report. We excluded carriers whose test date was after baseline survey completion or unknown. Fisher exact and Wilcoxon signed-rank tests were used to compare categorical and continuous variables, respectively, between carriers and non-carriers. Results: Of 1052 eligible women, 118 (11%) tested positive for a pathogenic variant (59% BRCA1, 32% BRCA2, 4% TP53, and 5% other unique pathogenic mutations) and 934 (89%) tested negative or were not tested. Carriers’ median age was 36 yrs (range 23-40) vs 37 (range 17-40, p = 0.01) in non-carriers. Similar proportions (p = 0.67) of carriers (38%, [45/118]) and non-carriers (37%, [343/934]) desired more biologic children before diagnosis. Desire declined after diagnosis similarly in both groups (carriers, 25% [29/118] vs non-carriers, 26% [242/934], p = 0.46). Among these women (n = 271), concern about passing on cancer risk to offspring was common and, although numerically higher among carriers, this difference was not statistically significant (carriers, 55% [16/29] vs non-carriers, 40% [96/242], p = 0.12). In contrast, among those not interested in or unsure about future fertility (n = 738), concern about cancer risk heritability was infrequently reported as affecting fertility decisions (carriers, 11% [9/83] vs non-carriers, 9% [56/655], p = 0.54). The same proportions (p = 0.89) of carriers (36% [43/118]) and non-carriers (36% [339/934]) were somewhat or very concerned about becoming infertile after cancer treatment, and fertility preservation strategy utilization was similar between groups (carriers, 11% [13/118] vs non-carriers, 12% [111/934], p = 0.21). Conclusions: Young women with breast cancer who carry germline pathogenic variants are similarly concerned about future fertility and as likely to pursue fertility preservation as non-carriers. Concern about cancer risk heritability was common among both carriers and non-carriers desiring future fertility, suggesting a gap between perceived and actual risk. Genetic counseling should be included in fertility discussions for all young women with breast cancer, with tailored, risk-mitigating recommendations for those who carry genetic variants.

524 Background: OFS is an important treatment component for premenopausal women with early and advanced HR+ BC and optimal efficacy may depend on complete E2 suppression with GnRHa, especially when combined with aromatase inhibitors (AI). However, standard assays lack sensitivity and accuracy at very low E2 concentrations, rendering detection of breakthrough ovarian function challenging. More informative data regarding endocrine effects of GnRHa are needed, particularly in young women who derive the most benefit from OFS yet more frequently had breakthrough E2 levels in the SOFT trial substudy, SOFT-EST. Methods: Using a prospective cohort study of women with BC diagnosed at age ≤ 40 years, we identified participants with stage I-IV HR+ BC on OFS treatment with leuprolide, goserelin or triptorelin and blood collected 1 year after diagnosis. Clinical data were obtained through surveys and medical records. Plasma estrogens were measured by liquid chromatography-tandem mass spectrometry, with a limit of detection of 0.2 pg/mL compared to 10 pg/mL with standard assays. We assessed the proportion of women on OFS with E2 > 2.72 pg/mL (10 pmol/L) and > 10 pg/mL. Patient characteristics, estrone (E1) and FSH levels, and disease-free (DFS) and overall survival (OS) were compared between those with and without elevated E2 using Fischer’s exact, Wilcoxon rank sum and log rank tests, respectively. Results: Of 84 patients who met inclusion criteria, 72 (86%) had stage I-III and 12 (14%) had stage IV BC; 25 were on OFS plus AI and 59 were on OFS plus tamoxifen (TAM). Median E2 was 3.1 pg/mL (range 0.2-30.9). 46 patients (55%) had E2 > 2.72 pg/mL, including 8 on AI and 38 on TAM; 4 (5%) had E2 > 10 pg/mL, including 1 on AI and 3 on TAM. Factors associated with E2 > 2.72 pg/mL were no prior chemotherapy, TAM and high E1 ( P ≤.05), but not age, BMI or GnRHa schedule (Table). After a median follow-up of 7 years, DFS events were seen in 6 patients with E2 > 2.72 pg/mL and 5 without ( P =.232); OS events were seen in 7 patients with E2 > 2.72 pg/mL and 5 without ( P =.608). Conclusions: More than half of young women with ER+ BC had E2 > 2.72 pg/mL on OFS, 91% of whom would not have been detected by standard assays. This may be an area amenable to intervention to improve outcomes in young women. However, larger studies are needed to elucidate the optimal E2 target on OFS and clinical implications of incomplete E2 suppression on ultrasensitive assays. [Table: see text]

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.

Abstract Purpose: Young age at breast cancer diagnosis correlates with unfavorable clinicopathologic features and worse outcomes compared with older women. Understanding biological differences between breast tumors in young versus older women may lead to better therapeutic approaches for younger patients. Experimental Design: We identified 100 patients ≤35 years old at nonmetastatic breast cancer diagnosis who participated in the prospective Young Women's Breast Cancer Study cohort. Tumors were assigned a surrogate intrinsic subtype based on receptor status and grade. Whole-exome sequencing of tumor and germline samples was performed. Genomic alterations were compared with older women (≥45 years old) in The Cancer Genome Atlas, according to intrinsic subtype. Results: Ninety-three tumors from 92 patients were successfully sequenced. Median age was 32.5 years; 52.7% of tumors were hormone receptor-positive/HER2-negative, 28.0% HER2-positive, and 16.1% triple-negative. Comparison of young to older women (median age 61 years) with luminal A tumors (N = 28 young women) revealed three significant differences: PIK3CA alterations were more common in older patients, whereas GATA3 and ARID1A alterations were more common in young patients. No significant genomic differences were found comparing age groups in other intrinsic subtypes. Twenty-two patients (23.9%) in the Young Women's Study cohort carried a pathogenic germline variant, most commonly (13 patients, 14.1%) in BRCA1/2. Conclusions: Somatic alterations in three genes (PIK3CA, GATA3, and ARID1A) occur at different frequencies in young versus older women with luminal A breast cancer. Additional investigation of these genes and associated pathways could delineate biological susceptibilities and improve treatment options for young patients with breast cancer. See related commentary by Yehia and Eng, p. 2209