Ruddy, Kathryn Jean

TPS1147 Background: Due to dramatic improvements in neoadjuvant and adjuvant HER2-directed therapy (tx), most patients (pts) with early HER2+ breast cancer are cured. As a result, over half of pts newly diagnosed with HER2+ metastatic breast cancer (MBC) now present with de novo stage IV disease. Anti-HER2 tx has also significantly extended survival for pts with HER2+ MBC, with a subgroup of exceptional responders alive many years (yrs) after diagnosis. However, the paradigm for HER2+ MBC remains non-curative, and pts receive tx indefinitely with significant toxicities and costs. The SAPPHO study is investigating whether an intensification approach of sequential, non-cross resistant anti-HER2 tx followed by tx discontinuation is associated with long-term disease control in pts with HER2+ MBC. Methods: SAPPHO is an open-label, phase II, single-arm trial testing a sequential regimen of non-cross resistant, HER2-targeted tx with curative intent in pts with de novo HER2+ MBC. Eligible pts must have biopsy-proven, de novo MBC with high HER2 expression (3+ by immunohistochemistry). Pts with brain metastases are eligible upon receipt of local tx. Treatment consists of an induction regimen (trastuzumab-pertuzumab-taxane [THP] x 4 cycles, followed by trastuzumab deruxtecan [TDXd] x 6 cycles, followed by trastuzumab emtansine [TDM1]-tucatinib x 4 cycles), followed by a maintenance regimen (HP-tucatinib for 1 yr). Given results from DESTINY-Breast09, the sequence of TDXd-P x 6 cycles followed by THP x 4 followed by TDM1-tucatinib x 4 can be chosen as alternative induction tx per investigator and patient choice. Pts who remain progression-free after completing maintenance will stop all anti-HER2 tx. Endocrine tx will be continued for pts with hormone receptor+/HER2+ tumors. Tumor specimens from breast and a metastatic site are collected at baseline and the end of induction. Serial plasma samples for ctDNA analysis are collected at baseline, during treatment, and during follow-up. The primary endpoint is the probability of being progression-free and off anti-HER2 tx 4 yrs from the start of induction. With a sample size of 72 pts, the study is designed to have 91% power to reject the null hypothesis that the probability of being off anti-HER2 tx and progression-free is less than 24%, with an alternative hypothesis of 40%. Key secondary endpoints are overall survival, overall response rate by modified RECIST 1.1 after induction, and safety. Correlative endpoints include the relationship between ctDNA dynamics and outcomes. Patient-reported outcomes will be analyzed, including quality of life, illness intrusiveness, financial toxicity, anxiety, distress about cancer progression, perception of benefit and risk of progression. SAPPHO began enrollment in Q3 2024, and the study is open at 4 US sites within the Translational Breast Cancer Research Consortium (NCT05721248). Clinical trial information: NCT05721248 .

e23276 Background: More than 50,000 patients with cancers of all stages were enrolled in the E2C2 trial, which captured patient-reported data across 6 symptom domains (SPPADE): sleep, pain, impaired physical function, anxiety, depression, and energy deficit or fatigue. This trial offers a unique opportunity to evaluate the evolution of symptom burden as prostate cancer (PCa) advances and the association of symptom burden with prognosis in the various disease states. Methods: The cohort was derived by cross-referencing participants in the E2C2 study with the Mayo Clinic Cancer Registry for more granular data on disease state and treatment characteristics, focusing on PCa. Symptoms were patient-reported on a 0-10 numerical rating scale, categorized as none/mild (0-3), moderate (4-6), and severe (7-10). We compared the prevalence of symptom burden across disease states, using the first survey completed by patients, in 3 groups: (1) non-metastatic (localized, locally advanced, and biochemically recurrent), (2) metastatic hormone sensitive (mHSPC), and (3) castration resistant (CRPC), using chi square tests. We then used log-rank tests to compare survival distributions based on symptom severity within each disease state. Results: A total of 1,011 patients were included. The distribution of moderate to severe symptoms by disease state is shown in Table 1. Fatigue, impaired physical function, and pain were more prevalent in patients with advanced disease, whereas the prevalence of depression and anxiety was not statistically different by disease state. Greater fatigue and physical impairment were consistently associated with poorer OS across all disease states, including patients with non-metastatic disease (p < 0.001). Pain was most strongly associated with inferior outcomes in the more advanced disease states of mHSPC (p < 0.001) and CRPC (p < 0.001). Anxiety (p < 0.001) and depression (p = 0.001) were only prognostic in CRPC patients. Conclusions: SPPADE symptoms are common in PCa. Physical symptoms are greater in more advanced disease, yet the high burden of unmet psychologic needs is similar across the disease states. Notably, severe patient-reported fatigue and physical dysfunction are strongly prognostic even in early disease, suggesting they are markers of physiologic vulnerability. Structured symptom monitoring may improve the identification of high-risk patients. Clinical trial information: NCT03892967 . Moderate to severe symptoms by disease state. Non-Metastatic (N= 243) mHSPC (N= 479) CRPC (N= 289) P-value Pain, n (%) 51 (21.3) 121 (25.5) 100 (35.1) 0.001 Fatigue, n (%) 92 (38.3) 230 (48.6) 163 (57.2) <0.001 Impaired Physical Function, n (%) 79 (32.5) 180 (37.7) 146 (50.7) <0.001 Sleep Disturbance, n (%) 72 (30.1) 167 (35.2) 104 (36.1) 0.3 Depression, n (%) 47 (19.6) 92 (19.4) 63 (22.0) 0.67 Anxiety, n (%) 56 (23.4) 93 (19.6) 68 (23.9) 0.3

e12697 Background: Postpartum-associated breast cancer (PABC) has been defined clinically as breast cancer (BC) diagnosed within the first 5 years of the most recent birth. Though generally rare, incidence rates are increasing in conjunction with delayed childbearing and older maternal age at first birth. Currently, there are limited data regarding serial patient-reported outcomes in this patient population compared to non-PABC patients. Methods: Patients with PABC from the Mayo Clinic Breast Disease Registry who completed baseline, 2, and 4-year surveys were matched 1:1 to BC patients whose cancers occurred more than 5 years after their most recent birth (or in the setting of nulliparity) based on age, clinical stage, treatment received, and tumor subtype. Survey results from the Patient Health Questionnaire-2 (PHQ-2), Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10), and Impact of Event Scale-Revised (IES-R) collected at approximately two and four years after diagnosis were compared between PABC and non-PABC patients. Univariable analyses used Wilcoxon rank sum tests, whereas multivariable analyses employed linear regression models adjusting for potential confounding effects. Results: A total of 222 individuals were included (111 with PABC). A higher proportion of individuals in the PABC cohort were married compared to the non-PABC cohort (80% vs. 42%, p < 0.001); otherwise, the groups were well-balanced across multiple categories, including age, gender, race/ethnicity, menopausal status, and germline mutation status. In univariable analyses, the Year 2 composite PHQ-2 score was significantly worse among individuals with non-PABC (p = 0.04), and the non-PABC cohort reported greater difficulty with sleep (p = 0.03) as measured by IES-R at Year 4. Both associations attenuated in a multivariable analysis controlling for marital status. In marital status-adjusted analyses of Year 4 survey results, PABC participants reported greater difficulty in carrying out social activities but were less likely to report emotional distress as evaluated by PROMIS-10 (compared with non-PABC participants). No other variables were significant univariably or multivariably (p > 0.05). Conclusions: In general, quality of life is similar among survivors of PABC compared to those diagnosed with breast cancer outside the postpartum period (or when nulliparous). However, our findings reveal that individuals with PABC are less likely to experience emotional distress 2 and 4 years after the BC diagnosis, which is unexpected, given that postpartum patients typically report higher levels of distress compared to their non-postpartum counterparts. Further investigation into these findings is warranted.

631 Background: Adolescent and young adult (AYA) women with breast cancer who have not completed their desired childbearing pre-diagnosis may be more likely to decline adjuvant endocrine therapy (ET) and/or to temporarily or permanently stop ET to pursue pregnancy. Fertility counseling and use of fertility preservation strategies (e.g., oocyte/embryo cryopreservation) might impact these decisions. Methods: In the Valuing Opinions and Insights from Cancer Experiences (VOICE) Study, we investigated whether use of fertility preservation strategies were associated with ET initiation and early discontinuation amongst AYAs with fertility concerns. Eligible females were diagnosed with stage 1–3 estrogen-receptor positive breast cancer at age 15-39 during 2013-2022 and responded to a survey in 2023-2024. Those who reported that they had not completed their desired family size or had been unsure about having completed their desired family size at the time of their cancer diagnosis were categorized as having had fertility concerns. ET initiation was defined as 2+ ET prescription fills within 18 months after diagnosis. Among ET initiators, we assessed early discontinuation (defined as lack of ET prescription fill over any 180 day period until 5 years after their first ET fill date). Due to inadequate power, we did not model the relationship between oocyte/embryo cryopreservation and ET initiation. However, we did have power to assess the association between oocyte/embryo cryopreservation and ET discontinuation using multivariable Cox regression to calculate Hazard Ratios (HR) and 95% Confidence Intervals (CI). HRs for discontinuation were adjusted for age at diagnosis, stage, study site, diagnosis year, income, and children before diagnosis (yes/no). Results: Among 518 AYA breast cancer survivors, 56% (N = 290) had fertility concerns at diagnosis. Of these 290, 41% had 1+ child before diagnosis, 90% received fertility counseling, 27% froze eggs or embryos, and 10% had 1+ child after diagnosis. The majority (89%) initiated ET. Among the 32 who did not initiate ET, 7 (22%) reported that fertility concerns impacted that decision. Oocyte/embryo cryopreservation was used by 26% of ET initiators and 34% of ET non-initiators. Among the 258 ET initiators, 89 (35%) discontinued ET early. Compared to those who did not use fertility preservation strategies, patients who froze oocytes/embryos were more likely to discontinue ET (HR 1.89; 95% CI 1.18–3.05). Among those who discontinued ET, 19% had 1+ child after diagnosis (compared to 2% among those who did not discontinue ET). Conclusions: This study confirmed prior studies showing that many AYAs with breast cancer have fertility concerns, and these concerns may impact decisions about ET. In our analysis, those who cryopreserved oocytes/embryos were more likely to discontinue ET early, and a higher proportion who discontinued ET had 1+ live birth after breast cancer.

632 Background: Prospective data on the risk of breast cancer (BC) recurrence among young BC survivors who have a subsequent pregnancy are limited. We sought to evaluate the long-term impact of pregnancy and live birth on BC outcomes in the Young Women’s Breast Cancer Study (NCT01468246), a prospective multicenter study of women aged ≤40 years at BC diagnosis. Methods: Women with stage 0-III BC without prior hysterectomy were included. The primary endpoint was breast cancer-free interval (BCFI) between patients with and without a (a) pregnancy and (b) live birth after BC. Secondary endpoints were distant recurrence-free interval (DRFI) and overall survival (OS). A time-varying Cox proportional hazards model was performed by estrogen receptor (ER) status, controlling for age at diagnosis, tumor stage, HER2 status, tumor grade, parity at diagnosis, and germline pathogenic variant status. Results: Among 1,016 BC survivors at a median follow-up of 12 (range, 0.5-18.5) years, 198 reported ≥1 pregnancy and 165 reported ≥1 live birth post-diagnosis. Among survivors who reported a post-diagnosis pregnancy, median age at diagnosis was 32 (range, 17-40) years; most had stage I (35%) or II (40%) BC, with 72% hormone receptor (HR)-positive and 25% HER2+; 42% were nulligravid and 60% were nulliparous at diagnosis. Among BC survivors who did not become pregnant post-diagnosis, median age at diagnosis was 37 (range, 21-40) years; most had stage I (35%) or II (43%) BC, with 75% HR-positive and 28% HER2+; 25% were nulligravid and 29% were nulliparous at diagnosis. Among BC survivors with ER-positive tumors (n = 737), pregnancy after BC was not associated with a difference in BCFI (adjusted hazard ratio [HR] 0.60, 95% CI 0.31-1.16, P = 0.130), DRFI (HR 0.73, 95% CI 0.35-1.55, P = 0.416), or OS (HR 0.58, 95% CI 0.24-1.40, P = 0.227). Similarly, live birth after BC did not impact BCFI (HR 0.83, 95% CI 0.45-1.55, P = 0.560), DRFI (HR 1.04, 95% CI 0.52-2.06, P = 0.923), or OS (HR 0.77, 95% CI 0.34-1.76, P = 0.541). Outcomes among BC survivors with ER-negative tumors (n = 278) were also not affected by post-diagnosis pregnancy (BCFI [HR 1.48, 95% CI 0.70-3.14, P = 0.304], DRFI [HR 1.59, 95% CI 0.68-3.75, P = 0.287], OS [HR 0.99, 95% CI 0.39-2.49, P = 0.975]) or live birth (BCFI [HR 1.02, 95% CI 0.41-2.53, P = 0.974], DRFI [HR 0.80, 95% CI 0.24-2.69, P = 0.722], OS [HR 0.39, 95% CI 0.09-1.69, P = 0.208]). Conclusions: In this multicenter, prospective study with 12 years of median follow-up, pregnancy and live birth after BC did not impact BC events or overall survival, irrespective of ER status. These long-term data from a modern cohort provide reassurance for young BC patients interested in future fertility. Clinical trial information: NCT01468246 .

635 Background: Prospective data on efficacy, quality of life, and treatment-related toxicities in older adults with breast cancer are limited. The ATOP trial (NCT03587740) evaluated T-DM1 in older adults and demonstrated favorable 5-year invasive disease-free survival. Here, we report patient-reported adverse events (AEs) and health-related quality of life (HRQOL) findings from ATOP. Methods: ATOP was a single-arm, phase II, multicenter study of adjuvant T-DM1 for those aged 60 with stage I-III HER2+ breast cancer. Protocol therapy included postoperative administration of T-DM1 (3.6 mg/kg) every 21 days for one year (17 cycles). PRO-CTCAE (assessing specific symptoms) and EQ-5D (a measure of HRQOL) surveys were administered electronically or on paper at baseline (pre-treatment), on Day 1 of each treatment cycle, and at a single 6–12-month post-treatment time point. Participants who responded to the baseline and at least one follow-up survey were included in the PRO analysis. EQ-5D changes from baseline were assessed using general linear mixed models. Summary statistics were used to assess PRO-CTCAE scores to evaluate which symptoms developed between baseline and 1 subsequent survey(s) and their severity. Results: Among the 111 patients enrolled on ATOP (median age=71, range 60-88 years), 98 responded to the baseline survey and 1 subsequent survey(s). 1435 surveys were returned that included at least one PRO-CTCAE response, and 1661 surveys were returned that included EQ-5D. The Table displays the % of participants who reported PRO-CTCAE symptoms that worsened from baseline to any severity level (scores >0) or to a severe level (scores ≥3). More than 60% of survey respondents reported new or increased dry mouth, fatigue, muscle aches, decreased appetite, nausea, pain, and/or numbness/tingling at some point during or after treatment, but these were usually not severe. EQ-5D scores did not change significantly from baseline at any time point. Conclusions: In this adjuvant trial for patients aged >60, participation rates for PRO data collection were high. Reassuringly, global HRQOL was not impacted by T-DM1, and though frequently reported, the vast majority of patient-reported symptoms were mild. Future analyses of this trial will focus on duration and predictors (clinical and biomarker-based) of severe AEs, agreement between patient-reported and clinician-reported AEs, and whether sharing PRO reports with clinicians impacted clinician-reported AE grades. Clinical trial information: NCT03587740 . Most common new or worsening symptoms reported via PRO-CTCAE in ATOP (n=95). Symptom % with score >0 n (%) with score 3+ Dry mouth 79% 26% Fatigue 71% 29% Muscle aches 69% 20% Decreased appetite 69% 12% Nausea 67% 6% Pain 66% 21% Numbness/tingling 65% 9% Blurry vision 60% 4% Mouth or throat sores 60% 5%

536 Background: Folate receptor alpha (FRα) is overexpressed in ~80% of triple-negative breast cancers (TNBC). We previously demonstrated that patients (pts) with breast cancer naturally mount immune responses to FRα. In prior Phase I and II studies, a GM-CSF-adjuvanted FRα peptide vaccine (FRPV) was safe and induced durable FRα-specific T-cell immunity in 83–90% of pts with breast and ovarian cancer. Methods: Eligible pts were women ≥18 years with TNBC (ER/PR ≤10%) with 1+ of the following: stage ≥T1c disease, node-positivity, or residual disease after neoadjuvant chemotherapy. Pts were randomized 2:1 to receive FRPV or placebo (GM-CSF alone) every 28 days for cycles 2-7 and then every six months for 7 booster doses, with cycle 1 consisting of cyclophosphamide 50mg orally twice daily for days 1-7 and 15-21 (in both arms). Randomization was stratified by chemotherapy setting (adjuvant only vs neoadjuvant) and stage (I/II vs III). FRα expression was evaluated by immunohistochemistry. The study was designed to detect (at 30 months after the last pt enrolled) a disease-free survival (DFS) difference of 14% assuming a 3.5-year DFS rate of 70% in the control group and with 78% power. Results: 280 pts were enrolled (median age 52). The majority had stage I or II tumors (n = 219, 78%). There were numerically more node-positive tumors in the vaccine arm, 78 (41%) vs 27 (32%), p = 0.15. Median follow-up was 3.5 years, and 33 (FRPV: 25, placebo: 8) DFS events were observed; 3.5-year DFS rate was 88% with FRPV and 90% with placebo (HR 1.42, 95% CI 0.64–3.15; p = 0.39). Overall survival (OS) also did not differ by arm (HR 2.48, 95% CI 0.55–11.20; p = 0.22). Among node-positive pts (n = 105), DFS did not differ between arms (HR 0.95, 95% CI 0.34–2.66; p = 0.92). However, a numerical DFS event rate improvement (14% for vaccine vs. 26% for placebo) was observed in 61 patients with stage III disease (HR 0.51, 95% CI 0.16–1.68; p = 0.26). DFS did not differ by chemotherapy setting or by receipt of anthracycline, capecitabine, and/or an immune checkpoint inhibitor. FRPV was well tolerated, with predominantly grade 1–2 adverse events (AEs) and no vaccine-related grade ≥4 AEs. FRα expression was available from tumor in 230 pts, with 72% expressing > 0. Overall, DFS was not significantly associated with FRα expression (0 vs > 0; HR 0.55, 95% CI 0.21–1.44; p = 0.21), and no significant differences in DFS by FRα expression were observed between treatment arms. Conclusions: FRPV following oral cyclophosphamide was safe, with no vaccine-related high-grade AEs. While no significant improvement in DFS or OS was observed overall, a numeric trend toward improved DFS was observed in pts with stage III TNBC. This finding is hypothesis-generating and supports further evaluation of FRα-targeted vaccination in higher-risk TNBC. Immune correlative analyses are ongoing to better define vaccine immunogenicity and its relationship to clinical outcomes. Clinical trial information: W81XWH-15-1-0293.

1587 Background: Rehabilitation services (physical medicine and rehabilitation [PM&R], physical therapy [PT], occupational therapy [OT], and speech-language pathology [SLP]) improve physical function, symptom burden, and quality of life for cancer survivors, yet utilization remains low due to persistent barriers. The collaborative care model–based Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial improved symptom burden and palliative care utilization. Using post hoc exploratory analyses of population-level trial data, we evaluated whether this EHR-facilitated approach also increased rehabilitation service use. Methods: E2C2 was conducted across Mayo Clinic Midwest medical oncology practices using an unblinded, stepped-wedge, cluster-randomized cohort design. The EHR-embedded intervention targeted SPPADE symptoms (sleep interference, pain, impaired physical function, anxiety, depression, and fatigue). Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Patients received self-management materials for moderate symptoms (4–6/10) and care manager support for severe symptoms (7–10/10). All outpatient rehabilitation encounters across the Mayo Clinic Enterprise were abstracted. Mixed-effects Poisson models estimated intervention effects on rehabilitation visits during the first 365 days of exposure. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled. Intervention and control conditions included 31,719 and 28,938 patients, respectively, with 10,450 contributing data to both periods. Cross-sectionally, 25% of participants reported moderate and 9% severe physical function impairment. Of 91,220 rehabilitation encounters scheduled, 57,669 (63.3%) were completed. Completed encounters were predominantly PT (68.3%), followed by OT (16.4%), physician visits (9.4%), and SLP (4.2%). The intervention was associated with a more than fourfold increase in completed rehabilitation encounters during the six weeks following index symptom assessment (adjusted mean 2.22 [95% CI, 0.14–4.29] vs 0.54 [0.40–0.68]; incidence rate ratio 4.11 [1.43–11.82]; P =0.009). Scheduled encounters also favored the intervention but did not reach statistical significance. Conclusions: An EHR-embedded symptom surveillance intervention increased short-term rehabilitation service completion, but overall utilization remained low relative to the prevalence of physical function impairment, highlighting the need for system-level strategies to translate symptom identification into sustained rehabilitation engagement.

1584 Background: Decades of evidence demonstrate that patients across the cancer continuum may benefit from validated rehabilitation services, yet delivery remains inconsistent. Prior reports of underuse have largely relied on small, single-site cohorts and have lacked population-level estimates of service need, referral, and visit completion, contributing to the assumption that provider reluctance to refer is a primary driver. Using post hoc exploratory analyses of population-level trial data, we evaluated patient- and system-level factors associated with non-use of rehabilitation services. Methods: This secondary analysis used data from the Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial, an unblinded, stepped-wedge, cluster-randomized cohort study comparing an EHR-embedded symptom surveillance and management system with usual care. All patients receiving care in Mayo Clinic Midwest medical oncology practices were enrolled regardless of cancer stage or phase. Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Sociodemographic and clinical characteristics and all outpatient rehabilitation encounters across the Mayo Clinic Enterprise were extracted from the EHR. Rates and types of completed, canceled, and no-show rehabilitation encounters were examined. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled; 34% reported moderate or severe physical function impairment during follow-up. Despite this, only 8,818 patients (17.6%) completed at least one rehabilitation encounter. Of 91,220 encounters scheduled, 57,669 (63.3%) were completed (mean 6.5; median 3 per participant), leaving a substantial proportion canceled or no-showed (n=33,523, 36.7%). Completed encounters were predominantly physical therapy (68.3%), with fewer occupational therapy (16.4%), physician (9.4%), and speech therapy (4.2%) visits. Encounters were concentrated among patients with breast, hematologic, gastrointestinal, and genitourinary cancers. Completion was more likely among patients who were older, female, partnered, retired, and federally insured, whereas cancellations and no-shows were more common among younger, racial or ethnic minority, urban, unpartnered, employed, college-educated, and commercially insured patients (all P <0.001). Virtual visits and encounters in community (vs academic) settings were more likely to be completed (all P <0.001). Conclusions: A substantial gap persists between cancer survivors’ rehabilitation needs and service receipt, varying by cancer type and sociodemographic factors. High cancellation and no-show rates suggest that underuse extends beyond referral and underscore the need for redesigned, more accessible rehabilitation delivery models.

1564 Background: Adolescent and young adult (AYA) females with early-stage ER-negative and/or HER2-positive breast cancer commonly receive chemotherapy to reduce risk of recurrence. Fertility concerns, counseling, and preservation may influence chemotherapy decisions and time to chemotherapy (TTC) initiation. Methods: We surveyed AYA survivors of stage I–III premenopausal ER-negative and/or HER2-positive breast cancer treated at Kaiser Permanente Northern and Southern California (2013-2022). Fertility concerns were defined as not having completed desired family size or being unsure about having completed desired family size at diagnosis. We summarized receipt of fertility counseling, receipt of chemotherapy, and use of oocyte/embryo cryopreservation for fertility preservation (FP). Among fertility-concerned patients who received chemotherapy, TTC (days from diagnosis) was assessed separately for neoadjuvant chemotherapy (NAC) vs for adjuvant chemotherapy (AdjC). Time to NAC was natural log–transformed and modeled with multivariable log-linear regression to estimate relative differences in TTC, adjusting for stage, study site, ER, HER2, age, and diagnosis year. Results: Of 363 respondents, 197 (54%) had fertility concerns at diagnosis; 183/197 (93%) received chemotherapy, similar to 153/166 (92%) among those without concerns (p=0.7). Of the concerned chemotherapy recipients, 45 (25%) saw a fertility specialist but did not pursue FP while 55 (30%) underwent FP. For the 112 fertility-concerned NAC recipients, FP was associated with longer TTC than no fertility specialist counseling (mean=41 vs. 30 days; adjusted ratio=1.39; 95% CI 1.15–1.69), whereas fertility specialist counseling without FP was not (mean= 31 vs. 30 days, adjusted ratio=1.04; 95% CI 0.86–1.25). For the 71 fertility-concerned AdjC recipients, TTC was similar for patients who did not see a fertility specialist (mean=63 days), those who froze oocytes/embryos (mean=65 days), and those who saw a fertility specialist but did not pursue FP (mean=69 days). Conclusions: In this AYA breast cancer cohort, there was no evidence that fertility concerns led patients to decline chemotherapy. FP was associated with a modest delay in NAC initiation (<2 weeks on average). Time to chemotherapy (TTC) among 183 AYA patients with ER− and/or HER2+ breast cancer and fertility concerns. Fertility-focused care N (n=183) Neoadjuvant chemotherapy (n=112) Mean TTC, days Relative difference in TTC, adjusted ratio (95%CI) Adjuvant chemotherapy (n=71) Mean TTC, days No fertility counseling from a specialist 83 (45%) 55 (49%) 29.6 Reference 28 (39%) 62.6 Received fertility counseling from a specialist No fertility preservation 45 (25%) 28 (25%) 30.7 1.04 (0.86,1.25) 17 (24%) 68.6 Fertility preservation 55 (30%) 29 (26%) 41.2 1.39 (1.15,1.69) 26 (37%) 64.6