Tamimi, Rulla M.

Abstract Purpose: The role of tumor-infiltrating lymphocytes (TIL) remains unclear in hormone receptor (HR)–positive/HER2-negative breast cancer, particularly in young patients, whose immune microenvironment could be altered by age-related host and tumor differences. Experimental Design: Patients with stage I to III HR-positive/HER2-negative tumors were identified from a prospective cohort study of patients with breast cancer diagnosed at age ≤40 years. Multiplexed immunofluorescence and semiautomated quantitative software measured cytotoxic T, non–CD8 T, T regulatory, exhausted T, and PDL1+ cells in stroma and tumor. Univariate analyses assessed differences in clinicopathologic characteristics by high versus low immune infiltration, divided based on median. TIL subtypes were evaluated as a continuous variable per 10% increase in Cox regression analyses for invasive breast cancer–free survival, distant disease–free survival (DDFS), and overall survival, adjusted for clinicopathologic parameters. Results: Among 390 patients, high immune infiltration was associated with increasing age, Black race, grade 3 tumors, and metaplastic or micropapillary histologic subtypes. Over a median follow-up of 8 years, higher stromal and intratumoral non–CD8 T-cell infiltration, T regulatory–cell infiltration, and PDL1 expression were associated with improved invasive breast cancer–free survival. Higher intratumoral non–CD8 T-cell infiltration, T regulatory–cell infiltration, and PDL1 expression were associated with improved DDFS; higher stromal PDL1 expression was also associated with improved DDFS. Higher intratumoral cytotoxic T-cell infiltration and PDL1 expression were associated with improved overall survival. Conclusions: Characterization of immune subpopulations could help refine the prognostic value of TILs in young patients with HR-positive breast cancer, who may benefit from risk stratification for treatment individualization. See related commentary by Salgado and Kok, p. 2133

PURPOSE Given the extended survivorship of young adults with breast cancer, characterizing health care utilization and adherence to surveillance guidelines can inform gaps in care. PATIENTS AND METHODS Patients age 40 years and younger at diagnosis of stage 0-III breast cancer enrolled in a prospective cohort study completed a survey 7 years after diagnosis assessing receipt of care and surveillance. We evaluated factors associated with transition to a primary care provider (PCP) for cancer-related follow-up and adherence to mammography and bone density scans. RESULTS Among 660 women, 92% reported having a PCP, although for cancer-related follow-up, 57% saw only an oncology provider, 29% saw both a PCP and oncology provider. In the past 2 years, 68% reported getting a flu shot, 76% a pap test/pelvic examination, 56% cholesterol screening, and 42% (n = 232 endocrine therapy [ET] users) a bone density scan. Among women who had a unilateral mastectomy or lumpectomy (n = 356), 82% reported a mammogram in the past year. In multivariate analyses, those with stage 0 ( v I disease) were more likely to see a PCP for follow-up ( v PCP + oncology provider); ET users and those more concerned about recurrence were less likely. Patients with human epidermal growth factor receptor 2-positive (HER2) disease were more likely to adhere to mammography; those with a BRCA mutation and those with a unilateral mastectomy were less likely. Patients with a BRCA mutation and who had chemotherapy were more likely to report a bone density scan. CONCLUSION Although most have a PCP, over half of young survivors continue to see an oncology provider for follow-up in long-term survivorship. Mammography uptake was high; uptake of other health maintenance practices was lower. Identification of barriers/facilitators to receipt of guideline-concordant care may inform strategies to optimize survivorship.

Importance Women diagnosed with breast cancer at a young age are felt to have a higher risk for locoregional recurrence (LRR) regardless of type of local therapy. Objective To assess the long-term incidence of isolated LRR by molecular subtype in a modern multicenter cohort of young women. Design, Setting, and Participants This cohort study, a multicenter prospective study named the Young Women’s Breast Cancer Study, enrolled 1302 women diagnosed with breast cancer at 40 years or younger from 2006 to 2016. Treatment information and incident LRR (ipsilateral breast/chest or lymph node recurrence) were self-reported on study surveys and confirmed with medical record review; molecular subtype was determined by record review. Analysis was reported from February 2023 to May 2025. Main Outcomes and Measures Cumulative incidence of isolated LRR was calculated using the Kaplan-Meier method; hazard ratios were estimated by Cox proportional hazards regression. Results The cohort included 1135 women with stage I through III breast cancer who had a median follow-up of 10.1 years (range, 0.4-16.3 years). The age at diagnosis was younger than 30 years for 145 patients (12.8%), 31 to 35 years for 318 patients (28.0%), and 36 to 40 years for 672 patients (59.2%). There were 59 isolated local recurrences (5.2%) and 4 isolated regional recurrences (0.4%). Among patients with local therapy and subtype data available (n = 1128), 366 (32%) had luminal A–like tumors; 240 (21%), luminal B–like tumors; 231 (20%) luminal ERBB2 positive (+)–like (formerly HER2 positive); 90 (8%) ERBB2 +-like; and 201 (18%) triple negative. A total of 346 women (30%) had breast-conserving therapy (BCT) (98% of whom had radiation), 296 (26%) unilateral mastectomy, and 487 (43%) bilateral mastectomy. Of women who had mastectomy, 425 (54%) had radiation. The cumulative incidence of LRR at 10.1 years by subtype was as follows: luminal A, 4.4% (range, 1.0%-6.9%); luminal B, 4.7% (range 1.8%-7.7%); luminal ERBB2 +, 6.1% (range, 3.1%-8.3%); ERBB2 +, 2.2% (range, 0%-6.3%); and triple negative, 6.5% (range, 4.2%-10.1%). The cumulative incidence of LRR by locoregional treatment type at 10.1 years was 6.7% after BCT (range, 4.3%-10.1%), 6.5% after mastectomy without radiation (range, 0%-7.7%), and 2.4% after mastectomy with radiation (range, 1%-4.2%). Although mastectomy with radiation was associated with the lowest risk of LRR on multivariable analysis, when examined within molecular subtype, there were no differences seen. Conclusions and Relevance In this contemporary cohort of women diagnosed with breast cancer at age 40 years or younger, risk of isolated LRR was relatively low (5.6%) at a median follow-up of 10.1 years, and significant differences were not seen by tumor subtype. Concerns for long-term risk of LRR should not influence surgical decision-making with young women, irrespective of molecular subtype.

Abstract Studies have identified genetic and epidemiologic factors associated with mammographic density (MD) phenotypes. However, MD-associated genetic variants only account for a small proportion of the total estimated heritability. Interrogating interactions between genetic and epidemiologic factors could potentially identify additional MD-associated loci, expand our understanding of the genetic basis of MD phenotypes, and clarify how epidemiologic factors modulate relationships between genetic variants and MD. We conducted six separate genome-wide, gene–environment (GxE) interaction analyses, applying 2 degrees of freedom (df) and 1df interaction tests, for each of three MD phenotypes (percent density, dense area (DA), and nondense area (NDA)). The six epidemiologic factors considered were height, ever parous, parity, ever menopausal hormone therapy, ever breastfeeding, and months of breastfeeding. We included European ancestry participants from multiple studies within the Markers of Density consortium and the Breast Cancer Association Consortium (n = 4895-16 218 depending on specific analyses). We identified 11 loci with genome-wide significant (P < 5 × 10−8) interaction tests including two novel common genetic signals interacting with parity (8p21.2) and ever breastfeeding (19p13.2) for NDA. Our results suggest that epidemiologic risk factors might influence relationships between common genetic variants and MD phenotypes at particular genomic loci.

363 Background: The incidence of BC in young adults is increasing; given their extended survivorship, characterizing healthcare utilization and adherence to surveillance guidelines can inform unmet health needs and gaps in care. Methods: The multi-center Young Women’s BC Cohort Study enrolled 1302 women ≤40 yrs with newly diagnosed (dx) BC from 2006-2016. Participants completed surveys every 6 mos for 3 yrs post-dx, then annually. The current analysis includes patients with Stage 0-III BC without recurrence who completed the 7-yr survey assessing survivorship care, including types of providers visited, BC surveillance, and other health maintenance practices. Multivariate logistic regression evaluated factors (clinical, demographics, concern about recurrence) associated with 1) full transition to a primary care provider (PCP) for follow-up; adherence to 2) mammography (among women who had a unilateral mastectomy or lumpectomy) and 3) bone density scans (among current hormonal therapy [HT] users), per ASCO/ACS guidelines. Results: Of 660 women with Stage 0-III BC, median age at dx was 37 (range: 17-40); 89% identified as White, 5%, Asian, 3%, Black, 3% as other/multiracial, and 4%, Hispanic. Most had received chemotherapy (75%) and radiation (61%) and 35% reported current HT; 12% had a BRCA1/2 mutation. For cancer-related follow-up, 57% reported seeing an oncology provider only, 12%, PCP only, and 29% saw a PCP + oncology provider. Among women with remaining breast(s) (n=348), 90% reported a mammogram in the last year. Adherence to other health maintenance practices varied: 68% reported having had a flu shot, 76% a pap test/pelvic exam, and 56% cholesterol screening within the last 2 yrs. Among current HT users (n=210), 46% reported a bone density scan within the last 2 yrs. In multivariate analyses assessing the odds of seeing a PCP only (vs. oncology + PCP), having stage 0 vs I disease (OR 2.74 95% CI 1.01-6.80) was associated with higher odds while any HT use (OR .31 95% CI .16-.58) and concern about recurrence (OR .23 95% CI .12-.47) were associated with lower odds. The table includes factors significantly associated with non-adherence to mammography and bone density scans. Conclusions: At 7-years post-dx, most young survivors participating in a cohort study receive cancer follow-up care from an oncology provider and have not fully transitioned their care to a PCP. Adherence to recommendations related to bone health among HT users was suboptimal. Additional research to identify barriers/facilitators to receipt of guideline-concordant follow-up care at the patient, provider, and systems levels may inform strategies to optimize survivorship in young BC survivors. Multivariable analysis: factors associated with non-adherence. MammogramOR 95% CI Bone density scanOR 95% CI Her2+ .38, .15 -.98 NS BRCA1/2 + 8.36, 1.38-50.47 .17, .05 -.62 Chemotherapy NS .22, .06 -.78 Unilateral mastectomy vs lumpectomy 6.64, 2.69-16.34 NS

ABSTRACTBackgroundFollowing breast cancer (BC), many young women are interested in future childbearing and some may wish to breastfeed. However, limited information is available regarding their lactation experiences.MethodsParticipants in the Young Women's Breast Cancer Study, a multicenter, prospective cohort study of women ≤40 years diagnosed with stage 0–III BC between 2006–2016 and who reported one or more live births following diagnosis, were surveyed about pregnancy and breastfeeding after BC treatment, including reasons for attempting and stopping breastfeeding, satisfaction, and supports.ResultsOf 143 eligible women sent a survey, 115 responded and 94 were included in the analytic cohort. Breastfeeding was attempted by 55% of women (52 of 94). Among those who had not attempted, 93% noted prior bilateral mastectomies (39 of 42). Among those who attempted breastfeeding, 69% had undergone lumpectomy and radiotherapy (36 of 52), 83% of whom reported no milk production from their treated breast (30 of 36). Most (65%, 34 of 52) were at least somewhat satisfied with their ability to breastfeed. Reasons for stopping breastfeeding included: having completed the planned duration (36%, 19 of 52); to start/resume endocrine therapy (21%, 11 of 52); and to resume breast imaging (8%, 4 of 52). Approximately half (27 of 55) of women who had not undergone bilateral mastectomies recalled receiving specific information about breastfeeding after BC, mostly from the oncology team (59%, 16 of 27), online resources (48%, 13 of 27), or a lactation consultant (44%, 12 of 27).ConclusionMost young BC survivors who attempted to breastfeed were able to and were satisfied with the experience, despite challenges. Specific resources to support BC survivors who wish to breastfeed are needed.

1518 Background: Despite high interest among young women diagnosed with breast cancer (BC) in future fertility, prior research has been hampered by short follow-up and lack of prospective assessment of pregnancy attempts. We sought to describe fertility outcomes among young women participating in a prospective cohort who reported pregnancy attempt post-BC diagnosis. Methods: Women with stage 0-III BC in the Young Women's Breast Cancer Study (YWS, NCT01468246), a multicenter, prospective cohort of women diagnosed at age ≤40 from 2006-2016 who reported attempting pregnancy post-diagnosis were included. Those with prior hysterectomy, bilateral oophorectomy, or metastatic disease at diagnosis were excluded. Data on attempting pregnancy and fertility outcomes were obtained from serial surveys. Multivariable logistic regression with stepwise model selection was used to identify factors associated with pregnancy and live birth. Results: Among 1213 eligible participants, 197 reported any attempt of pregnancy (16%) over a median follow-up of 11 years (range: 3-17). Among attempters, median age at diagnosis was 32 years (range: 17-40); 74% were non-Hispanic White; 41% had stage I, 35% stage II, 10% stage III, and 14% stage 0 BC; 76% had HR+ disease; 68% received chemotherapy; 57% received endocrine therapy within one year post-diagnosis; 13% were BRCA1/2 pathogenic variant (PV) carriers; 51% reported financial comfort at baseline; 51% were nulligravida and 72% nulliparous at diagnosis; 28% had undergone fertility preservation consisting of egg/embryo freezing at diagnosis; 15% reported a history of infertility before BC diagnosis. Most (73%) reported ≥1 pregnancy after diagnosis and 65% reported ≥1 live birth. Median time from diagnosis to first pregnancy was 48 months (range: 6-125). In the multivariable model, greater age at diagnosis (odds ratio [OR] 0.82 per year increase, 95% CI 0.74-0.90, P<0.0001) was negatively associated with pregnancy, while financial comfort at baseline (OR 2.04, 95% CI 1.01-4.12, P=0.047) was predictive of pregnancy. For live births, greater age at diagnosis was negatively associated (OR 0.82 per year increase, CI 95% 0.76-0.90, P<0.0001) while having undergone fertility preservation at diagnosis was predictive (OR 2.78, 95% CI 1.29-6.00, P=0.009). History of infertility, nulliparity at diagnosis, tumor characteristics, cancer treatment, race, ethnicity, and BRCA1/2 PV status were not associated with either outcome. Conclusions: This is the first prospective study with greater than 10 years of follow-up to report fertility outcomes in young BC survivors accounting for attempting pregnancy. The majority achieved a pregnancy and most reported a live birth. Our findings can be incorporated into the counseling of young BC patients and survivors, and highlight the need for accessibility of fertility preservation services for this population. Clinical trial information: NCT01468246 .

Abstract Background. Approximately 12,000 women aged 40 years or younger are diagnosed with breast cancer every year in the United States alone. Limited data exist regarding survival in young women with metastatic breast cancer (MBC), particularly when considering modern tumor subtyping and treatment, though previous studies have suggested that patients presenting with MBC at diagnosis (de novo stage IV) have better prognosis than those who develop recurrent MBC after initial diagnosis of stage 0-III disease. We sought to determine survival rates in young patients with MBC stratified by disease presentation (de novo versus recurrent) and subtype. Methods. The Young Women’s Breast Cancer Study (YWS) is a multicenter, prospective cohort which enrolled 1,302 women diagnosed with stage 0-IV breast cancer at age ≤40 from 13 North American academic and community-based sites from 2006-2016. The current median follow-up is 10.1 (range 0.4-16.3) years. Histopathology slides were centrally reviewed for 97% of the participants, and clinical tumor molecular subtypes have been detailed. In the recurrent group, receptors were obtained from the initial breast surgery. Descriptive analyses were used to characterize patients with de novo or recurrent MBC, including demographic and disease characteristics, and survival rates. Overall survival was estimated using the Kaplan-Meier method and compared by log-rank test between those who presented with de novo and relapsed disease overall and within tumor subtypes. Results. Among 246 patients included in this analysis, 74.0% (n=182) had recurrent MBC and 26.0% (n=64) had de novo MBC. Most patients were white (n=208, 84.6%), while 6.9% were Asian (n=17), 4.5% Black (n=11), 0.8% Native American (n=2), 0.8% multiracial (n=2) and 2.4% other/unknown (n=6). A total of 4.5% of patients were Hispanic (n=11). Median age at diagnosis of de novo MBC was 37 years and 40 years for diagnosis of metastasis in the recurrent group. Median disease-free interval was 3.23 (range 0.32 – 13.84) years for the recurrent MBC group. Among all patients with MBC, most (55.7%, n=137) had estrogen receptor (ER) and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, whereas 17.9% (n=44) had ER and/or PR-positive HER2-positive, 7.3% (n=18) had ER/PR-negative HER2-positive, and 18.7% (n=46) had triple-negative tumors. A greater proportion of participants (43.8%, n=28) had HER2-positive disease in the de novo group than in the recurrent group (18.7%, n=34), P=&lt; 0.0001. A total of 10.9% (n=7) of de novo patients had a germline BRCA mutation, compared to 13.7% (n=25) in the recurrent group. Median survival was 5.09 (95% CI: 3.74 – 6.38) years in the de novo group and 2.63 (95% CI: 1.98 – 3.21) years in the recurrent MBC group (P=0.0004). When stratifying by subtype, survival among patients with de novo ER and/or PR-positive HER2-positive disease was longer than among patients with recurrent disease (P=0.0149), whereas there were no statistically significant differences in survival between the de novo and recurrent disease groups in other disease subtypes (Table 1). Conclusion. Survival in young women with MBC is highly heterogeneous and varies substantially by tumor subtype and disease presentation. Those with de novo ER and/or PR-positive HER2-positive subtype appear to have better outcomes than those with recurrent MBC with the same subtype. These findings can inform patient care and potential future research to improve outcomes for young patients with MBC. Table 1: Median survival by disease presentation and subtype * 1 patient with recurrent MBC was not included because the initial diagnosis was DCIS MBC: metastatic breast cancer; OS: overall survival; CI: confidence interval; ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor 2 Citation Format: Leticia Varella, Yue Zheng, Shoshana Rosenberg, Gregory Kirkner, Craig Snow, Kathryn Ruddy, Rulla Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia Borges, Steven Come, Laura Collins, Ellen Warner, Kate Dibble, Eric Winer, Ann Partridge. Survival in Young Women with De Novo or Recurrent Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-14.

Abstract Adolescent and young adults (AYAs) (15-39 years) have a heightened risk of developing a second primary malignancy due to extended periods of survivorship, higher incidence of germline cancer predisposing variants, and increased susceptibility to treatment-induced malignancies. Research on survivors of specific AYA cancer types, including breast cancer (BC) survivors, is limited. Among BC survivors, while much survivorship research focuses on risk of locoregional recurrence or contralateral BC, little is known about overall risk, and risk factors, of developing second non-breast primaries. This prospective cohort study examined women diagnosed with BC from 2006-2016 at age ≤40 years enrolled in the Young Women’s BC Study (YWS) (N=1297). Women were excluded from the analytic cohort if initially diagnosed with Stage IV breast cancer (N=64). To enable investigation of how BC treatments may impact second primary risk, women were also excluded if they reported another cancer before primary BC diagnosis (N=3). Patient characteristics, treatment information, and clinical events were collected via serial surveys. Tumor characteristics and detailed treatment data were obtained from medical record review. Five- and 10-year risk of second non-breast primary was estimated via the cumulative incidence function after applying the Fine-Gray competing risks model with time starting at primary BC diagnosis. Death, metastasis, or diagnosis with a second primary BC were considered as competing events. Univariate and multivariate Fine-Gray sub-distribution models were used to estimate sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CI) for second non-breast primary cancer risk. Risk factors considered included age, race, body mass index, smoking, alcohol use, income, family history of cancer, germline pathogenic variant (PV) carrier status, tumor stage, grade, and ER status, primary surgery type, and receipt of radiation, chemotherapy, or endocrine therapy (yes/no). Multivariate models tested individual associations with additional adjustment for radiation therapy and PV carrier status, as both are consistently associated with second primary in the literature. Over a median follow-up of 10.1 years (inter-quartile range (IQR) =7.9-12.1 y), 47 patients (4%) developed a second non-breast primary cancer. Median age at second non-breast primary was 43 years (IQR=39-46), and median time between primary BC and second non-breast primary was 7.3 years (IQR=4.1-9.3). Second primary types included melanoma (n=10), thyroid (n=10), ovarian (n=4), sarcoma (n=4), uterine (n=3), rectal (n=3), bladder (n=2), cervical (n=2), head and neck (n=2), lung (n=2), lymphoma (n=2), pancreatic (n=2), and kidney (n=1). During the study, 22 patients (2%) developed a second primary BC, 167 (19%) developed metastasis, and 15 (1%) died from causes other than BC. Among the patients who developed a second primary BC, two later developed another non-breast cancer (ovarian and brain cancer). When incorporating competing risks, five and 10-year cumulative incidence of second non-breast primary was 1.4% and 3.2%, respectively. No patient or treatment factors were statistically significantly associated with second non-breast primary in univariate or multivariate models, including radiation and PV carrier status. In this population of young BC survivors, 10-year cumulative incidence of second non-breast primary cancer was 3.2%, with the most common second cancers being melanoma and thyroid cancer. Incidence rates of all second primary cancer types in this cohort were higher than population-based incidence rates for healthy women under 50 years of age, highlighting the importance of long-term surveillance for other cancer events in this young population. While risk of second non-breast primary was not associated with primary BC treatment in this study, cases were limited, and the follow-up interval was relatively short. Citation Format: Bessie Zhang, Kristen Brantley, Shoshana Rosenberg, Gregory Kirkner, Laura Collins, Kathryn Ruddy, Rulla Tamimi, Lidia Schapira, Virginia Borges, Ellen Warner, Steven Come, Eric Winer, Ann Partridge. Second primary non-breast cancers in young breast cancer survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-10.

Abstract Background: Young BC survivors are at risk for impaired QOL in part due to issues that are unique to their life stage. We sought to characterize trajectories of QOL in the 5 years following diagnosis among young BC survivors as well as evaluate patient and clinical characteristics associated with poorer or deteriorating QOL trajectories over time. Methods: Women diagnosed with stage I-III BC at age ≤40 enrolled in the Young Women’s BC Study, a prospective cohort in North America, who completed ≥2 study surveys through 5 years of post-diagnosis follow-up. QOL was evaluated with the Cancer Rehabilitation Evaluation System (CARES) physical, psychosocial, and sexual subscale scores. Demographic, treatment, and clinical characteristics were ascertained through surveys and chart review. Longitudinal trajectories for each CARES subscale were defined using group-based trajectory modeling; associations between patient/clinical characteristics and trajectory group membership were estimated for each subscale using multivariable multinomial logistic regression. Results: Among 900 women, median age at diagnosis was 36 (range: 17-40) 89% were white, 2% Black, and 4% Hispanic. At baseline, 73% were partnered, 61% parous and 49% perceived themselves as financially comfortable. Most had hormone-receptor positive (74%), HER2-negative (70%) BC, and most received chemotherapy (82%); 36% underwent mastectomy with radiation. Physical and psychosocial scores each clustered into 4 trajectories, with &gt;75% of participants clustering in groups reflecting excellent or good QOL that was stable over time and few (6% for physical and 4% for psychosocial) clustering into groups that reflected poorer QOL at baseline that did not improve over time. Sexual health trajectories were more variable, clustering into 5 trajectories, with over half of participants clustered into groups reflecting good (35%) or excellent (20%) QOL that remained relatively stable over time, 22% clustered into a trajectory that was poor at baseline but moderately improved over follow-up, 13% in a group that reflected deteriorating from moderate-to-poor QOL and 11% in a group with poor QOL at baseline that did not improve over time. In multivariable regression analyses (Table), factors associated with clustering in a poorer trajectory (vs. clustering in an excellent trajectory), in multiple QOL domains included baseline financial discomfort (associated with poorer QOL across all 3 domains), mastectomy+radiation (vs. lumpectomy, associated with poorer QOL across all 3 domains); chemotherapy receipt (associated with poorer physical and sexual health trajectories); and baseline BMI &gt;25 (vs. 18.5-24.9, associated with poorer physical and poorer/deteriorating sexual health trajectories). Conclusions: Young BC survivors follow distinct QOL trajectories in survivorship. While most will not experience substantial QOL impairment through the first 5 years following diagnosis, a substantial minority report persistently poor or deteriorating QOL. The association between more extensive local therapy and poorer physical/psychosocial/sexual health trajectories underscores the importance of communicating the potential for negative QOL outcomes when women are making surgical decisions. Additionally, the pervasive impact of financial wellbeing on multiple QOL domains supports the potential value of systematic screening for and addressing of financial distress to prevent or mitigate financial toxicity in survivorship Factors associated with clustering in poorer/deteriorating (vs. excellent) QOL trajectories *Reference trajectory=excellent QOL Citation Format: Tal Sella, Zheng Yue, Kathryn Ruddy, Shari Gelber, Rulla Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia Borges, Steven Come, Eric Winer, Ann Partridge, Shoshana Rosenberg. Five-year quality of life (QOL) trajectories among young breast cancer (BC) survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-01.