Borges, Virginia F.

Abstract Background: Breast cancer (BC) is the most common malignancy among women of reproductive age. Given limited data describing the conception and pregnancy experience of young BC survivors, we sought to explore these outcomes to inform counseling of women interested in future childbearing. Methods: Participants with stage 0-III BC in the Young Women’s Breast Cancer Study (NCT01468246), a multi-center, prospective cohort of women diagnosed at age ≤ 40 from 2006-2016 who reported ≥ 1 live birth from a pregnancy after diagnosis were sent a survey with investigator-developed questions focused on their first post-diagnosis live birth. Women who had been diagnosed with BC during pregnancy were excluded from this analysis. The survey assessed conception, use of assisted reproductive technology (ART), pre-implantation genetic testing (PGT), endocrine therapy (ET), and peripartum complications. Summary statistics are presented. Results: 92/119 eligible women completed the survey (response rate: 77%). Median age at diagnosis was 32 (range:17-40) years and at delivery was 37 (range: 29-47) years. Median time from diagnosis to delivery was 58 months (range: 11-154). Most women had stage 2 BC (43%, 40/92); 68% received chemotherapy (63/92); about half (51%, 47/92) were nulligravida at diagnosis. Overall, 61% of pregnancies were conceived naturally (56/92) and 39% with ART (36/92): 32% by in-vitro fertilization (IVF, 29/92), 7% with fertility medications only (6/92), and 1 with intrauterine insemination. 38% of IVF pregnancies were conceived using products from fertility preservation prior to BC treatment (11/29). Among women who used ART, 74% attempted to conceive naturally (25/36) for a median of 9 (range: 2-48) months prior to pursuing ART. The most common reasons for pursuing ART include infertility following BC treatment (33%, 12/36) and expediting conception to resume treatment (17%, 6/36). 11% of those with known inherited pathologic variant mutations underwent PGT (2/19). Reasons for not pursuing PGT included belief in more effective cancer risk reduction in the future (29%, 5/17), not being offered PGT (24%, 4/17), high cost (12%, 2/17), no interest in IVF (12%, 2/17), acceptable odds for inheriting the mutation (24%, 4/17), and belief in other risk reduction strategies (18%, 3/17); 1 woman reported ethical concerns. Of 57 women who took ET pre-pregnancy (63%), nearly all (96%, 55/57) discontinued ET > 3 months prior to attempting to conceive; 1 discontinued after awareness of pregnancy. Of those who had received prior ET, 60% resumed ET (34/57) a median of 3 (range: 1-50) months after pregnancy. Among 23 women who did not resume, 13 (23%) had completed the recommended duration; the remaining 10 reported one or more of the following reasons: felt better while off (28%, 6/23), desire for another child (22%, 5/23), and desire to breastfeed (17%, 4/23). Median time to delivery was 39 (range: 28-42) weeks with 12% delivering preterm < 37 weeks (11/92). 47% had a Caesarean section (43/92), with prolonged labor the most common indication (33%, 14/43). Hypertensive disorders of pregnancy (HDP, 20%, 18/92), gestational diabetes (7%, 6/92), small for gestational age (7%, 6/92), and postpartum hemorrhage (5%, 5/92) were the most common obstetrical complications. 9% of women had newborns requiring NICU admission (8/92) and 9% had low birth weight (8/92). Conclusion: Among young BC survivors with a live birth following diagnosis, most conceived naturally, with the majority who used ART first attempting natural conception. There was limited use of PGT among mutation carriers with ¼ not having been offered testing. Patient reported peripartum complications appear consistent with population norms, though the relatively higher rate of HDP bears further research. Among those yet to complete their ET, a notable proportion did not resume following delivery. This novel data may help to inform the care of young breast cancer survivors pursuing pregnancy. Citation Format: Kimia Sorouri, Tal Sella, Shoshana Rosenberg, Margaret Loucks, Kathryn Ruddy, Shari I. Gelber, Rulla M. Tamimi, Jeffrey M. Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Ellen Warner, Ann Partridge. Conception and Pregnancy Among Young Breast Cancer Survivors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-05.

Abstract Background: Breast cancer (BC) is the most common malignancy in women of reproductive age, and the incidence of the disease is rising in this population. Many of these women are interested in childbearing after their BC treatment and a substantial minority will go on to have a live birth. Some will also want to breastfeed. However, there is only limited information available regarding the experience of young BC survivors breastfeeding following treatment. Methods: Participants in the Young Women’s Breast Cancer Study (YWS), a multi-center, prospective cohort study of women diagnosed with BC at age ≤ 40 years between 2006-2016, who reported at least one live birth following their diagnosis with stage 0-III BC were sent an additional survey including investigator-developed questions focused on breastfeeding after breast cancer treatment. Women who had been diagnosed with BC during pregnancy were excluded from this analysis. The survey assessed whether they breastfed, reasons for attempting and stopping breastfeeding, breastfeeding with the treated breast and untreated breast, and supports. Summary statistics, including medians and proportions, are presented. Results: Of 118 eligible women sent a survey, 92 completed the survey (78% response rate). Median age at diagnosis of BC was 32 (range: 17-40) years and at delivery was 37 (range: 29-47) years. 54% of women had attempted to breastfeed (50/92). Among those who had not, 93% noted a history of bilateral mastectomies (39/42). Additional reasons for not attempting to breastfeed included no interest regardless of BC history (5%, 2/42) and 1 woman underwent a unilateral mastectomy and did not think her supply would be sufficient. Among the women who did attempt breastfeeding, 68% had undergone lumpectomy and radiotherapy (34/50) with 85% of those women reporting that the treated breast did not produce milk (29/34). The 5 women who produced milk from the treated breast noted that the supply was substantially less than the untreated breast. To assist with breastfeeding, 76% used a pump only on the untreated breast (38/50) and 14% on both breasts (7/50). Women breastfed for a median of 5.5 (range:< 1-60) months and 64% were “somewhat”/“very much” satisfied with their ability to breastfeed (32/50). The most common reasons cited for stopping breastfeeding included having completed the planned duration (36%, 18/50), to start/resume endocrine therapy (22%, 11/50), and to resume breast imaging (8%, 4/50). Among patients who had not undergone a double mastectomy, 47% recalled receiving specific information about breastfeeding after a history of breast cancer (25/53), most commonly from the oncology team (56%, 14/25), lactation consultant (48%, 12/25), or online resources (44%, 11/25). Conclusion: In the largest series to date detailing the breastfeeding experiences of young BC survivors, approximately half of young BC survivors with a successful pregnancy attempted to breastfeed. Among those who had undergone prior lumpectomy and radiotherapy, women reported no milk production or only limited supply from the treated breast. Despite these limitations, most women who attempted to breastfeed were satisfied with their ability to do so. Specific resources to support the experience of breastfeeding in BC survivors are needed. Citation Format: Tal Sella, Kimia Sorouri, Shoshana Rosenberg, Margaret Loucks, Kathryn Ruddy, Shari I. Gelber, Rulla M. Tamimi, Jeffrey M. Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Ellen Warner, Ann Partridge. Breastfeeding in Survivors of Early Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-06.

Abstract Background: Pregnancy after breast cancer (BC) is of substantial importance for many young women at diagnosis and during follow-up. BC treatment including standard endocrine therapy (ET) (5-10 years) may reduce ovarian reserve and the chances of subsequent successful pregnancy, given conception is contraindicated during ET. A temporary interruption of ET to attempt and carry a pregnancy in this population has never been prospectively studied. Methods: POSITIVE is a single-arm, prospective, investigator-initiated, international trial evaluating the safety and pregnancy outcomes of interrupting ET for young women with early-stage hormone-receptor-positive (HR+) BC who desire pregnancy. The primary objective is to assess the risk of BC relapse associated with ET interruption for ~2 years to achieve pregnancy. Women ≤42 years with stage I-III HR+ BC who received adjuvant ET (SERM alone, GnRH analogue plus SERM or AI) for 18 to 30 months and wished to interrupt ET to attempt pregnancy were eligible. The primary endpoint is breast cancer free interval (BCFI) defined as the time from enrollment to the first BC event (local, regional, distant recurrence or a new invasive contralateral BC). Planned sample size was 500 patients. Three interim analyses of BCFI were reviewed by the Data Safety Monitoring Committee (DSMC) to assure a 95% chance of stopping the trial early if the annual BCFI event rate exceeded 4%; with primary analysis triggered after 1600 patient years of follow-up (pyfu) and no more than 46 BCFI events defined as the safety threshold. The DSMC recommended continuing the study following each interim analysis. We now report the primary results. Results: From 12/2014 to 12/2019, 518 women were enrolled. At enrollment, the median age of participants was 37 years (27-43 years); 75.0% were nulliparous, 93.4% had stage I/II disease, 66.3% node-negative. Median time from BC diagnosis to enrollment was 29 months (IQR: 25-32). Tamoxifen alone was the most prescribed ET (41.7%), followed by tamoxifen+ovarian function suppression (35.7%). 62.0% of participants had received neo/adjuvant chemotherapy. At a median follow-up of 41 months (1638 pyfu), 44 participants had experienced a BCFI event, not exceeding the pre-specified safety threshold of 46 events. The 3-year BCFI failure percent was 8.9% (95% CI: 6.3 to 11.6%), similar to the 9.2% (95% CI: 7.6 to 10.8%) calculated in the comparative external control cohort from the SOFT/TEXT trials (Sun et al, Breast 2020). Of 497 women followed for pregnancy status, 368 (74.0%) had at least one pregnancy, 317 (63.8%) had at least one live birth, with a total of 365 babies born. Based on competing risk analysis, 76.3% of patients resumed ET (half within 26 months), 8.3% had BCFI event/death before ET resumption, and 15.4% had not resumed ET yet. Conclusions: The POSITIVE trial demonstrates that for young women with early HR+ BC desiring pregnancy, temporary interruption of ET to attempt pregnancy does not confer a greater short-term risk of recurrence than that observed in a modern historical control group that did not interrupt ET. Most participants have had a live birth. Further follow-up is planned to confirm long-term safety. These results should be considered in counselling BC patients desiring future pregnancy. Citation Format: Ann Partridge, Olivia Pagani, Samuel M. Niman, Monica Ruggeri, Fedro Alessandro A. Peccatori, Hatem A. Azim, Marco Colleoni, Cristina Saura, Chikako Shimizu, Anna Saetersdal, Judith Kroep, Audrey Mailliez, Ellen Warner, Virginia F. Borges, Frédéric Amant, Andrea Gombos, Akemi Kataoka, Christine Rousset-Jablonski, Simona Borstnar, Junko Takei, Jeong Eon Lee, Janice Walshe, Manuel Ruiz Borrego, Halle Moore, Christobel Saunders, Vesna Bjelic-Radisic, Snezana Susnjar, Fatima Cardoso, Karen L. Smith, Teresa Ferreiro Vilarino, Karin Ribi, Kathryn Ruddy, Sarra El-Abed, Martine Piccart, Larissa A. Korde, Aron Goldhirsch, Richard D. Gelber. Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer: Primary Results from the POSITIVE Trial (IBCSG 48-14/BIG 8-13) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-09.

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.

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]

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.