Sella, Tal

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.

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

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

514 Background: The 21- gene Breast Recurrence Score predicts benefit from adjuvant chemotherapy in estrogen receptor positive (ER+), HER-2 negative (-) breast cancer (BC). We aimed to examine whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NAC). Methods: We identified patients with stage I-III ER+/HER2− BC treated with NAC from the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤ 40 years. The 21-gene assay was performed on tumor specimens removed prior to NAC either as part of clinical care or retrospectively for research. Pathologic complete response (pCR) was defined as no residual invasive tumor (ypT0/is ypN0). The relationship between Recurrence Score result (RS) and pCR was evaluated using logistic regression modeling. Results: 76 women in the cohort had undergone NAC for ER+, HER2- BC and were eligible for this analysis: 5 had undergone clinical 21-gene assay testing, 71 had banked specimens retrospectively tested. Median age at diagnosis was 36.7 (24.3-40). Most tumors were of ductal histology (78%), high grade (51%), progesterone receptor (PgR) positive (86%), ≥T2 (88%), clinically node positive (74%), and anthracycline and taxane containing protocols were administered in 86% of cases. RS ranged between 5-75 with 50% > 25 and only 4 < 11. Mean RS was significantly higher among tumors achieving pCR vs. non-pCR response (51.9 vs. 26.6, pwilcoxon= 0.0005). pCR rate in patients with RS > 25 was 21% (8/38) vs. 5% in patients with RS < 25 (2/38), with both pCRs in the <25 group in patients with RS 21-25. In univariable analysis, PgR negativity (odds ratio (OR) 5.62, 95% confidence interval (CI) 1.27-24.89, p = 0.02), high grade (OR 9.03, 95%CI 1.07-76.32, p = 0.04) and higher RS as a continuous variable (OR 1.08, 95%CI 1.04-1.13, p = 0.0003) were associated with a greater likelihood of pCR. In multivariable analysis only RS remained significantly associated with pCR (OR: 1.07, 95%CI 1.01-1.12, p = 0.01): a 7% increase in the odds of pCR for every 1-point increase in RS. Conclusions: In young women with ER+, HER2- BC who received NAC, higher pretreatment RS was associated with an increased likelihood of pCR. Genomic expression profiling assays may have a role in decision-making in young women in need of neoadjuvant therapy. For women with low likelihood of benefiting from NAC, alternative approaches are clearly warranted. Given the demonstrated efficacy of neoadjuvant endocrine therapy in post-menopausal women, further evaluation in young women should be pursued.

11574 Background: Weight gain after cancer diagnosis is common in cancer survivors and has been linked to increased treatment toxicity, poor quality of life, and increased risk of second cancers and overall mortality. Young breast cancer (BC) survivors may be especially susceptible to weight changes given the impact of treatments such as chemotherapy and hormonal therapy on menopausal status. Methods: We identified women with Stage 0-III breast cancer diagnosed at ≤40 years (y) between 2006-2016 from a multi-center prospective cohort study. Clinical data including self-reported pre-diagnosis and follow-up weights were obtained using baseline and follow-up patient surveys. Participants missing baseline weight, pregnant at diagnosis/within 1y of diagnosis or with BC recurrence within 1y were excluded; those pregnant or with BC recurrence between 1-3y from diagnosis were excluded from the 3y analysis. Menopausal status at baseline and treatment-related amenorrhea (TRA) in follow-up were defined by self-reported last menstrual period. Factors associated with weight gain (>5%) were evaluated using univariate two-sided Fisher's exact test. Results: At baseline, 1y and 3y post diagnosis, 956, 899 and 687 women were eligible for analysis respectively. Median age at diagnosis was 37y (17 - 40), 65% received endocrine therapy and 74% chemotherapy. Premenopausal status was verified in 94% at baseline. Mean BMI at baseline was 24.4 (SD 5.3) kg/m2; 20% (187/956) were overweight and 12% (116/956) obese. At 1y and 3y, mean BMI increased modestly to 24.7 (SD 5.6) and 24.9 (SD 5.2), respectively with weight gain (>5%) observed in 18% (164/899) and 13% (87/687) respectively. 37% (300/804) and 32% (196/615) of eligible premenopausal subjects experienced TRA at 1y and 3y, respectively. Receipt of chemotherapy, receipt of endocrine therapy and TRA were not associated with weight gain at any timepoint. Conclusions: In this large prospective cohort of young BC survivors, mean BMI increased only modestly over time. Self-reported weight gain was not associated with treatment and not exacerbated by TRA. Further analysis to understand the effects of physical activity and other predictors of weight gain in this population are ongoing.

6575 Background: Delays in diagnosis (dx) and treatment (tx) affect breast cancer (BC) outcomes. We sought to identify factors associated with delays among young women, who do not undergo routine screening and often have pregnancy or breastfeeding-related breast changes that may mask a BC. Methods: The Young Women’s Breast Cancer Study is a multicenter, prospective cohort that enrolled 1302 women with newly dx BC age ≤40 between 2006-2016. Women reported the method and timing of cancer detection on the baseline survey. 231 were ineligible or excluded due to missing information. Among those reporting self-detected cancers, using multivariable regression we evaluated factors associated with delays ≥90 days (d) from symptom to presentation (self delay) and presentation to dx (care delay); in stage 0-III BC we evaluated delays ≥60d from dx to tx (tx delay). Results: 1071 eligible women had median age at dx of 37 yrs (17-40) and 74% reported self-detected cancers. Self delay or care delay ≥90d was reported in 17% and 13%, respectively. Factors inversely associated with self delay included pregnancy at dx (vs nulliparous, OR 0.10, CI 0.01-0.78) and perceived financial comfort (vs not, OR 0.62, CI 0.41-0.93). Women dx ≤1 year post-partum who breastfed (vs nulliparous, OR 2.60, CI 1.14-5.93) and those with a family history of breast/ovarian cancer (vs none, OR 1.79, CI 1.00-3.19) were more likely to have a care delay. Age was inversely associated with care delays (OR 0.94, CI 0.89-0.99). Tx delay was reported by 10% (105/1015), and associated with being single (vs partnered, OR 1.61, CI 1.02-2.56 ), non-white (vs white, OR 1.85, CI 1.09-3.13) and having Stage 0 BC (vs stage 1, OR: 3.08, CI 1.65-5.77); women with stage 3 BC (vs stage 1, OR 0.13, CI 0.03-0.56) were less likely to have a tx delay. Conclusions: In this cohort, most young women with BC underwent timely dx and tx initiation. Women dx ≤1 year post-partum who breastfed were more likely to experience a care delay, likely because lactational changes may mask BC signs and symptoms. The associations of perceived financial status with self delay and non-white race with tx delay underscore the need for additional support to ensure timely care for underserved populations with the goal of eliminating disparities in outcomes.