Rosenberg, Shoshana M.

Abstract Background: Young age at diagnosis is an independent risk factor for recurrence and death from breast cancer (BC), with the greatest impact of young age demonstrated in hormone receptor positive (HR+) disease. Younger women are less likely to be adherent to endocrine therapy (ET), which may contribute to disparate outcomes. Methods: As part of a prospective cohort that enrolled women with BC diagnosed at age ≤40 between 2006-2016, we identified women with HR+, Stage I-III BC. Serial surveys with items assessing socio-demographic and treatment information including medication use are administered 1-2 times per year. Medical record review was used to ascertain stage and HR status and to confirm recurrent disease (locoregional, distant, or new primary breast cancer). Women who initiated ET but discontinued it <5-years post-diagnosis without resumption were classified as non-persistent. Univariable and multivariable regression models were fit to identify predictors of non-persistence and recurrence.Results: Among 607 women who initiated ET (median age at diagnosis: 36, range:17-40; 38%, 45%, 17% were Stage 1, 2, and 3, respectively).16% (99/607) were non-persistent, of whom 30% (30/99) discontinued ET ≤2 years post-diagnosis and over half had discontinued (54%, 54/99) by 3 years. In multivariable regression, those who were younger at diagnosis (age ≤30 vs. 36-40: OR: 3.39, 95% CI: 1.84-6.24; age 31-36 vs. 36-40: OR: 2.81 95% CI: 1.70-4.64) were more likely to discontinue ET while those with a higher stage at diagnosis were less likely to discontinue ET (Stage 2 vs. 1: OR: 0.46, 95% CI: 0.29-0.74; Stage 3 vs 1: OR: 0.32, 95% CI: 0.15-0.68). At a median follow-up time from diagnosis of 7.8 years (range 1-13 years), 15% of women (88/607) recurred or developed a new primary BC at a median time from diagnosis of 3.5 years (range 1-12 years). Of these, 66% (58/88) were distant recurrences, 32% (28/88) loco-regional, and 2% (2/88) new primary BCs. Rates of recurrence were higher among women who were persistent (81/508, 16%) vs. non-persistent (7/99, 7%, p=0.02). In multivariable regression, those who were non-persistent were less likely to recur (OR: 0.43, 95% CI: 0.19-0.98) while those with a higher stage were more likely to recur (Stage 3 vs. 1: OR: 2.36, 95% CI: 1.03-5.41). Sociodemographic, patient, and other treatment factors did not predict recurrence. Conclusions: Approximately 16% of young women with HR+ BC stop ET earlier than indicated, however non-persistence was not a risk factor for BC recurrence a median of 8 years following diagnosis in our cohort. Importantly, women with higher risk disease who are likely to benefit most from adherence to ET were less likely to discontinue treatment. Extended follow-up will further inform the impact of non-persistence on the incidence of late recurrences for which women with HR+ BC are at increased risk. Citation Format: Shoshana M Rosenberg, Yue Zheng, Philip Poorvu, Kathryn Ruddy, Rachel Gaither, Rulla Tamimi, Lidia Schapira, Jeffrey Peppercorn, Steven Come, Virginia Borges, Ann Partridge. Endocrine therapy non-persistence and recurrence in young women with early stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD2-08.

Objective: We aimed to investigate eligibility for breast conserving surgery (BCS) pre- and post-neoadjuvant systemic therapy (NST), and trends in the surgical treatment of young breast cancer patients. Background: Young women with breast cancer are more likely to present with larger tumors and aggressive phenotypes, and may benefit from NST. Little is known about how response to NST influences surgical decisions in young women. Methods: The Young Women's Breast Cancer Study, a multicenter prospective cohort of women diagnosed with breast cancer at age ≤40, enrolled 1302 patients from 2006 to 2016. Disease characteristics, surgical recommendations, and reasons for choosing mastectomy among BCS-eligible patients were obtained through the medical record. Trends in use of NST, rate of clinical and pathologic complete response, and surgery were also assessed. Results: Of 1117 women with unilateral stage I-III breast cancer, 315 (28%) received NST. Pre-NST, 26% were BCS eligible, 17% were borderline eligible, and 55% were ineligible. After NST, BCS eligibility increased from 26% to 42% (P < 0.0001). Among BCS-eligible patients after NST (n = 133), 41% chose mastectomy with reasons being patient preference (53%), BRCA or TP53 mutation (35%), and family history (5%). From 2006 to 2016, the rates of NST (P = 0.0012), clinical complete response (P < 0.0001), and bilateral mastectomy (P < 0.0001) increased, but the rate of BCS did not increase (P = 0.34). Conclusion: While the proportion of young women eligible for BCS increased after NST, many patients chose mastectomy, suggesting that surgical decisions are often driven by factors beyond extent of disease and treatment response.

BackgroundMany young women with newly diagnosed breast cancer are interested in future pregnancies. Prospective data regarding fertility interest and reproductive patterns after diagnosis are needed to counsel patients.MethodsThe Young Women's Breast Cancer Study is a multicenter, prospective cohort of women who were diagnosed with breast cancer at age ≤40 years between 2006 and 2016. Women complete surveys at baseline, every 6 months for 3 years, then annually. Here, the authors describe fertility interest and pregnancies within 5 years of diagnosis for women with stage 0 through III breast cancer.ResultsOf 1026 eligible participants, 368 (36%) reported interest in future biologic children at least once within 5 years after diagnosis, including 16% at 5 years after diagnosis. Among 130 women who attempted to become pregnant, 90 (69.2%) conceived; and, among 896 women who did not attempt to conceive, 18 (2.0%) became pregnant, with a total of 152 pregnancies resulting in 91 live births. Factors associated with pregnancy included younger versus older age at diagnosis (aged ≤30 vs 36‐40 years: odds ratio [OR], 6.63; 95% CI, 3.18‐13.83; P < .0001; aged 31‐35 vs 36‐40 years: OR, 5.86; 95% CI, 3.37‐10.17; P < .0001) and being nulliparous versus parous (OR, 2.66; 95% CI, 1.56‐4.53; P = .001). The receipt of endocrine therapy versus no endocrine therapy (OR, 0.35; 95% CI, 0.20‐0.59; P = .001) was inversely associated with pregnancy.ConclusionsMany women remain interested in future fertility in the 4 years after a breast cancer diagnosis, indicating that longitudinal fertility discussions are needed. Although a minority of those interested in having children attempted to become pregnant in the first 5 years, most who attempted to conceive did so and had live births.

AbstractObjectiveYoung breast cancer patients experience greater psychosocial distress compared with older patients, which raises concern for their risk of posttraumatic stress disorder (PTSD). We sought to characterize the prevalence of clinically significant symptoms of PTSD and associated factors among breast cancer survivors diagnosed at a young age.MethodsThe Young Women's Breast Cancer Study, an ongoing prospective cohort study, enrolled 1302 women diagnosed with breast cancer at age ≤ 40 between 2006 and 2016. Participants complete serial surveys, and we obtained additional information from medical record review. Socio‐demographics, anxiety and depression, social support, and psychiatric co‐morbidities and medications were assessed at study baseline (median, 5 months post‐diagnosis). We defined a participant as having clinically significant posttraumatic stress symptoms (PTSS) by scoring ≥50 on the PTSD Checklist‐Specific Version, administered on the 30‐month survey.ResultsAmong 700 women with stage 1‐3 disease, the prevalence of PTSS was 6.3% (95%CI = 4.5‐8.1). In multivariable analyses, PTSS was significantly associated with anxiety (OR 12.43, 95%CI = 5.81‐26.59, P < .0001) and stage 2 vs 1 disease (OR 2.26, 95%CI = 1.04‐4.93, P = .04). PTSS was inversely associated with having a college degree (OR 0.29, 95%CI = 0.13‐0.62, P = .002) and greater social support (OR 0.44, 95%CI = 0.21‐0.94, P = .03).ConclusionsWe found similar rates of cancer‐related PTSS in breast cancer survivors diagnosed at a young age compared with the general breast cancer population despite their well‐documented increased risk of overall distress. Nevertheless, factors associated with posttraumatic stress should be considered at diagnosis and in survivorship to identify young patients who may benefit from psychosocial resources.

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.

Abstract Background: Breast cancer arising in young women is more likely to have higher risk features than in older women and more likely to be associated with germline BRCA1 or BRCA2 mutations. We previously reported a higher distribution of luminal B-like tumors among young women. Here we present the clinical and pathologic features of invasive disease in a large prospective cohort of young women with breast cancer, and associations between surrogate molecular subtype and BRCA 1/2 mutation status. Methods: Among 1,297 young women (aged ≤40 years) with breast cancer enrolled from 2006-2016, tumor histopathological features were examined by central review, and biomarker status was extracted from pathology reports. Based on histologic grade and biomarker expression, invasive tumors were categorized as luminal A-like (LA=ER/PR+ and HER2-, histologic grade 1 or 2), luminal B-like (LB=ER/PR+ and HER2+, or ER/PR+, HER2-, and grade 3), HER2 enriched (E) (ER/PR- and HER2+) or triple negative (TN=ER-, PR- and HER2-). Tumor stage, clinical characteristics, and BRCA status were retrieved by medical record review (and patient survey for BRCA status if not in medical record). Results: The majority of women presented with early stage invasive disease (8% stage 0, 32% stage 1, 40% stage 2, 15% stage 3; 5% stage 4). Among invasive tumors with evaluable molecular phenotype (n=1,136), 57% were high grade and the distribution of subtypes was: 33% LA, 42% LB, 8% HER2E, and 16% TN (Table 1). Among different age groups (≤ 30, 31-35, and 36-40 years), there were no significant differences in molecular phenotype, tumor stage, tumor grade or histopathological features including presence of tumor necrosis, lymphocytic infiltration, and central fibrotic focus. 96% of women were tested for BRCA1 and BRCA2 germline mutations, and 127 (11%) tested positive: 65% were BRCA1+, and 35% were BRCA2+ (table 2). Among BRCA1+ patients, 2% of cancers were LA, 30% LB, 5% HER2E, and 62% TN; among BRCA2+, 29% were LA, 56% LB, 2% HER2E, and 13% TN. These proportions were relatively consistent across age groups. BRCA1+ patients’ tumors were proportionately more TN and BRCA2+ patients’ tumors more likely to be LB/HER2 negative (p&lt;0.0001), irrespective of age category. Conclusion: In a large cohort of women diagnosed with breast cancer at age ≤40, there was no association between age group (≤ 30, 31-35, vs. 36-40 years) and tumor stage, grade, or tumor molecular phenotype among women with invasive disease. As in older women, tumor molecular phenotype does vary by BRCA1 or BRCA2 mutation status, which has implications for prevention and treatment. Table 1. Subtype by age groupTotal (n=1136)≤30 yrs (n=144)31-35 yrs (n=314)36-40 yrs (n=678)p=0.42Luminal A-like377 (33%)48 (33%)99 (32%)230 (34%)Luminal B-like477 (42%)59 (41%)137 (44%)281 (41%)• ER/PR+, HER2-, grade 3245 (22%)27 (19%)68 (22%)150 (22%)• ER/PR+, HER2+232 (20%)32 (22%)69 (22%)131 (19%)HER2E95 (8%)13 (9%)34 (11%)48 (7%)Triple Negative187 (16%)24 (17%)44 (14%)119 (18%) Table 2. Subtype by BRCA statusTotal(n=1136)BRCA1+(n=82)BRCA2+(n=45)No mutation/not tested(n=1009)p&lt;0.0001Luminal A-like377 (33%)2 (2%)13 (29%)362 (36%)Luminal B-like477 (42%)25 (30%)25 (56%)427 (42%)• ER/PR+, HER2-, grade 3245 (22%)21 (26%)18 (40%)206 (20%)• ER/PR+, HER2+232 (20%)4 (5%)7 (16%)221 (22%)HER2E95 (8%)4 (5%)1 (2%)90 (9%)Triple Negative187 (16%)51 (62%)6 (13%)130 (13%) Citation Format: Yaileen D Guzman-Arocho, Shoshana M. Rosenberg, Philip Poorvu, Kathryn J. Ruddy, Greg Kirkner, Craig Snow, Rulla M. Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Elena F. Brachtel, Ellen Warner, Ann H. Partridge, Laura C. Collins. Clinicopathological features and BRCA 1/2 status in a large prospective cohort of young women with breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-07-02.

Abstract BACKGROUND Fertility can be diminished by adjuvant chemotherapy or by age-related decline in ovarian reserve in young women with breast cancer (BC). We sought to better understand the burden of concern about fertility, utilization of fertility preservation strategies, and the impact of fertility concerns on treatment decision-making among young women newly diagnosed with BC enrolled in a large multi-site study. METHODS The Young and Strong study was a cluster-randomized study that tested the effect of an educational and supportive care intervention for young women with BC (≤45) and their oncologists, at community and academic sites across the US. Patients were surveyed following diagnosis at enrollment (within 3 months of diagnosis), and at 3, 6 and 12 months thereafter. The surveys included sociodemographic and psychosocial measures (HADS anxiety and depression; Perceived Stress Scale), as well as a modified Fertility Issues Survey, which assessed fertility concerns and preservation. Treatment and tumor pathology data were abstracted from the medical record. Logistic regression was used to identify sociodemographic, clinical, and psychosocial factors that were associated with fertility concern. Variables with p ≤ 0.20 in univariable analyses were evaluated in the multivariable model using stepwise selection; variables achieving significance at p &lt; 0.05 were included in the final model. RESULTS Of 467 women enrolled from 54 sites (14 academic, 40 community), 419 had evaluable data regarding treatment decision-making. Median age of participants at diagnosis was 40 yrs (range 22-45), 11% were African American, 80% were married/lived with a partner, and 75% had children. 35% of tumors were stage I, 51% stage II, and 14% stage III; 82% of women were treated with chemotherapy. At the time of treatment decision-making, 133 (32%) were concerned about fertility, varying by age, with fertility concern reported by 73%, 28% and 13% of those age ≤35, 36-40 and &gt;40 (p&lt;.01), respectively. 67 (16%) said their treatment decisions had been affected by fertility concerns, including 62 of the 133 (47%) with fertility concern. 12/419 (3%) chose one chemotherapy regimen over another, 4 (1%) chose not to take hormonal medication, and 32 (8%) chose or may choose to take it for less than 5 years. 251 (60%) reported having discussed fertility issues with their physician before starting therapy, including 117/133 (88%) of women with fertility concern. 29 (7%), including 27/133 (20%) of the concerned, took special steps to lessen the chance of infertility: 14 underwent cryopreservation of embryos, 14 cryopreservation of eggs and 12 took GnRH agonist or pursued other strategies. In the multivariable model, history of difficulty becoming pregnant (versus none, OR=3.86, 95%CI: 1.84-8.1) was associated with greater concern about fertility. Older age (OR=.75 per 1-year increase, 95%CI: 0.69-0.81) and having more than one child at diagnosis (versus never delivered, OR=0.14, 95%CI: 0.05-0.40) were associated with less concern about fertility. Race, being partnered, high-education, income, symptoms of depression, stress or anxiety at diagnosis, tumor stage, hormone receptor status and receipt of chemotherapy were not independently associated with concern about fertility in the multivariable model. CONCLUSION In a geographically and ethnically diverse study of young women with newly diagnosed BC in the U.S., many were concerned about fertility, with potential impact on their treatment decisions. For the majority of women, these concerns were discussed with their providers, though only a minority underwent fertility preservation strategies prior to treatment. Citation Format: Elisabeth Etaix, Yue Zheng, Shoshana Rosenberg, Kathryn J Ruddy, J Russel Hoverman, Karen M Emmons, Ann H Partridge. Fertility concerns and treatment decision-making among young women with breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-17.

Abstract Background: Fear of cancer recurrence (FCR) is prevalent among breast cancer survivors and more intense in younger women. Given that FCR is a powerful determinant of quality of life and is associated with healthcare utilization, identifying who may be at risk for experiencing elevated FCR without resolution can inform the timing and targeting of interventions. Methods: Participants included women diagnosed (dx’d) at age ≤40 enrolled in the Young Women’s Breast Cancer Study, a multi-site prospective cohort surveyed at baseline and regularly in follow-up. Surveys include the 3-item Lasry Fear of Recurrence Index which measures the degree of concern about recurrence and current health using 4-point Likert response options that provide a score ranging from 3-12; higher scores indicate greater concern. Group-based trajectory modeling was used to classify distinct FCR patterns from baseline (median of 5 months from dx) through 3 years post-dx. Multinomial logistic regression was used to identify the associated patient (socio-demographics and BRCA status), disease (stage, ER/PR/HER2) and treatment (surgery, chemotherapy) characteristics associated with each trajectory. Variables significant at p&lt;0.05 in univariable models were entered into the final multivariable model. Results: 965 women with Stages 0-III breast cancer were included in the analysis, with a median age at dx of 37. Participants were predominantly non-Hispanic White (85%), partnered (76%) and had completed college (84%). There was a significant decrease in median FCR scores from baseline to year 3 (9 vs. 8, Wilcoxon signed-rank test P&lt;0.01). Five FCR trajectories (Table) were identified: 1) 10.5% of participants reported low/stable FCR from baseline over follow-up; 2) 33.1% had moderate FCR that improved over time; 3) 5.5% had moderate FCR scores at baseline that worsened over time; 4) 30% had high FCR scores at baseline that improved over time; 5) 20.8% had high FCR at baseline that remained high at all time points. In the fully adjusted multinomial model, younger age at dx and Stage 3 and 2 (vs. 1) disease were associated with higher odds of being in the high/stable trajectory. Having a lumpectomy (vs. mastectomy) was associated with higher odds of being in a high/stable as well as moderate/improving trajectory while White (vs. non-White) women had higher odds of being in a trajectory of improving FCR. Receipt of chemotherapy and financial discomfort were significantly associated with assignment to specific FCR trajectories in univariate analyses, however did not remain significant in the adjusted model. Being partnered, BRCA mutation status, and ER/PR/HER2 status were not significantly associated with any FCR trajectory classification in univariate or multivariate analyses. Conclusion: While FCR improves over time for many young women with breast cancer, a substantial minority (26%) had FCR that was severe and did not improve or worsened over time. Younger women with higher stage disease who are at risk for high levels of unresolved FCR may benefit from intervention including early referral to mental health professionals. Ongoing monitoring of women at risk for developing FCR following active treatment is warranted. Table Mean FCR score for each trajectoryBaselineYear 1Year 2Year 3TrajectoriesLow/Stable (N=103)5.725.605.545.45Moderate/Improving (N=331)7.907.487.287.09Moderate/Worsening (N=34)6.748.329.6410.54High/Improving (N=294)9.889.419.088.67High/Stable (N=203)11.0211.0811.0310.88 Citation Format: Lidia Schapira, Yue Zheng, Shari Gelber, Philip Poorvu, Kathryn J Ruddy, Rulla Tamini, Jeffrey Peppercorn, Steve Come, Virginia Borges, Ann Partridge, Shoshana Rosenberg. Trajectories of fear of cancer recurrence in young breast cancer survivors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-09.