Rosenberg, Shoshana M.

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: 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.

Importance Among women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC. Objective To estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC. Design, Setting, and Participants Participants were enrolled in the Young Women’s Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023. Main Outcomes and Measures The 5- and 10- year cumulative incidence of SPBC. Results In all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70). Conclusions Findings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.

Abstract Background Diagnosis of breast cancer in young women has been shown to affect their decision‐making with regard to fertility and family planning. Limited data are available from populations across the U.S. regarding this issue; thus, we sought to describe fertility concerns and efforts to preserve fertility in a national clinical trial population of young breast cancer patients. Methods The young and strong study was a cluster‐randomized controlled trial testing an intervention program for young women with breast cancer. Patients were surveyed within 3 months after diagnosis and at 3, 6, and 12 months after. Surveys asked about sociodemographics, psychosocial domains, fertility concerns, and fertility preservation strategies. Univariable and multivariable models were used to investigate sociodemographic, clinical, and psychosocial predictors of fertility concerns. Results Of 467 women from 54 clinical sites across the U.S. (14 academic, 40 community), 419 were evaluable regarding fertility concerns. Median age was 40 years (range 22–45), 11% were Black, 6% Hispanic, and 75% had children. Tumor stage was I (35%), II (51%), or III (14%); 82% received chemotherapy. At time of the treatment decision, 133 (32%) participants had fertility concerns, among whom 47% indicated this affected their treatment decisions. Sixty percent of participants reported having discussed fertility with their physician. Twenty percent of those with fertility concerns used fertility preservation strategies. History of difficulty becoming pregnant and younger age were associated with higher odds of fertility concerns in multivariable modeling. Conclusion Many young women with newly diagnosed breast cancer are concerned about fertility in a way that impacts their treatment decisions. Concerns were discussed, but few used fertility preservation strategies. These findings have implications for counseling young patients.

AbstractBackgroundIdentifying patient‐ and disease‐specific characteristics associated with clinical trial enrollment of adolescents and young adults (AYAs) with cancer may target efforts to improve accrual.MethodsAlliance for Clinical Trials in Oncology (Alliance) trials opened from January 1, 2000, and closed before January 1, 2018, for common AYA cancers were identified. Proportions of AYAs (aged 18–39 years old) versus non‐AYAs (aged ≥40 years old) enrolled by cancer type were summarized by descriptive statistics. Among studies with ≥20 AYAs enrolled, demographic and disease characteristics of AYAs versus non‐AYAs were compared with χ2 and Kruskal–Wallis tests. A qualitative review was also conducted of therapeutic trials included in analysis in PubMed through December 31, 2021, that reported AYA‐specific survival.ResultsAmong 188 trials enrolling 40,396 patients, AYAs represented 11% (4468 of 40,396) of accrual. AYA accrual varied by cancer type (leukemia, 23.6%; breast, 9.9%; lymphoma, 14.8%; colorectal, 6.2%; central nervous system, 8.1%; melanoma, 11.8%; sarcoma, 12%). Across ages, the proportion of Black and Hispanic patients enrolled was 1%–10%. Compared to non‐AYAs, AYAs in breast and colorectal cancer trials were less likely to be White and more likely to be Hispanic. Disease characteristics differed by age for selected trials. Two trials reported AYA‐specific survival, with no significant differences observed by age.ConclusionsAYA accrual to Alliance trials was comparable to or exceeded population‐based, age‐specific prevalence estimates for most cancer types. Greater proportional representation of Hispanic and non‐White patients among AYAs reflects US demographic trends. The small number of minority patients enrolled across ages underscores the persistent challenge of ensuring equitable access to trials, including for AYAs.

AbstractBackgroundBreast cancer (BC) is the most common malignancy in women of reproductive age. This study sought to explore the postcancer conception and pregnancy experience of young BC survivors to inform counseling.MethodsIn the Young Women's Breast Cancer Study (NCT01468246), a multicenter, prospective cohort, participants diagnosed at age ≤40 years with stage 0‐III BC who reported ≥1 postdiagnosis live birth were sent an investigator‐developed survey.ResultsOf 119 eligible women, 94 (79%) completed the survey. Median age at diagnosis was 32 years (range, 17–40) and at first postdiagnosis delivery was 38 years (range, 29–47). Most had stage I or II (77%) and HR+ (78%) BC; 51% were nulligravida at diagnosis. After BC treatment, most (62%) conceived naturally, though 38% used assisted reproductive technology, 74% of whom first attempted natural conception for a median of 9 months (range, 2–48). Among women with a known inherited pathogenic variant (n = 20), two underwent preimplantation genetic testing. Of 59 women on endocrine therapy before pregnancy, 26% did not resume treatment. Hypertensive disorders of pregnancy (20%) was the most common obstetrical condition. Nine percent of newborns required neonatal intensive care unit admission and 9% had low birth weight.ConclusionAmong women with live births after BC treatment, most conceived naturally and having a history of BC did not appear to negatively impact pregnancy complications, though the high rate of hypertensive disorders of pregnancy warrants further investigation. The prolonged period of attempting natural conception for some survivors suggests the potential need for improved understanding and counseling surrounding family planning goals after BC.

Purpose: In light of disparities in breast cancer care and outcomes, we explored whether attention to fertility, genetic, and emotional health concerns, as well as satisfaction with care, differs by race/ethnicity among young breast cancer patients. Methods: The Young and Strong Study was a cluster randomized trial of an intervention for patients and providers at 54 U.S. oncology practices enrolling women diagnosed with breast cancer at ≤45 years of age. Provider attention to fertility, genetics, and emotional health was evaluated by medical record review. The proportions of patients with attention to these concerns were compared by race/ethnicity (Hispanic, non-Hispanic Black [NHB], Asian, non-Hispanic White [NHW], or multiracial/other). Satisfaction with care was assessed with the Patient Satisfaction Questionnaire-18 (PSQ-18) at 3 months, with median scores for each of 7 PSQ-18 subscales (general satisfaction, interpersonal manner, communication, financial, time spent with doctor, accessibility, and technical quality) compared by race/ethnicity. Results: Among 465 patients, median age at diagnosis was 40; 6% were Hispanic, 11% NHB, 4% were Asian, 75% NHW, and 3% multiracial/other. Provider attention to genetics, emotional health, and fertility did not differ by race/ethnicity. Median PSQ-18 scores did not differ by race/ethnicity, with median subscale scores ranging from 3.0 to 4.5 across groups, indicating high levels of satisfaction. Conclusion: Satisfaction with care and provider attention to age-specific concerns were similar across racial/ethnic groups among young patients enrolled in an educational and supportive care intervention study. These data suggest that high-quality, equitable care is feasible. Further care delivery research is warranted in more diverse patient and practice settings. Clinical Trial Registration number: NCT01647607.

PURPOSE Erb-B2 receptor tyrosine kinase 2 ( ERBB2)–positive breast cancer (BC) is particularly common in young women. Genomic features of ERBB2-positive tumors before and after chemotherapy and trastuzumab (chemo + H) have not been described in young women and are important for guiding study of therapeutic resistance in this population. METHODS From a large prospective cohort of women age 40 years or younger with BC, we identified patients with ERBB2-positive BC and tumor tissue available before and after chemo + H. Whole-exome sequencing (WES) was performed on each tumor and on germline DNA from blood. Tumor-normal pairs were analyzed for mutations and copy number (CN) changes. RESULTS Twenty-two women had successful WES on samples from at least one time point; 12 of these had paired sequencing results from before and after chemo + H and 10 had successful sequencing from either time point. TP53 was the only significantly recurrently mutated gene in both pre- and post-treatment samples. MYC gene amplification was observed in four post-treatment tumors. Seven of 12 patients with paired samples showed acquired and/or clonally enriched alterations in cancer-related genes. One patient had an increased clonality putative activating mutation in ERBB2. Another patient acquired a clonal hotspot mutation in TP53. Other genomic changes acquired in post-treatment specimens included alterations in NOTCH2, STIL, PIK3CA, and GATA3. There was no significant change in median ERBB2 CN (20.3 v 22.6; Wilcoxon P = .79) between paired samples. CONCLUSION ERBB2-positive BCs in young women displayed substantial genomic evolution after treatment with chemo + H. Approximately half of patients with paired samples demonstrated acquired and/or clonally enriched genomic changes in cancer genes. ERBB2 CN changes were uncommon. We identified several genes warranting exploration as potential mechanisms of resistance to therapy in this population.

10503 Background: Prior data suggests that the risk of second primary breast cancer (SPBC) is higher among women diagnosed with primary breast cancer (BC) before age 40. There is evidence that risk differs by primary tumor characteristics, cancer treatments, and genetic predisposition. However, studies investigating risk of SPBC by clinical risk factors are often limited by low numbers of young women and lack of complete patient data, particularly regarding germline genetic risk. Methods: Using the Young Women’s BC Study (YWS), a prospective cohort of 1,302 women ≤40 years diagnosed with BC from 2006-2016, we sought to compare clinical and treatment characteristics among women who developed an SPBC vs. those who did not. The analytic cohort included women diagnosed with Stage 0-III BC who did not undergo bilateral mastectomy (N = 685). Demographics, genetic testing and results, clinical events, and treatment data were collected through self-report on baseline and follow-up surveys (every 6 months for 3 years, then annually). Detailed tumor and treatment information, confirmation of genetic testing results, and new and recurrent cancer events were obtained through regular and triggered medical record review. Univariate and multivariate Cox proportional hazards models were used to examine associations of age, race, genetic testing results, hormone receptor status, stage, and grade of primary tumor, and cancer treatments with SPBC. Participants were censored at the time of local recurrence, metastasis, death, or loss of follow-up. Results: At a median follow-up time of 9.9 years [inter-quartile range (IQR) = 6.6-12.0 y], 17 patients developed an SPBC (2.5%), in whom 3 occurred in the ipsilateral breast after lumpectomy as primary BC surgery. Median time from primary BC diagnosis to SPBC diagnosis was 4.2 years (IQR = 3.3-5.6 y). Compared to those who did not develop an SPBC, a greater percentage of women who developed an SPBC had in situ disease as their primary BC (24% v. 6%) and were of Ashkenazi descent (12% v. 5%). In the 577 women who had had genetic testing, 544 (94%) were non-carriers of pathogenic variants. Risk of SPBC was 2.2% (N = 12) in non-carriers and 9.1% (N = 3) in the 33 carriers. In Cox univariate analyses, carriers had a 4.1 times higher risk of SPBC compared to non-carriers (HR = 4.14, 95% confidence interval (CI) = 1.67-14.66, p = 0.03), and primary diagnosis with in situ BC was associated with a 5-fold increased risk of SPBC (HR = 5.02, 95% CI = 1.63-15.41, p = 0.005). Both factors remained strongly associated with SPBC when tested together in a multivariate model. Conclusions: This prospective study demonstrated a low risk of SPBC in the first 10 years after diagnosis of early BC in young women who are not germline pathogenic variant carriers. The finding that risk of SPBC was higher after in situ primary BC at a young age warrants further investigation. These findings have important implications for the treatment and follow-up care of young women with BC.