Peppercorn, Jeffrey

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 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.

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.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701 .

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

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.