Peppercorn, Jeffrey

12081 Background: Young women with breast cancer may be at increased risk for premature development of cardiovascular disease (CVD) in part due to their cancer treatment. Limited data are available on CVD risk among young breast cancer survivors. Methods: Women aged 30-40 years at diagnosis with stage 0-III breast cancer enrolled in a prospective cohort study of women diagnosed with breast cancer at ≤40 were eligible for inclusion in this analysis. Data were obtained from serial surveys and electronic medical records at breast cancer diagnosis and 5-year follow-up. We calculated “excess heart age,” which incorporates a CVD risk-based score (calculated using age, systolic blood pressure, blood pressure medication, diabetes, smoking, body mass index) to estimate the difference in years between an individual’s chronological age and their CVD-risk adjusted age. Multivariable logistic regression models (adjusting for age at diagnosis, stage, and race) were fitted to evaluate associations between treatment (radiation, endocrine therapy, anthracyclines, and trastuzumab) and having a change in excess heart age ≥2 years from baseline to 5 years. Results: Among 372 young breast cancer survivors, mean age at diagnosis was 36.6 (SD 2.89), 93% were white, and 79% were diagnosed with stage I or II breast cancer. Mean excess heart age was.32 (SD: 6.16) years at baseline, which declined to -.07 (SD 6.64) at 5-year follow-up (p=.17). At 5 years, 31% (n=114) of women experienced an increase of at least 2 years in their excess heart age since diagnosis, and their mean excess heart age was 4.34 years (range -9 to 30). In multivariable analyses, receipt of trastuzumab was associated with higher odds (OR: 1.68, 95% CI: 1.02-2.77) of experiencing an increase of ≥2 years in excess heart age between diagnosis and 5 years of follow-up. Endocrine therapy, anthracyclines, and radiation were not significantly associated with a change in excess heart age of ≥2 years at 5 years post-diagnosis. Conclusions: At 5 years post-diagnosis, approximately 1/3 of young breast cancer survivors experienced a change from baseline in their excess heart age of ≥2 years. Further research is warranted to confirm findings regarding trastuzumab and excess heart age, and potential effects on longer-term cardiac outcomes in this population. Extended follow-up of this cohort may further quantify CVD risk over time.[Table: see text]

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.

Effective delivery of cancer care via telehealth requires a planned care system that accounts for myriad patient, provider, and practice/cancer center resources before, during, and after the care episode. Telehealth is broadly defined as a method to have virtual, bidirectional communication between patients and providers. Telehealth can include methods such as audio-only, video-consultation, and tele-monitoring, which can occur in a synchronous, asynchronous, or blended format. The purpose of this review is to present common foundational principles for providing clinical cancer care via telehealth, followed by an overview of three distinct examples of comprehensive telehealth programs that have been developed to meet the needs of patients and families across the cancer trajectory, including survivorship, rehabilitation, and palliative care phases. The programs described are exemplars that were developed and implemented prior to the coronavirus pandemic, so they reflect many years of planning and evidence. Lessons learned include the need for ongoing patient support, clinician training, and cancer health system/practice programmatic considerations such as billing, scheduling, reimbursement, software, and hardware/platform security. Although the COVID-19 pandemic produced an explosive shift in regulations and implementation, sustainability of these changes may not be long-term. Nevertheless, a permanent shift in cancer care to include telehealth is likely here to stay.

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.

Abstract Background: Overall, patients with cancer experience a greater risk of adverse outcomes following SARS-CoV-2 infection; however, little is known for those with BC. Methods: CCC19 (NCT04354701) is an international cohort study aimed at investigating the impact of COVID-19 in patients with a history of or active cancer using de-identified data on patient demographics, cancer history, clinical course and outcomes of COVID-19. The current analysis includes patients from U.S. and Canada with invasive BC and laboratory-confirmed SARS-CoV-2 entered between March 17, 2020 and July 2, 2020. Co-primary outcomes were hospitalization during COVID-19 illness and 30-day all-cause mortality. Frequencies for categorical variables and medians (range) for continuous variables were estimated. Final presentation will include bivariable and multivariable Cox proportional hazards regression analysis to identify risk factors (including BC subtypes and therapies, for which data collection is ongoing) associated with 30-day all-cause mortality and severe COVID-19 illness (composite of any hospitalization requiring supplemental oxygen, admission to an intensive care unit [ICU], use of mechanical ventilation, or death). Results: During the study period, a total of 2683 patients with cancer and COVID-19 were accrued in the CCC19 registry including 529 (20%) with invasive BC. Among patients with BC, 352 (67%) were 60 years or older; 518 (98%) were women; 275 (52%) non-Hispanic White, 116 (22%) non-Hispanic Black, 70 (13%) Hispanic, 56 (11%) in other categorizations; 178 (34%) had a smoking history; 75 (14%) ECOG performance status ≥2; 191 (36%) with &gt;2 active comorbidities; 64 (12%) with AJCC stage IV disease at BC diagnosis; and 267 (50%) were on anti-cancer treatment including systemic therapy, radiation, or surgery within 3 months of COVID-19 diagnosis. At least 323 (61%) patients with BC had 30-day follow-up after COVID-19 diagnosis, and 35 (7%) had 90-day follow-up. COVID-19 illness at initial diagnosis required outpatient care in 288 (54%), inpatient care in 193 (36%), and ICU care in 40 (8%). Overall, 247 (47%) were hospitalized and 30-day all-cause mortality was 9%. 30-day all-cause mortality rates by receipt of major BC treatment modalities (within past 3 months) were: 10% for those on cytotoxic systemic therapy vs 5% and 12% for noncytotoxic systemic therapy and local therapy, respectively. The table shows hospitalization and mortality outcomes by major demographic and BC treatment strata. The final presentation will incorporate the latest patient accrual and evaluate independent clinical risk factors associated with serious COVID-19 outcomes in patients with BC. Conclusions: This represents the largest study to date of COVID-19 outcomes in patients with invasive BC. Nearly half of the patients with BC required hospitalization during their COVID-19 disease course and we observed a 9% 30-day all-cause mortality. Submitted on behalf of the COVID-19 and Cancer Consortium (ccc19us.org) Table 1. COVID-19 related hospitalization and 30-day all-cause mortality for all patients with invasive BCNAny Hospitalization30-day all-cause MortalityN% [95% CI]N% [95% CI]Total population52924747 [42-51]499 [7-12]Age&lt;601774425 [19-32]21 [0-4]60-691155144 [35-54]87 [3-13]70-791206655 [46-64]1714 [8-22]80+1178674 [65-81]2219 [12-27]ECOG PS0-132212238 [33-43]165 [3-8]2+756181 [71-89]1621 [13-32]Active Comorbidities0741014 [7-23]00 [0-5]1-22239442 [36-49]178 [5-12]&gt;219112968 [60-74]2915 [10-21]Treatment IntentCurative1866434 [28-42]95 [2-9]Palliative743953 [41-64]1216 [9-27]Cancer StatusRemission/NED33115447 [41-52]247 [5-11]Active disease, stable or responding to treatment1194840 [31-50]76 [2-12]Active disease, progressing372773 [56-86]1130 [16-47]Treatment Modality (within 3 months)Cytotoxic chemotherapy833542 [31-54]810 [4-18]Noncytotoxic therapy1856435 [28-42]105 [3-10]Local therapy (surgery or radiation)341750 [32-68]412 [3-27] Citation Format: Ali Raza Khaki, Dimpy P Shah, Maryam B Lustberg, Melissa K Accordino, Daniel G Stover, Gayathri Nagaraj, Donna R Rivera, Edith A Perez, Sara M Tolaney, Jeffrey Peppercorn, Petros Grivas, Jeremy L Warner, Corrie A Painter, Gilberto de Lima Lopes, Jr, Solange Peters, Michael A Thompson, Toni K Choueiri, Brian I Rini, Gary H Lyman, Nicole M Kuderer, Shaveta Vinayak. Characteristics and outcomes of SARS-CoV-2 infection in patients with invasive breast cancer (BC) from the COVID-19 and cancer consortium (CCC19) cohort study [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 PS7-01.

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 &lt;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.