Citations

Abstract Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Methods: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p<0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p=0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p<0.001). Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.

Introduction: Eculizumab is a monoclonal antibody that binds to complement protein C5, inhibiting complement-mediated thrombotic microangiopathy. It is approved for several indications including atypical hemolytic uremic syndrome. Additionally, eculizumab is used off-label for antibody-mediated rejection and C3 glomerulopathy in renal transplant recipients. Due to limited data available, the purpose of this study was to describe the use of eculizumab treatment in renal transplant recipients. Design: This retrospective single-center study evaluated the safety and efficacy of eculizumab for on- and off-label indications in renal transplant recipients. Adult renal transplant recipients receiving at least 1 dose of eculizumab posttransplant between October 2018 and September 2021 were included. The primary outcome evaluated was graft failure in patients treated with eculizumab. Results: Forty-seven patients were included in analysis. The median age at eculizumab initiation was 51 years [IQR 38-60], with 55% being female. Indications for eculizumab included atypical hemolytic uremic syndrome/thrombotic microangiopathy (63.8%), antibody-mediated rejection (27.7%), C3 glomerulopathy (4.3%), and other (4.3%). Graft failure occurred in 10 patients (21.3%) with a median of 2.4 weeks [IQR 0.5-23.3] from transplant to graft failure. At last follow-up (median 56.1 weeks), 44 (93.6%) patients were alive. After eculizumab initiation, renal function improved at 1 week, 1 month, and last follow-up. Conclusion: Eculizumab treatment demonstrated a benefit on graft and patient survival compared to reported incidence in thrombotic microangiopathy and antibody-mediated rejection. Due to the small sample size and retrospective design, further research is warranted to confirm these results.

9 Background: The efficacy of neoadjuvant platinum-based chemotherapy (NAPC) in penile squamous cell carcinoma (PSCC) was provided by small clinical trials, leaving clinicians with scant evidence-based guidance. Thus, we aimed to analyze real-world outcomes of patients with PSCC who received NAPC prior to surgical resection. Methods: Patients from 9 tertiary care centers who had undergone NAPC prior surgical resection for PSCC were included with locally advanced (cTany, cN+), non-metastatic (M0) disease. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), Response was determined via best overall response measured with RECIST 1.1 criteria. Results: 167 patients were included, 137 (84%), of which received TIP prior to surgical resection. Ninety-two (55%) patients died during follow up, and the mean follow up for survivors was 57 months. The median OS was 42 months, while the median PFS was 17 months. The table details the response rates to NAPC, the associated survival, and Cox Proportional Hazards Modelling of OS and PFS. Predictors for OS and RFS included lymphovascular invasion, positive number of lymph nodes, extranodal extension, downstaging, best overall response, and ypN status. Figure 1 demonstrates OS outcomes by RECIST best response after chemotherapy, presence of downstaging after NAPC, ypN stage, and presence of extranodal extension. Conclusions: Upfront NAPC is effective in patients with lymph node metastases from penile carcinoma. Unsurprisingly, patients who demonstrated a robust response to therapy had improved survival outcomes compared to those who had not—as measured by RECIST criteria, tumor downstaging, pN staging, and presence of extranodal extension. This study represents the largest conglomeration of multi-institutional penile carcinoma patients treated with NAPC, and provides further supportive data for multimodal therapy for advanced penile cancer patients while prospective clinical trials complete accrual. [Table: see text]

Introduction: Hypothalamic amenorrhea (HA) is a neuroendocrine disorder characterized by ovulatory dysfunction, anovulation, and infertility, which can be prolonged for months to years. Menstrual cycle irregularity and amenorrhea identify individuals with higher CVD risk, but existing evidence has not examined HA separately from polycystic ovary syndrome (PCOS). It remains unknown whether HA is associated with CVD events across the lifecourse. Hypothesis: We hypothesized that the HA phenotype (oligo/amenorrhea without PCOS traits) would identify individuals at increased risk for CVD. Methods: Nurses’ Health Study II participants with available information on menstrual cycle characteristics who were premenopausal and free of CVD at baseline comprised the analytic sample (n=83,281). Menstrual cycle regularity was retrospectively reported for ages 18-22y on the baseline questionnaire in 1989 while the 1993 biennial questionnaire captured current menstrual cycle regularity (at ages 29-49y); PCOS traits (severe acne, hirsutism) were additionally ascertained in 1993. Participants were followed for confirmed incident CVD (MI, stroke, and fatal CHD) from 1993 through 2017. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for the relationship between HA and CVD, adjusted for age, race/ethnicity, parental education, parental history of CVD <60y, and behavioral risk factors (smoking, physical activity, diet, alcohol intake, body mass index). Results: Thirteen percent of participants (n=11,071) ever had HA: 8.5% of participants (n=7,081) had HA at ages 18-22y while 6.5% (n=5,428) had HA at ages 29-46y. Persistent HA (HA at both 18-22y and 29-46 y) was identified in 1.7% of participants (n=1,438). CVD events occurred in 253 individuals who ever had HA (HA at either 18-22y or 29-46y) and 1,228 individuals without the HA phenotype. Individuals who ever had HA had a 20% higher rate of CVD (CI: 1.05-1.38). HA phenotype at ages 18-22y was not associated with CVD risk (HR=1.14; CI: 0.96-1.35) while HA phenotype at ages 29-46y was associated with a 30% higher rate of CVD (CI: 1.10-1.54) compared to individuals without HA phenotype. Individuals with persistent HA across both age ranges had a 69% higher rate of CVD (CI: 1.24-2.28). Underlying associations were strongest between ever HA and stroke (HR=1.25; CI: 1.03-1.51) and between persistent HA and CHD (HR=1.90; CI: 1.27-2.86), although case counts were small. Conclusions: HA phenotype in mid-adulthood identified individuals at increased risk of CVD compared to those without HA. As there are multiple HA subtypes, defined by varying combinations of psychosocial stress, anxiety, physical activity and weight loss, future studies should examine which HA subtypes are associated with CVD risk.

Objective: We aimed to characterize seasonal variation in US population-based blood pressure (BP) control and BP-related metrics and evaluate the association between outdoor temperature and BP control variation. Methods: We queried electronic health records (EHRs) from 26 health systems, representing 21 states, to summarize BP metrics by quarters of 12-month periods from January 2017 to March 2020. Patients with at least one ambulatory visit during the measurement period and a hypertension diagnosis during the first 6 months or prior to the measurement period were included. Changes in BP control, BP improvement, medication intensification, average SBP reduction after medication intensification across quarters and association with outdoor temperature were analyzed using weighted generalized linear models with repeated measures. Results: Among 1 818 041 people with hypertension, the majority were more than 65 years of age (52.2%), female (52.1%), white non-Hispanic (69.8%) and had stage 1/2 hypertension (64.8%). Overall, BP control and process metrics were highest in quarters 2 and 3, and lowest in quarters 1 and 4. Quarter 2 had the highest percentage of improved BP (31.95 ± 0.90%) and average SBP reduction after medication intensification (16 ± 0.23 mmHg). Quarter 3 had the highest percentage of BP controlled (62.25 ± 2.55%) and lowest with medication intensification (9.73 ± 0.60%). Results were largely consistent in adjusted models. Average temperature was associated with BP control metrics in unadjusted models, but associations were attenuated following adjustment. Conclusion: In this large, national, EHR-based study, BP control and BP-related process metrics improved during spring/summer months, but outdoor temperature was not associated with performance following adjustment for potential confounders.

AbstractBackgroundRisk‐stratified follow‐up guidelines that account for the absolute risk and timing of recurrence may improve the quality and efficiency of breast cancer follow‐up. The objective of this study was to assess the relationship of anatomic stage and receptor status with timing of the first recurrence for patients with local‐regional breast cancer and generate risk‐stratified follow‐up recommendations.MethodsThe authors conducted a secondary analysis of 8007 patients with stage I–III breast cancer who enrolled in nine Alliance legacy clinical trials from 1997 to 2013 (ClinicalTrials.gov identifier NCT02171078). Patients who received standard‐of‐care therapy were included. Patients who were missing stage or receptor status were excluded. The primary outcome was days from the earliest treatment start date to the date of first recurrence. The primary explanatory variable was anatomic stage. The analysis was stratified by receptor type. Cox proportional‐hazards regression models produced cumulative probabilities of recurrence. A dynamic programming algorithm approach was used to optimize the timing of follow‐up intervals based on the timing of recurrence events.ResultsThe time to first recurrence varied significantly between receptor types (p < .0001). Within each receptor type, stage influenced the time to recurrence (p < .0001). The risk of recurrence was highest and occurred earliest for estrogen receptor (ER)‐negative/progesterone receptor (PR)‐negative/Her2neu‐negative tumors (stage III; 5‐year probability of recurrence, 45.5%). The risk of recurrence was lower for ER‐positive/PR‐positive/Her2neu‐positive tumors (stage III; 5‐year probability of recurrence, 15.3%), with recurrences distributed over time. Model‐generated follow‐up recommendations by stage and receptor type were created.ConclusionsThis study supports considering both anatomic stage and receptor status in follow‐up recommendations. The implementation of risk‐stratified guidelines based on these data has the potential to improve the quality and efficiency of follow‐up.

Abstract Background: The ATEMPT trial primary analysis found that one year of adjuvant trastuzumab emtansine (T-DM1) achieved a 3-year iDFS of 97.8% for patients with stage I HER2+ breast cancer, but was not associated with fewer clinically relevant toxicities (CRTs) compared with paclitaxel and trastuzumab (TH). In this end-of-study analysis, we report 5-year survival outcomes and correlative analyses from the trial. Methods: Patients with stage I centrally confirmed HER2+ breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for one year or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or paclitaxel 80 mg/m2 IV with weekly trastuzumab IV followed by trastuzumab for 9 months. The co-primary objectives were to compare the incidence of CRTs between the 2 arms and to evaluate iDFS in patients receiving T-DM1. To investigate proteomic correlates of recurrence, spatial proteomic analyses were performed on samples from 13 patients experiencing iDFS events (cases) and 24 matched controls using the NanoString GeoMx Digital Spatial Profiler. The impact of HER2 heterogeneity on outcomes was investigated among 17 cases and 51 matched controls by fluorescence in-situ hybridization (FISH). HER2 genetic heterogeneity was assessed by scrutinizing the whole tumor area and defined as the occurrence of HER2 gene amplification in &gt;5% but &lt; 50% invasive tumor cells. The risk of recurrence was evaluated centrally with the HER2DX genomic assay from 225 primary tumor samples. Germline whole genome sequencing (WGS) was conducted among 55 patients experiencing T-DM1-induced thrombocytopenia and/or bleeding and 55 matched controls to identify genomic correlates for this side effect. Results: A total of 497 patients who initiated protocol therapy were included in this analysis (383 T-DM1 and 114 TH). After a median follow up 5.8 years, among patients receiving T-DM1 there were a total of 11 iDFS events, with 3 distant recurrences. The 5-year iDFS for T-DM1 was 97.0% (95% CI, 95.3-98.8%), the 5-year recurrence-free interval (RFI) was 98.6% (95% CI: 97.4-99.8%) and the 5-year overall survival (OS) for T-DM1 was 97.8 % (95% CI, 96.3-99.3%). Although the study was not powered to evaluate the efficacy of TH, among the 114 patients receiving TH, a total of 9 iDFS events were observed, including 2 distant events; the 5-year iDFS with TH was 91.3% (95% CI: 86.0-96.9%), 5-year RFI was 93.3% (95% CI: 88.6-98.2%) and 5-year OS was 97.9% (95% CI: 95.2-100%). A total of 56 samples were evaluable for heterogeneity analyses, among which 14% (n=8) harbored HER2 genetic heterogeneity. Spatial proteomic analyses found that NF1 (adjusted p=0.72 × 10-6) and CTLA-4 (adjusted p=0.15 × 10-3) were significantly upregulated in primary samples from cases, while cleaved caspase 9, CD25, GITR, ICOS, p53 and PD-L2 were significantly upregulated in controls (all with adjusted p&lt; 0.05). Germline WGS found that the top gene associations with thrombocytopenia and thrombocytopenia or bleeding were ALMS1 (p=0,19 × 10-3) and APBA3 (p=0,23 × 10-3), respectively, although none reaching the threshold for genome wide significance. rs62143195 and rs114169776 were the top single nucleotide polymorphisms associated with thrombocytopenia and thrombocytopenia or bleeding, respectively. Data on the impact of HER2 heterogeneity and of HER2DX score on survival outcomes will be presented. Conclusion: With longer follow-up, adjuvant T-DM1 confirmed outstanding long-term outcomes among patients with stage I HER2+ breast cancer, demonstrating a 5-year RFI of 98.6%. Spatial proteomic analyses identified a potential association between NF1 and CTLA-4 expression with recurrence. Details on the impact of HER2 heterogeneity and HER2DX assay on prognosis will be presented. Citation Format: Paolo Tarantino, Nabihah Tayob, Chau T Dang, Denise Yardley, Steven J. Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Douglas Weckstein, Antonio C. Wolff, Katherine Reeder-Hayes, Hope Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna K. Gadi, Michael Constantine, Kit Cheng, Audrey Merrill Garrett, Paul K. Marcom, Kathy S. Albain, Patricia DeFusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel C. Jankowitz, Mothaffar Rimawi, Vandana Abramson, Paula R. Pohlmann, Catherine Van Poznak, Andres Forero-Torres, Minetta C. Liu, Kathryn Ruddy, Yue Zheng, Romualdo Barroso-Sousa, Adrienne Waks, Michelle K. DeMeo, Molly K. DiLullo, Giuseppe Curigliano, Harold Burstein, Ann Partridge, Eric Winer, Giuseppe Viale, Winnie Hui, Elizabeth A. Mittendorf, Bryan P. Schneider, Aleix Prat, Ian Krop, Sara Tolaney. Adjuvant Trastuzumab Emtansine Versus Paclitaxel plus Trastuzumab for Stage I HER2+ Breast Cancer: 5-year results and correlative analyses from ATEMPT (TBCRC033) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-01.

Abstract Introduction Breast cancer is uncommon in men. Almost all male breast cancers are hormone receptor-positive, HER2-negative, although the pathogenesis is not always attributable to an endocrine condition. A few studies have compared biological characteristics or molecular signatures with breast cancers in women. We sought to evaluate whether hormone receptor-related gene expression is different in cancers from men compared to equivalent cancers from women. SET2,3 index measures non-proliferative hormone receptor-related transcriptional activity in the cancer (SET-ER/PR index) and adjusts this for a Baseline Prognosis Index (BPI) that combines the measurements of tumor and nodal stage with a 4-gene molecular subtype (ESR1, PGR, ERBB2, and AURKA). Methods We received aliquots of total RNA from male patients with breast cancer included in the retrospective cohort study of the EORTC 10085/BCG/TBCRC/BIG/NCTN International Male Breast Cancer Program (NCT01101425). SET2,3 assay was performed using the QuantiGene assay (Thermo Fisher) using bead-based hybridization and laser spectroscopy (Luminex). The statistical analyses were performed by the EORTC statistician. The primary objective of the study was the assessment of the prognostic value of the SET2,3 index score in patients with early-stage hormone receptor-positive, HER2-negative male breast cancer, treated with endocrine therapy. Clinical outcomes (recurrence-free survival – RFS; overall survival – OS) were estimated by Kaplan-Meier curves and secondarily compared using multivariable Cox models adjusted for continuous SET2,3 index, tumor size, nodal status, age, and chemotherapy and radiotherapy use. An exploratory analysis to compare the SET2,3 index scores distribution in female and male breast cancer patients was also performed using results from the same assay performed on cancers from women selected on the same inclusion criteria. Due to the low numbers of male patients treated with neoadjuvant treatment (N=6), this analysis was restricted to patients treated with adjuvant treatment (n=315 male and 660 female). Results Of the 321 male patients with breast cancer analyzed, treated between 1990 and 2010, 211 (65.7%) were categorized as high SET2,3 index score, reflecting a high endocrine activity in the cancer and low risk of recurrence, and 110 patients (34.3%) categorized as being low score, reflecting low endocrine activity and high risk of recurrence. At 5 years, the RFS was 75.0% (95% CI, 67.4-81.1) in the high SET2,3 group versus 60.7% (95% CI, 49.1-70.5) in the low SET2,3 group (HR univariate, 0.49; 95% CI, 0.34-0.70; P&lt; 0.0001). The 5-year OS rate among patients with a high SET2,3 index was 84.3% (95% CI, 45.5-73.8), in contrast of 67.8% (95% CI, 56.6-76.7) in the low SET2,3 group (HR univariate, 0.44; 95% CI, 0.30-0.65; P&lt; 0.0001). SET2,3 was independently prognostic for OS, but not RFS in multivariable Cox models. In patients classified as low SET2,3, the addition of neo/adjuvant chemotherapy to adjuvant endocrine therapy was associated with 5-year OS of 76.0% (95% CI, 59.5-86.4) and in patients who received endocrine therapy alone the 5-year OS was 61.3% (95% CI, 45.5-73.8), an absolute difference of 14.7 percentage points. Overall, we did not observe a difference in the distributions (median, interquartile range) of SET2,3 index between men (2.4, 1.9–2.6) and women (2.3, 2.0–2.7). Conclusion SET2,3 index measurements of endocrine-related transcriptional activity in male patients with breast cancer were not different from measurements in female patients with breast cancer. SET2,3 was prognostic in male breast cancer and our exploratory analysis suggests that chemotherapy might improve the poor prognosis for men with breast cancer that has low SET2,3 index. This study was funded by the Breast Cancer Research Foundation (BCRF). Citation Format: Danielle B. Zakon, Coralie Poncet, Fatima Cardoso, Neven Anouk, Vicente Valero, Stefan Aebi, Kim Benstead, Oliver Bogler, Lissandra Dal Lago, Judith Fraser, Carmela Caballero, Ingrid A. Hedenfalk, Larissa A. Korde, Barbro Linderholm, John WM Martens, Lavinia P. Middleton, Melissa Murray, Catherine M. Kelly, Cecilia Nilsson, Monika Nowaczyk, Stephanie Peeters, Melanie Beauvois, Peggy Porter, Carolien P. Schroder, Isabel T. Rubio, Kathryn Ruddy, Christi van Asperen, Danielle Van Den Weyngaert, Carolien HM van Deurzen, Elise van Leeuwen-Stok, Joanna M. Vermeij, John MS Bartlett, Antonio C. Wolff, Sharon H. Giordano, W. Fraser Symmans. PD6-11 Evaluation of the Sensitivity to Endocrine Therapy Index (SET2,3) in Early Male Breast Cancer: Results from an analysis in the EORTC 10085/TBCRC/BIG/NCTN International Male Breast Cancer Program [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-11.

Abstract Background. Patient-reported outcomes (PROs) are increasingly recognized as a valuable component to understand treatment tolerability and toxicity among patients on clinical trials. We have implemented a system for monitoring patient reported outcomes (PROs), symptoms, and quality of life (QOL) using electronic PRO (ePRO) instruments for patients enrolled in the I-SPY2 trial. I-SPY2 is a phase II multi-site clinical trial evaluating the effect of novel neoadjuvant therapies for locally advanced breast cancer. We correlated patient demographic factors with symptoms, investigated the trajectory of symptoms throughout treatment, and sought to characterize symptoms associated with decline in physical function (PF). Methods. Our study population included 259 I-SPY2 patients that completed surveys on one of 9 study arms (including novel oral taxane/immunotherapy combinations, IV paclitaxel, checkpoint inhibitor+/- LAG3 inhibitor, and control IV paclitaxel +/- trastuzumab/pertuzumab). After the 12 week period of investigational agents, most patients received standard adriamycin and cyclophosphamide (AC). Symptom severity, frequency, and interference was assessed weekly using 33 items from the PRO-CTCAE item bank. PF was assessed using the NIH PROMIS instrument and was evaluated at baseline, inter-regimen (after 12 weeks of treatment), pre-surgery, and 1 and 6 months at follow-up. An odds ratio was used to assess univariate associations between age and race, and symptoms. Regularized multi-variate regression was used to evaluate early symptoms (prior to week 6) predictive of a clinically significant (&gt;5 point T-score) decline in PF from baseline to post-treatment follow-up among all races and age groups. Results. Of 259 patients (mean age (SD) = 46.8 (13.6)), 160 (58%) were White, 13 (5%) were Asian, 26 (10%) were African American (AA), 25 (9.3%) were Hispanic, and 35 (13.5%) self-reported “Other”. At baseline, AA patients had a higher severity of joint pain than White patients (OR = 14.9, P &lt; 0.05). During study treatment with paclitaxel and/or novel agent within the first 12 weeks of treatment, AA patients and non-white (NW) patients were more likely to report severe vomiting than White patients (OR =13.22 and 12.72, P&lt; 0.05 and P&lt; 0.03 respectively). During treatment with AC, NW patients were more likely to report higher severity of neuropathy than White patients (OR = 5.43, P&lt; 0.03). Among all patients, in analysis of early symptoms predictive of a clinically significant decline in PF between baseline and 1 month post treatment, predictors included high frequency of diarrhea, severity of itching, and severity of joint pain. Further analysis of symptom trajectories revealed that frequency of diarrhea reported rose sharply between baseline and Cycle 2 with 9 patients (7%) reporting occasional or frequent diarrhea to 39 patients (28%) reporting occasional to almost constant diarrhea and remained stable at that proportion for the remainder of treatment. Frequency of diarrhea declined slightly during AC (17%) and dropped to baseline levels by follow-up. In contrast, severity of joint pain persisted post-treatment, rising consistently from baseline through follow- up with 3 patients (2%) reporting moderate to severe joint pain at baseline to 18 patients (35%) reporting moderate to severe joint pain at follow-up. Conclusion. Among I-SPY2 participants, when higher grade of diarrhea is persistent (or uncontrolled), it impacts physical function even after end of therapy. In some cases, race was also a determinant in symptom trajectory, although a higher enrollment of AA and NW patients will enable more robust estimates to be computed. While some of these early symptom predictors are transient and resolve by the time of follow-up, others persist long-term and contribute more directly towards impaired physical function at follow-up. Citation Format: Amrita Basu, Saumya Umashankar, Kaylee Blevins, Anna Northrop, Anika Christofferson, Ebunoluwa Olunuga, Jaeyoon Cha, Ananya Mittal, Julissa Molina-Vega, Laura Sit, Thelma Brown, Bev Parker, Diane Heditsian, Susie Brain, Carol Simmons, Alessandra Taboada, Tina J. Hieken, Kathryn Ruddy, Carolina Salvador, Candace Mainor, Anosheh Afghahi, Sarah Tevis, Anne Blaes, Irene M. Kang, Jane Perlmutter, Hope Rugo, Sai Kanaparthi, Garry Peterson, Lisa T. Weiss, Adam Asare, Laura J. Esserman, Michelle Melisko, Dawn Hershman. The Association Between Symptom Severity and Physical Function among Participants in I-SPY2 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-07-03.

Abstract Background: Breast cancer (BC) is the most common malignancy among women of reproductive age. Given limited data describing the conception and pregnancy experience of young BC survivors, we sought to explore these outcomes to inform counseling of women interested in future childbearing. Methods: Participants with stage 0-III BC in the Young Women’s Breast Cancer Study (NCT01468246), a multi-center, prospective cohort of women diagnosed at age ≤ 40 from 2006-2016 who reported ≥ 1 live birth from a pregnancy after diagnosis were sent a survey with investigator-developed questions focused on their first post-diagnosis live birth. Women who had been diagnosed with BC during pregnancy were excluded from this analysis. The survey assessed conception, use of assisted reproductive technology (ART), pre-implantation genetic testing (PGT), endocrine therapy (ET), and peripartum complications. Summary statistics are presented. Results: 92/119 eligible women completed the survey (response rate: 77%). Median age at diagnosis was 32 (range:17-40) years and at delivery was 37 (range: 29-47) years. Median time from diagnosis to delivery was 58 months (range: 11-154). Most women had stage 2 BC (43%, 40/92); 68% received chemotherapy (63/92); about half (51%, 47/92) were nulligravida at diagnosis. Overall, 61% of pregnancies were conceived naturally (56/92) and 39% with ART (36/92): 32% by in-vitro fertilization (IVF, 29/92), 7% with fertility medications only (6/92), and 1 with intrauterine insemination. 38% of IVF pregnancies were conceived using products from fertility preservation prior to BC treatment (11/29). Among women who used ART, 74% attempted to conceive naturally (25/36) for a median of 9 (range: 2-48) months prior to pursuing ART. The most common reasons for pursuing ART include infertility following BC treatment (33%, 12/36) and expediting conception to resume treatment (17%, 6/36). 11% of those with known inherited pathologic variant mutations underwent PGT (2/19). Reasons for not pursuing PGT included belief in more effective cancer risk reduction in the future (29%, 5/17), not being offered PGT (24%, 4/17), high cost (12%, 2/17), no interest in IVF (12%, 2/17), acceptable odds for inheriting the mutation (24%, 4/17), and belief in other risk reduction strategies (18%, 3/17); 1 woman reported ethical concerns. Of 57 women who took ET pre-pregnancy (63%), nearly all (96%, 55/57) discontinued ET &gt; 3 months prior to attempting to conceive; 1 discontinued after awareness of pregnancy. Of those who had received prior ET, 60% resumed ET (34/57) a median of 3 (range: 1-50) months after pregnancy. Among 23 women who did not resume, 13 (23%) had completed the recommended duration; the remaining 10 reported one or more of the following reasons: felt better while off (28%, 6/23), desire for another child (22%, 5/23), and desire to breastfeed (17%, 4/23). Median time to delivery was 39 (range: 28-42) weeks with 12% delivering preterm &lt; 37 weeks (11/92). 47% had a Caesarean section (43/92), with prolonged labor the most common indication (33%, 14/43). Hypertensive disorders of pregnancy (HDP, 20%, 18/92), gestational diabetes (7%, 6/92), small for gestational age (7%, 6/92), and postpartum hemorrhage (5%, 5/92) were the most common obstetrical complications. 9% of women had newborns requiring NICU admission (8/92) and 9% had low birth weight (8/92). Conclusion: Among young BC survivors with a live birth following diagnosis, most conceived naturally, with the majority who used ART first attempting natural conception. There was limited use of PGT among mutation carriers with ¼ not having been offered testing. Patient reported peripartum complications appear consistent with population norms, though the relatively higher rate of HDP bears further research. Among those yet to complete their ET, a notable proportion did not resume following delivery. This novel data may help to inform the care of young breast cancer survivors pursuing pregnancy. Citation Format: Kimia Sorouri, Tal Sella, Shoshana Rosenberg, Margaret Loucks, Kathryn Ruddy, Shari I. Gelber, Rulla M. Tamimi, Jeffrey M. Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Ellen Warner, Ann Partridge. Conception and Pregnancy Among Young Breast Cancer Survivors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-05.