Citations 2
Outcomes and treatment patterns in germline BRCA1/2 carriers from two matched cohort studies
Morganti, Stefania , Kim, Se Eun , Jin, Qingchun , Cha, Jaeyoon , Zeigler, Jacqueline E, Newman, Alexandra Bili, Kirkner, Gregory J. , Snow, Craig , Zheng, Yue, Vincuilla, Julie, Parker, Tonia , Buehler, Ryan M. , Bychkovsky, Brittany L , Dibble, Kate E. , Sella, Tal , Ruddy, Kathryn J, Rosenberg, Shoshana M, Collins, Laura C. , Peppercorn, Jeffrey, Schapira, Lidia, Guzman-Arocho, Yaileen D, Come, Steven E. , Warner, Ellen, Poorvu, Philip D. , Lambertini, Matteo, Curigliano, G, Hughes, Melissa E. , Mittendorf, Elizabeth A, King, Tari A, Lin, Nancy U, Garber, Judy E, Tayob, Nabihah, Tolaney, S M, Partridge, Ann H, Zheng, Yue , Newman, Alexandra B , Zheng, Yue , Ruddy, Kathryn J , Peppercorn, Jeffrey M , Borges, Virginia F , Guzman-Arocho, Yaileen D , Come, Steven , Poorvu, Philip D , Lambertini, Matteo , Curigliano, Giuseppe , Mittendorf, EA , King, Tari A , Lin, Nancy U , Garber, J. E. , Tayob, Nabihah , Tolaney, Sara , Partridge, Ann H , Lynce, Filipa , Kirkner, Gregory , Snow, Craig , Vincuilla, Julie, Ruddy, Kathryn J. , Rosenberg, Shoshana M. , Peppercorn, Jeffrey , Schapira, Lidia , Borges, Virginia F. , Guzmán‐Arocho, Yaileen D. , Warner, Ellen , Lambertini, Matteo , Curigliano, Giuseppe , King, Tari A. , Lin, Nancy U. , Garber, Judy E. , Partridge, Ann H.
JNCI Cancer Spectrum | May 23, 2026 | Volume: 10 | Issue: 4 | Pages: No page available
Abstract Background Whether outcomes of germline BRCA1/2 (gBRCA1/2)-associated breast cancer differ compared with sporadic tumors is controversial. We explored the impact of gBRCA1/2 pathogenic variant (PV) status beyond established prognostic features. Methods We conducted 2 retrospective, matched cohort studies comparing gBRCA1/2 PV carriers and noncarriers with HER2-negative, stage I-III breast cancer (Clinical Outcomes Quality Database [COQD] cohort: 185 carriers, 555 noncarriers; Young Women’s Breast Cancer Study [YWS] cohort: 113 carriers, 226 noncarriers). Matching factors were age, stage, hormone receptor status, and year of diagnosis. Clinicopathological features, treatments, and survival outcomes were compared between carriers and noncarriers. Results Most patients in COQD had stage I-II disease (87.2%), and more carriers than noncarriers had genetic testing before diagnosis (33% vs 5.6%, P < .001). In YWS, 22.7% of patients had stage III tumors, and few were tested before diagnosis (14.8% of carriers vs 1.7% of noncarriers; P < .001). Carriers in COQD received chemotherapy more often than noncarriers (81.1 vs 67.0%, P < .001), including platinum (P = .010); the proportion was similar for carriers and noncarriers in YWS. After adjusting for chemotherapy, relapse-free survival was longer in carriers than noncarriers in COQD (adjusted hazard ratio = 0.48 [95% CI = 0.26 to 0.87], P = .016), and a favorable trend was observed for other survival outcomes in both cohorts. Triple-negative tumors appeared to drive the differences. Conclusions We observed a trend toward improved outcomes in gBRCA1/2 PV carriers compared with noncarriers. These findings suggest that carriers should not receive more aggressive treatment solely based on their germline mutation status. Prospective clinical trials in this population are warranted.
Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression
Nishida, Jun , Cristea, Simona , Bodapati, Sudheshna , Puleo, Julieann , Bai, Gali , Patel, Ashka, Hughes, Melissa E. , Ruddy, Kathryn J. , Collins, Laura C. , Feeney, Anne-Marie , Slowik, Kara, Bossuyt, Veerle , Dillon, Deborah , Polyák, Kornélia , Polyak, Kornelia , Patel, Ashka , Snow, Craig , Borges, Virginia F. , Lin, Nancy U. , Partridge, Ann H. , Michor, Franziska
Proceedings of the National Academy of Sciences | November 27, 2023 | Volume: 120 | Issue: 49 | Pages: No page available
Immune escape is a prerequisite for tumor growth. We previously described a decline in intratumor activated cytotoxic T cells and T cell receptor (TCR) clonotype diversity in invasive breast carcinomas compared to ductal carcinoma in situ (DCIS), implying a central role of decreasing T cell responses in tumor progression. To determine potential associations between peripheral immunity and breast tumor progression, here, we assessed the peripheral blood TCR clonotype of 485 breast cancer patients diagnosed with either DCIS or de novo stage IV disease at younger (<45) or older (≥45) age. TCR clonotype diversity was significantly lower in older compared to younger breast cancer patients regardless of tumor stage at diagnosis. In the younger age group, TCR-α clonotype diversity was lower in patients diagnosed with de novo stage IV breast cancer compared to those diagnosed with DCIS. In the older age group, DCIS patients with higher TCR-α clonotype diversity were more likely to have a recurrence compared to those with lower diversity. Whole blood transcriptome profiles were distinct depending on the TCR-α Chao1 diversity score. There were more CD8 + T cells and a more active immune environment in DCIS tumors of young patients with higher peripheral blood TCR-α Chao1 diversity than in those with lower diversity. These results provide insights into the role that host immunity plays in breast cancer development across different age groups.