Citations 2
Clarifying risk-factor associations with quantitative breast tumor features: a pooled analysis of 24 studies
Adams, Daniel , Hurson, Amber N. , Ahearn, Thomas U, Andrulis, Irene L, Antoniou, Antonis C, Auvinen, Päivi, Bane, Anita, González, Amy Berrington de , Bodelon, Clara, Bolla, Manjeet K. , Borrero, Maria , Brenner, Hermann, Brock, Ian W., Camp, Nicola J. , Cessna, Melissa H., Chanock, Stephen J, Chenevix-Trench, G, Copson, ER, Fh, Couch, Devilee, P, Easton, Douglas F, Eccles, Diana, Figueroa, Jonine D, Glendon, Gord, Hamann, U, Hartman, Mikael, Heemskerk-Gerritsen, Bernadette A M, Hodge, James M, Holleczek, Bernd, Hollestelle, A M, Mj, Hooning, Investigators, kConFab, Amor, David, Andrews, Lesley , Antill, Y , Rl, Balleine, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Bodek, Simon, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Caldon, Liz, Campbell, Ian, Chakrabarti, Anannya , Chauhan, Deepa, Chauhan, Manisha, Christian, Alice, Cohen, Paul, Colley, Alison, Cui, James, Courtney, Eliza, Cummings, Margaret, Delatycki, Martin, Dickson, Rebecca, Dixon, Joanne, Duijf, Pascal, Edwards, Stacey, Farshid, Gelareh , Fellows, AM, Fenton, Georgina, Field, Michael, Flanagan, James, Fong, Peter, Forrest, Laura, Fox, Stephen, French, Juliet , Friedlander, Michael, Gattas, Mike, George, Peter, Greening, Sian, Harris, Marion, Harraka, Philip, Hayward, Nick, Hoskins, Cass , Hunt, Clare, James, Paul, Jenkins, Mark, Kidd, Alexa, Koehler, Jessica, Kollias, J, Lakhani, Sunil, Lawrence, Mitchell, Lee, Jason , Li, Shuai, Lindeman, Geoff, Lippey, Jocelyn, Lipton, Lara, Loi, Sherene, Mann, Graham, Marsh, Deborah, McLachlan, Sue Anne, Reed, Amy McCart, Milne, Roger, Nightingale, Sophie , O’Connell, Shona, O’Sullivan, Sarah, Reilly, Robert O', Ortega, David Gallego, Pachter, Nick, Pang, Jia-Min, Pathak, Gargi, Patterson, Briony, Phillips, Kelly, Pieper, Ellen, Ramus, Susan, Rickard, Edwina, Ragunathan, Abi, Robinson, Bridget, Skandarajah, Anita, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Scott, Rodney, Scott, Clare, Sexton, Adrienne, Shaw, Joanne, Shelling, Andrew, Srinivasa, Shweta , Simpson, Peter, Mc, Southey, Spurdle, Amanda, Taylor, Jessica, Taylor, Renea, Thorne, Heather, Trainer, A H, Tucker, Kathy , Visvader, Jane, Walker, Logan, Williams, Rachael, Winship, I, Young, Mary Ann, Zaheed, Milita , Investigators, S On Behalf Of The Chlovis Study, Tan, Veronique Kiak Mien , Lim, Geok Hoon, Tan, Ern Yu , Tan, Su-Ming, Iau, Philip Tsau Choong , Jakubowska, A, Jones, Michael E. , Jones, Louise , Jones, Brandt, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske , Lawrence, Scott, Li, J M, Lubiński, J, Mannermaa, Arto, Manoochehri, Mehdi, Martens, John W M, Mesker, Wilma E, Muhammad, Noor , Obi, Nadia, Olson, Janet E, Patel, Alpa V, Prajzendanc, Karolina , Ruddy, Kathryn J, Safizadeh, Fatemeh , Schöttker, Ben, Tengström, Maria , Le, Teras, Timmermans, M, Tollenaar, RA, Vachon, Celine M, Wang, Q, Yang, Xiaohong R, Zamora, M Pilar, Chang-Claude, Jenny, Schmidt, M K, Pharoah, Paul D P, Abubakar, Mustapha, Eccles, Diana , Ahearn, Thomas U. , Eccles, Diana , Jones, Michael E , Jones, J. Louise , Berrington de Gonzalez, Amy , Antoniou, Antonis C. , Bane, Anita, Behrens, Sabine , Białkowska, Katarzyna , Bodelón, Clara , Brenner, Hermann , Broeks, Annegien , Chanock, Stephen Jacob , Chenevix‐Trench, Georgia , Copson, Ellen , Couch, Fergus J, Cox, Angela , Cross, Simon S. , Devilee, Peter , Dunning, Alison M. , Easton, Douglas F. , Figueroa, Jonine D. , Glendon, Gord, González‐Neira, Anna , Hartikainen, Jaana M. , Hartman, Mikael , Heemskerk‐Gerritsen, Bernadette A. M. , Ho, Peh Joo , Hodge, James M. , Holleczek, Bernd , Hollestelle, Antoinette , Hooning, Maartje J. , Investigators, kConFab, Balleine, Rosemary L. , Bennett, Ian, Bogwitz, Michael R. , Bodek, Simon , Botes, Leon P., Buckley, Michael , Cohen, Paul A. , Crook, Ashley , Courtney, Eliza , Dawson, Sarah‐Jane , DeFazio, Anna , Delatycki, Martin B. , Duijf, Pascal H. G. , Fellows, Andrew, Fenton, Georgina L. , Flanagan, James M. , Forrest, Laura Elenor , Friedländer, Michael , Harraka, Philip A. , Kidd, Alexa, Kollias, James, Lakhani, Sunil R. , Lawrence, Mitchell, Lindeman, Geoffrey J. , Lippey, Jocelyn , Loi, Sherene , Reed, Amy E. McCart , Milne, Roger L , Gallego‐Ortega, David , Pathak, Gargi, Pearn, Amy , Robinson, Bridget A. , Skandarajah, Anita Rohini , Salisbury, Elizabeth, Saunders, Christobel , Saunus, Jodi M. , Savas, Peter Stephen , Sexton, Adrienne , Shelling, Andrew Neil , Simpson, Peter, Spurdle, Amanda B. , Visvader, Jane E. , Williams, Rachael, Tan, Bien‐Keem , Lim, Geok Hoon , Kaaks, Rudolf , Lawrence, Scott M. , Lissowska, Jolanta , Mannermaa, Arto , Manoochehri, Mehdi, Mesker, Wilma E. , Mulligan, Anna Marie , Obi, Nadia , Olson, Janet E. , Osório, Ana , Ottewell, Penelope Dawn , Patel, Alpa V , Pita, Guillermo , Rashid, Muhammad Usman , Ruddy, Kathryn J. , Schöttker, Ben , Seibold, Petra , Tapper, William , Teras, Lauren R , Timmermans, Mieke, Vachon, Celine M. , Wesseling, Jelle , Yadav, Siddhartha , Chang‐Claude, Jenny , Schmidt, Marjanka K. , Abubakar, Mustapha , García‐Closas, Montserrat
JNCI: Journal of the National Cancer Institute | July 18, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.
Abstract PD9-05: Stromal tumor-infiltrating lymphocytes identify early-stage triple-negative breast cancer patients with favorable outcomes at 10-year follow-up in the absence of systemic therapy: a pooled analysis of 1835 patients
Leon‐Ferre, Roberto A. , Jonas, Sarah Flora , Salgado, Roberto, Jong, Vincent de, Nielson, Torsten, Leung, Samuel , Riaz, Nazia , Linderholm, Barbro, Deurzen, Carolien HM van, Timmermans, Mieke, Yazaki, Shu, Yoshida, Masayuki , Kok, Marleen , Salgado, Roberto , Loi, Sherene , Carter, Jodi M. , Curigliano, Giuseppe , Criscitiello, Carmen , Cockenpot, Vincent , Lambertini, Matteo , Suman, Vera J. , Linderholm, Barbro Kristina , Martens, John W.M. , Deurzen, Carolien HM van, Shimoi, Tatsunori , Kim, Sung-Bae , Lee, Hee Jin , Dieci, Maria Vittoria , Bataillon, Guillaume , Vincent‐Salomon, Anne , André, Fabrice , Linn, Sabine C. , Goetz, Matthew P. , Michiels, Stefan
Cancer Research | March 2, 2023 | Volume: 83 | Issue: 5_Supplement | Pages: PD9-05-PD9-05
10.1158/1538-7445.sabcs22-pd9-05
Abstract Background: The prognostic value of stromal tumor-infiltrating lymphocytes (TILs) as a biomarker for triple-negative breast cancer (TNBC) has been extensively demonstrated in patients (pts) receiving (neo)adjuvant systemic therapy. In addition, several small studies suggest that a subset of pts with early-stage TNBC and high TILs have excellent long-term outcomes, even in the absence of systemic therapy [1-3]. However, data on the absolute risk of TNBC recurrence according to TIL levels in the absence of systemic therapy are limited and critical to inform the design of future systemic therapy de-escalation clinical trials. Methods: We conducted an individual patient data pooled analysis of 12 international cohorts of pts with TNBC treated with locoregional therapy but no systemic therapy. TNBC was defined as tumors with estrogen and progesterone receptor of < 1% and HER2 negative (IHC 0, 1+ or IHC 2+ and FISH negative) per local evaluation. TILs were locally assessed in hematoxylin & eosin-stained slides according to the International Immuno-Oncology Biomarker Working Group guidelines (www.tilsinbreastcancer.org). We used the Kaplan-Meier method to assess survival outcomes according to prespecified TIL thresholds: 30% and 50%. Confidence intervals (CI) for survival probabilities were calculated using a percentile bootstrap method. The primary endpoint was invasive disease-free survival (iDFS, STEEP 2.0 definition). Key secondary outcomes included recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS). Results: 1,835 pts diagnosed with TNBC between 1982 and 2017 who did not receive systemic therapy were included. The median age at diagnosis was 56 (IQR 38-71). Menopausal status was known in 1,184 women, of whom 78% were post-menopausal. The median tumor size was 2.0 cm (IQR 1.2-2.6). Most pts (87%) had no axillary lymph node involvement (N0). Most tumors were invasive ductal carcinoma (74%) and grade 3 (70%). The median level of TILs was 15% (IQR 5-40). The median duration of follow-up was 30.4 years (95% CI 29.9, 31.1). A total of 950 (52%) iDFS, 828 (45%) RFS, 767 (42%) DDFS events, and 604 (33%) deaths were observed. In multivariable analyses, higher TILs were independently associated with improved iDFS, RFS, DDFS, and OS beyond clinicopathological factors (likelihood ratio p< 10e-6). Each 10% increment in stromal TILs was associated with an 8% (95% CI: 6-11), 10% (95% CI: 7-13), and 13% (95% CI: 10-15) reduction in the risk of experiencing an iDFS, RFS or DDFS event, and with a 12% (95% CI: 9-15) reduction in the risk of death. iDFS, RFS, DDFS and OS rates according to different TIL thresholds and nodal status are shown in the Table. Of note, the RFS estimates (which exclude second non-breast primaries and contralateral breast cancers) were consistently higher than the iDFS counterparts (which include both), consistent with a high rate of contralateral breast cancers and second primary tumors in this cohort. Notably, patients with node-negative—and especially stage I—TNBC with high TILs had excellent survival rates at 10-year follow-up. Conclusion: TILs are highly prognostic in pts with systemically untreated early-stage TNBC. Pts with pN0 (and especially stage I) TNBC with high TILs exhibited very favorable long-term outcomes even in the absence of systemic therapy. These data define the natural history of TIL-rich TNBC pts and are crucial to identifying the optimal patient population for future chemotherapy and immunotherapy de-escalation clinical trials. References: [1] Leon-Ferre et al, 2017, PMID: 28913760 [2] Park et al, 2019, PMID: 31566659 [3] de Jong et al, 2022, PMID: 35353548 Table 5 and 10-year survival endpoints according TIL level, nodal status, and stage Citation Format: Roberto A. Leon-Ferre, Sarah Flora Jonas, Roberto Salgado, Sherene Loi, Vincent De Jong, Jodi M. Carter, Torsten Nielson, Samuel Leung, Nazia Riaz, Giuseppe Curigliano, Carmen Criscitiello, Vincent Cockenpot, Matteo Lambertini, Vera Suman, Barbro Linderholm, John WM Martens, Carolien HM van Deurzen, Mieke Timmermans, Tatsunori Shimoi, Shu Yazaki, Masayuki Yoshida, Sung-Bae Kim, Hee Jin Lee, Maria Vittoria Dieci, Guillaume Bataillon, Anne Salomon, Fabrice Andre, Marleen Kok, Sabine Linn, Matthew P. Goetz, Stefan Michiels. Stromal tumor-infiltrating lymphocytes identify early-stage triple-negative breast cancer patients with favorable outcomes at 10-year follow-up in the absence of systemic therapy: a pooled analysis of 1835 patients [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 PD9-05.