447. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of ovarian ablation or suppression on breast cancer recurrence and survival: patient-level meta-analysis of 14,993 pre-menopausal women in 25 randomized trials. Lancet 2026;47(10540):1699-1711. doi: 10.1016/S0140-6736(26)00313-2. Epub 2026 May 2. (IBCSG 24-02) (Journal Impact Factor 88.5).
The EBCTCG (Early Breast Cancer Trialists’ Collaborative Group) evaluated the effects of ovarian function suppression (OFS) on breast cancer outcomes among premenopausal women and how they vary by patient or tumour characteristics and receipt of other treatments. A meta-analysis of individual participant data from 23 randomised trials comparing OFS versus no OFS, in women with ER-positive (ER+) or ER-unknown early breast cancer who were premenopausal at randomisation and younger than 55 years was performed. Primary outcomes were invasive breast cancer recurrence, breast cancer mortality, other mortality, and all-cause mortality. ER-weighted log-rank methods estimated event rate ratios for ER+ disease. Among 15075 premenopausal women with ER+ or ER-unknown tumours, the ER-weighted analyses corroborated that, for women with ER+ disease who are confirmed to be premenopausal (after any other treatments), OFS substantially diminishes the risk of recurrence and death from breast cancer, with the breast cancer death rate reduced considerably not only during the first decade but also during the second decade. Proportional risk reductions appeared similar for women regardless of their individual or tumour characteristics. Overall for premenopausal women with ER+ early breast cancer, even if chemotherapy or tamoxifen are given, OFS significantly reduces the 15 year risk of recurrence and death. Results were published in The Lancet.
The article may be freely accessed at The Lancet link is here: https://doi.org/10.1016/S0140-6736(26)00313-2
446. Wang Y, Drubay D, Jonas SF, Dixon-Douglas J, Acs B, Adams S, Andre F, Badve S, Bataillon G, Carter JM, Chia S, Cockenpot V, Colleoni MA, Criscitiello C, Curigliano G, Dackus GMHE, Demaria S, Denkert C, van Deurzen CHM, Dieci MV, Giardiello D, Goetz MP, Gray RJ, Hauptmann M, ter Hoeve ND, Jozwiak K, Koop EA, de Jong VMT, Joensuu H, Jules-Clement G, Kammler R, Kellokumpu-Lehtinen P-L, Kim S-B, Kok M, Lacroix-Triki M, Lambertini M, Lee HJ, Lemonnier J, Leon-Ferre R ,Leung S, Linderhol B, Loibl S, Martens JWM, Nielsen TO, Pharoah P, Penault-Llorca F, Piccart M, Pustzai L, Riaz N, Vincent-Salomon A, Shimoi T, Sotiriou C, Suman VJ, Timmermans AM, van Diest PJ, Voogd AC, Viale G, Wolff AC, Yazaki S, Yoshida M, Salgado R, Linn SC, Schmidt MK, Loi S, Michiels S, A report on behalf of the International Immuno-Oncology Biomarker Working Group. Including tumor-infiltrating lymphocytes into the PREDICT prognostic model for triple-negative-breast cancer survival. Ann Oncol 2026. doi: 10.1016/j.annonc.2026.04.011. Epub 2026 Apr 21. (IBCSG Trial 22-00) (Journal Impact Factor 65.4).
Evidence indicates that sTILs (stromal tumor infiltrating lymphocytes) are a strong prognostic maker particularly in triple-negative breast cancer (TNBC). The International Immuno-Oncology Biomarker Working Group aimed to incorporate sTILs into the PREDICT model, the most widely used, online breast cancer prognostication and treatment benefit tool, for patients with early-stage TNBC to better identify patients at low risk who may consider chemotherapy de-escalation, and to evaluate the updated model’s performance and clinical utility in chemotherapy decision-making for clinicians and patients. To update the PREDICT model (version 2.3), 3698 women with early-stage TNBC, diagnosed between 1979 and 2017, from two pooled cohorts with sTILs scored according to international guidelines were included in the updated model (PREDICT_sTILs, a Cox regression model with sTILs and the PREDICT prognostic index as predictors and breast cancer-specific survival as the outcome). The clinical values of PREDICT_sTILs and PREDICT were compared using decision curve analysis, examining net true high-risk and low-risk classifications across risk thresholds of 10-year breast cancer mortality above 8-15%. Among the 3698 patients, 1806 received chemotherapy while 1892 were chemotherapy-naïve. Compared to PREDICT, PREDICT_sTILs identified 19 to 60 additional net true low-risk patients, and 3-10 additional net true high-risk patients per 1000 chemotherapy-naïve patients at the risk thresholds of 8-15% at 10 years. Overall including sTILs to PREDICT improves its ability to inform chemotherapy decisions for early-stage TNBC patients. Results have been published in Annals of Oncology.
The Annals of Oncology article link is here: https://doi.org/10.1016/j.annonc.2026.04.011
445. O’Regan RM, Ren Y, Zhang Y, Fleming GF, Francis PA, Pagani O, Walley BA, Kammler R, Dell’Orto P, Viale G, Loi S, Colleoni M, Treuner K, Regan MM. Identifying premenopausal patients with early-stage hormone receptorpositive breast cancer at minimal risk of distant recurrence by Breast Cancer Index. The Breast 2026:86:104714. doi: 10.1016/j.breast.2026.104714. Epub 2026 Jan 29. (IBCSG 24-02 and IBCSG 25-02) (Journal Impact Factor 7.9).
The Breast Cancer Index (BCI) was previously shown to predict the benefit from ovarian function suppression (OFS)–containing endocrine therapy (ET) vs tamoxifen alone for premenopausal women with hormone receptor-positive (HR+) early-stage breast cancer when assessed in the SOFT and TEXT trials (separately) and in the combined TEXT and SOFT cohort. In the current study, Dr. O’Regan et al evaluated an adjusted BCI model, in which an additional cutpoint identified postmenopausal women with HR+ N0 disease at minimal (<5%) risk of distant recurrence within 10 years, to assess its prognostic value for supporting decision-making about OFS-containing adjuvant ET. The adjusted BCI model re-classified 18% and 20% of N0 patients in SOFT and TEXT into the BCI minimal-risk group; 43% and 38% remained classified in the low-risk group, respectively. In SOFT, the estimated 10-year risk of distant recurrence was 2.3% (95% CI: 0.9-6.0) among those patients reclassified as minimal risk and for the revised low risk group was 4.1% (95% CI: 2.6-6.5). In TEXT, the estimated 10-year risk of distant recurrence was 2.0% (95% CI 0.7-6.2) among the new minimal-risk group and for the revised low-risk group was 4.6% (95% CI: 2.8-7.7). The study confirmed prognostic ability of the additional BCI cutpoint to classify patients estimated to have minimal risk of distant recurrence within 10 years among premenopausal patients treated for HR+ N0 breast cancer, providing relevant information for personalizing adjuvant endocrine therapy. Results are reported in the journal The Breast.
The manuscript is freely available from The Breast at: https://doi.org/10.1016/j.breast.2026.104714
444. Mayer EL, Hlauschek D, Gnant M, O’Brien PJ, Bellet-Ezquerra M, Goetz MP, Ruiz-Borrego M, Chan A, Clifton K, Egle D, Lake D, Cabrera P, Mamounas T, Pristauz-Telsnigg G, Dayao Z, Gill Gil M, Cameron D, Traina T, Morris PG, Sabanathan D, Rinnerthaler G, Meisel J, Prat A, Wolff AC, Tseng LM, Issacs C, Singer CF, Rubovszky G, Foukakis T, Jassem J, Winder EP, Vetter M, Federmann J, Metzger O, Schurmans C, Gauthier E, Lu DR, Fesl C, Dueck A, DeMichele A. Palbociclib with adjuvant endocrine therapy in early breast cancer: 5-year follow-up analysis of the global multicenter, open-label, randomized phase III PALLAS trial (ABCSG-42/AFT-05/PrE0109BIG-14-13). Ann Oncol 2026;37(2):271-277. doi; 10.1016/j.annonc.2025.10.003. Epub 2025 Oct 17. (IBCSG 52-15) (Journal Impact Factor 65.4).
443. O’Regan RM, Ren Y, Zhang Y, Siuliukina N, Schnabel CA, Kammler R, Viale G, Dell’Orto P, Munzone E, Lang I, Tondini C, Gomez HL, Chini C, Nicoletti SVL, Puglisi F, Zaman K, Goetz MP, Stearns V, Martino S, Salim M, Loibl S, Geyer CE Jr, Bonnefoi HR, Ciruelos EM, Loi S, Colleoni M, Fleming GF, Francis PA, Walley BA, Pagani O, Treuner K, Regan MM. Assessment of adjuvant endocrine therapy with ovarian function suppression by Breast Cancer Index. JAMA Netw Open 2025;8(11):e2540931. doi: 10.1001/jamanetworkopen.2025.40931. Epub 2025 Nov 3. (IBCSG 24-02 and IBCSG 25-02) (Journal Impact Factor 9.7).
The Breast Cancer Index (BCI) is a gene expression test validated to provide an individualized risk of distant recurrence and predict the likelihood of benefit from extended endocrine therapy (ET) in patients with early-stage hormone receptor-positive (HR+) breast cancer. The expression ratio of the HOXB13 and IL17BR (H/I) genes is used to measure endocrine sensitivity and represents the predictive component of BCI (H/I). BCI was previously shown to predict the benefit from ovarian function suppression (OFS)–containing ET vs tamoxifen alone for premenopausal women with HR+ early-stage breast cancer in the SOFT trial. In the current study, Dr. O’Regan et al assessed the BCI in the TEXT trial. The study aimed to test BCI (H/I) as a predictive biomarker of benefit from exemestane plus OFS vs tamoxifen plus OFS and to validate BCI in the TEXT population (n = 1782) who were premenopausal upon enrollment and initiated systemic therapy with adjuvant OFS, with or without concomitant chemotherapy. The predictive performance of BCI (H/I) in the combined TEXT and SOFT cohort overall and in prespecified subgroups (defined by chemotherapy use) was also examined. While BCI (H/I) status in the TEXT population did not unequivocally predict greater benefit of adjuvant exemestane plus OFS vs tamoxifen plus OFS for women with BCI (H/I)-low tumors when compared with those with BCI (H/I)-high tumors; the analysis did reconfirm continuous BCI and BCI N+ indices as prognostic for distant recurrence in premenopausal women with HR+ N0 or N1 early-stage breast cancer who received OFS from initiation of adjuvant therapy with or without concomitant chemotherapy. The analysis from TEXT, and the combined cohort with 1114 patients from SOFT (n = 2896), revealed a numerically greater, but not statistically significantly different, benefit for exemestane plus OFS vs tamoxifen plus OFS in patients with BCI (H/I)–low compared with BCI (H/I)–high tumors over a median follow-up of 13 years. Overall the results did not show BCI (H/I) to be predictive of incremental benefit of exemestane vs tamoxifen when combined with OFS but did provide further support of prior SOFT results indicating premenopausal patients with BCI (H/I)-low tumors may benefit from more intensive ET. Results are reported in the journal JAMA Network Open. The manuscript is freely available from JAMA Network Open at: https://doi.org/10.1001/jamanetworkopen.2025.40931
442. Malorni L, Tyekucheva S, Gombos A, Hasler-Stub U, Zamgani C, Chakiba-Brugere, Colleoni M, Mueller A, Minisini AM, Taylor D, Salmon JP, Gallerani E, Cariello A, Fontana A, Roschitzki-Voser H, Kammler R, Rueep B, Loi S, Viale G, Regan MM, Brain E, Biganzoli L; International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation) and the TOUCH Trial (IBCSG 55-17) Investigators. Palbociclib plus letrozole versus weekly paclitaxel, both in combination with trastuzumab plus pertuzumab, as neoadjuvant treatment for patients with HR+/HER2+ early breast cancer: primary results from the randomized phase II TOUCH trial (IBCSG 55-17). Ann Oncol 2025. doi: 10.1016/j.annonc.2025.10.016. Epub 2025 October 16. (IBCSG 55-17) (Journal Impact Factor 65.4).
TOUCH is a phase II randomized trial with an integral translational primary objective to explore the interaction between the retinoblastoma gene signature (RBsig) status of pretreatment tumor and treatment activity, of palbociclib plus letrozole vs paclitaxel when given with trastuzumab plus pertuzumab (HP) in the neoadjuvant setting for postmenopausal patients with hormone receptor (HR)-positive HR+/human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer. Dr. Malorni et al explored the interaction between the RBsig status (HIGH or LOW, as determined centrally by RNA-seq on mandatory pre-treatment biopsy FFPE specimen) and treatment activity, assessed by pathological complete response (pCR), of palbociclib plus letrozole vs paclitaxel, when given with HP for HR+/HER2+ early breast cancer. A total of 147 patients were enrolled and randomly assigned (74 paclitaxel + HP, 73 palbociclib + letrozole + HP). 145 patients (with a median age of 69 years) composed the treated population. Results showed that a de-escalated, chemotherapy-free neoadjuvant treatment approach using letrozole and palbociclib with HP for 16 weeks achieved a pCR rate in about one-third of patients with HR+/HER2-positive primary breast cancer. Among patients assigned paclitaxel with HP, a similar pCR rate was achieved. While the TOUCH primary results did not support the biological hypothesis of greater paclitaxel efficacy for RBsig-high tumors and greater palbociclib plus letrozole efficacy for RBsig-low tumors; the results suggest that dual anti-HER2 blockade with a chemotherapy-free backbone of palbociclib + letrozole engenders pCR rates analogous to paclitaxel, representing an attractive alternative treatment strategy. Results are reported in the journal Annals of Oncology. The link to the publication from Annals of Oncology is at: https://doi.org/10.1016/j.annonc.2025.10.016.
441. Burstein HJ, Curigliano G, Gnant M, Loibl S, Regan MM, Loi S, Denkert C, Poortmans P, Cameron D, Thurlimann B, Weber WP; Panelists of the St Gallen International Breast Cancer Consensus 2025. Tailoring treatment to cancer risk and patient preference: The 2025 St Gallen International Breast Cancer Consesnsus Statement on individualizing therapy for patients with early breast cancer. Ann Oncol 2025;36(12):1433-1446. doi: 10.1016/j.annonc.2025.09.007. Epub 2025 October 8. (Journal Impact Factor 65.4).
440. Ribi K, Cole BF, Fleming GF, Walley BA, Francis PA, Abdi E, Burstein HJ, Cheng KL, Chia SKL, Dakhil SR, Davidson NE, Della-Fiorentina SA, Frith AE, Levine E, Lupichuk S, Pritchard K, Salim M, Stearns V, Stewart J, Valero V, van der Westhuizen A, Pagani O, Loi S, Colleoni M, Gelber RD, Goldhirsch A, Coates AS, Regan MM, Bernhard J. Prognostic value of patient-reported depression in women with hormone-responsive early breast cancer in TEXT and SOFT. Cancer 2025;131(19):e70094. doi: 10.1002/cncr.70094. Epub 2025 September 23. (IBCSG 24-02 and 25-02) (Journal Impact Factor 5.1).
Dr. Ribi et al prospectively assessed the association of depression at baseline with disease-free survival (DFS) and overall survival (OS) in women with hormone-responsive breast cancer treated in the TEXT and SOFT clinical trials. Using the CES-D (the Center for Epidemiologic Studies-Depression scale), a 20-item, self-report measure for depressive symptomatology during the previous week, the association between depression with outcomes at follow-up time points (6, 12, and 24 months) was also explored. Of the 5738 women enrolled in the TEXT and SOFT trials, 2287 (40%) were included in the analysis (TEXT, n=1028; SOFT, n=1259). The overall completion rate of the CES-D was 89% among women who met inclusion criteria for the analysis. Results showed an association between self-reported depression at baseline and poorer DFS as well as OS outcomes. Results are reported in the journal Cancer. The manuscript is freely available from Cancer at: https://doi.org/10.1002/cncr.70094
439. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Reductions in recurrence in women with early breast cancer entering clinical trials between 1990 and 2009: a pooled analysis of 155,746 women in 151 trials. Lancet 2024;404(10461):1407-1418. doi: 10.1016/S0140-6736(24)01745-8. Epub 2024 Oct 12. (IBCSG VI, VIII, IX, 10-93, 11-93, 12a-93, 13-93, 14a-93, 15-95, 24-02, 25-02, 30-04, and BIG 1-98) (Journal Impact Factor 88.5).
The Lancet article link is here https://www.thelancet.com/action/showPdf?pii=S0140-6736%2824%2901745-8
438. Demeestere I, Niman SM, Partridge AH, Diego DS, Kammler R, Ruggeri M, Colleoni M, Shimizu C, Saura C, Gelmon KA, Saetersdal AB, Kroep JR, Mailliez A, Amant F, Ruiz-Borrego M, Lee JE, Kataoka A, Walshe JM, Takei J, Borstnar S, Borges VF, Saunders C, Susnjar S, Bjelic-Radisic V, Cardoso F, Meisel JL, Kawwass JF, Spanic T, El-Abed S, Piccart M, Korde LA, Goldhirsch A, Gelber RD, Pagani O, Azim HA Jr, Peccatori FA, for the International Breast Cancer Study Group and the POSITIVE Trial Collaborators. Hormonal factors predictive of fertility in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy in the POSITIVE Trial. Breast 2025;83:104547. doi: 10.1016/j.breast.2025.104547. Epub 2025 July 26. (IBCSG 48-14) (Journal Impact Factor 7.9 suppl_1 suppl_2 suppl_3).
Hormone assessment was a predefined secondary endpoint of the POSITIVE trial, an international, single-arm, prospective trial in which 518 women, with early hormone receptor-positive breast cancer, temporarily interrupted adjuvant endocrine therapy (ET) to attempt pregnancy. Dr. Demeestere et al. sought to evaluate the risk of low ovarian reserve and premature ovarian insufficiency (POI) and characterize the association of AMH (anti-Mullerian hormone) and FSH (follicle stimulating hormone) levels with the likelihood of pregnancy. Other factors assessed included thyroid function, prolactin and ovulatory status. Covariates such as age, adjuvant therapy (ET + chemotherapy), and use of assisted reproductive technology (ART) were considered. Hormonal factors were appraised in non-pregnant women at months 3, 6, and 12 after ET interruption. Of the 497 women comprising the secondary analysis, 438 women were eligible for the low ovarian reserve analysis. Of the 438 women, 209 women experienced low ovarian reserve after the 3-month ET washout. In a multivariable logistic regression model, younger age (<35 years vs 35-39 or 40-42 years) and no prior chemotherapy (vs prior chemotherapy) were found to be associated with lower odds of low ovarian reserve. Further low ovarian reserve was not found to be associated with ET type or duration. In young women who did not achieve pregnancy at 12 months after ET interruption, POI incidence was observed to be low. FSH at month 3 was found to be associated with POI, but only modestly with spontaneous pregnancy. Other factors were not found predictive of pregnancy. Overall low ovarian reserve was observed in about half of the population and was associated with reduced odds of pregnancy. Expectedly, age and chemotherapy were found to be associated with low ovarian reserve, but not in relation to ET type or duration. Findings emphasize the importance of providing comprehensive fertility counseling to young women interrupting ET to pursue pregnancy. Results have been published in The Breast.
The Breast article link is here: https://www.sciencedirect.com/science/article/pii/S0960977625005648
437. Peccatori FA, Niman SM, Partridge AH, Ruggeri M, Colleoni M, Saura C, Shimizu C, Saetersdal AB, Kroep JR, Gelmon K, Amant F, Mailliez A, Moore HCF, Ruiz-Borrego M, Walshe JM, Borges VF, Gombos A, Kataoka A, Rousset-Jablonski C, Borstnar S, Takei J, Lee JE, Saunders C, Bjelic-Radisic V, Susnjar S, Cardoso F, Klar NJ, Ferreiro T, El-Abed S, Piccart M, Korde LA, Goldhirsch A, Gelber RD, Pagani O, Azim HA Jr, for the International Breast Cancer Study Group and the POSITIVE Trial Collaborators. Breastfeeding after hormone receptor-positive breast cancer: Results from the Positive Trial. J Clin Oncol 2025;43(24):2712-2719. doi: 10.1200/JCO-24-02697. Epub 2025 July 9. (IBCSG 48-14) (Journal Impact Factor 42.1).
Dr. Peccatori et al. sought to determine the feasibility and safety of breastfeeding in women who had a live birth in the POSITIVE trial, a prospective, international, multicenter, single-arm trial in which women, with early hormone receptor-positive breast cancer (BC), temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. At a median follow-up of 41 months, 317 women had at least one live birth; 313 were eligible for this breastfeeding analysis. Results indicated that about two thirds (196 of 313) of women who gave birth, after BC diagnosis, breastfed. The frequency of breastfeeding was found to be higher in women who underwent breast-conserving surgery (130 of 167). Among those women who had breast-conserving surgery, breastfeeding was predominantly from the contralateral breast (90 of 130). Additionally the frequency of breastfeeding was found to be higher in women older than 35 years and those with no previous children. Over half (103 of 196) of women breastfed their first live birth for greater than 4 months. Furthermore differences in BC-related events were not observed in women who breastfed compared with those who did not. Overall this study’s data demonstrated that breastfeeding is feasible and shown not to be associated with a higher short-term rate of BC-related events. Results have been published in the Journal of Clinical Oncology.
The J Clin Oncol link is here: https://ascopubs.org/doi/10.1200/JCO-24-02697
436. Joaquin Garcia A, Semba T, Rediti M, McGrail DJ, Xie X, Wang X, Rampa DR, Venet D, Buisseret L, Majjaj S, Kammler R, Colleoni M, Loi S, Viale G, Regan MM, Rothe F, Sotiriou C, Ueno NT. Role of immunosuppressive JNK pathway in the tumor microenvironment among TNBC subtypes in IBCSG Trial 22-00. iScience 2025;28(8):112964. doi: 10.1016/j.isci.2025.112964. Epub 2025 June 20. (IBCSG 22-00) (Journal Impact Factor 4.6 suppl).
Phosphorylation of JNK (c-Jun N-terminal kinase) has been previously associated with the activation of immunosuppressive status in the tumor microenvironment (TME) of triple-negative breast cancer (TNBC). Using a TNBC cohort, comprising 347 patients with RNA sequenced tumors, from IBCSG Trial 22-00, Dr. Joaquin Garcia et al evaluated the prevalence and prognostic impact of the immunosuppressive phosphorylated JNK (pJNK) pathway across different TNBC molecular subtypes. Possible interactions of pJNK signaling among TNBC subtypes in relation to their response to maintenance therapy using low-dose CM (cyclophosphamide and methotrexate) were also assessed. Results supported the heterogeneity of immune TME in immune-related TNBCs through the pJNK pathway. Additionally, Dr. Joaquin Garcia et al developed a gene expression signature capable of estimating the phosphorylation level of the JNK protein. A benefit from low-dose CM in immune-related tumors with high pJNK levels was also observed. Overall results suggest a potential role for the pJNK signature as a biomarker for immunotherapy in TNBC. To validate these results further, additional tudies should be performed. Results have been published in iScience.
The iScience article link is here: https://www.cell.com/iscience/fulltext/S2589-0042(25)01225-8
435. Biganzoli G, Richard F, Isnaldi E, Marano G, Boracchi P, Maetens M, Floris G, Neven P, Jerusalem G, Munzone E, Hitre E, Gombos A, Thompson A, Aebi S, Kammler R, Dell’Orto P, Viale G, Regan MM, Colleoni M, Biganzoli E, Desmedt C. Prognostic relation of body mass index on extended aromatase inhibition treatment in postmenopausal patients with estrogen receptor positive breast cancer: A retrospective analysis of the SOLE trial. Eur J Cancer 2025;222:115438. doi: 10.1016/j.ejca.2025.115438. Epub 2025 Apr 17. (IBCSG 35-07) (Journal Impact Factor 7.6 suppl app).
Given obesity has been shown to be associated with enhanced risk of developing distant recurrences in patients with estrogen receptor-positive (ER+) breast cancers and the limited evidence available in patients treated with extended endocrine therapy (ET), Dr. Biganzoli et al retrospectively explored the prognostic role of body mass index (BMI) in the SOLE trial (Study of Letrozole Extension, SOLE), a phase 3 randomized, open-label trial examining the effect of extended intermittent letrozole treatment in comparison with continuous letrozole for five years in women with ER+/HER2-negative breast cancer. 3606 SOLE patients with ER+/HER2-negative lymph node-positive breast cancer with available BMI were considered for inclusion in the analysis. Results indicated that BMI was associated with age, tumor size, number of positive lymph nodes, menopausal status and type of prior ET. In adjusted analyses the prognostic value of BMI was dependent on prior ET and extended ET. Overall the prognostic relationship of BMI in postmenopausal women with ER+/HER2-negative breast cancer was shown to be more complex than originally anticipated as the relationship may vary by the type of adjuvant ET and the modality of administration of extended ET. Results are published in European Journal of Cancer.
The European Journal of Cancer link is here: https://www.ejcancer.com/article/S0959-8049(25)00219-9/fulltext
434. Zdenkowski N, Kuper-Hommel MJJ, Niman SM, Francis PA, Baron-Hay S, Fox W, Menzies AM, Angus R, Punie K, Zardawi, Regan MM, Loi S. Timing of nivolumab with neoadjuvant carboplatin and paclitaxel for early triple-negative breast cancer (BCT1902/IBCSG 61-20; Neo-N): A non-comparative, open-label, randomised, phase 2 trial. Lancet Oncol 2025;26(3):367-377. doi:10.1016/S1470-2045(24)00757-5. Epub 2025 Mar. (IBCSG 61-20) (Journal Impact Factor 41.6 suppl app).
In the primary analysis of the Neo-N trial, an international, multicenter, randomized, open-label phase II clinical trial, Dr. Zdenkowski et al prospectively investigated whether different sequencing strategies of nivolumab (a monoclonal antibody against programmed cell death protein 1, PD-1) with 12 weeks carboplatin and paclitaxel chemotherapy could improve the primary endpoint of pathological complete response (pCR) rates in patients with previously untreated non-metastatic stage I or II triple-negative breast cancer. Between July 6, 2020 and April 1, 2022, 110 patients were randomized at 14 centers in 3 countries. Of the 110 women, 108 patients were included in the modified intention-to-treat analysis, 53 in the lead group and 55 in the concurrent group. Overall results did not support the hypothesis that lead-in nivolumab prior to chemotherapy was associated with a pCR benefit. However results did indicate that shorter duration, non-anthracycline containing regimens in combination with PD-1 targeted therapy particularly in patients with high stromal tumor-infiltrating lymphocytes or PD-L1 positive tumors may warrant further exploration. Event-free and overall survival rates are maturing. The Results have been published in Lancet Oncology.
The Lancet Oncology link is here: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00757-5/abstract
433. Ignatiadis M, Bailey A, McArthur H, El-Abed S, de Azambuja E, Metzger O, Chui SY, Dieterich M, Perretti T, Shearer-Kang E, Molinero L, Steger GG, Jassem J, Chin Lee S, Higgins M, Zarba J, Schmidt M, Gomez H, Guerrero Zotano A, Moscetti L, Chiu J, Munzone E, Efrat Ben-Baruch N, Bajetta E, Ohno S, Im S-A, Werutsky G, Nili Gal-Yam E, Gonzalez Farre X, Tseng L-M, Jacot W, Gluz O, Shao Z, Shparyk Y, Zimina A, Winer E, Cameron DA, Viale G, Saji S, Gelber R, Piccart M. Adjuvant atezolizumab for early triple-negative breast cancer: The ALEXANDRA/Impassion030 randomized clinical trial. JAMA 2025:e2426886. doi: 10.1001/jama.2024.26886. Epub 2025 Jan 30. (IBCSG 56-17) (Journal Impact Factor 63.5 suppl).
432. Luen SJ, Brown LC, van Geelen CT, Savas P, Kammler R, Dell’Orto P, Biasi O, Coates AS, Gelber RD, Thuerlimann B, Colleoni M, Fleming GF, Francis PA, Regan MM, Viale G, Loi S. Genomic characterization and prognostic significance of HER2-low, hormone receptor-positive, early breast cancers from the BIG 1-98 and SOFT clinical trials. JCO Precis Oncol 2025:9e2400599. suppl doi: 10.1200/PO-24-00599. Epub 2025 Jan 24.
Using data from the BIG 1-98 and SOFT trials, Dr. Luen et al explored whether hormone receptor-positive, human epidermal growth factor receptor 2-low (HR+/HER2-low) as compared with HR+/HER2-zero early breast cancer of pre- and postmenopausal women treated with endocrine therapy have perceptible genomic and clinical characteristics. A total of 1795 tumors were evaluable for the study (BIG 1-98, n=520; SOFT, n=1275). The frequency of HER2-low tumors was 37% and 21% in the postmenopausal BIG 1-98 and premenopausal SOFT cohorts respectively. Results did not show significant differences in clinicopathological variables between HR+/HER2-low and HR+/HER2-zero cohorts. Somatic genomic profiles were found to be similar with the exception of MAP3K1 mutations which were significantly more frequent in HR+/HER2-zero tumors (postmenopausal 19% vs 5%, premenopausal 11% vs 6%). Both ERBB2 copy number and ERBB2 gene expression abundance were significantly higher in HR+/HER2-low tumors compared with HR+/HER2-zero tumors, however the absolute difference was small. Overall distinct genomic profiles were not found between HR+/HER2-low and HR+/HER2-zero tumors, suggesting that these tumors are not unique entities at the genomic level. The only exception to this was MAP3K1 mutations, which were shown to be at higher frequences, but not exclusive, in HR+/HER2-zero tumors. Absolute differences in median ERBB2 copy number levels or gene expression were shown to be small and of unclear biological relevance. The results have been published in JCO Precision Oncology.
Donating & Supporting