Breast Cancer Research And Treatment[JOURNAL]
Sun
200 papers
Association of baseline tumor-infiltrating lymphocytes and cell-cycle regulation markers on prognosis and mortality in patients with advanced breast cancer according to tumor characteristics and treatment type: an observational study.
Vuoti S, Saari M, Lahti J … +2 more , Narasimha K, Reinikainen K
Breast Cancer Res Treat · 2026 Jun · PMID 42243565 · Full text
BACKGROUND: Tumor proliferation and immune infiltration are key determinants of breast cancer biology, yet their prognostic value in the advanced setting remains incompletely defined. We evaluated the clinical relevance...
BACKGROUND: Tumor proliferation and immune infiltration are key determinants of breast cancer biology, yet their prognostic value in the advanced setting remains incompletely defined. We evaluated the clinical relevance of tumor‑infiltrating lymphocytes (TILs) and four cell cycle regulation biomarkers-Ki67, MCM2, Cyclin A, and PHH3-across major breast cancer subtypes in a contemporary real‑world cohort. METHODS: We conducted a retrospective analysis of the outcomes of 398 patients with advanced breast cancer treated between 2020 and 2024. Clinicopathological variables were compared across HER2-/HR+, HER2+, and triple‑negative breast cancer (TNBC). Progression‑free survival (PFS) was assessed using Kaplan-Meier analysis and log‑rank tests. Multivariable polytomous logistic regression identified factors associated with PFS < 2 years. Subtype‑specific associations between TILs and PFS > 2 years were evaluated using multivariable Cox models adjusted for age, ECOG status, tumor grade, and prior therapies. Additional Cox regression models assessed predictors of overall survival (OS). RESULTS: Low TIL density was independently associated with early progression (RRR 2.28, 95% CI 1.19-4.03). Proliferation markers showed consistent associations with PFS: elevated Ki67, MCM2, Cyclin A, and PHH3 each correlated with shorter survival, with MCM2 showing the strongest effect. TIL-PFS associations were subtype‑dependent. In HR+/HER2 - disease, high TILs were linked to shorter PFS (HR 2.27, 95% CI 1.18-4.02), whereas in TNBC, low TILs predicted markedly worse outcomes (HR 2.33, 95% CI 1.88-2.86). TIL levels were not prognostic in HER2 + disease. Across all subtypes, high expression of Ki67, MCM2, Cyclin A, and PHH3 was significantly associated with reduced OS in multivariable models. CONCLUSIONS: Subtype‑specific immune infiltration and elevated proliferation activity are key predictors of disease trajectory in advanced breast cancer. TILs carry divergent prognostic meaning across subtypes, whereas proliferation markers consistently identify high‑risk disease. Integrating immune and proliferative biomarkers may enhance risk stratification and guide treatment tailoring, particularly within TNBC and hormonally driven tumors.
Post-neoadjuvant and peri-operative ctDNA-defined minimal residual disease in triple-negative breast cancer: a systematic review and meta-analysis.
Barjij I, Naciri S, Lkhoyaali S … +6 more , Kharmoum S, Inrhaouen H, Elghissassi I, Boutayeb S, Mrabti H, Errihani H
Breast Cancer Res Treat · 2026 Jun · PMID 42243561 · Publisher ↗
BACKGROUND: Post-neoadjuvant circulating tumor DNA (ctDNA) has been investigated as a minimal residual disease (MRD) marker in stage I-III triple-negative breast cancer (TNBC), but landmark timing and assay approaches va...
BACKGROUND: Post-neoadjuvant circulating tumor DNA (ctDNA) has been investigated as a minimal residual disease (MRD) marker in stage I-III triple-negative breast cancer (TNBC), but landmark timing and assay approaches vary. OBJECTIVES: To assess whether post-neoadjuvant and/or peri-operative ctDNA MRD positivity is associated with poorer recurrence-related outcomes in TNBC with residual invasive disease, with overall survival evaluated as a secondary outcome and the association between ctDNA and pathologic complete response (pCR) assessed exploratorily. METHODS: PubMed/MEDLINE, Embase, Web of Science Core Collection, and Scopus were searched through January 15, 2026. Eligible studies enrolled adults with TNBC treated with neoadjuvant systemic therapy and surgery and reported post-neoadjuvant or peri-operative ctDNA with time-to-event outcomes; recurrence-related quantitative syntheses focused on residual invasive disease or extractable non-pCR/residual cancer burden (RCB) subgroups. Risk of bias was assessed using QUIPS. Random-effects meta-analysis was performed when studies were comparable; otherwise, findings were summarized narratively. RESULTS: Twenty-two studies were included. Four studies contributed to the primary meta-analysis. Post-treatment ctDNA positivity was associated with poorer recurrence-related outcomes (pooled hazard ratio 4.63, 95% CI 3.07-6.98; I²=0%), although this estimate should be interpreted cautiously given the small number of contributing studies. Overall survival could not be synthesized quantitatively. Two studies assessed the ctDNA-pCR association, but results were summarized narratively because TNBC-specific data were not extractable in one study. CONCLUSION: In TNBC patients with residual invasive disease or extractable non-pCR/RCB subgroup data after neoadjuvant therapy, post-neoadjuvant and peri-operative ctDNA MRD positivity is associated with poorer recurrence-related outcomes, supporting further standardized prospective evaluation.
Long-term patient-reported outcomes in a randomized controlled trial of Mepitel Film versus standard of care for the prevention of acute breast radiation dermatitis.
Bayrakdarian S, Hircock C, Wong HCY … +16 more , Zhang L, Ding K, Karam I, Gallant F, Rakovitch E, Tran W, Soliman H, Leung E, Vesprini D, Szumacher E, Chen H, Donovan E, Lam J, Spadafora S, Carothers K, Chow E
Breast Cancer Res Treat · 2026 Jun · PMID 42243522 · Publisher ↗
INTRODUCTION: This study aims to evaluate the long-term skin-related patient-reported outcomes (PROs) of a randomized controlled trial (RCT) comparing Mepitel Film (MF) to standard of care (SOC) for the prevention of acu...
INTRODUCTION: This study aims to evaluate the long-term skin-related patient-reported outcomes (PROs) of a randomized controlled trial (RCT) comparing Mepitel Film (MF) to standard of care (SOC) for the prevention of acute radiation dermatitis (ARD) in breast cancer patients undergoing radiation therapy (RT). METHODS: Patients were contacted via telephone at 6 months, 12 months, and 24 months post-RT to complete the Skin Symptom Assessment (SSA) and Radiation-induced Skin Reaction Assessment Scale (RISRAS). SSA and RISRAS scores at follow-up visits were compared to baseline using a generalized estimation equation with Poisson distribution and log link function. To account for multiple testing, the Bonferroni-adjusted p-value of < 0.001 was considered statistically significant. RESULTS: From April 2020 to August 2024, 376 patients were included in the modified intention-to-treat analysis and followed at the pre-specified time points. When comparing MF and SOC, no significant differences were captured longitudinally regardless of the severity of ARD (Common Terminology Criteria for Adverse Events grade [G] 0-1 versus G2-3). Comparing to the baseline scores, patients reported worse pruritis at 6 months and pigmentation at 6 months, 12 months, and 24 months (p < 0.001) for the SSA. For the RISRAS, tenderness/discomfort/pain, itchiness and burning sensation were worse at 6 months (p < 0.001), but only itchiness was worse at 12 and 24 months (p = 0.0007, p < 0.001, respectively) compared to baseline. In the subgroup analysis of patients based on the severity of ARD, pigmentation was worse at all follow-up visits (p < 0.001) in both G0-1 and G2-3 cohorts. CONCLUSION: PROs returned to baseline at 6 months to 2 years after RT, except pigmentation and pruritis that persist regardless of the severity of ARD, necessitating confirmation with physical signs and further research to understand the pathophysiology of these chronic symptoms to guide preventative strategies. No long-term issues were identified in patients treated with MF, confirming it as a safe and effective strategy for the prevention of ARD.
Retrospective study on regional nodal irradiation after omission of axillary lymph node dissection in sentinel lymph node-positive breast cancer: a propensity score matching analysis.
Xia K, Tang N, Li D … +2 more , Wang L, Xiao H
Breast Cancer Res Treat · 2026 Jun · PMID 42243510 · Publisher ↗
BACKGROUND AND OBJECTIVES: With the de-escalation of axillary surgery in early breast cancer, sentinel lymph node biopsy (SLNB) has largely replaced axillary lymph node dissection (ALND) for patients with limited nodal d...
BACKGROUND AND OBJECTIVES: With the de-escalation of axillary surgery in early breast cancer, sentinel lymph node biopsy (SLNB) has largely replaced axillary lymph node dissection (ALND) for patients with limited nodal disease. However, whether regional nodal irradiation (RNI) is necessary for SLN-positive patients who forgo ALND remains controversial. This study aimed to evaluate the clinical value of RNI in such patients. METHODS: We conducted a retrospective, multi-center study of early breast cancer patients with positive SLNs who did not undergo ALND between February 2011 and February 2021. Patients were divided into an RNI group and a no-RNI group based on whether postoperative radiotherapy included regional nodal fields. Propensity score matching (PSM) was used to balance baseline characteristics. Survival outcomes were compared using Kaplan-Meier curves and Cox regression. RESULTS: Among 8328 screened patients, 356 met the inclusion criteria. After PSM, 151 matched pairs were analyzed. The RNI group showed significantly better disease-free survival (DFS) than the no-RNI group (92.5% vs. 83.0%, P = 0.031), while overall survival (OS) did not differ significantly (92.5% vs. 86.8%, P = 0.168). Multivariate analysis confirmed that omitting RNI was an independent risk factor for worse DFS (HR = 2.387, 95% CI: 1.154-4.938, P = 0.019). Subgroup analyses revealed that the DFS benefit of RNI was particularly evident in patients with T2-3 tumors or more than one metastatic SLN. CONCLUSION: For SLN-positive breast cancer patients who omit ALND, the addition of RNI is associated with improved DFS, especially in those with higher T stage or multiple SLN metastases. These findings suggest that RNI was associated with improved DFS in higher-risk patients and may be considered in this subset, although confirmation in prospective studies is needed.
The value of innovation in breast cancer treatment: real option value of olaparib for first-line treatment of gBRCA-mutated HER2 negative metastatic breast cancer.
Gong CL, Chavez-MacGregor M, Xu X … +5 more , Park L, Elsea D, Katsandres S, Migliaccio-Walle K, Veenstra DL
Breast Cancer Res Treat · 2026 Jun · PMID 42243369 · Publisher ↗
PURPOSE: Novel drugs for metastatic breast cancer (mBC) can provide patients not only with improved survival but also the opportunity to benefit from future treatment innovations, a concept referred to as real option val...
PURPOSE: Novel drugs for metastatic breast cancer (mBC) can provide patients not only with improved survival but also the opportunity to benefit from future treatment innovations, a concept referred to as real option value (ROV). Quantifying the ROV of first-line (1L) olaparib may help clinicians and patients better understand the additional value increased survival provides through access to future innovative therapies. METHODS: We developed a Markov model with progression-free, progression, and death states to estimate long-term survival gain of 1L olaparib versus treatment of physician's choice (TPC; chemotherapy) among patients with HER2-negative mBC. To derive ROV, a scenario without future drug innovation was compared to one including anticipated innovations as of January 2023. ROV parameters were informed by literature, trial data, ongoing studies, and mBC treatment patterns. Clinician expert-reviewed assumptions generated high-, mid-, and low-ROV scenarios. The primary outcome was aggregated life expectancy, weighted between HR+ and TNBC per OlympiAD trial characteristics. RESULTS: Without innovation, modeled aggregate survival was 3.16 years with olaparib versus 1.81 years with TPC (Δ1.35 LYs). With innovation, survival increased to 3.91 vs. 2.42 LYs in the high scenario (Δ1.49 LYs; +0.139 LYs vs. no innovation), 3.44 vs. 2.02 LYs in the mid-scenario (Δ1.42 LYs; +0.069 LYs), and 3.24 vs. 1.87 LYs in the low-scenario (Δ1.37 LYs; +0.022 LYs), for olaparib vs. TPC respectively. This corresponded to relative survival increases of 10.3%, 5.1%, and 1.6%, respectively. CONCLUSIONS: First-line olaparib directly improves survival and can further extend survival by providing access to future innovations. These findings may guide early treatment selection to optimize sequencing and support further evaluation of ROV for additional guideline-recommended treatments in mBC.
Non-BRCA germline pathogenic variants and response to neoadjuvant systemic therapy in triple-negative breast cancer patients enrolled in a prospective clinical trial.
Lee KL, Yam C, Zhao L … +19 more , Bassett RL, Song X, Thompson AM, White JB, Layman RM, Huo L, Gutierrez AM, Valero V, Ueno NT, Litton JK, Zhang J, Ravenberg E, Korkut A, Adrada BE, Candelaria RP, Rauch GM, Tripathy D, Shaitelman SF, Arun BK
Breast Cancer Res Treat · 2026 Jun · PMID 42223695 · Full text
PURPOSE: Most patients with triple-negative breast cancer (TNBC) undergo neoadjuvant therapy (NAT). Prospective studies on the landscape of non-BRCA germline pathogenic variants (PVs) in patients with TNBC and their impa...
PURPOSE: Most patients with triple-negative breast cancer (TNBC) undergo neoadjuvant therapy (NAT). Prospective studies on the landscape of non-BRCA germline pathogenic variants (PVs) in patients with TNBC and their impact on response to NAT are sparse. METHODS: On a prospective trial, patients received NAT with doxorubicin and cyclophosphamide with or without immunotherapy followed by paclitaxel with or without carboplatin vs. targeted therapy. Before NAT, DNA was extracted from blood samples and sequenced. Germline variants were identified. Variants deemed deleterious and present in genes found in a 103 pan-cancer susceptibility gene panel were tabulated. Univariate logistic regression models assessed the relationship between variants and pathologic complete response (pCR), pCR and minimal residual cancer burden I (RCB I) as a combined outcome, and radiologic response. RESULTS: Of 184 patients, 72% were White, 19% were Black, and 8% were Asian. 36% had PVs in pan-cancer susceptibility genes. PVs were found in 31 genes not previously found to have PVs in other known US cohorts. Of 181 patients with NAT response data, 67 (37%) had pCR; 22 (12%), 69 (38%), and 23 (13%) had RCB I, II, and III, respectively. There was no significant difference in pCR rates vs. RCB I/II/III, achievement of a pCR/RCB I vs. RCB II/III, or radiologic response between those with and without a PV. CONCLUSION: Over one-third of patients had germline PVs in pan-cancer susceptibility genes, suggesting multigene panels should be considered. The presence of non-BRCA germline PVs was not associated with a difference in pathologic response.
Association of cumulative lifetime estrogen exposure and reproductive factors with breast cancer molecular subtype among Nigerian women in the MEND study.
Byemerwa J, Neish D, Olunuga E … +19 more , Osazuwa-Peters O, Deveaux A, Joshi A, Salako O, Daramola A, Alatise O, Ogun G, Hall A, Adeniyi A, Ayandipo O, Olajide T, Olasehinde O, Arowolo O, Adisa A, Afuwape O, Olusanya A, Adegoke A, H3 Africa Kidney Research Network, Akinyemiju T
Breast Cancer Res Treat · 2026 Jun · PMID 42223563 · Publisher ↗
PURPOSE: Cumulative lifetime endogenous estrogen exposure (CLEEE) is an established breast cancer (BC) risk factor, yet Nigeria faces increasing BC incidence and mortality despite reproductive patterns typically associat...
PURPOSE: Cumulative lifetime endogenous estrogen exposure (CLEEE) is an established breast cancer (BC) risk factor, yet Nigeria faces increasing BC incidence and mortality despite reproductive patterns typically associated with lower estrogen exposure. We evaluated the association of endogenous estrogen exposure and BC risk in this population. METHODS: We analyzed 609 Nigerian BC cases and 609 controls from the MEND case-control study to examine associations between CLEEE and BC risk by molecular subtype. CLEEE was defined as time from menarche to menopause (or enrollment), minus pregnancy duration; a breastfeeding-adjusted measure (CLEEE-b) subtracted breastfeeding duration. RESULTS: Most cases were grade 2 (67.2%) or grade 3 (27.9%), with 42.8% triple-negative breast cancer (TNBC), 33.7% luminal A, 12.6% HER2-enriched, and 10.9% luminal B. Compared with controls (medians), cases had lower BMI (25.4 vs. 26.7, p < 0.001), earlier menarche (mean: 14.9 vs. 15.2 years, p < 0.001), and higher CLEEE (330 vs. 321 months, p < 0.018) and CLEEE-b (273 vs. 264 months, p = 0.043). In multivariable models adjusting for BMI and menopausal status, each standard deviation increase in CLEEE was associated with 33% higher BC odds (aOR 1.33, 95% CI 1.13-1.57), with stronger association for postmenopausal women (aOR: 1.62, 95% CI: 1.22-2.19), women with BMI ≥ 3025 (aOR: 1.52, 95% CI: 1.07-2.20), and for TNBC (highest vs. low CLEEE tertile: aOR 1.90, 95% CI 1.12-3.26). Associations for CLEEE-b remained significant but modestly attenuated. CONCLUSION: Higher CLEEE was associated with increased BC odds, particularly for TNBC. Larger studies among African women are needed to confirm these associations to inform prevention strategies.
Predictors of pathologic complete response in early-stage triple-negative breast cancer treated with neoadjuvant chemo-immunotherapy: a multi-institution study.
LeVee A, Santos B, Wong M … +6 more , Ruel N, Schmolze D, Kang I, Tsai K, Mortimer J, McArthur H
Breast Cancer Res Treat · 2026 May · PMID 42207343 · Full text
INTRODUCTION: The KEYNOTE-522 clinical trial demonstrated that the addition of pembrolizumab to 8 cycles of neoadjuvant chemotherapy (NAC) improves pathologic complete response (pCR) rates and overall survival in early-s...
INTRODUCTION: The KEYNOTE-522 clinical trial demonstrated that the addition of pembrolizumab to 8 cycles of neoadjuvant chemotherapy (NAC) improves pathologic complete response (pCR) rates and overall survival in early-stage triple-negative breast cancer (TNBC). However, predictors of response and the benefit of alternative NAC backbones with immunotherapy are not known. This multi-institutional study evaluates clinical factors and treatment variables associated with pCR following NAC plus pembrolizumab in a diverse, real-world cohort. METHODS: This multi-institution retrospective study analyzed patients with early-stage TNBC diagnosed between July 1, 2021, and December 31, 2023, across three hospital systems. Eligible patients received at least one cycle of NAC and pembrolizumab. Predictors of pCR were assessed using logistic regression. RESULTS: Of the 374 patients included, the pCR rate was 61.2%. The cohort was racially and ethnically diverse, with 29.1% of patients identifying as non-White. Almost half (48.4%) had a BMI ≥30, and 70 patients (18.7%) had pre-existing diabetes mellitus. Approximately two-thirds (64.4%) completed 8 cycles of neoadjuvant pembrolizumab, while 72.5% completed 8 cycles of NAC. On univariate analysis, age less than 55 years (p = 0.03), absence of diabetes mellitus (p = 0.03), high tumor grade (p = 0.005), the completion of 8 or more cycles of neoadjuvant pembrolizumab (p = 0.04) and 8 cycles of NAC (p = 0.03) were associated with pCR. There was a trend towards higher pCR rates with the receipt of at least one cycle of anthracycline-cyclophosphamide (p = 0.07). Lack of diabetes mellitus (p = 0.03) and high tumor grade (p = 0.004) remained significant on multivariate analysis. CONCLUSION: This study supports the use of KEYNOTE-522 in a diverse, real-world population of patients with early-stage TNBC. Patients with diabetes were less likely to achieve a pCR, suggesting a potential impact of glucose metabolism on chemo-immunotherapy resistance.
The applicability of the 21-gene assay to inform chemotherapy benefit in lymph node positive hormone receptor positive male breast cancer.
Gaba AG, Cao L, Renfrew RJ
Breast Cancer Res Treat · 2026 May · PMID 42159964 · Full text
PURPOSE: Our study aimed to determine if chemotherapy administration based on the 21-gene Oncotype DX Recurrence Score (RS) in men with hormone receptor positive (HR+) Her2 negative (Her2-) lymph node positive(LN+) breas...
PURPOSE: Our study aimed to determine if chemotherapy administration based on the 21-gene Oncotype DX Recurrence Score (RS) in men with hormone receptor positive (HR+) Her2 negative (Her2-) lymph node positive(LN+) breast cancers (BC) impacted overall survival (OS). PATIENTS AND METHODS: We conducted a retrospective cohort study on adult men and women with HR+ Her2-, 1-3 axillary LN + BC, with a valid oncotype DX RS assay, diagnosed between the years 2004-2020, using the National Cancer Database. RS risk categories were defined as low risk: 0-13, intermediate risk:14-25, and high risk: ≥26. RESULTS: Of the 77,820 patients included in the study, 900 (1.2%) were male and 76,920 (98.8%) were female. Higher RS (both as a continuous and categorical variable) was significantly associated with worse OS in males (p = 0.003 continuous, p = 0.006 categorical), females ≤ 50 years old and females > 50 years old (p < 0.001 both continuous and categorical, in both groups). In the stratified adjusted models, there was no association between receipt of chemotherapy and OS in males for all RS risk groups. Conversely, chemotherapy improved OS for women ≤ 50 and for women > 50 who belonged to the intermediate and high RS risk groups (p = 0.001 and p < 0.001 respectively (women ≤ 50); p = 0.005 and p < 0·001 respectively (women > 50)). CONCLUSION: RS as determined by the Oncotype DX assay is associated with OS in men and women with HR+ Her2- LN+ BC. However, RS is not an indicator of the benefit of chemotherapy on OS in men, in contrast to women, with HR+ Her2- LN+ BC.
Change in practice patterns over time for endocrine therapy and radiation therapy in women with breast cancer age 65 and older.
Stickland A, Tao X, Kidwell K … +1 more , Henry NL
Breast Cancer Res Treat · 2026 May · PMID 42159636 · Full text
PURPOSE: In 2017, the National Comprehensive Cancer Center (NCCN) recommended omitting radiation therapy (RT) for women aged 70 + with stage 1, hormone receptor-positive breast cancer after lumpectomy. However, the optim...
PURPOSE: In 2017, the National Comprehensive Cancer Center (NCCN) recommended omitting radiation therapy (RT) for women aged 70 + with stage 1, hormone receptor-positive breast cancer after lumpectomy. However, the optimal treatment remains uncertain given challenges with delivering endocrine therapy (ET) and RT. METHODS: Females with hormone receptor positive, HER2 negative, clinically node negative breast cancer aged 65 + diagnosed 2012-2021 who underwent lumpectomy with or without axillary surgery at a single institution were included. The treatment groups of ET only, RT only, both ET and RT (ET/RT), and neither ET nor RT were compared by patient age, year of diagnosis, and recurrence rates. Fisher's Exact Test was used to compare treatment groups, and competing risk analysis was used to examine recurrence rates. RESULTS: Of 383 patients analyzed, 28% received ET only, 8% RT only, 53% ET/RT, and 10% neither ET nor RT. Over time, fewer participants received ET/RT or RT alone and more participants received ET alone or neither ET nor RT (p=.006). Compared to those treated with ET/RT, those treated with neither ET nor RT (hazard ratio [HR] 10.60 [95% CI 4.13-27.21]) and with ET alone (HR 3.02 [95% CI 1.28-7.16]) had higher risk of disease recurrence. CONCLUSIONS: Fewer participants received ET/RT or RT alone after the NCCN guideline publication. However, these cohorts had lower recurrence risks than those treated with ET only and neither ET nor RT. These results support consideration of larger prospective studies evaluating RT alone following lumpectomy in this population.
Impact of BRCA1/2 pathogenic variants on ipsilateral breast tumor recurrence and prognosis following breast-conserving surgery.
Kondo S, Kida K, Suzuki M … +5 more , Kajiura Y, Takei J, Kanomata N, Yamanaka M, Yoshida A
Breast Cancer Res Treat · 2026 May · PMID 42133182 · Publisher ↗
PURPOSE: The risk of ipsilateral breast tumor recurrence (IBTR) and the prognostic outcomes of breast-conserving surgery (BCS) for germline BRCA1/2 pathogenic variant carriers (BRCA+) remain controversial. This study aim...
PURPOSE: The risk of ipsilateral breast tumor recurrence (IBTR) and the prognostic outcomes of breast-conserving surgery (BCS) for germline BRCA1/2 pathogenic variant carriers (BRCA+) remain controversial. This study aimed to investigate the differences in the incidence of IBTR and prognosis between BRCA + and noncarriers (BRCA-) after BCS. METHODS: A retrospective chart review was performed in patients with stage 0-III breast cancer who underwent genetic testing for germline BRCA1/2 and BCS between 1996 and 2020. We compared the incidence of IBTR and the characteristics and prognostic outcomes of IBTR, including overall survival (OS), breast cancer-specific survival (BCSS), and distant recurrence-free survival (DRFS), between BRCA + and BRCA- after BCS. RESULTS: We analyzed 551 patients (587 breasts with cancer), including 61 carriers (64 breasts with cancer). During the median follow-up period of 5.3 years, the 5-year IBTR rates were 3.6% in the BRCA+ group and 5.1% in the BRCA- group, and the 10-year IBTR rates were 9.5% and 8.8%, respectively (p = 0.489). The median times to IBTR were 10.2 years in BRCA + and 3.5 years in BRCA-. The discordance rate of cancer subtypes between IBTR and primary cancer was significantly higher in BRCA+ than in BRCA- (p = 0.012). No significant differences were observed in the OS, BCSS, or DRFS between the two cohorts. CONCLUSION: No significant differences were observed in the IBTR risk or prognostic outcomes between BRCA + and BRCA- after BCS. However, the longer time to IBTR and the clinicopathological features potentially consistent with new primary cancers in BRCA+ suggest the importance of shared decision-making regarding BCS and long-term intensive breast surveillance after BCS in BRCA+.
Characteristics, treatment and survival in de novo and metachronous metastatic breast cancer: a nationwide comparative analysis.
Slotman E, de Munck L, Jager A … +7 more , Honkoop AH, Siemerink EJM, Heijns JB, van der Wall E, Raijmakers NJH, Fransen HP, Siesling S
Breast Cancer Res Treat · 2026 May · PMID 42118359 · Full text
PURPOSE: To compare patient characteristics, treatment patterns, and survival between de novo and metachronous metastatic breast cancer (MBC) using nationwide data. METHODS: A total of 2,366 MBC patients (900 de novo, 1,...
PURPOSE: To compare patient characteristics, treatment patterns, and survival between de novo and metachronous metastatic breast cancer (MBC) using nationwide data. METHODS: A total of 2,366 MBC patients (900 de novo, 1,466 metachronous) diagnosed in 2019 were selected from the Netherlands Cancer Registry. Patient- and tumor characteristics and systemic treatment patterns were compared using chi-squared or Fisher's exact tests. Overall survival (OS) was compared using Kaplan-Meier curves and Cox proportional hazard analyses. All analyses were stratified by clinical subtype (HR+/HER2-, HR+/HER2+, HR-/HER2+, HR-/HER2-). For patients with HR+/HER2 - tumors, a sub-analysis examined OS in de novo versus metachronous MBC, stratifying the latter by receipt of prior (neo)adjuvant systemic treatment. RESULTS: De novo MBC patients were younger, had more HER2-positive (22% vs. 11%) and fewer triple-negative tumors (11% vs. 16%). Patients with metachronous MBC more often had CNS metastases and metastases in other localizations than the lymph nodes, bone, visceral organs and CNS. Among HER2 + patients, chemotherapy and targeted therapy were more often administered in de novo versus metachronous MBC. Median OS was longer in de novo MBC for HR+/HER2- tumors (40.8 vs. 30.3 months, aHR 1.27, 95%CI 1.12-1.43) and HR-/HER2 + tumors (51.1 vs. 9.1 months, aHR 1.62, 95%CI 1.03-2.54). In HR+/HER2 - patients, metachronous MBC patients who received prior (neo)adjuvant systemic treatment had worse OS than de novo cases (prior chemotherapy: aHR 1.52, 95%CI 1.29-1.78); prior hormonal therapy only: aHR 1.33, 95%CI 1.10-1.61), whereas those without prior systemic treatment had similar outcomes. CONCLUSION: De novo and metachronous MBC have different tumor biology, treatment patterns, and survival. In metachronous MBC patients, prior (neo)adjuvant systemic treatment was associated with worse survival compared to de novo MBC or patients with metachronous MBC without prior (neo)adjuvant treatment.
Exploring the potential of postmastectomy radiotherapy in cN + and ypN0 breast cancer patients following neoadjuvant chemotherapy.
Jin Y, Li H, Yang Z … +6 more , Luo S, Zhang S, Tang L, Thomas SM, Plichta JK, Zhang J
Breast Cancer Res Treat · 2026 May · PMID 42118193 · Publisher ↗
PURPOSE: This study aims to determine the potential association of postmastectomy radiotherapy and survival in patients with clinically node-positive axillary breast cancer who achieved ypN0 after neoadjuvant chemotherap...
PURPOSE: This study aims to determine the potential association of postmastectomy radiotherapy and survival in patients with clinically node-positive axillary breast cancer who achieved ypN0 after neoadjuvant chemotherapy. METHODS: We conducted a retrospective cohort study using the National Cancer Database. Eligible patients were women aged 18-80 with cT1-2, cN+ invasive breast cancer and achieving ypN0 status. Inverse probability weighting (IPW)-based analyses were used to assess the differences in overall survival (OS) between the radiotherapy and no radiotherapy groups. Absolute 5-year OS rates between the two groups were analyzed by nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) analysis. Sensitivity analyses were conducted using multivariable Cox regressions. RESULTS: We identified 3,351 patients who met eligibility criteria, of whom 57.0% (N = 1,910) did not receive radiotherapy and 43.0% (N = 1,441) did receive radiotherapy. No significant differences in OS were observed between the radiotherapy and non-radiotherapy groups after adjustment (hazard ratio = 1.01, P = .96). The STEPP analysis demonstrated no significant differences between the RT and no RT groups, regardless of the composite risk. Subgroup analyses showed that the difference in OS rates between the two groups was significantly correlated with cN category, and the advantage associated with radiotherapy receipt was only observed in cN2-3 patients but not in cN1 patients (hazard ratio = 0.55; P-interaction = 0.024). CONCLUSIONS: This study further supports the NSABP B51 findings, suggesting that omitting postmastectomy radiotherapy may be reasonable for cT1-2N1M0 patients who achieved ypN0. However, postmastectomy radiotherapy may be a consideration for patients with more advanced nodal disease (cN2-3) who achieve ypN0 status after NAC, indicating that a more tailored approach may be warranted.
Retrospective study of comparable survival after neoadjuvant versus adjuvant chemotherapy in cT1-2N0M0 triple-negative breast cancer.
Olsson M, Janeva S, Martikainen J … +3 more , Tzikas AK, Karlsson P, Parris TZ
Breast Cancer Res Treat · 2026 May · PMID 42118180 · Full text
PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype commonly treated with chemotherapy and radiotherapy, administered preoperatively as neoadjuvant chemotherapy (NACT) or postoperatively as adjuvant tr...
PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype commonly treated with chemotherapy and radiotherapy, administered preoperatively as neoadjuvant chemotherapy (NACT) or postoperatively as adjuvant treatment (AT; defined here as adjuvant chemotherapy [ACT] with or without adjuvant radiotherapy [ART]). As NACT is increasingly favored, the relative survival outcomes of these approaches and the added benefit of postoperative therapy after NACT remain uncertain. This study aimed to assess their impact on survival. METHODS: In this nationwide registry-based cohort study, data for women diagnosed with cT1-2N0M0 TNBC in Sweden between 2007 and 2021 were retrieved from the Swedish National Quality Register for Breast Cancer. Survival outcomes for patients receiving NACT ± AT were compared with those receiving AT only. Propensity score matching (1:1) was performed, adjusting for age, clinical T-stage, and comorbidity. Overall survival (OS) and breast cancer-specific survival (BCSS) were estimated using Kaplan-Meier and Cox proportional hazards models. RESULTS: Of 3747 eligible patients, 711 received NACT ± AT and 3036 received AT alone. Median follow-up for BCSS was 3.61 years (IQR 2.37-5.50) for NACT and 6.95 years (IQR 4.36-9.62) for AT. After matching, 711 patients remained in each group. Both prior and post matching, 5-year OS and BCSS did not differ significantly between AT and NACT. These findings remained consistent after adjustment for potential confounders. CONCLUSION: OS and BCSS were similar between AT and NACT. These findings suggest that chemotherapy sequencing was not associated with a detectable survival difference, although treatment selection should be individualized and evaluated in the context of contemporary regimens.
Comparative efficacy of prevention strategies for oral mucositis in breast cancer patients: a network meta-analysis.
Liu Q, Wang R, Jiang S … +7 more , Yuan J, He G, Wang Q, Cheng S, Chen L, Zhao L, Liu S
Breast Cancer Res Treat · 2026 May · PMID 42101732 · Publisher ↗
BACKGROUND: This study aimed to evaluate the efficacy of various interventions for preventing and alleviating oral mucositis (OM), a dose-limiting toxicity induced by cancer treatment. METHODS: PubMed, Embase, Web of Sci...
BACKGROUND: This study aimed to evaluate the efficacy of various interventions for preventing and alleviating oral mucositis (OM), a dose-limiting toxicity induced by cancer treatment. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched from their inception to March 19, 2026. The quality of included studies was assessed using version 2 of the Cochrane risk-of-bias tool (ROB 2). A Bayesian network meta-analysis (NMA) was conducted utilizing R 4.5.1 and the JAGS package (version 4.3.1). The interventions were compared using league tables, surface under the cumulative ranking curve (SUCRA), and heterogeneity testing. RESULTS: A total of 7,790 articles were retrieved. Ultimately, 10 randomized controlled trials (RCTs) involving 869 patients were included. According to the NMA, zinc most effectively reduced overall OM (RR = 0.53, 95%CrI: 0.27 to 0.95), while propolis dry extract was optimal for grade ≥ 2 OM (RR = 0.15, 95%CrI: 0.01 to 0.99). bifico significantly decreased overall OM (RR = 0.58, 95%CrI: 0.44 to 0.73) and ranked second for grade ≥ 2 OM. Subgroup analyses showed that professional oral health care and zinc were superior in chemotherapy patients, while MuGard and professional oral health care performed best in targeted therapy patients. Professional oral health care was most effective against grade ≥ 2 OM in the targeted therapy subgroup (SUCRA = 96.17%). CONCLUSION: Zinc and propolis dry extract are the most optimal strategies for overall and grade ≥ 2 OM in BC patients, respectively. bifico shows promising clinical potential. Professional oral health care is effective in both chemotherapy and targeted therapy subgroups. Further large-scale RCTs are needed to validate these findings. CLINICAL TRIAL NUMBER: Not applicable.
Whole transcriptome analysis reveals MammaPrint and BluePrint-associated gene expression patterns with early lymph node metastasis in early-stage breast cancer.
Fa'ak F, Haan J, Chmielewski-Stivers N … +9 more , Menicucci A, Audeh W, Soe PP, Logman Z, Ahn S, D'Abreo N, Baum J, Marks DK, FLEX Investigators’ Group
Breast Cancer Res Treat · 2026 May · PMID 42101710 · Full text
INTRODUCTION: Early lymph node (LN) metastasis often precedes systemic metastasis and corresponds with significantly inferior survival for patients diagnosed with early-stage breast cancer (EBC). To understand the biolog...
INTRODUCTION: Early lymph node (LN) metastasis often precedes systemic metastasis and corresponds with significantly inferior survival for patients diagnosed with early-stage breast cancer (EBC). To understand the biological pathways involved in early LN metastasis, differential gene expression (DGE) analysis compared large tumors without evidence of LN metastasis (pT2-3pN0) to small tumors with LN metastasis (pT1pN+). METHODS: This study included 2,349 patients with EBC who underwent MammaPrint and BluePrint testing as part of the FLEX (NCT03053193). DGE was performed between pT2-3pN0/pT1pN + and across their MP/BP subtypes. Immune deconvolution was assessed using gene-signature-based methods, complemented by conventional tumor-infiltrating lymphocyte (TIL) analyses on a representative subset of patients. RESULTS: Greater DGE was observed within the MammaPrint High Risk and BluePrint Luminal B subgroups compared to pathological stages. MammaPrint High Risk tumors saw 73 differentially expressed genes (DEGs), while 34 were found for Luminal B tumors. Gene set enrichment analysis (GSEA) of MammaPrint High Risk/Luminal B tumors showed upregulated proliferation pathways and downregulated epithelial-to-mesenchymal transition (EMT) and immune profiles in pT2-3pN0 vs. pT1pN+, respectively. Immune deconvolution analyses showed a higher abundance of T gamma delta cells and CD4 + Th1 cells and a lower abundance of T regulatory cells, M2 macrophages, and cancer-associated fibroblasts within pT2-3pN0 tumors. Conventional histological assessment revealed no significant differences in TILs. CONCLUSION: This study lays the groundwork for exploring mechanisms of LN metastasis in EBC and their relation to MammaPrint High Risk and Luminal B subtypes. These data support previous studies' association of LN metastasis with EMT and immune dysregulation.
Racial differences in pathologic complete response rate and clinical outcomes following neoadjuvant chemotherapy for breast cancer.
Matusz-Fisher A, Livasy CA, Donahue EE … +9 more , Hadzikadic-Gusic L, Martin AY, Wallander ML, Neelands B, Buch D, Griffin A, Heeke AL, Tan AR, White RL
Breast Cancer Res Treat · 2026 May · PMID 42084744 · Full text
PURPOSE: Neoadjuvant chemotherapy (NAC) is commonly used in early-stage breast cancer. A complete pathologic response (pCR) after NAC is associated with improved outcomes. This study investigated differences in pCR and c...
PURPOSE: Neoadjuvant chemotherapy (NAC) is commonly used in early-stage breast cancer. A complete pathologic response (pCR) after NAC is associated with improved outcomes. This study investigated differences in pCR and clinical outcomes by race. METHODS: A single-institution, retrospective chart review identified patients with early-stage breast cancer who received NAC between January 1, 2010, and December 31, 2017. Associations between race and pathologic and clinical outcomes were evaluated using multivariable logistic regression and Cox proportional hazard models. Kaplan-Meier estimates and log rank tests assessed differences in recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 532 patients with breast cancer of all receptor subtypes were identified; 323 (60.7%) White, 188 (35.3%) Black and 21 (3.9%) other/unknown. The pCR rate was different between the 3 race categories; White 27.2%, Black 19.1% and other/unknown 9.5% (P = 0.03). In multivariate analysis, pCR rates were higher in White versus Black patients (P = 0.02). Patients with triple-negative disease demonstrated the largest difference in pCR (White 44.3% versus Black 27.1%; P = 0.04). Black patients had inferior OS compared to White patients (P = 0.03). There was no difference in RFS by race (P = 0.07). CONCLUSION: Black patients demonstrated a lower pCR rate compared to White patients, and this was more pronounced in the triple-negative subgroup. There was no difference in RFS by race, but OS was inferior among Black patients. It is possible that the lower pCR rate in Black patients may contribute to lower OS; however, more investigation is needed to explain these differences.
Long-term outcomes in triple-negative breast cancer after a pathologic complete response: does the type of neoadjuvant therapy matter?
Ravani LV, Wander SA, Kok M … +10 more , McCann K, Cortes J, Barroso-Sousa R, Lustberg M, Bines J, Michelon I, Testa L, Wang M, Deng D, Colombo Bonadio R
Breast Cancer Res Treat · 2026 May · PMID 42084743 · Publisher ↗
BACKGROUND: Neoadjuvant chemotherapy is standard for stage IB-III triple-negative breast cancer (TNBC), with pathological complete response (pCR) strongly associated with survival. Although escalation with platinum and i...
BACKGROUND: Neoadjuvant chemotherapy is standard for stage IB-III triple-negative breast cancer (TNBC), with pathological complete response (pCR) strongly associated with survival. Although escalation with platinum and immune checkpoint inhibitors (ICI) improves pCR and long-term outcomes, patients with pCR in control arms of pivotal trials also show favorable outcomes. Whether the regimen leading to pCR impacts long-term survival is largely unknown. METHODS: We conducted a systematic review and meta-analysis, searching phase II and III trials including early-stage TNBC patients with pCR. A pooled analysis of Kaplan-Meier-derived individual patient data was performed for event-free survival (EFS) and overall survival (OS), with subgroup analyses by treatment regimens. RESULTS: Of 2830 identified publications, 18 trials comprising 3430 patients were included. Neoadjuvant ICI with chemotherapy improved EFS (HR 0.67; 95%CI 0.50-0.89; p < 0.01) compared with chemotherapy-only regimens, with no significant OS difference (HR 0.84; 95%CI 0.50-1.41; P = 0.51). In contrast, EFS and OS were not significantly different regardless of platinum use (HR 0.55; 95%CI 0.20-1.50; P = 0.24 and HR 0.33; 95%CI 0.09-1.22; P = 0.10, respectively). Similarly, anthracycline-containing regimens showed comparable EFS to anthracycline-free regimens (HR 0.86; 95%CI 0.51-1.45; P = 0.58). For patients with pCR after ICI therapy, no benefit of adjuvant ICI for EFS or OS was observed (HR 1.16; 95%CI 0.55-2.44; P = 0.70 and HR 2.91; 95%CI 0.40-21.37; P = 0.29, respectively). CONCLUSION: These findings suggest that the context in which a pCR is achieved may influence long-term outcomes. Neoadjuvant ICI-based regimens improve EFS in patients with early-stage TNBC and pCR. However, EFS seems not to be impacted by neoadjuvant chemotherapy type.
Preoperative breast cancer screening before chest masculinization surgery.
Schuster CR, Aslami ZV, Taccheri C … +5 more , Azizi A, Saab D, Coon D, Camp MS, Liang F
Breast Cancer Res Treat · 2026 Apr · PMID 42018242 · Publisher ↗
PURPOSE: Detecting malignancy before gender-affirming chest masculinization surgery (GACMS) can alter surgical planning and prevent reoperation, yet a lack of standardized preoperative breast imaging guidelines has resul...
PURPOSE: Detecting malignancy before gender-affirming chest masculinization surgery (GACMS) can alter surgical planning and prevent reoperation, yet a lack of standardized preoperative breast imaging guidelines has resulted in inconsistent, surgeon-dependent practices and potential missed diagnoses. Limited data evaluating the efficacy of pre-GACMS imaging further contributes to this gap. This study aimed to characterize patterns, indications, and outcomes of preoperative breast imaging before GACMS, and to assess the impact of preoperative imaging on cancer detection, surgical decision-making, and timing to surgery. METHODS: A single-institution, retrospective review of adults who underwent GACMS between January 2017-September 2024 was conducted. Descriptive statistics summarize preoperative imaging frequency, indications, modalities, outcomes, and postoperative pathology. Alterations in surgical management based on preoperative versus postoperative cancer detection, as well as an institution-wide screening algorithm, are described. RESULTS: Of 368 patients, 91.8% (n = 338) were under 40 (mean 27.2, range 18-63). Preoperative breast imaging was recommended in 11.7% (n = 43) and performed in 11.1% (n = 41). Modalities included screening mammography (70.7%, n = 29), diagnostic mammography (29.3%, n = 12), MRI (9.8%, n = 4), and ultrasound (7.3%, n = 3). Indications included age (41.9%, n = 18), family history (30.2%, n = 13), physical exam finding (23.3%, n = 10), and BRCA2 mutation (2.3%, n = 1). Imaging revealed irregular findings in 17.1% (n = 7), with malignancy confirmed in 2 patients (4.9% of imaged; 0.5% overall). One patient who did not receive preoperative imaging was found to have invasive ductal carcinoma on postoperative pathology, resulting in 0.8% (n = 3) overall breast cancer diagnoses perioperatively. Preoperative detection altered surgical planning. Median time to surgery did not significantly differ between imaged and non-imaged patients (3.1 vs. 3.7 months, p = 0.2). CONCLUSION: Preoperative breast cancer imaging before GACMS identified malignancies that significantly influenced surgical planning, preventing additional procedures postoperatively. Implementing a decision-making algorithm could guide and standardize breast imaging before GACMS.
Correction: mTORC1 is a target of nordihydroguaiaretic acid to prevent breast tumor growth in vitro and in vivo.
Zhang Y, Xu S, Lin J … +10 more , Yao G, Han Z, Liang B, Zou Z, Chen Z, Song Q, Dai Y, Gao T, Liu A, Bai X
Breast Cancer Res Treat · 2026 Apr · PMID 42018063 · Publisher ↗
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