Breast Cancer Research And Treatment[JOURNAL]
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200 papers
Comments on: Cost-effectiveness of DPYD genotyping prior to capecitabine administration for metastatic breast cancer.
Jayaswal RP, Rana AK, Badyal RK
Breast Cancer Res Treat · 2026 Jun · PMID 42360572 · Publisher ↗
DPYD genotyping before capecitabine therapy represents a clinically actionable pharmacogenomic strategy to reduce avoidable fluoropyrimidine-related toxicity in metastatic breast cancer. Commenting on the cost-effectiven...
DPYD genotyping before capecitabine therapy represents a clinically actionable pharmacogenomic strategy to reduce avoidable fluoropyrimidine-related toxicity in metastatic breast cancer. Commenting on the cost-effectiveness analysis by Chiddarwar, Blaes and Kuntz, this correspondence supports the authors' findings while extending the discussion from economic value to implementation readiness. We propose that DPYD testing should be evaluated through a globally transferable framework incorporating ancestry-aware variant coverage, rapid turnaround pathways, genotype-linked dose decision support, budget-impact assessment and real-world toxicity surveillance. Such an approach may help translate cost-effective pharmacogenomics into equitable, operationally feasible breast cancer care across diverse health systems.
Comments on: Predictors of pathologic complete response in early-stage triple-negative breast cancer treated with neoadjuvant chemo-immunotherapy.
Jayaswal RP, Thapliyal S, Badyal RK
Breast Cancer Res Treat · 2026 Jun · PMID 42360520 · Publisher ↗
This correspondence comments on LeVee et al.'s real-world study of neoadjuvant chemo-immunotherapy in early-stage triple-negative breast cancer. We highlight diabetes as a potentially modifiable host-state factor influen...
This correspondence comments on LeVee et al.'s real-world study of neoadjuvant chemo-immunotherapy in early-stage triple-negative breast cancer. We highlight diabetes as a potentially modifiable host-state factor influencing pathologic complete response and propose a metabolic immunotherapy-readiness framework integrating glycaemic control, treatment delivery, endocrine monitoring, and equity-focused implementation. This perspective aims to support globally applicable strategies for improving chemo-immunotherapy effectiveness and access.
Discrimination, spectrum, and clinical utility: ICG lymphography drainage time in axillary staging.
Akalın Ç, Zaim G, Demir M
Breast Cancer Res Treat · 2026 Jun · PMID 42360511 · Publisher ↗
This Correspondence responds to the prospective study by Anuszkiewicz et al., which assessed dynamic indocyanine green (ICG) lymphography drainage time as a marker of axillary nodal burden. We raise three methodological...
This Correspondence responds to the prospective study by Anuszkiewicz et al., which assessed dynamic indocyanine green (ICG) lymphography drainage time as a marker of axillary nodal burden. We raise three methodological points relevant to how the results should be read. First, the cohort included only patients selected for axillary lymph node dissection, so it represents a narrow, non-representative spectrum in which discrimination tends to be optimistic; the reported area under the curve of 0.995 was obtained without internal or external validation. Second, an ipsilateral-to-contralateral ratio may be more transportable than the absolute threshold that was used. Third, discrimination is not the same as clinical utility, which also depends on calibration and net benefit. We outline directions for validation and future study.
Tumor infiltrating lymphocytes (TILs) as a predictive marker of pathological complete response (pCR) in a diverse patient population with early triple negative breast cancer (TNBC) treated with neoadjuvant real-world KEYNOTE-522 regimen.
Albert R, Thomas J, Sadeghi N … +6 more , Reddy SM, Ramos GD, McArthur H, Syed S, Farr D, Unni N
Breast Cancer Res Treat · 2026 Jun · PMID 42360368 · Full text
INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by poor prognosis. Based on the KEYNOTE-522 trial, neoadjuvant pembrolizumab plus chemotherapy has become the standard of care due...
INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by poor prognosis. Based on the KEYNOTE-522 trial, neoadjuvant pembrolizumab plus chemotherapy has become the standard of care due to significantly improved pathological complete response (pCR) rates. The presence of tumor-infiltrating lymphocytes (TILs) is a predictive biomarker of pCR. This retrospective cohort study examines a diverse patient population treated with the K522 regimen to determine if TILs predict pCR relative to other clinical and tumor-specific factors. METHODS: We retrospectively reviewed 187 patients with early-stage TNBC at two institutions (one tertiary care, one safety-net) who completed neoadjuvant K522 treatment between 2021 and 2024. Statistical analyses included Chi-squared tests, Z-tests, and univariate logistic regression to evaluate associations between TILs, ethnicity, tumor grade, and pCR, and multivariate logistic regression to assess whether the association between dose intensity and pCR differed by the presence of TILs at baseline. RESULTS: The overall pCR rate was 57%; TILs were present in 52.8% of cases. TILs were associated with a significantly higher pCR rate (70% vs. 48% without TILs; p = 0.0027). While pCR rates were similar across ethnicities, Hispanic patients with TILs had significantly higher pCR than those without (80.0% vs. 51.5%; p = 0.0254). Controlling for grade, patients with TILs were 2.442 times more likely to achieve pCR (CI: 1.310-4.553; p = 0.0050). Grade 3 tumors and node-positivity with TILs also showed statistically significant rates of pCR. Logistic regression analysis revealed a significant interaction between TIL status and immunotherapy dose intensity on pCR. While dose intensity did not influence pCR in TIL-negative patients, TIL-positive patients achieved higher pCR rates with lower dose intensity (OR = 1.54, p = 0.036). CONCLUSION: TILs serve as a strong predictive biomarker for immunotherapy response in a real-world TNBC population. Our findings regarding Hispanic, node-positive patients, and the interaction between TIL status and dose intensity suggest that TILs could guide treatment de-escalation to reduce K522-related toxicity. Standardizing TILs reporting is critical to optimizing treatment strategies and improving outcomes in underrepresented populations.
Role of individualized intervention(s) on quality of life and adherence to adjuvant endocrine therapy in premenopausal women with early-stage breast cancer: MyCHOICE study.
Ahmed S, Mannala S, Mondal P … +15 more , Mahmood W, Chalchal HI, Dwernychuk L, Iqbal N, Salim M, Khan MI, Ahmed O, Manna M, Leverick DG, Chandrasekhar A, Bashir A, Haider K, Leis A, Kontulainen S, Sami A
Breast Cancer Res Treat · 2026 Jun · PMID 42360361 · Publisher ↗
BACKGROUND: Premenopausal women receiving combination endocrine therapy often experience substantial declines in quality of life (QOL), cognitive functioning, and treatment adherence. The MyChoice study evaluated whether...
BACKGROUND: Premenopausal women receiving combination endocrine therapy often experience substantial declines in quality of life (QOL), cognitive functioning, and treatment adherence. The MyChoice study evaluated whether individualized behavioral and complementary interventions could help maintain or improve QOL and treatment adherence in women with early-stage hormone receptor-positive breast cancer undergoing aromatase inhibitor- or tamoxifen-based therapy with ovarian suppression. METHODS: In this prospective multicenter phase II study, premenopausal women with newly diagnosed hormone receptor-positive breast cancer were enrolled prior to initiation of combination endocrine therapy. Tailored supportive interventions, including structured exercise programs, restorative yoga, acupuncture, and massage therapy, were offered, and women could choose one or more interventions either alone or in combination. QOL and cognitive function were assessed at baseline, 3 months, and every 6 months for up to 3 years using FACT-B, FACT-ES, and FACT-Cognitive Function instruments. Adherence to endocrine therapy was assessed at each follow-up visit using physician-conducted patient interviews and pharmacy refill records. Longitudinal changes in QOL and their demographic and clinical predictors were analyzed using linear mixed-effects models. RESULTS: Forty premenopausal women participated, with a median age of 43 years. Exercise was the most frequently selected intervention (61%), followed by massage therapy (44%), acupuncture (35%), and yoga (30%). Functional well-being improved significantly over time (1.65 points per year, p = 0.0005). Emotional well-being, social/family well-being, physical well-being, endocrine symptoms, and perceived cognitive abilities remained stable. Adherence to endocrine therapy was high at 92.5% over the follow-up period. In multivariable analyses, younger age (< 35 years) was associated with less favorable outcomes across several domains, including lower FACT-ES scores and lower physical well-being. CONCLUSION: Individualized, patient-selected supportive interventions may help maintain key aspects of quality of life and support adherence to endocrine therapy in premenopausal women with early-stage breast cancer. These findings support further evaluation in larger, controlled trials.
Subjective socioeconomic status moderates the relationship between objective neighborhood disadvantage and quality of life in middle- and older-aged women with breast cancer.
Plotke RL, Kanaya MR, Popok PJ … +9 more , Webster SN, Hansen JL, Krueger MJ, Roberts M, Ebrahimi S, Saez-Clarke E, Taub CJ, Goel N, Antoni MH
Breast Cancer Res Treat · 2026 Jun · PMID 42360360 · Full text
PURPOSE: Living in a disadvantaged neighborhood is linked to higher mortality rates and poorer quality of life (QoL) among patients with breast cancer (BC). Subjective socioeconomic status (SSS), reflecting one's perceiv...
PURPOSE: Living in a disadvantaged neighborhood is linked to higher mortality rates and poorer quality of life (QoL) among patients with breast cancer (BC). Subjective socioeconomic status (SSS), reflecting one's perceived socioeconomic "rank" or social standing relative to others, may be associated with differences in the relationship between objective neighborhood disadvantage and QoL. Therefore, we sought to evaluate whether SSS moderated the association between objective neighborhood disadvantage and QoL in middle- and older-aged women undergoing BC treatment. METHODS: Women (≥ 50yrs) diagnosed with non-metastatic BC participating in a stress management trial completed a baseline assessment of SSS (MacArthur Network Sociodemographic Questionnaire) and QoL (Functional Assessment of Cancer Therapy-Breast) in the weeks after surgery. The Area Deprivation Index (ADI), which ranks the degree of neighborhood disadvantage via participants' addresses, measured objective neighborhood disadvantage. Multivariate linear regressions related ADI, SSS, and QoL, adjusting for age, cancer stage, and race/ethnicity. RESULTS: Greater SSS relative to the community (B = 3.60, SE = 1.12, p=.002) and the USA (B = 3.01, SE = 1.09, p=.006) related to better QoL. Also, SSS USA interacted with ADI in predicting QoL (B = 0.95, SE = 0.45, p=.038), such that greater ADI related to poorer QoL in women with lower but not higher SSS. CONCLUSION: Greater SSS relative to one's community and the USA population related to better QoL in women treated for BC. Conversely, greater objective neighborhood disadvantage related to poorer QoL but not among those with greater SSS. Future work could examine whether SSS is a modifiable intervention target through coping effectiveness training, or by enhancing community and social engagement.
Is endothelial dysfunction induced by aromatase inhibitors reversible after treatment?
Dabour MS, Shaaban A, Duprez DA … +2 more , Zordoky BN, Blaes AH
Breast Cancer Res Treat · 2026 Jun · PMID 42329476 · Full text
PURPOSE: Aromatase inhibitors (AIs) are standard therapy for postmenopausal women with hormone receptor-positive breast cancer. However, prolonged AI use is associated with increased cardiovascular (CV) risk, including h...
PURPOSE: Aromatase inhibitors (AIs) are standard therapy for postmenopausal women with hormone receptor-positive breast cancer. However, prolonged AI use is associated with increased cardiovascular (CV) risk, including hypertension, and endothelial dysfunction. This study evaluated the longitudinal changes in endothelial function during AI therapy, and whether AI-induced endothelial dysfunction is reversible post-discontinuation. METHODS: Patients were recruited before or within one month of AI initiation (Pre/early AI), during AI therapy, and after discontinuation (Post-AI) from two prospective studies. Patients with hypertension, hyperlipidemia, diabetes, or tobacco use were excluded. Vascular assessments included peripheral arterial tonometry (EndoPAT) for endothelial function (abnormal if ratio < 1.67) and artery elasticity indices. Estradiol, lipid profiles, and inflammatory markers were also measured. RESULTS: The study included 12 Pre/early AI patients, 67 visits from 41 patients during AI (median 2.89 years on AI), and 9 Post-AI patients (median 4.17 years follow-up). EndoPAT ratio was significantly impaired during AI therapy compared to the Pre/early AI (median: 0.86 vs 2.19). The EndoPAT ratio declined as early as six months and showed a progressive decline over time. Post-discontinuation, the EndoPAT ratio was only partially and not significantly restored (median: 1.08) despite full estradiol restoration and long follow-up. Arterial elasticity showed no significant changes. Systolic blood pressure increased modestly during AI therapy and returned to baseline after discontinuation, while diastolic pressure remained unchanged. Circulating interleukin-6 and tumor necrosis factor-α significantly decreased following AI discontinuation. CONCLUSIONS: AI therapy is associated with significant and progressive endothelial dysfunction, which does not fully recover after treatment cessation, highlighting the importance of CV monitoring in patients receiving long-term AI therapy.
Receptor discordance between primary tumors and nodal metastases and correlation with the 21-gene recurrence score in early-stage, estrogen receptor-positive, node-positive breast cancer.
Zheng S, Sullivan P, Vadehra K … +7 more , Kim J, Levee A, Callahan R, Teshome M, Tseng CH, Bardia A, Kapoor NS
Breast Cancer Res Treat · 2026 Jun · PMID 42329472 · Full text
BACKGROUND: In estrogen receptor (ER)-positive, HER2-negative breast cancer, systemic therapy decisions are often made on the biomarker status of the primary tumor, along with the Oncotype DX Recurrence Score (RS). Bioma...
BACKGROUND: In estrogen receptor (ER)-positive, HER2-negative breast cancer, systemic therapy decisions are often made on the biomarker status of the primary tumor, along with the Oncotype DX Recurrence Score (RS). Biomarker testing of nodal metastases is not routine, despite reported receptor discordance. We quantified ER/PR/HER2 discordance between primary tumors and axillary lymph node metastases and evaluated associations with RS and clinicopathologic features. METHODS: We conducted a retrospective study of women with stage II-III, ER-positive, HER2-negative, node-positive invasive breast cancer who underwent upfront surgery and Oncotype DX testing of the primary tumor between 2016 and 2020. ER, PR, and HER2 immunohistochemistry (IHC) was performed on archived nodal metastases. Discordance in ER/PR percent positivity and HER2 IHC score between primary and lymph node metastases was scored ordinally from 0 to 2 for no, mild, or marked difference, respectively. Associations with RS, tumor and nodal burden, and treatment were analyzed using standard parametric and nonparametric tests with statistical significance set at p < 0.05. RESULTS: Of 555 patients with RS testing, 91 patients met inclusion criteria and 73 had available nodal tissue. Discordance in at least one receptor was high overall, occurring in 56/73 (77%) cases. The discordance rate for ER was 15%, PR was 32%, and HER2 was 66% (58% mild, 8% marked). One case demonstrated loss of ER positivity in the node, and 14 demonstrated loss of PR positivity in the node; no primary HER2-negative tumor converted to HER2-positive (IHC 3+) disease in the node. Greater amount of HER2 discordance was associated with larger primary tumors and larger size of nodal metastatic deposits. Higher RS correlated with lower primary ER and PR expression and higher volume of nodal burden (p < 0.05 for each) but was not significantly associated with receptor discordance. CONCLUSIONS: Receptor discordance between primary tumors and nodal metastases is common, with most shifts occurring within the HER2-spectrum. There was a trend toward higher RS and ER or HER2-receptor discordance. HER2 discordance was also associated with larger tumor size and larger size of nodal metastasis. As strategies emerge to target HER2-low cohorts and to include ER-low/HER2-negative disease within treatment regimens for TNBC, it may become important to consider receptor testing of nodal disease in the future.
Efficacy and toxicity of neoadjuvant chemotherapy versus chemo-immunotherapy in triple-negative breast cancer patients with and without germline BRCA mutations.
Etan T, Cohen L, Bar Y … +6 more , Leshem Y, Lerner S, Stepansky I, Shiran I, Sonnenblick A, Shachar SS
Breast Cancer Res Treat · 2026 Jun · PMID 42329463 · Full text
BACKGROUND: The addition of pembrolizumab (KN522) to neoadjuvant doxorubicin, cyclophosphamide (AC), carboplatin and paclitaxel (TC) has significantly improved survival, albeit with increased toxicity. This study aims to...
BACKGROUND: The addition of pembrolizumab (KN522) to neoadjuvant doxorubicin, cyclophosphamide (AC), carboplatin and paclitaxel (TC) has significantly improved survival, albeit with increased toxicity. This study aims to evaluate the effectiveness and toxicity of KN522 and to decouple the relative contributions of germline BRCA mutations (gBRCAmut) and pembrolizumab addition. METHODS: A retrospective analysis of patients with stage II-III triple negative breast cancer, treated at a single tertiary medical center with either KN522 or ACTC. RESULTS: Among 127 patients, four cohorts were evaluated: (1) KN522-gBRCAmut (n = 26), (2) KN522-BRCA wildtype (n = 53), (3) ACTC-gBRCAmut (n = 18), (4) ACTC-BRCA wildtype (n = 30). The KN522-gBRCAmut cohort achieved a remarkable pCR rate of 92.3%, compared to 60.4%, 55.6% and 36.7% in cohorts (2), (3) and (4) respectively. Multivariable analysis identified the KN522 protocol (OR 3.69, 95% CI 1.66-8.20; p = 0.001) and gBRCAmut status (OR 3.78, 95% CI 1.57-9.12; p = 0.003) as independent predictors of pCR. Achieving pCR was associated with improved event-free and overall survival (OS) in univariate analyses. In multivariable models, however, pCR remained a significant independent predictor of OS only (HR = 0.15, 95% CI: 0.03-0.72, p = 0.018). KN522 was associated with higher hospitalization rates (40.5% vs. 14.6%, p = 0.003) and more neutropenic fever (NF) events (32.9% vs. 2.1%, p < 0.001), likely due to lower G-CSF prophylaxis during the AC part of the KN522 protocol (21.5% vs. 68.8%, p < 0.001). CONCLUSIONS: In this analysis, gBRCAmut carriers treated with KN522 achieved remarkably high pCR rates. The observed 40% hospitalizations, primarily due to NF, highlights the need for supportive care optimization, including G-CSF consideration.
Clinical implications of discordance in HER2 reassessment from HercepTest to 4B5 in metastatic breast cancer.
Yamaguchi Y, Hoshino M, Shimoi T … +16 more , Tamura H, Natori Y, Saiki T, Yamanaka T, Kitadai R, Saito A, Kita S, Maejima A, Kojima Y, Sudo K, Maeshima AM, Murata T, Takayama S, Naoi Y, Yonemori K, Yoshida M
Breast Cancer Res Treat · 2026 Jun · PMID 42329461 · Full text
PURPOSE: HER2-low breast cancer has emerged as a therapeutic category following the DESTINY-Breast04 trial, where trastuzumab deruxtecan (T-DXd) improved survival. As the Ventana 4B5 assay was the companion diagnostic in...
PURPOSE: HER2-low breast cancer has emerged as a therapeutic category following the DESTINY-Breast04 trial, where trastuzumab deruxtecan (T-DXd) improved survival. As the Ventana 4B5 assay was the companion diagnostic in this trial, many patients previously tested with the Dako HercepTest required reassessment. However, the frequency and clinical predictors of discrepancies between these assays remain unclear. This study aimed to evaluate discordance frequency between HercepTest and 4B5 and identify associated clinicopathological factors. METHODS: We retrospectively analyzed patients who underwent prior HER2 testing with HercepTest and subsequent reassessment with 4B5 between May 2023 and November 2024 at our institution. The primary endpoint was reassessment discordance, and secondary analyses examined the clinicopathological predictors of discordance. RESULTS: Eighty-four patients (median age: 58 years) were included. Specimens were obtained from primary tumors (28.6%) and metastatic lesions (71.4%); 15.5% were resections and 84.5% were biopsies. The discordance rate between HercepTest and 4B5 was 60.7%, most commonly a shift from 2 + to 1+, followed by 1 + to 0. Multivariable analysis identified progesterone receptor negativity (odds ratio [OR] 3.84, 95% confidence interval [CI] 1.39-11.59, p = 0.01) and metastatic site sampling (OR 3.77, 95% CI 1.14-13.67, p = 0.03) as independent predictors. Approximately one-quarter of discordant patients lost their HER2-low status and potential eligibility for T-DXd. CONCLUSIONS: Discordance between HercepTest and 4B5 is frequent and clinically consequential, leading to reclassification based on 4B5 that affects eligibility assessment in a substantial subset of patients. These findings highlight the need for careful interpretation of HER2 results in real-world reassessment and increased awareness of diagnostic variability in HER2-low classification.
Surgeon interpretation of margin status utilizing intraoperative 3D tomosynthesis during breast-conserving surgery.
Leonard LD, Cohen E, Perry R … +12 more , Sun J, Ehlers R, Refinetti A, Johnson HM, Akay C, Colen JS, DeSnyder S, Fallahian F, Hwang R, Hunt KK, Wu Y, Tamirisa N
Breast Cancer Res Treat · 2026 Jun · PMID 42329454 · Full text
INTRODUCTION: Obtaining negative margins at the time of segmental mastectomy (SM) is important to reduce risk of local recurrence and avoid the need for a second surgery due to positive margins. Our current institutional...
INTRODUCTION: Obtaining negative margins at the time of segmental mastectomy (SM) is important to reduce risk of local recurrence and avoid the need for a second surgery due to positive margins. Our current institutional standard practice (ISP) includes intraoperative assessment of the gross specimen and specimen radiographs by a multidisciplinary team including radiologists and pathologists. METHODS: In this study, we utilized digital breast tomosynthesis (DBT) images of SM specimens in the operating room and recorded when additional (selective) shave margins were proposed by the surgeon. A breast radiologist later reviewed the archived DBT images. The timing and accuracy of surgeon and breast radiologists' margin assessment using DBT was then compared to our ISP. RESULTS: There were 193 patients enrolled and included in the analysis. Of 196 SM specimens, 9.7% (n = 19) had positive margins prior to excision of selective shave margins. Of these, 16 were identified by ISP with a sensitivity of 84%, specificity of 29%, false-negative rate (FNR) of 16%, positive predictive value (PPV) of 11%, and negative predictive value (NPV) of 95%. Surgeon assessment of DBT images identified 16/19 specimens with positive margins, with a sensitivity of 84% (p > 0.05), specificity of 49% (p < 0.001), FNR of 16% (> 0.05), PPV of 15% (p > 0.05), and NPV of 97% (p > 0.05). The median time for surgeon interpretation was 6 (range 2-35) minutes vs. 33 (range 15-88) for ISP. CONCLUSIONS: Surgeon interpretation of DBT images offers an alternative to a more time- and labor-intensive ISP for detecting positive margins during breast-conserving surgery, with comparable accuracy and higher sensitivity.
Impact of axillary surgery on survival in de novo metastatic breast cancer with primary tumor resection.
Vasigh M, Ruth K, Bleicher RJ … +3 more , Lyons W, Aggon AA, Williams AD
Breast Cancer Res Treat · 2026 May · PMID 42329252 · Full text
PURPOSE: The role of axillary surgery in patients with de novo metastatic breast cancer (dnMBC) undergoing primary site surgery is unclear. We evaluated patterns of axillary management and associations with overall survi...
PURPOSE: The role of axillary surgery in patients with de novo metastatic breast cancer (dnMBC) undergoing primary site surgery is unclear. We evaluated patterns of axillary management and associations with overall survival (OS) in this population. METHODS: We used the National Cancer Database (2012-2020) to identify patients with dnMBC. Patients were grouped by receipt of breast surgery and axillary surgery (none, sentinel lymph node biopsy [SLNB] or axillary lymph node dissection [ALND]). Multivariable Cox proportional hazards models assessed factors associated with axillary surgery and OS. RESULTS: Among 39,946 eligible patients, 7,808 (19.5%) underwent surgery of the primary site, of whom 79.8% underwent axillary surgery (79.5% ALND, 20.4% SLNB). Compared with no axillary surgery, those who underwent axillary surgery had more favorable clinicodemographic characteristics (younger, fewer comorbidities, lower T stage, bone-only metastases). In patients with clinically node-negative disease, 41.6% had pathologically negative nodes, with higher rates among those with HR+/HER- disease and those who did not have systemic therapy prior to surgery. On multivariable analysis, axillary surgery was independently associated with improved OS (HR 0.70; 95% CI 0.63-0.78; p<0.001). CONCLUSION: Among patients with dnMBC undergoing primary site surgery, axillary surgery was associated with improved survival in this retrospective analysis, though the effect is likely influenced by selection bias. Until prospective data define which subgroups may benefit, axillary surgery should be considered selectively, with SLNB preferred over ALND for patients without palpable adenopathy to minimize morbidity. Multidisciplinary evaluation remains essential to tailor surgical decisions that balance survival, function, and quality of life.
Extracellular vesicles in nipple discharge for breast cancer screening.
Ozaki Y, Yoshida K, Ichikawa T … +14 more , Kitagawa M, Kato M, Velaga R, Iwase M, Takano Y, Takeuchi D, Kikumori T, Murata K, Yasui T, Nagahashi M, Ebata T, Kajiyama H, Masuda N, Yokoi A
Breast Cancer Res Treat · 2026 Jun · PMID 42307695 · Full text
PURPOSE: Nipple discharge (ND) is one of its major symptoms of breast cancer. However, the low volume of NDs has limited their diagnostic capability. This study aimed to identify extracellular vesicles (EVs) miRNAs in ND...
PURPOSE: Nipple discharge (ND) is one of its major symptoms of breast cancer. However, the low volume of NDs has limited their diagnostic capability. This study aimed to identify extracellular vesicles (EVs) miRNAs in ND using cellulose nanofiber (CNF) sheets to develop clinical biomarkers. METHODS: Patients with ND from two independent institutions between 2023 and 2024 were included. ND-EVs were isolated from 23 samples [normal, n = 8; intraductal papilloma, n = 1; ductal carcinoma in situ (DCIS), n = 8; invasive ductal carcinoma, n = 6] using CNF sheets. Additionally, miRNAs were also analyzed from intracystic fluid, tumor tissue, and tissue surface EVs from the same patients, and miRNA sequencing was performed. RESULTS: miRNA sequencing for ND-EVs revealed distinct clustering between cancer and normal groups, identifying miR-342-3p, miR-20b-5p, and miR-550a-5p as candidate biomarkers. ND-EV miRNA profiles reflected tumor tissue characteristics, especially in DCIS. Four additional miRNAs (miR-92b-3p, miR-375-3p, miR-182-5p, miR-96-5p) were commonly upregulated in DCIS tissue, tissue surface, and ND-EVs. These miRNAs were validated by qRT-PCR. ROC curve analyses demonstrated that combining the five miRNAs yielded high diagnostic performance, with AUCs of 0.902 for breast cancer and 0.938 for DCIS. A subset of three miRNAs also showed robust discrimination ability. CONCLUSION: ND-EV miRNAs collected via CNF sheets show great potential as noninvasive biomarkers for early breast cancer detection.
Rediscovering the Ciucci pathway: in-vivo evidence of a palmar lymphatic channel.
Givant M, Fanning JE, Chen A … +7 more , Lefevre A, Thomson S, Shillue K, Fleishman A, Posso AN, Ciucci JL, Singhal D
Breast Cancer Res Treat · 2026 Jun · PMID 42295461 · Publisher ↗
BACKGROUND: In 1996, Ciucci et al. described the presence of a lymphatic channel in the palmar skin that spanned the first interdigital space and anastomosed with lymphatic collaterals on the dorsal surface of the hand....
BACKGROUND: In 1996, Ciucci et al. described the presence of a lymphatic channel in the palmar skin that spanned the first interdigital space and anastomosed with lymphatic collaterals on the dorsal surface of the hand. This palmar lymphatic channel (a pathway we have named the Ciucci pathway) has yet to be described with in-vivo imaging. As the Ciucci pathway is a superficial-to-deep lymphatic communication, its visualization may provide insight into altered lymphatic routing following axillary lymph node dissection (ALND). Therefore, we investigated our ability to image this pathway with indocyanine green (ICG) lymphography. METHODS: Healthy female volunteer and female breast cancer survivors without a history of BCRL at least two years after ALND underwent lymphatic mapping of the upper extremities with ICG lymphography. ICG was injected in six standard sites in the hand/wrist and upper arm. The presence of the Ciucci pathway was recorded and compared between cohorts with Fisher's exact test. RESULTS: 110 arms of 55 healthy volunteers and 31 at-risk arms of 31 breast cancer survivors without BCRL were included. The Ciucci pathway was present in one of 110 (0.9%) healthy female volunteer arms and present in five of 31 (16.1%) at-risk arms of breast cancer survivors (p = 0.002). CONCLUSION: The Ciucci pathway was more frequently observed in the at-risk arms of volunteers with a history of ALND without BCRL than in the arms of healthy female volunteers. While the functional significance of this pathway remains unclear, its presence may represent superficial-to-deep lymphatic collateralization following ALND.
Adenoid cystic carcinoma of the breast: a case series of 26 patients.
Taleb I, Witmeyer S, Huck C … +10 more , Fournier M, Auriol S, Debled M, Petit A, de la Rochefordiere A, Grogan GM, Tredan O, Bouleftour W, Méry B, Magné N
Breast Cancer Res Treat · 2026 Jun · PMID 42283891 · Publisher ↗
BACKGROUND: Although triple-negative, adenoid cystic carcinoma of the breast (ACCB) is an uncommon, slow-growing malignancy with a favorable prognosis. There are no treatment standards or therapeutic consensus because of...
BACKGROUND: Although triple-negative, adenoid cystic carcinoma of the breast (ACCB) is an uncommon, slow-growing malignancy with a favorable prognosis. There are no treatment standards or therapeutic consensus because of its scarcity. METHODS: Data on 26 patients with ACCB from two distinct French cancer centers were presented in this study. Clinical, histological and molecular features of these carcinomas were described. Therapeutic management and patient follow-up was also reported. RESULTS: The median age of this cohort was 59 years [22-82] and the median follow-up was 4.2 years [0.5-23.9]. The most represented stages were IA (45.5%) and IIA (31.8%), with T1-T2 representing nineteen cases (86.3%). Four patients had axillary node metastases. Only 3 tumors were ER or PR positive. All tumors were HER-2 negative. Nine patients had a rearrangement of the MYB gene. Twenty-five patients had initial surgery. Adjuvant chemotherapy was administered to three patient. Twenty patients received adjuvant radiotherapy. At last follow-up, five of the patients had died from complications of the disease. CONCLUSION: Although ACCB generally has a good prognosis, the treatment of this rare type of breast cancer remains challenging to ensure favorable outcomes with minimal sequelae. Initial staging and long-term follow-up using appropriate imaging modalities are essential for selecting tailored treatment strategies and detecting early relapses.
Correction: The impact of cardiovascular risk factors on cancer progression: a prospective study in female breast cancer survivors.
Feng X, Deng Z, McCullough MS … +6 more , May BJ, Selznick E, Sheng JY, Connor AE, Armstrong DK, Visvanathan K
Breast Cancer Res Treat · 2026 Jun · PMID 42283870 · Publisher ↗
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Impact of cardiometabolic health on treatment outcomes in early-stage triple-negative breast cancer receiving chemoimmunotherapy.
Hundal J, Cheema A, Abushamma A … +4 more , Arora K, Chen X, Fargo K, Baidehi M
Breast Cancer Res Treat · 2026 Jun · PMID 42283783 · Full text
BACKGROUND: Triple-negative breast cancer (TNBC) lacks effective targeted therapies, and pivotal trials of pembrolizumab with neoadjuvant chemotherapy (KEYNOTE-522) underrepresent patients with cardiometabolic comorbidit...
BACKGROUND: Triple-negative breast cancer (TNBC) lacks effective targeted therapies, and pivotal trials of pembrolizumab with neoadjuvant chemotherapy (KEYNOTE-522) underrepresent patients with cardiometabolic comorbidities. We evaluated how metabolic dysfunction affects treatment tolerability, pathologic complete response (pCR), and overall survival (OS) in routine care. METHODS: We conducted a retrospective cohort study of women with early-stage triple-negative breast cancer (TNBC) treated with the KEYNOTE-522 regimen at the Cleveland Clinic between January 1, 2020, and March 31, 2025. Metabolic syndrome was defined using a constellation of cardiometabolic risk factors consistent with criteria proposed by the American Heart Association and the National Heart, Lung, and Blood Institute, adapted to available real-world clinical data (BMI, HbA1c in place of fasting glucose, hypertension, chronic kidney disease, HDL < 50 mg/dL, triglycerides > 150 mg/dL; ≥3 criteria). Data included demographics, tumor characteristics, treatment details, cardiometabolic comorbidities, CTCAE-graded adverse events, pathologic complete response (pCR), and overall survival (OS). Kaplan-Meier methods estimated survival; logistic regression evaluated predictors of pCR; Cox proportional hazards models assessed OS. Median follow-up was 28.8 months. RESULTS: Among 222 patients with early-stage TNBC treated with the KEYNOTE-522 regimen, 55 (24.8%) met criteria for metabolic syndrome. Patients with metabolic syndrome were older (median 65 vs. 55 years, p = 0.0004) and more frequently Black (43.6% vs. 18.0%). Cardiometabolic comorbidities were more prevalent, including obesity (85.5% vs. 35.9%), diabetes (72.7% vs. 7.8%), hypertension (69.1% vs. 24.6%), CKD (21.8% vs. 4.8%), low HDL (83.6% vs. 12.0%), and elevated triglycerides (58.2% vs. 6.0%) (all p < 0.001). Dose reductions were more frequent among patients with metabolic syndrome (32.7% vs. 20.4%), with similar treatment discontinuation rates. pCR rates did not differ significantly (72.7% vs. 68.9%, p = 0.62), and no cardiometabolic factors independently predicted pCR. With median follow-up of 28.8 months, metabolic syndrome was associated with worse overall survival. Hypertension (HR 3.83, 95% CI 1.47-9.96, p = 0.006) and diabetes (HR 3.07, 95% CI 1.33-7.08, p = 0.009) were independent predictors of mortality. CONCLUSION: Cardiometabolic comorbidities, particularly hypertension, were associated with poorer survival and greater treatment intolerance despite preserved pCR. Systematic cardiometabolic assessment and proactive management should be integrated into TNBC care.
Three-monthly gonadotropin-releasing hormone agonist for ovarian function suppression in premenopausal breast cancer: a systematic review and meta-analysis.
de Liz CD, Reis PCA, Blanchard-Cavagis ER … +3 more , Diniz IC, Brito HC, Visani FLV
Breast Cancer Res Treat · 2026 Jun · PMID 42283761 · Full text
PURPOSE: Ovarian function suppression (OFS) with gonadotropin-releasing hormone agonists (GnRHa) improves outcomes in premenopausal women with hormone receptor-positive (HR +) breast cancer (BC), most commonly using mont...
PURPOSE: Ovarian function suppression (OFS) with gonadotropin-releasing hormone agonists (GnRHa) improves outcomes in premenopausal women with hormone receptor-positive (HR +) breast cancer (BC), most commonly using monthly administration. The potential equivalence of 3-monthly (3 M) versus monthly (1 M) schedules has been suggested but remains uncertain. METHODS: We performed a systematic review and meta-analysis of interventional studies comparing 3 M and 1 M GnRHa regimens in premenopausal women with HR + BC receiving endocrine therapy. Outcomes included ovarian escape (OE), mean estradiol (E2) levels, disease-free survival (DFS), progression-free survival (PFS), and adverse events. Subgroup analyses were performed by estradiol assay type, and a sensitivity analysis restricted to RCTs. RESULTS: Fifteen studies comprising 4,324 patients were included, of whom 2,098 (48%) received a 3 M regimen. The pooled OE was 10% and showed no significant difference between schedules (RR 0.86; 95% CI 0.60-1.22; p = 0.39). Ultrasensitive assays yielded higher OE detection (31%) without inter-regimen differences (RR 0.90; 95% CI 0.38-2.14). Mean E2 concentrations at 12 weeks were similar (MD 1.36 pg/mL; 95% CI -3.66 to 6.38), with consistent findings in RCT-only analyses (MD -1.77 pg/mL; 95% CI -5.71 to 2.17). DFS (RR 1.02; 95% CI 0.67-1.56) and PFS (RR 0.86; 95% CI 0.72-1.04) were also comparable. No clinically relevant differences were observed in reported safety outcomes. CONCLUSION: 3 M GnRHa achieved OFS efficacy comparable to 1 M regimens, with no meaningful differences in survival or safety. The findings support 3 M GnRHa as a valid and practical alternative for OFS in appropriately selected premenopausal women with HR + BC.
Age-related differences in psychological distress and persistent postsurgical pain after surgery for management of non-invasive breast lesions.
Wilson JM, Rosenberg SM, Crowell KA … +11 more , Lynch T, Collyar D, Basila D, Frank ES, Darai S, Hyslop T, Valenza C, Thompson AM, Partridge AH, Hwang ES, Schreiber KL
Breast Cancer Res Treat · 2026 Jun · PMID 42257780 · Publisher ↗
PURPOSE: Younger women who have undergone surgery for non-invasive breast lesions may experience heightened psychological distress and persistent postsurgical pain (PPSP). We investigated whether younger age was associat...
PURPOSE: Younger women who have undergone surgery for non-invasive breast lesions may experience heightened psychological distress and persistent postsurgical pain (PPSP). We investigated whether younger age was associated with worse PPSP outcomes, and whether depression or anxiety contributed to these associations. METHODS: This was a secondary analysis of a cross-sectional survey of women (N = 821; Mean age = 60, range:26-88) who underwent surgical management of ductal carcinoma in situ (DCIS) or high-risk lesions (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ). Participants completed assessments of surgical-site pain severity, frequency, and impact of pain on cognitive/emotional and physical functioning, as well as measures of depression and anxiety. Mediation analyses tested whether depression or anxiety contributed to associations between younger age and worse PPSP outcomes, controlling for relevant surgical and treatment factors. RESULTS: Overall, 15% of women reported clinically significant PPSP (≥ 3/10). Younger age was associated with higher rates of clinically significant PPSP, higher pain severity index (PSI) scores, greater impact of pain on cognitive/emotional functioning, and higher depression and anxiety (all p-values < 0.001). Mediation analyses indicated that depression, but not anxiety, partially contributed to the association between younger age and worse PPSP outcomes. CONCLUSION: Depression contributed to the association of younger age with worse PPSP outcomes among women undergoing surgery for non-invasive breast lesions. These results underscore the importance of screening for PPSP and depression following surgery, particularly in younger women. Targeted psychological interventions may help improve long-term recovery in this vulnerable group.
Risk of malignancy after diagnosis of radial sclerosing lesion without atypia.
Delgado Casanova LB, Dhamne S, Resetkova E … +6 more , Guirguis MS, Puvvala A, Bevers TB, Bedrosian I, Huo L, Wanis KN
Breast Cancer Res Treat · 2026 Jun · PMID 42257745 · Full text
PURPOSE: Surgical excision of radial sclerosing lesions (RSLs) has historically been recommended to rule out malignancy. Contemporary guidelines support imaging surveillance instead whenever these lesions are "adequately...
PURPOSE: Surgical excision of radial sclerosing lesions (RSLs) has historically been recommended to rule out malignancy. Contemporary guidelines support imaging surveillance instead whenever these lesions are "adequately sampled." However, uncertainty exists around what suffices for sampling prior to observation, and the outcomes of imaging surveillance. METHODS: We conducted an observational cohort study including all RSLs diagnosed on image-guided needle biopsy performed at our institution from 2020 to 2025. We excluded lesions with a concurrent diagnosis of invasive cancer, ductal carcinoma in situ, or epithelial atypia in the ipsilateral breast. For lesions that underwent repeat percutaneous biopsy or surgical excision, we estimated the probability that additional sampling revealed malignancy. For the entire population, whether excision was performed or not, we estimated the cumulative incidence of malignancy at the site of RSL during follow-up. RESULTS: A total of 419 RSLs were diagnosed in 390 patients. 262 (62.5%) lesions were diagnosed by stereotactic-guided vacuum-assisted biopsy (VAB), 100 (23.9%) by MRI-guided VAB, and 57 (13.6%) by ultrasound-guided core needle biopsy. During initial work-up or follow-up, 35 lesions underwent repeat image-guided biopsy and 28 underwent surgical excision. None of these additional sampling procedures revealed malignancy. The estimated 3-year cumulative incidence of malignancy at the RSL site was 0% (95% CI: 0, 2.0%). CONCLUSIONS: These findings support a management strategy of imaging surveillance when radiologic-pathologic concordance is established. Even for less extensively sampled lesions, routine repeat biopsy or surgical excision may not be necessary for RSLs without atypia.
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