Breast Cancer Research最新文献

{"title":"Disparities in receipt of 1-^st line CDK4/6 inhibitors with endocrine therapy for treatment of hormone receptor positive, HER2 negative metastatic breast cancer in the real-world setting.","authors":"Asal Pilehvari, Gretchen Kimmick, Wen You, Gloribel Bonilla, Roger Anderson","doi":"10.1186/s13058-024-01902-w","DOIUrl":"https://doi.org/10.1186/s13058-024-01902-w","url":null,"abstract":"<p><strong>Objective: </strong>This study used real-world observational data to compare profiles of patients receiving different first-line treatment for hormone receptor positive (ER+), HER2 negative, metastatic breast cancer (MBC): CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) versus ET alone.</p><p><strong>Method: </strong>From a nationwide electronic health record-derived Flatiron Health de-identified database including 280 US cancer clinics, we identified patients with hormone receptor positive, HER2 negative, metastatic breast cancer receiving 1st -line therapy with ET alone or CDK4/6i plus ET between February 2015 and November 2021. Patient sociodemographic status, MBC treatment regimen and outcomes were the focus of this analysis. Patient characteristics were compared using t-tests and chi-square tests. Logistic regression analysis was performed to examine the association of patient characteristics with the likelihood of receiving 1st -line CDK4/6i plus ET vs. ET alone. Kaplan-Meier method and Cox proportional hazards were used to test the impact of 1st -line treatment regimen on real-world progression-free survival (PFS) and overall survival (OS). Baseline characteristics were balanced using inverse probability weighting (IPW).</p><p><strong>Results: </strong>The study population included 3,917 patients receiving CDK4/6i plus ET (n = 2170) and ET alone (n = 1747) for their MBC. Compared to patients receiving ET alone, those receiving CDK4/6i plus ET were younger (mean age 66.8 vs. 68.6, p < 0.001), more likely to present with de novo MBC (p < 0.001), had better performance status (50.2% vs. 40.5% patients with ECOG value 0, p = 0.001) and lower number of comorbidities (29.7% vs. 26.6% ≥ 1 comorbidity, p < 0.001). Logistic regression revealed increased odds of CDK4/6i plus ET in individuals aged 50-64 (OR: 3.42, 95% CI [2.41, 4.86]) and 65-74 (OR: 3.18, 95% CI [1.68, 6.02]) versus those aged 18-49 years of age. Black individuals had lower odds of CDK4/6i plus ET (OR: 0.76, 95% CI [0.58, 1.00]) compared to White individuals. Other characteristics associated with lower odds of CDK4/6i plus ET included patients with stage III disease (OR: 0.69, 95% CI [0.52, 0.92]), lower performance status (OR: 0.50, 95% CI [0.40, 0.62]), and Medicare insurance (OR: 0.73, 95% CI [0.30, 1.78]) compared to those with commercial and Medicaid insurance. After IPW adjustment, use of CDK4/6i plus ET as 1st -line treatment was associated with significantly longer median PFS compared to ET alone (27 vs. 17 months; hazard ratio [HR] = 0.61, p < 0.001). Median OS was 52 months in the CDK4/6i plus ET group and was 42 months with ET alone (HR = 0.74, p < 0.001).</p><p><strong>Conclusion: </strong>In this real-world database, disparities in receiving 1st -line CDK4/6 inhibitors were seen by age, diagnosis stage, baseline performance status, comorbidity, and insurance status. In adjusted analysis, the use of 1st -line CDK4/6i plus ET yielded bett","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy is required for mammary tumor recurrence by promoting dormant tumor cell survival following therapy.","authors":"Samantha Dwyer, Jason Ruth, Hans E Seidel, Amelie A Raz, Lewis A Chodosh","doi":"10.1186/s13058-024-01878-7","DOIUrl":"https://doi.org/10.1186/s13058-024-01878-7","url":null,"abstract":"<p><strong>Background: </strong>Mortality from breast cancer is principally due to tumor recurrence. Recurrent breast cancers arise from the pool of residual tumor cells, termed minimal residual disease, that survive treatment and may exist in a dormant state for 20 years or more following treatment of the primary tumor. As recurrent breast cancer is typically incurable, understanding the mechanisms underlying dormant tumor cell survival is a critical priority in breast cancer research. The importance of this goal is further underscored by emerging evidence suggesting that targeting dormant residual tumor cells in early-stage breast cancer patients may be a means to prevent tumor recurrence and its associated mortality. In this regard, the role of autophagy in dormant tumor cell survival and recurrence remains unresolved, with conflicting reports of both pro-survival/recurrence-promoting and pro-death/recurrence-suppressing effects of autophagy inhibition in dormant tumor cells. Resolving this question has important clinical implications.</p><p><strong>Methods: </strong>We used genetically engineered mouse models that faithfully recapitulate key features of human breast cancer progression, including minimal residual disease, tumor dormancy, and recurrence. We used genetic and pharmacological approaches to inhibit autophagy, including treatment with chloroquine, genetic knockdown of ATG5 or ATG7, or deletion of BECN and determined their effects on dormant tumor cell survival and recurrence.</p><p><strong>Results: </strong>We demonstrate that the survival and recurrence of dormant mammary tumor cells following therapy is dependent upon autophagy. We find that autophagy is induced in vivo following HER2 downregulation and remains activated in dormant residual tumor cells. Using genetic and pharmacological approaches we show that inhibiting autophagy by chloroquine administration, ATG5 or ATG7 knockdown, or deletion of a single allele of the tumor suppressor Beclin 1 is sufficient to inhibit mammary tumor recurrence, and that autophagy inhibition results in the death of dormant mammary tumor cells in vivo.</p><p><strong>Conclusions: </strong>Our findings demonstrate a pro-tumorigenic role for autophagy in tumor dormancy and recurrence following therapy, reveal that dormant tumor cells are uniquely reliant upon autophagy for their survival, and indicate that targeting dormant residual tumor cells by inhibiting autophagy impairs tumor recurrence. These studies identify a pharmacological target for a cellular state that is resistant to commonly used anti-neoplastic agents and suggest autophagy inhibition as an approach to reduce dormant minimal residual disease in order to prevent lethal tumor recurrence.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing rates of early-onset Luminal A breast cancers correlate with binge drinking patterns.","authors":"Jianjiu Chen, Rebecca Kehm, Wan Yang, Mary Beth Terry","doi":"10.1186/s13058-024-01894-7","DOIUrl":"https://doi.org/10.1186/s13058-024-01894-7","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) rates have been increasing in young women in the U.S. Alcohol is an established risk factor for breast cancer and has been consistently associated with hormone receptor positive cancers, the type of breast cancer that has been increasing the fastest in young women. Given these trends, we conducted an ecological study to examine whether alcohol consumption, and specifically binge drinking trends, were correlated with female breast cancer diagnosed under 40 years of age using breast cancer data from the Surveillance, Epidemiology, and End Results (SEER) Cancer Registry. We accounted for a latent period before cancer diagnosis by using exposure 10 years before the outcome (lag model); we also conducted a separate cumulative analysis of 10-year aggregate exposure.</p><p><strong>Findings: </strong>Moderate (Incidence Rate Ratio (IRR) = 1.05, 95% Confidence Interval (CI) = 1.02-1.07) and heavy (IRR = 1.05, 95% CI = 1.02-1.07)(≥ 1 and ≥ 2 drinks/day, respectively) alcohol consumption were each associated with Luminal A breast cancer but not the other molecular subtypes. Binge drinking was associated with an increased rate of early-onset Luminal A BC in both the 10-year lag model (IRR = 1.06, 95% CI = 1.02 to 1.11) and the cumulative model (IRR = 1.05, 95% CI = 1.02-1.07). Binge drinking was also associated with early-onset Luminal B BC in the cumulative model (IRR = 1.04, 95% CI = 1.01-1.07), but not associated with ERBB2-enriched or triple negative early-onset BC in either model.</p><p><strong>Conclusion: </strong>These trends support the hypothesis that one reason for the increase in early-onset breast cancer is from increased alcohol intake including binge drinking.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pro-inflammatory cytokines increase temporarily after adjuvant treatment for breast cancer in postmenopausal women: a longitudinal study.","authors":"Agnes Lindholm, Marie-Louise Abrahamsen, Kristian Buch-Larsen, Djordje Marina, Michael Andersson, Jørn Wulff Helge, Peter Schwarz, Flemming Dela, Linn Gillberg","doi":"10.1186/s13058-024-01898-3","DOIUrl":"https://doi.org/10.1186/s13058-024-01898-3","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer patients have an increased risk of cardiometabolic disease and for many patients, adjuvant therapy causes an altered lipid profile, insulin resistance and inflammation. Previous follow-up studies are inconclusive regarding the duration of therapy-induced inflammation. We examined the acute and persistent changes of adjuvant chemotherapy on inflammatory and metabolic health markers in breast cancer patients.</p><p><strong>Methods: </strong>Plasma levels of IL-6, IL-8, IL-10, IFN-γ, TNF-α, high-sensitivity C-reactive protein (hsCRP) and metabolic health parameters were analyzed before, shortly after and every six months up to two years after adjuvant chemotherapy treatment in 51 postmenopausal early breast cancer (EBC) patients, as well as in 41 healthy age- and BMI-matched controls. A target-specific multiplex assay was applied for cytokine measurements.</p><p><strong>Results: </strong>Before initiation of adjuvant therapy, plasma IL-8 levels were higher in EBC patients (31%, p = 0.0001). Also, a larger proportion of the patients had a hsCRP level above 2 mg/L (41%) compared to the controls (17%, Χ² = 5.15, p = 0.023). Plasma levels of all five cytokines, but not hsCRP, were significantly increased after compared to before adjuvant chemotherapy (15-48% increase; all p ≤ 0.05). Already six months after ending chemotherapy treatment, all plasma cytokine levels were significantly reduced and close to pre-chemotherapy levels. Adjuvant chemotherapy caused a worsened lipid profile (increased triglycerides, lower HDL levels), insulin resistance and increased plasma insulin levels that remained high during the first year after chemotherapy.</p><p><strong>Conclusion: </strong>Postmenopausal women with EBC have temporarily increased plasma levels of pro-inflammatory cytokines after adjuvant chemotherapy. Although transient, the therapy-induced increase in plasma cytokine levels, together with dyslipidemia and insulin resistance, may contribute to cardiometabolic risk in breast cancer patients treated with adjuvant chemotherapy.</p><p><strong>Trial registration: </strong>The clinical trial (registration number NCT03784651) was registered on www.</p><p><strong>Clinicaltrials: </strong>gov on 24 December 2018.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma metabolomics profiles and breast cancer risk.","authors":"Hui-Chen Wu, Yunjia Lai, Yuyan Liao, Maya Deyssenroth, Gary W Miller, Regina M Santella, Mary Beth Terry","doi":"10.1186/s13058-024-01896-5","DOIUrl":"10.1186/s13058-024-01896-5","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is the most common cancer in women and incidence rates are increasing; metabolomics may be a promising approach for identifying the drivers of the increasing trends that cannot be explained by changes in known BC risk factors.</p><p><strong>Methods: </strong>We conducted a nested case-control study (median followup 6.3 years) within the New York site of the Breast Cancer Family Registry (BCFR) (n = 40 cases and 70 age-matched controls). We conducted a metabolome-wide association study using untargeted metabolomics coupling hydrophilic interaction liquid chromatography (HILIC) and C₁₈ chromatography with high-resolution mass spectrometry (LC-HRMS) to identify BC-related metabolic features.</p><p><strong>Results: </strong>We found eight metabolic features associated with BC risk. For the four metabolites negatively associated with risk, the adjusted odds ratios (ORs) ranged from 0.31 (95% confidence interval (CI): 0.14, 0.66) (L-Histidine) to 0.65 (95% CI: 0.43, 0.98) (N-Acetylgalactosamine), and for the four metabolites positively associated with risk, ORs ranged from 1.61 (95% CI: 1.04, 2.51, (m/z: 101.5813, RT: 90.4, 1,3-dibutyl-1-nitrosourea, a potential carcinogen)) to 2.20 (95% CI: 1.15, 4.23) (11-cis-Eicosenic acid). These results were no longer statistically significant after adjusting for multiple comparisons. Adding the BC-related metabolic features to a model, including age, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk score improved the accuracy of BC prediction from an area under the curve (AUC) of 66% to 83%.</p><p><strong>Conclusions: </strong>If replicated in larger prospective cohorts, these findings offer promising new ways to identify exposures related to BC and improve BC risk prediction.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109).","authors":"Guilherme Nader-Marta, Christian Singer, Dominik Hlauschek, Angela DeMichele, Paolo Tarantino, Evandro de Azambuja, Georg Pfeiler, Miguel Martin, Justin M Balko, Zbigniew Nowecki, Marija Balic, Adam M Brufsky, Arlene Chan, Patrick G Morris, Tufia Haddad, Sibylle Loibl, Yuan Liu, Lidija Soelkner, Christian Fesl, Erica L Mayer, Michael Gnant","doi":"10.1186/s13058-024-01899-2","DOIUrl":"10.1186/s13058-024-01899-2","url":null,"abstract":"<p><strong>Background: </strong>Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC).</p><p><strong>Methods: </strong>PALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression's value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models.</p><p><strong>Results: </strong>From the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 - 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS.</p><p><strong>Conclusions: </strong>In this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.","authors":"Jessica O'Driscoll, Anya Burton, Gertraud Maskarinec, Beatriz Perez-Gomez, Celine Vachon, Hui Miao, Martín Lajous, Ruy López-Ridaura, A Heather Eliassen, Ana Pereira, Maria Luisa Garmendia, Rulla M Tamimi, Kimberly Bertrand, Ava Kwong, Giske Ursin, Eunjung Lee, Samera A Qureshi, Huiyan Ma, Sarah Vinnicombe, Sue Moss, Steve Allen, Rose Ndumia, Sudhir Vinayak, Soo-Hwang Teo, Shivaani Mariapun, Farhana Fadzli, Beata Peplonska, Chisato Nagata, Jennifer Stone, John L Hopper, Graham Giles, Vahit Ozmen, Mustafa Erkin Aribal, Joachim Schüz, Carla H Van Gils, Johanna O P Wanders, Reza Sirous, Mehri Sirous, John Hipwell, Jisun Kim, Jong Won Lee, Mikael Hartman, Jingmei Li, Christopher Scott, Anna M Chiarelli, Linda Linton, Marina Pollan, Anath Arzee Flugelman, Dorria Salem, Rasha Kamal, Norman Boyd, Isabel Dos-Santos-Silva, Valerie McCormack, Maeve Mullooly","doi":"10.1186/s13058-024-01890-x","DOIUrl":"10.1186/s13058-024-01890-x","url":null,"abstract":"<p><strong>Background: </strong>Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD).</p><p><strong>Methods: </strong>ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest.</p><p><strong>Results: </strong>Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (β: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD.</p><p><strong>Conclusions: </strong>Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On-treatment biopsies to predict response to neoadjuvant chemotherapy for breast cancer.","authors":"Bruno Valentin Sinn, Katharina Sychra, Michael Untch, Thomas Karn, Marion van Mackelenbergh, Jens Huober, Wolfgang Schmitt, Frederik Marmé, Christian Schem, Christine Solbach, Elmar Stickeler, Hans Tesch, Peter A Fasching, Andreas Schneeweiss, Volkmar Müller, Johannes Holtschmidt, Valentina Nekljudova, Sibylle Loibl, Carsten Denkert","doi":"10.1186/s13058-024-01883-w","DOIUrl":"10.1186/s13058-024-01883-w","url":null,"abstract":"<p><strong>Background: </strong>Patients with pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) have better outcomes, potentially warranting less extensive surgical and systemic treatments. Early prediction of treatment response could aid in adapting therapies.</p><p><strong>Methods: </strong>On-treatment biopsies from 297 patients with invasive BC in three randomized, prospective neoadjuvant trials were assessed (GeparQuattro, GeparQuinto, GeparSixto). BC quantity, tumor-infiltrating lymphocytes (TILs), and the proliferation marker Ki-67 were compared to pre-treatment samples. The study investigated the correlation between residual cancer, changes in Ki-67 and TILs, and their impact on pathologic complete response (pCR) and disease-free survival (DFS).</p><p><strong>Results: </strong>Among the 297 samples, 138 (46%) were hormone receptor-positive (HR+)/human epidermal growth factor 2-negative (HER2-), 87 (29%) were triple-negative (TNBC), and 72 (24%) were HER2+. Invasive tumor cells were found in 70% of on-treatment biopsies, with varying rates across subtypes (HR+/HER2-: 84%, TNBC: 62%, HER2+: 51%; p < 0.001). Patients with residual tumor on-treatment had an 8% pCR rate post-treatment (HR+/HER2-: 3%, TNBC: 19%, HER2+: 11%), while those without any invasive tumor had a 50% pCR rate (HR+/HER2-: 27%; TNBC: 48%, HER2+: 66%). Sensitivity for predicting residual disease was 0.81, with positive and negative predictive values of 0.92 and 0.50, respectively. Increasing TILs from baseline to on-treatment biopsy (if residual tumor was present) were linked to higher pCR likelihood in the overall cohort (OR 1.034, 95% CI 1.013-1.056 per % increase; p = 0.001) and with a longer DFS in TNBC (HR 0.980, 95% CI 0.963-0.997 per % increase; p = 0.026). Persisting or increased Ki-67 was associated with with lower pCR probability in the overall cohort (OR 0.957, 95% CI 0.928-0.986; p = 0.004) and shorter DFS in TNBC (HR 1.023, 95% CI 1.001-1.047; p = 0.04).</p><p><strong>Conclusion: </strong>On-treatment biopsies can predict patients unlikely to achieve pCR post-therapy. This could facilitate therapy adjustments for TNBC or HER2 + BC. They also might offer insights into therapy resistance mechanisms. Future research should explore whether standardized or expanded sampling enhances the accuracy of on-treatment biopsy procedures. Trial registration GeparQuattro (EudraCT 2005-001546-17), GeparQuinto (EudraCT 2006-005834-19) and GeparSixto (EudraCT 2011-000553-23).</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WHO-recommended levels of physical activity in relation to mammographic breast density, mammographic tumor appearance, and mode of detection of breast cancer.","authors":"Öykü Boraka, Hanna Sartor, Li Sturesdotter, Per Hall, Signe Borgquist, Sophia Zackrisson, Ann H Rosendahl","doi":"10.1186/s13058-024-01889-4","DOIUrl":"https://doi.org/10.1186/s13058-024-01889-4","url":null,"abstract":"<p><strong>Background: </strong>Despite known benefits of physical activity in reducing breast cancer risk, its impact on mammographic characteristics remain unclear and understudied. This study aimed to investigate associations between pre-diagnostic physical activity and mammographic features at breast cancer diagnosis, specifically mammographic breast density (MBD) and mammographic tumor appearance (MA), as well as mode of cancer detection (MoD).</p><p><strong>Methods: </strong>Physical activity levels from study baseline (1991-1996) and mammographic information from the time of invasive breast cancer diagnosis (1991-2014) of 1116 women enrolled in the Malmö Diet and Cancer Study cohort were used. Duration and intensity of physical activity were assessed according to metabolic equivalent of task hours (MET-h) per week, or World Health Organization (WHO) guideline recommendations. MBD was dichotomized into low-moderate or high, MA into spiculated or non-spiculated tumors, and MoD into clinical or screening detection. Associations were investigated through logistic regression analyses providing odds ratios (OR) with 95% confidence intervals (CI) in crude and multivariable-adjusted models.</p><p><strong>Results: </strong>In total, 32% of participants had high MBD at diagnosis, 37% had non-spiculated MA and 50% had clinical MoD. Overall, no association between physical activity and MBD was found with increasing MET-h/week or when comparing women who exceeded WHO guidelines to those subceeding recommendations (OR_adj 1.24, 95% CI 0.78-1.98). Likewise, no differences in MA or MoD were observed across categories of physical activity.</p><p><strong>Conclusions: </strong>No associations were observed between pre-diagnostic physical activity and MBD, MA, or MoD at breast cancer diagnosis. While physical activity is an established breast cancer prevention strategy, it does not appear to modify mammographic characteristics or screening detection.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning applications in breast cancer histopathological imaging: diagnosis, treatment, and prognosis.","authors":"Bitao Jiang, Lingling Bao, Songqin He, Xiao Chen, Zhihui Jin, Yingquan Ye","doi":"10.1186/s13058-024-01895-6","DOIUrl":"https://doi.org/10.1186/s13058-024-01895-6","url":null,"abstract":"<p><p>Breast cancer is the most common malignant tumor among women worldwide and remains one of the leading causes of death among women. Its incidence and mortality rates are continuously rising. In recent years, with the rapid advancement of deep learning (DL) technology, DL has demonstrated significant potential in breast cancer diagnosis, prognosis evaluation, and treatment response prediction. This paper reviews relevant research progress and applies DL models to image enhancement, segmentation, and classification based on large-scale datasets from TCGA and multiple centers. We employed foundational models such as ResNet50, Transformer, and Hover-net to investigate the performance of DL models in breast cancer diagnosis, treatment, and prognosis prediction. The results indicate that DL techniques have significantly improved diagnostic accuracy and efficiency, particularly in predicting breast cancer metastasis and clinical prognosis. Furthermore, the study emphasizes the crucial role of robust databases in developing highly generalizable models. Future research will focus on addressing challenges related to data management, model interpretability, and regulatory compliance, ultimately aiming to provide more precise clinical treatment and prognostic evaluation programs for breast cancer patients.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}