Pub Date : 2024-01-11DOI: 10.1186/s13058-023-01753-x
Tasleem J. Padamsee, Christina Bijou, Paige Swinehart-Hord, Megan Hils, Anna Muraveva, Rachel J. Meadows, Kate Shane-Carson, Lisa D. Yee, Celia E. Wills, Electra D. Paskett
To understand the dynamics that limit use of risk-management options by women at high risk of breast cancer, there is a critical need for research that focuses on patient perspectives. Prior research has left important gaps: exclusion of high-risk women not in risk-related clinical care, exclusion of non-white populations, and lack of attention to the decision-making processes that underlie risk-management choices. Our objective was to create a more inclusive dataset to facilitate research to address disparities related to decision making for breast cancer risk management. The Daughter Sister Mother Project survey collects comprehensive information about the experiences of women at high risk of breast cancer. We collected novel measures of feelings about and reactions to cancer screenings; knowledge, barriers, and facilitators of risk-management options; beliefs related to cancer risk and risk management; and involvement with loved ones who had cancer. Eligible individuals were non-Hispanic white and non-Hispanic Black adult women who self-identified as having high risk of breast cancer and had no personal history of cancer. Between October 2018 and August 2019, 1053 respondents completed the online survey. Of these, 717 were confirmed through risk prediction modeling to have a lifetime breast cancer risk of ≥ 20%. Sociodemographic characteristics of this sample were compared to those of nationally representative samples of the US population: the 2019 Health Information National Trends Survey and the Pew Research Center report: Jewish Americans in 2020. The sample of 717 women at objectively high risk of breast cancer was largely (95%) recruited from non-clinical sources. Of these respondents, only 31% had seen a genetic counselor, 34% had had genetic testing specific to breast cancer risk, and 35% had seen at least one breast or cancer care specialist. The sample includes 35% Black respondents and 8% with Ashkenazi Jewish ancestry. Although encompassing a substantial range of ages, incomes, and education levels, respondents are overall somewhat younger, higher-income, and more educated than the US population as a whole. The DSM dataset offers comprehensive data from a community-based, diverse sample of women at high risk of breast cancer. The dataset includes substantial proportions of Black and Ashkenazi Jewish women and women who are not already in clinical care related to their breast cancer risk. This sample will facilitate future studies of risk-management behaviors among women who are and are not receiving high-risk care, and of variations in risk-management experiences across race and ethnicity.
为了了解限制乳腺癌高危女性使用风险管理方案的动态因素，亟需开展以患者视角为重点的研究。之前的研究还存在一些重要缺陷：排除了未接受风险相关临床治疗的高危女性、排除了非白人群体，以及缺乏对风险管理选择的决策过程的关注。我们的目标是创建一个更具包容性的数据集，以促进研究，解决与乳腺癌风险管理决策相关的差异问题。女儿-姐妹-母亲项目调查收集了有关乳腺癌高危女性经历的全面信息。我们收集了以下方面的新指标：对癌症筛查的感受和反应；对风险管理方案的了解、障碍和促进因素；与癌症风险和风险管理相关的信念；与罹患癌症的亲人的关系。符合条件者为非西班牙裔白人和非西班牙裔黑人成年女性，她们自我认定为乳腺癌高风险人群，且无个人癌症病史。2018 年 10 月至 2019 年 8 月期间，共有 1053 名受访者完成了在线调查。其中，717 名受访者通过风险预测建模确认终生乳腺癌风险≥ 20%。该样本的社会人口特征与具有全国代表性的美国人口样本进行了比较：2019 年健康信息全国趋势调查（2019 Health Information National Trends Survey）和皮尤研究中心报告（Pew Research Center report）：2020 年的美国犹太人。717 名客观上面临乳腺癌高风险的女性样本大部分（95%）是从非临床来源招募的。在这些受访者中，只有 31% 的人看过遗传咨询师，34% 的人做过专门针对乳腺癌风险的遗传检测，35% 的人至少看过一位乳腺或癌症护理专家。样本中有 35% 的黑人受访者和 8% 有阿什肯纳兹犹太血统的受访者。虽然受访者的年龄、收入和受教育程度差别很大，但总体而言，受访者比美国整体人口更年轻、收入更高、受教育程度更高。DSM 数据集提供了以社区为基础的、多样化的乳腺癌高危女性样本的综合数据。该数据集中包括大量黑人和阿什肯纳兹犹太妇女，以及尚未接受与乳腺癌风险有关的临床治疗的妇女。该样本将有助于今后对接受和未接受高风险护理的妇女的风险管理行为以及不同种族和族裔的风险管理经验差异进行研究。
{"title":"Risk-management decision-making data from a community-based sample of racially diverse women at high risk of breast cancer: rationale, methods, and sample characteristics of the Daughter Sister Mother Project survey","authors":"Tasleem J. Padamsee, Christina Bijou, Paige Swinehart-Hord, Megan Hils, Anna Muraveva, Rachel J. Meadows, Kate Shane-Carson, Lisa D. Yee, Celia E. Wills, Electra D. Paskett","doi":"10.1186/s13058-023-01753-x","DOIUrl":"https://doi.org/10.1186/s13058-023-01753-x","url":null,"abstract":"To understand the dynamics that limit use of risk-management options by women at high risk of breast cancer, there is a critical need for research that focuses on patient perspectives. Prior research has left important gaps: exclusion of high-risk women not in risk-related clinical care, exclusion of non-white populations, and lack of attention to the decision-making processes that underlie risk-management choices. Our objective was to create a more inclusive dataset to facilitate research to address disparities related to decision making for breast cancer risk management. The Daughter Sister Mother Project survey collects comprehensive information about the experiences of women at high risk of breast cancer. We collected novel measures of feelings about and reactions to cancer screenings; knowledge, barriers, and facilitators of risk-management options; beliefs related to cancer risk and risk management; and involvement with loved ones who had cancer. Eligible individuals were non-Hispanic white and non-Hispanic Black adult women who self-identified as having high risk of breast cancer and had no personal history of cancer. Between October 2018 and August 2019, 1053 respondents completed the online survey. Of these, 717 were confirmed through risk prediction modeling to have a lifetime breast cancer risk of ≥ 20%. Sociodemographic characteristics of this sample were compared to those of nationally representative samples of the US population: the 2019 Health Information National Trends Survey and the Pew Research Center report: Jewish Americans in 2020. The sample of 717 women at objectively high risk of breast cancer was largely (95%) recruited from non-clinical sources. Of these respondents, only 31% had seen a genetic counselor, 34% had had genetic testing specific to breast cancer risk, and 35% had seen at least one breast or cancer care specialist. The sample includes 35% Black respondents and 8% with Ashkenazi Jewish ancestry. Although encompassing a substantial range of ages, incomes, and education levels, respondents are overall somewhat younger, higher-income, and more educated than the US population as a whole. The DSM dataset offers comprehensive data from a community-based, diverse sample of women at high risk of breast cancer. The dataset includes substantial proportions of Black and Ashkenazi Jewish women and women who are not already in clinical care related to their breast cancer risk. This sample will facilitate future studies of risk-management behaviors among women who are and are not receiving high-risk care, and of variations in risk-management experiences across race and ethnicity.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139422407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-10DOI: 10.1186/s13058-023-01762-w
Kevin Dell’Aquila, Abhinav Vadlamani, Takouhie Maldjian, Susan Fineberg, Anna Eligulashvili, Julie Chung, Richard Adam, Laura Hodges, Wei Hou, Della Makower, Tim Q. Duong
Generalizability of predictive models for pathological complete response (pCR) and overall survival (OS) in breast cancer patients requires diverse datasets. This study employed four machine learning models to predict pCR and OS up to 7.5 years using data from a diverse and underserved inner-city population. Demographics, staging, tumor subtypes, income, insurance status, and data from radiology reports were obtained from 475 breast cancer patients on neoadjuvant chemotherapy in an inner-city health system (01/01/2012 to 12/31/2021). Logistic regression, Neural Network, Random Forest, and Gradient Boosted Regression models were used to predict outcomes (pCR and OS) with fivefold cross validation. pCR was not associated with age, race, ethnicity, tumor staging, Nottingham grade, income, and insurance status (p > 0.05). ER−/HER2+ showed the highest pCR rate, followed by triple negative, ER+/HER2+, and ER+/HER2− (all p < 0.05), tumor size (p < 0.003) and background parenchymal enhancement (BPE) (p < 0.01). Machine learning models ranked ER+/HER2−, ER−/HER2+, tumor size, and BPE as top predictors of pCR (AUC = 0.74–0.76). OS was associated with race, pCR status, tumor subtype, and insurance status (p < 0.05), but not ethnicity and incomes (p > 0.05). Machine learning models ranked tumor stage, pCR, nodal stage, and triple-negative subtype as top predictors of OS (AUC = 0.83–0.85). When grouping race and ethnicity by tumor subtypes, neither OS nor pCR were different due to race and ethnicity for each tumor subtype (p > 0.05). Tumor subtypes and imaging characteristics were top predictors of pCR in our inner-city population. Insurance status, race, tumor subtypes and pCR were associated with OS. Machine learning models accurately predicted pCR and OS.
{"title":"Machine learning prediction of pathological complete response and overall survival of breast cancer patients in an underserved inner-city population","authors":"Kevin Dell’Aquila, Abhinav Vadlamani, Takouhie Maldjian, Susan Fineberg, Anna Eligulashvili, Julie Chung, Richard Adam, Laura Hodges, Wei Hou, Della Makower, Tim Q. Duong","doi":"10.1186/s13058-023-01762-w","DOIUrl":"https://doi.org/10.1186/s13058-023-01762-w","url":null,"abstract":"Generalizability of predictive models for pathological complete response (pCR) and overall survival (OS) in breast cancer patients requires diverse datasets. This study employed four machine learning models to predict pCR and OS up to 7.5 years using data from a diverse and underserved inner-city population. Demographics, staging, tumor subtypes, income, insurance status, and data from radiology reports were obtained from 475 breast cancer patients on neoadjuvant chemotherapy in an inner-city health system (01/01/2012 to 12/31/2021). Logistic regression, Neural Network, Random Forest, and Gradient Boosted Regression models were used to predict outcomes (pCR and OS) with fivefold cross validation. pCR was not associated with age, race, ethnicity, tumor staging, Nottingham grade, income, and insurance status (p > 0.05). ER−/HER2+ showed the highest pCR rate, followed by triple negative, ER+/HER2+, and ER+/HER2− (all p < 0.05), tumor size (p < 0.003) and background parenchymal enhancement (BPE) (p < 0.01). Machine learning models ranked ER+/HER2−, ER−/HER2+, tumor size, and BPE as top predictors of pCR (AUC = 0.74–0.76). OS was associated with race, pCR status, tumor subtype, and insurance status (p < 0.05), but not ethnicity and incomes (p > 0.05). Machine learning models ranked tumor stage, pCR, nodal stage, and triple-negative subtype as top predictors of OS (AUC = 0.83–0.85). When grouping race and ethnicity by tumor subtypes, neither OS nor pCR were different due to race and ethnicity for each tumor subtype (p > 0.05). Tumor subtypes and imaging characteristics were top predictors of pCR in our inner-city population. Insurance status, race, tumor subtypes and pCR were associated with OS. Machine learning models accurately predicted pCR and OS.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139413355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-05DOI: 10.1186/s13058-023-01760-y
Stephanie J. Hachey, Christopher J. Hatch, Daniela Gaebler, Aneela Mocherla, Kevin Nee, Kai Kessenbrock, Christopher C. W. Hughes
Triple-negative breast cancer (TNBC) is highly aggressive with limited available treatments. Stromal cells in the tumor microenvironment (TME) are crucial in TNBC progression; however, understanding the molecular basis of stromal cell activation and tumor–stromal crosstalk in TNBC is limited. To investigate therapeutic targets in the TNBC stromal niche, we used an advanced human in vitro microphysiological system called the vascularized micro-tumor (VMT). Using single-cell RNA sequencing, we revealed that normal breast tissue stromal cells activate neoplastic signaling pathways in the TNBC TME. By comparing interactions in VMTs with clinical data, we identified therapeutic targets at the tumor–stromal interface with potential clinical significance. Combining treatments targeting Tie2 signaling with paclitaxel resulted in vessel normalization and increased efficacy of paclitaxel in the TNBC VMT. Dual inhibition of HER3 and Akt also showed efficacy against TNBC. These data demonstrate the potential of inducing a favorable TME as a targeted therapeutic approach in TNBC.
{"title":"Targeting tumor–stromal interactions in triple-negative breast cancer using a human vascularized micro-tumor model","authors":"Stephanie J. Hachey, Christopher J. Hatch, Daniela Gaebler, Aneela Mocherla, Kevin Nee, Kai Kessenbrock, Christopher C. W. Hughes","doi":"10.1186/s13058-023-01760-y","DOIUrl":"https://doi.org/10.1186/s13058-023-01760-y","url":null,"abstract":"Triple-negative breast cancer (TNBC) is highly aggressive with limited available treatments. Stromal cells in the tumor microenvironment (TME) are crucial in TNBC progression; however, understanding the molecular basis of stromal cell activation and tumor–stromal crosstalk in TNBC is limited. To investigate therapeutic targets in the TNBC stromal niche, we used an advanced human in vitro microphysiological system called the vascularized micro-tumor (VMT). Using single-cell RNA sequencing, we revealed that normal breast tissue stromal cells activate neoplastic signaling pathways in the TNBC TME. By comparing interactions in VMTs with clinical data, we identified therapeutic targets at the tumor–stromal interface with potential clinical significance. Combining treatments targeting Tie2 signaling with paclitaxel resulted in vessel normalization and increased efficacy of paclitaxel in the TNBC VMT. Dual inhibition of HER3 and Akt also showed efficacy against TNBC. These data demonstrate the potential of inducing a favorable TME as a targeted therapeutic approach in TNBC.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-03DOI: 10.1186/s13058-023-01756-8
Joanna I. López-Velazco, Sara Manzano, María Otaño, Kepa Elorriaga, Núria Bultó, Julio Herrero, Ainhara Lahuerta, Virginia Segur, Isabel Álvarez-López, Maria M. Caffarel, Ander Urruticoechea
Neoadjuvant endocrine therapy (NET) in oestrogen receptor-positive (ER+) /HER2-negative (HER2-) breast cancer allows real-time evaluation of drug efficacy as well as investigation of the biological and molecular changes that occur after estrogenic deprivation. Clinical and pathological evaluation after NET may be used to obtain prognostic and predictive information of tumour response to decide adjuvant treatment. In this setting, clinical scales developed to evaluate response after neoadjuvant chemotherapy are not useful and there are not validated biomarkers to assess response to NET beyond Ki67 levels and preoperative endocrine prognostic index score (mPEPI). In this prospective study, we extensively analysed radiological (by ultrasound scan (USS) and magnetic resonance imaging (MRI)) and pathological tumour response of 104 postmenopausal patients with ER+ /HER2- resectable breast cancer, treated with NET for a mean of 7 months prior to surgery. We defined a new score, tumour cellularity size (TCS), calculated as the product of the residual tumour cellularity in the surgical specimen and the tumour pathological size. Our results show that radiological evaluation of response to NET by both USS and MRI underestimates pathological tumour size (path-TS). Tumour size [mean (range); mm] was: path-TS 20 (0–80); radiological-TS by USS 9 (0–31); by MRI: 12 (0–60). Nevertheless, they support the use of MRI over USS to clinically assess radiological tumour response (rad-TR) due to the statistically significant association of rad-TR by MRI, but not USS, with Ki67 decrease (p = 0.002 and p = 0.3, respectively) and mPEPI score (p = 0.002 and p = 0.6, respectively). In addition, we propose that TCS could become a new tool to standardize response assessment to NET given its simplicity, reproducibility and its good correlation with existing biomarkers (such as ΔKi67, p = 0.001) and potential added value. Our findings shed light on the dynamics of tumour response to NET, challenge the paradigm of the ability of NET to decrease surgical volume and point to the utility of the TCS to quantify the scattered tumour response usually produced by endocrine therapy. In the future, these results should be validated in independent cohorts with associated survival data.
对雌激素受体阳性（ER+）/HER2-阴性（HER2-）乳腺癌进行新辅助内分泌治疗（NET）可实时评估药物疗效，并研究雌激素剥夺后发生的生物和分子变化。NET后的临床和病理评估可用于获得肿瘤对辅助治疗反应的预后和预测信息。在这种情况下，为评估新辅助化疗后的反应而开发的临床量表并不实用，而且除了Ki67水平和术前内分泌预后指数评分（mPEPI）外，还没有有效的生物标志物来评估NET的反应。在这项前瞻性研究中，我们广泛分析了104例绝经后ER+/HER2-可切除乳腺癌患者的放射学（超声扫描（USS）和磁共振成像（MRI））和病理学肿瘤反应，这些患者术前平均7个月接受NET治疗。我们定义了一个新的评分标准，即肿瘤细胞大小（TCS），计算方法是手术标本中残留的肿瘤细胞大小与肿瘤病理大小的乘积。我们的结果表明，USS和MRI对NET反应的放射学评估低估了病理肿瘤大小（path-TS）。肿瘤大小[平均值（范围）；毫米]为：路径-TS 20（0-80）；USS放射学-TS 9（0-31）；MRI：12（0-60）。然而，他们支持使用 MRI 而非 USS 来临床评估肿瘤放射学反应（rad-TR），因为 MRI 而非 USS 的放射学反应与 Ki67 下降（分别为 p = 0.002 和 p = 0.3）和 mPEPI 评分（分别为 p = 0.002 和 p = 0.6）有显著的统计学关联。此外，鉴于TCS的简便性、可重复性及其与现有生物标志物（如ΔKi67，p = 0.001）的良好相关性和潜在附加值，我们建议TCS可成为规范NET反应评估的新工具。我们的研究结果阐明了肿瘤对NET反应的动态变化，挑战了NET能减少手术量的模式，并指出了TCS在量化通常由内分泌治疗产生的分散肿瘤反应方面的实用性。未来，这些结果应在具有相关生存数据的独立队列中得到验证。
{"title":"A prospective study on tumour response assessment methods after neoadjuvant endocrine therapy in early oestrogen receptor-positive breast cancer","authors":"Joanna I. López-Velazco, Sara Manzano, María Otaño, Kepa Elorriaga, Núria Bultó, Julio Herrero, Ainhara Lahuerta, Virginia Segur, Isabel Álvarez-López, Maria M. Caffarel, Ander Urruticoechea","doi":"10.1186/s13058-023-01756-8","DOIUrl":"https://doi.org/10.1186/s13058-023-01756-8","url":null,"abstract":"Neoadjuvant endocrine therapy (NET) in oestrogen receptor-positive (ER+) /HER2-negative (HER2-) breast cancer allows real-time evaluation of drug efficacy as well as investigation of the biological and molecular changes that occur after estrogenic deprivation. Clinical and pathological evaluation after NET may be used to obtain prognostic and predictive information of tumour response to decide adjuvant treatment. In this setting, clinical scales developed to evaluate response after neoadjuvant chemotherapy are not useful and there are not validated biomarkers to assess response to NET beyond Ki67 levels and preoperative endocrine prognostic index score (mPEPI). In this prospective study, we extensively analysed radiological (by ultrasound scan (USS) and magnetic resonance imaging (MRI)) and pathological tumour response of 104 postmenopausal patients with ER+ /HER2- resectable breast cancer, treated with NET for a mean of 7 months prior to surgery. We defined a new score, tumour cellularity size (TCS), calculated as the product of the residual tumour cellularity in the surgical specimen and the tumour pathological size. Our results show that radiological evaluation of response to NET by both USS and MRI underestimates pathological tumour size (path-TS). Tumour size [mean (range); mm] was: path-TS 20 (0–80); radiological-TS by USS 9 (0–31); by MRI: 12 (0–60). Nevertheless, they support the use of MRI over USS to clinically assess radiological tumour response (rad-TR) due to the statistically significant association of rad-TR by MRI, but not USS, with Ki67 decrease (p = 0.002 and p = 0.3, respectively) and mPEPI score (p = 0.002 and p = 0.6, respectively). In addition, we propose that TCS could become a new tool to standardize response assessment to NET given its simplicity, reproducibility and its good correlation with existing biomarkers (such as ΔKi67, p = 0.001) and potential added value. Our findings shed light on the dynamics of tumour response to NET, challenge the paradigm of the ability of NET to decrease surgical volume and point to the utility of the TCS to quantify the scattered tumour response usually produced by endocrine therapy. In the future, these results should be validated in independent cohorts with associated survival data.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139082943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-02DOI: 10.1186/s13058-023-01748-8
Gary R. Zirpoli, Ruth M. Pfeiffer, Kimberly A. Bertrand, Dezheng Huo, Kathryn L. Lunetta, Julie R. Palmer
Previous work in European ancestry populations has shown that adding a polygenic risk score (PRS) to breast cancer risk prediction models based on epidemiologic factors results in better discriminatory performance as measured by the AUC (area under the curve). Following publication of the first PRS to perform well in women of African ancestry (AA-PRS), we conducted an external validation of the AA-PRS and then evaluated the addition of the AA-PRS to a risk calculator for incident breast cancer in Black women based on epidemiologic factors (BWHS model). Data from the Black Women’s Health Study, an ongoing prospective cohort study of 59,000 US Black women followed by biennial questionnaire since 1995, were used to calculate AUCs and 95% confidence intervals (CIs) for discriminatory accuracy of the BWHS model, the AA-PRS alone, and a new model that combined them. Analyses were based on data from 922 women with invasive breast cancer and 1844 age-matched controls. AUCs were 0.577 (95% CI 0.556–0.598) for the BWHS model and 0.584 (95% CI 0.563–0.605) for the AA-PRS. For a model that combined estimates from the questionnaire-based BWHS model with the PRS, the AUC increased to 0.623 (95% CI 0.603–0.644). This combined model represents a step forward for personalized breast cancer preventive care for US Black women, as its performance metrics are similar to those from models in other populations. Use of this new model may mitigate exacerbation of breast cancer disparities if and when it becomes feasible to include a PRS in routine health care decision-making.
{"title":"Addition of polygenic risk score to a risk calculator for prediction of breast cancer in US Black women","authors":"Gary R. Zirpoli, Ruth M. Pfeiffer, Kimberly A. Bertrand, Dezheng Huo, Kathryn L. Lunetta, Julie R. Palmer","doi":"10.1186/s13058-023-01748-8","DOIUrl":"https://doi.org/10.1186/s13058-023-01748-8","url":null,"abstract":"Previous work in European ancestry populations has shown that adding a polygenic risk score (PRS) to breast cancer risk prediction models based on epidemiologic factors results in better discriminatory performance as measured by the AUC (area under the curve). Following publication of the first PRS to perform well in women of African ancestry (AA-PRS), we conducted an external validation of the AA-PRS and then evaluated the addition of the AA-PRS to a risk calculator for incident breast cancer in Black women based on epidemiologic factors (BWHS model). Data from the Black Women’s Health Study, an ongoing prospective cohort study of 59,000 US Black women followed by biennial questionnaire since 1995, were used to calculate AUCs and 95% confidence intervals (CIs) for discriminatory accuracy of the BWHS model, the AA-PRS alone, and a new model that combined them. Analyses were based on data from 922 women with invasive breast cancer and 1844 age-matched controls. AUCs were 0.577 (95% CI 0.556–0.598) for the BWHS model and 0.584 (95% CI 0.563–0.605) for the AA-PRS. For a model that combined estimates from the questionnaire-based BWHS model with the PRS, the AUC increased to 0.623 (95% CI 0.603–0.644). This combined model represents a step forward for personalized breast cancer preventive care for US Black women, as its performance metrics are similar to those from models in other populations. Use of this new model may mitigate exacerbation of breast cancer disparities if and when it becomes feasible to include a PRS in routine health care decision-making.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139077535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-02DOI: 10.1186/s13058-023-01758-6
Jinqiu Tao, Cailin Xue, Meng Cao, Jiahui Ye, Yulu Sun, Hao Chen, Yinan Guan, Wenjie Zhang, Weijie Zhang, Yongzhong Yao
Despite radiotherapy ability to significantly improve treatment outcomes and survival in triple-negative breast cancer (TNBC) patients, acquired resistance to radiotherapy poses a serious clinical challenge. Protein disulfide isomerase exists in endoplasmic reticulum and plays an important role in promoting protein folding and post-translational modification. However, little is known about the role of protein disulfide isomerase family member 4 (PDIA4) in TNBC, especially in the context of radiotherapy resistance. We detected the presence of PDIA4 in TNBC tissues and paracancerous tissues, then examined the proliferation and apoptosis of TNBC cells with/without radiotherapy. As part of the validation process, xenograft tumor mouse model was used. Mass spectrometry and western blot analysis were used to identify PDIA4-mediated molecular signaling pathway. Based on paired clinical specimens of TNBC patients, we found that PDIA4 expression was significantly higher in tumor tissues compared to adjacent normal tissues. In vitro, PDIA4 knockdown not only increased apoptosis of tumor cells with/without radiotherapy, but also decreased the ability of proliferation. In contrast, overexpression of PDIA4 induced the opposite effects on apoptosis and proliferation. According to Co-IP/MS results, PDIA4 prevented Tax1 binding protein 1 (TAX1BP1) degradation by binding to TAX1BP1, which inhibited c-Jun N-terminal kinase (JNK) activation. Moreover, PDIA4 knockdown suppressed tumor growth xenograft model in vivo, which was accompanied by an increase in apoptosis and promoted tumor growth inhibition after radiotherapy. The results of this study indicate that PDIA4 is an oncoprotein that promotes TNBC progression, and targeted therapy may represent a new and effective anti-tumor strategy, especially for patients with radiotherapy resistance.
{"title":"Protein disulfide isomerase family member 4 promotes triple-negative breast cancer tumorigenesis and radiotherapy resistance through JNK pathway","authors":"Jinqiu Tao, Cailin Xue, Meng Cao, Jiahui Ye, Yulu Sun, Hao Chen, Yinan Guan, Wenjie Zhang, Weijie Zhang, Yongzhong Yao","doi":"10.1186/s13058-023-01758-6","DOIUrl":"https://doi.org/10.1186/s13058-023-01758-6","url":null,"abstract":"Despite radiotherapy ability to significantly improve treatment outcomes and survival in triple-negative breast cancer (TNBC) patients, acquired resistance to radiotherapy poses a serious clinical challenge. Protein disulfide isomerase exists in endoplasmic reticulum and plays an important role in promoting protein folding and post-translational modification. However, little is known about the role of protein disulfide isomerase family member 4 (PDIA4) in TNBC, especially in the context of radiotherapy resistance. We detected the presence of PDIA4 in TNBC tissues and paracancerous tissues, then examined the proliferation and apoptosis of TNBC cells with/without radiotherapy. As part of the validation process, xenograft tumor mouse model was used. Mass spectrometry and western blot analysis were used to identify PDIA4-mediated molecular signaling pathway. Based on paired clinical specimens of TNBC patients, we found that PDIA4 expression was significantly higher in tumor tissues compared to adjacent normal tissues. In vitro, PDIA4 knockdown not only increased apoptosis of tumor cells with/without radiotherapy, but also decreased the ability of proliferation. In contrast, overexpression of PDIA4 induced the opposite effects on apoptosis and proliferation. According to Co-IP/MS results, PDIA4 prevented Tax1 binding protein 1 (TAX1BP1) degradation by binding to TAX1BP1, which inhibited c-Jun N-terminal kinase (JNK) activation. Moreover, PDIA4 knockdown suppressed tumor growth xenograft model in vivo, which was accompanied by an increase in apoptosis and promoted tumor growth inhibition after radiotherapy. The results of this study indicate that PDIA4 is an oncoprotein that promotes TNBC progression, and targeted therapy may represent a new and effective anti-tumor strategy, especially for patients with radiotherapy resistance.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139077531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-19DOI: 10.1186/s13058-023-01754-w
Yufan Guan, Jie Shen, Juan Lu, Bernard F. Fuemmeler, Lisa S. Shock, Hua Zhao
Allostatic load (AL) reflects the collective load of chronic stress during lifetime. Previous studies have shown that higher AL is associated with poor clinical outcomes among breast cancer patients. However, the relationship between AL and breast cancer risk is still unclear. To fill the gap, we analyzed the association between AL and the development of breast cancer in 181,455 women identified from the UK Biobank. During the follow-up from 2006 to 2020, 5,701 women were diagnosed with incident breast cancer. Significantly higher AL was observed among incident breast cancer cases than all study participants (mean: 2.77 vs. 2.63, P < 0.01). Univariate Cox regression analysis indicated the risk of breast cancer was increased by 5% per one AL unit increase (hazard ratio (HR) = 1.05, 95% confidence interval (CI) 1.04, 1.07). In multivariate analyses, after adjusting demographics, family history of breast cancer, reproductive factors, socioeconomic status, lifestyle factors, and breast cancer polygenic risk score (PRS), the significant association remained (HR = 1.05, 95%CI 1.03, 1.07). The significant relationship was further confirmed in the categorical analysis. Compared with women in the low AL group (AL: 0 ~ 2), those in the high AL group (AL: 3 ~ 11) had a 1.17-fold increased risk of breast cancer (HR = 1.17, 95%CI 1.11, 1.24). Finally, in the stratified analysis, joint effects on the risk of breast cancer were observed between the AL and selected known breast cancer risk factors, including age, family history of breast cancer, PRS, income, physical activity, and alcohol consumption. In summary, those findings have demonstrated that higher AL was associated with an increased breast cancer risk in women. This association is likely independent of known breast cancer risk factors. Thus, the AL could be a valuable biomarker to help breast cancer risk prediction and stratification.
静态负荷（AL）反映了人一生中慢性压力的集体负荷。以往的研究表明，AL 越高，乳腺癌患者的临床预后越差。然而，AL 与乳腺癌风险之间的关系仍不清楚。为了填补这一空白，我们分析了英国生物库中 181,455 名女性的 AL 与乳腺癌发病之间的关系。在 2006 年至 2020 年的随访期间，有 5701 名女性被诊断为乳腺癌。观察发现，乳腺癌病例中的AL值明显高于所有研究参与者（平均值：2.77 vs. 2.63，P < 0.01）。单变量 Cox 回归分析表明，AL 每增加一个单位，患乳腺癌的风险就会增加 5%（危险比 (HR) = 1.05，95% 置信区间 (CI) 1.04，1.07）。在多变量分析中，对人口统计学、乳腺癌家族史、生殖因素、社会经济地位、生活方式因素和乳腺癌多基因风险评分（PRS）进行调整后，仍存在显著关联（HR = 1.05，95%CI 1.03，1.07）。分类分析进一步证实了这一重要关系。与低 AL 组（AL：0 ~ 2）的妇女相比，高 AL 组（AL：3 ~ 11）的妇女罹患乳腺癌的风险增加了 1.17 倍（HR = 1.17，95%CI 1.11，1.24）。最后，在分层分析中，观察到 AL 与某些已知乳腺癌风险因素（包括年龄、乳腺癌家族史、PRS、收入、体力活动和饮酒量）之间对乳腺癌风险的共同影响。总之，这些研究结果表明，AL 值越高，女性患乳腺癌的风险越高。这种关联可能与已知的乳腺癌风险因素无关。因此，AL 可以作为一种有价值的生物标志物，帮助预测和分层乳腺癌风险。
{"title":"Association between allostatic load and breast cancer risk: a cohort study","authors":"Yufan Guan, Jie Shen, Juan Lu, Bernard F. Fuemmeler, Lisa S. Shock, Hua Zhao","doi":"10.1186/s13058-023-01754-w","DOIUrl":"https://doi.org/10.1186/s13058-023-01754-w","url":null,"abstract":"Allostatic load (AL) reflects the collective load of chronic stress during lifetime. Previous studies have shown that higher AL is associated with poor clinical outcomes among breast cancer patients. However, the relationship between AL and breast cancer risk is still unclear. To fill the gap, we analyzed the association between AL and the development of breast cancer in 181,455 women identified from the UK Biobank. During the follow-up from 2006 to 2020, 5,701 women were diagnosed with incident breast cancer. Significantly higher AL was observed among incident breast cancer cases than all study participants (mean: 2.77 vs. 2.63, P < 0.01). Univariate Cox regression analysis indicated the risk of breast cancer was increased by 5% per one AL unit increase (hazard ratio (HR) = 1.05, 95% confidence interval (CI) 1.04, 1.07). In multivariate analyses, after adjusting demographics, family history of breast cancer, reproductive factors, socioeconomic status, lifestyle factors, and breast cancer polygenic risk score (PRS), the significant association remained (HR = 1.05, 95%CI 1.03, 1.07). The significant relationship was further confirmed in the categorical analysis. Compared with women in the low AL group (AL: 0 ~ 2), those in the high AL group (AL: 3 ~ 11) had a 1.17-fold increased risk of breast cancer (HR = 1.17, 95%CI 1.11, 1.24). Finally, in the stratified analysis, joint effects on the risk of breast cancer were observed between the AL and selected known breast cancer risk factors, including age, family history of breast cancer, PRS, income, physical activity, and alcohol consumption. In summary, those findings have demonstrated that higher AL was associated with an increased breast cancer risk in women. This association is likely independent of known breast cancer risk factors. Thus, the AL could be a valuable biomarker to help breast cancer risk prediction and stratification.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138745555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-14DOI: 10.1186/s13058-023-01746-w
Jeongmin Seo, Jiwon Koh, Dae-Won Lee, Jinyong Kim, Han Suk Ryu, Kyung-Hun Lee, Tae-Yong Kim, Seock-Ah Im
The role of HER2 amplification level in predicting the effectiveness of HER2-directed therapies has been established. However, its association with survival outcomes in advanced HER2-positive breast cancer treated with dual HER2-blockade remains unexplored. This is a single-center retrospective study of patients with advanced HER2-positive breast cancer treated with first-line pertuzumab, trastuzumab, and docetaxel. The primary objective was to ascertain the relationship between treatment outcomes and the level of HER2 amplification by in situ hybridization (ISH). A total of 152 patients were included with a median follow-up duration of 50.0 months. Among the 78 patients who received ISH, a higher HER2/CEP17 ratio correlated significantly with longer PFS (HR 0.50, p = 0.022) and OS (HR 0.28, p = 0.014) when dichotomized by the median. A higher HER2 copy number also correlated significantly with better PFS (HR 0.35, p < 0.001) and OS (HR 0.27, p = 0.009). In multivariate analysis, the HER2/CEP17 ratio was an independent predictive factor for PFS (HR 0.66, p = 0.004) and potentially for OS (HR 0.64, p = 0.054), along with HER2 copy number (PFS HR 0.85, p = 0.004; OS HR 0.84, p = 0.049). Furthermore, the correlation between HER2 amplification level by ISH with PFS and OS was consistent across the HER2 IHC 1+/2+ and 3+ categories. This is the first study to report that a higher level of HER2 amplification by ISH is associated with improved PFS and OS in advanced HER2-positive breast cancer treated with dual HER2-blockade. Notably, HER2 amplification level had a predictive role regardless of IHC results. Even in patients with HER2 protein expression of 3+, treatment outcome to HER2-directed therapy was dependent on the level of HER2 gene amplification.
{"title":"HER2 amplification level by in situ hybridization predicts survival outcome in advanced HER2-positive breast cancer treated with pertuzumab, trastuzumab, and docetaxel regardless of HER2 IHC results","authors":"Jeongmin Seo, Jiwon Koh, Dae-Won Lee, Jinyong Kim, Han Suk Ryu, Kyung-Hun Lee, Tae-Yong Kim, Seock-Ah Im","doi":"10.1186/s13058-023-01746-w","DOIUrl":"https://doi.org/10.1186/s13058-023-01746-w","url":null,"abstract":"The role of HER2 amplification level in predicting the effectiveness of HER2-directed therapies has been established. However, its association with survival outcomes in advanced HER2-positive breast cancer treated with dual HER2-blockade remains unexplored. This is a single-center retrospective study of patients with advanced HER2-positive breast cancer treated with first-line pertuzumab, trastuzumab, and docetaxel. The primary objective was to ascertain the relationship between treatment outcomes and the level of HER2 amplification by in situ hybridization (ISH). A total of 152 patients were included with a median follow-up duration of 50.0 months. Among the 78 patients who received ISH, a higher HER2/CEP17 ratio correlated significantly with longer PFS (HR 0.50, p = 0.022) and OS (HR 0.28, p = 0.014) when dichotomized by the median. A higher HER2 copy number also correlated significantly with better PFS (HR 0.35, p < 0.001) and OS (HR 0.27, p = 0.009). In multivariate analysis, the HER2/CEP17 ratio was an independent predictive factor for PFS (HR 0.66, p = 0.004) and potentially for OS (HR 0.64, p = 0.054), along with HER2 copy number (PFS HR 0.85, p = 0.004; OS HR 0.84, p = 0.049). Furthermore, the correlation between HER2 amplification level by ISH with PFS and OS was consistent across the HER2 IHC 1+/2+ and 3+ categories. This is the first study to report that a higher level of HER2 amplification by ISH is associated with improved PFS and OS in advanced HER2-positive breast cancer treated with dual HER2-blockade. Notably, HER2 amplification level had a predictive role regardless of IHC results. Even in patients with HER2 protein expression of 3+, treatment outcome to HER2-directed therapy was dependent on the level of HER2 gene amplification.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138689498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The homologous recombination (HR) repair pathway for DNA damage, particularly the BRCA1 and BRCA2 genes, has become a target for cancer therapy, with poly ADP-ribose polymerase (PARP) inhibitors showing significant outcomes in treating germline BRCA1/2 (gBRCA1/2) mutated breast cancer. Recent studies suggest that some patients with somatic BRCA1/2 (sBRCA1/2) mutation or mutations in HR-related genes other than BRCA1/2 may benefit from PARP inhibitors as well, particularly those with PALB2 mutations. The current analysis aims to evaluate the prevalence of genetic alterations specific to BRCA1, BRCA2, and PALB2 in a large cohort of Taiwanese breast cancer patients through tumor-targeted sequencing. A total of 924 consecutive assays from 879 Taiwanese breast cancer patients underwent tumor-targeted sequencing (Thermo Fisher Oncomine Comprehensive Assay v3). We evaluated BRCA1, BRCA2, and PALB2 mutational profiles, with variants annotated and curated by the ClinVAR, the Oncomine™ Knowledgebase Reporter, and the OncoKB™. We also conducted reflex germline testing using either whole exome sequencing (WES) or whole genome sequencing (WGS), which is ongoing. Among the 879 patients analyzed (924 assays), 130 had positive mutations in BRCA1 (3.1%), BRCA2 (8.6%), and PALB2 (5.2%), with a total of 14.8% having genetic alterations. Co-occurrence was noted between BRCA1/BRCA2, BRCA1/PALB2, and BRCA2/PALB2 mutations. In BRCA1-mutated samples, only p.K654fs was observed in three patients, while other variants were observed no more than twice. For BRCA2, p.N372H was the most common (26 patients), followed by p.S2186fs, p.V2466A, and p.X159_splice (5 times each). For PALB2, p.I887fs was the most common mutation (30 patients). This study identified 176 amino acid changes; 60.2% (106) were not documented in either ClinVAR or the Oncomine™ Knowledgebase Reporter. Using the OncoKB™ for annotation, 171 (97.2%) were found to have clinical implications. For the result of reflex germline testing, three variants (BRCA1 c.1969_1970del, BRCA1 c.3629_3630del, BRCA2 c.8755-1G > C) were annotated as Pathogenic/Likely pathogenic (P/LP) variants by ClinVar and as likely loss-of-function or likely oncogenic by OncoKB; while one variant (PALB2 c.448C > T) was not found in ClinVar but was annotated as likely loss-of-function or likely oncogenic by OncoKB. Our study depicted the mutational patterns of BRCA1, BRCA2, and PALB2 in Taiwanese breast cancer patients through tumor-only sequencing. This highlights the growing importance of BRCA1/2 and PALB2 alterations in breast cancer susceptibility risk and the treatment of index patients. We also emphasized the need to meticulously annotate variants in cancer-driver genes as well as actionable mutations across multiple databases.
{"title":"Prevalence of BRCA1, BRCA2, and PALB2 genomic alterations among 924 Taiwanese breast cancer assays with tumor-only targeted sequencing: extended data analysis from the VGH-TAYLOR study","authors":"Han-Fang Cheng, Yi-Fang Tsai, Chun-Yu Liu, Chih-Yi Hsu, Pei-Ju Lien, Yen-Shu Lin, Ta-Chung Chao, Jiun-I. Lai, Chin-Jung Feng, Yen-Jen Chen, Bo-Fang Chen, Jen-Hwey Chiu, Ling-Ming Tseng, Chi-Cheng Huang","doi":"10.1186/s13058-023-01751-z","DOIUrl":"https://doi.org/10.1186/s13058-023-01751-z","url":null,"abstract":"The homologous recombination (HR) repair pathway for DNA damage, particularly the BRCA1 and BRCA2 genes, has become a target for cancer therapy, with poly ADP-ribose polymerase (PARP) inhibitors showing significant outcomes in treating germline BRCA1/2 (gBRCA1/2) mutated breast cancer. Recent studies suggest that some patients with somatic BRCA1/2 (sBRCA1/2) mutation or mutations in HR-related genes other than BRCA1/2 may benefit from PARP inhibitors as well, particularly those with PALB2 mutations. The current analysis aims to evaluate the prevalence of genetic alterations specific to BRCA1, BRCA2, and PALB2 in a large cohort of Taiwanese breast cancer patients through tumor-targeted sequencing. A total of 924 consecutive assays from 879 Taiwanese breast cancer patients underwent tumor-targeted sequencing (Thermo Fisher Oncomine Comprehensive Assay v3). We evaluated BRCA1, BRCA2, and PALB2 mutational profiles, with variants annotated and curated by the ClinVAR, the Oncomine™ Knowledgebase Reporter, and the OncoKB™. We also conducted reflex germline testing using either whole exome sequencing (WES) or whole genome sequencing (WGS), which is ongoing. Among the 879 patients analyzed (924 assays), 130 had positive mutations in BRCA1 (3.1%), BRCA2 (8.6%), and PALB2 (5.2%), with a total of 14.8% having genetic alterations. Co-occurrence was noted between BRCA1/BRCA2, BRCA1/PALB2, and BRCA2/PALB2 mutations. In BRCA1-mutated samples, only p.K654fs was observed in three patients, while other variants were observed no more than twice. For BRCA2, p.N372H was the most common (26 patients), followed by p.S2186fs, p.V2466A, and p.X159_splice (5 times each). For PALB2, p.I887fs was the most common mutation (30 patients). This study identified 176 amino acid changes; 60.2% (106) were not documented in either ClinVAR or the Oncomine™ Knowledgebase Reporter. Using the OncoKB™ for annotation, 171 (97.2%) were found to have clinical implications. For the result of reflex germline testing, three variants (BRCA1 c.1969_1970del, BRCA1 c.3629_3630del, BRCA2 c.8755-1G > C) were annotated as Pathogenic/Likely pathogenic (P/LP) variants by ClinVar and as likely loss-of-function or likely oncogenic by OncoKB; while one variant (PALB2 c.448C > T) was not found in ClinVar but was annotated as likely loss-of-function or likely oncogenic by OncoKB. Our study depicted the mutational patterns of BRCA1, BRCA2, and PALB2 in Taiwanese breast cancer patients through tumor-only sequencing. This highlights the growing importance of BRCA1/2 and PALB2 alterations in breast cancer susceptibility risk and the treatment of index patients. We also emphasized the need to meticulously annotate variants in cancer-driver genes as well as actionable mutations across multiple databases.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138689493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-14DOI: 10.1186/s13058-023-01750-0
Davut Dayan, Stefan Lukac, Brigitte Rack, Florian Ebner, Visnja Fink, Elena Leinert, Kristina Veselinovic, Sabine Schütze, Ziad El Taie, Wolfgang Janni, Thomas W. P. Friedl
Invasive lobular breast carcinomas (ILC) have different histological features compared to non-special type carcinomas (NST), but the effect of histological subtypes on survival is controversial. In this study, we compared clinicopathological characteristics and outcomes between ILC and NST based on a large pooled data set from three adjuvant breast cancer trials (SUCCESS A, B, and C) and investigated a potential differential effect of recurrence risk related to nodal stage on survival. From 2005 to 2017, the large randomized controlled SUCCESS A, B, and C trials enrolled 8190 patients with primary, intermediate-to-high-risk breast carcinoma. All patients received adjuvant chemotherapy, and endocrine and/or HER2-targeted treatment was given where appropriate. Survival outcomes in terms of disease-free survival (DFS), overall survival (OS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were estimated using the Kaplan–Meier method and analyzed using log-rank tests as well as univariable and adjusted multivariable Cox regression models. In the SUCCESS trials, 6284 patients had NST and 952 had ILC. The median follow-up time was 64 months. ILC patients were older, more likely to receive mastectomy, and more likely to have larger tumor sizes, lymph node infiltration, hormone receptor-positive, HER2neu-negative, and luminal A-like tumors than NST patients. In the overall cohort, no significant differences between ILC and NST were detectable regarding the four survival endpoints, with hazard ratios obtained in adjusted multivariable cox regressions of 0.96 (95% CI 0.77–1.21, p = 0.743) for DFS, 1.13 (95% CI 0.85–1.50, p = 0.414) for OS, 1.21 (95% CI 0.89–1.66, p = 0.229) for BCSS, and 0.95 (95% CI 0.73–1.24, p = 0.689) for DDFS. However, a differential effect of nodal stage on survival was observed, with better survival for ILC patients with pN0/pN1 tumors and worse survival for ILC patients with pN2/pN3 tumors compared to NST patients. Our results revealed that ILC was associated with worse survival compared to NST for patients at high risk of recurrence due to advanced lymph node infiltration. These findings should be taken into account for treatment decisions and monitoring.
浸润性小叶乳腺癌（ILC）与非特殊类型乳腺癌（NST）相比具有不同的组织学特征，但组织学亚型对生存期的影响尚存争议。在本研究中，我们基于三项乳腺癌辅助治疗试验（SUCCESS A、B和C）的大型汇总数据集，比较了ILC和NST的临床病理特征和预后，并研究了与结节分期相关的复发风险对生存率的潜在不同影响。从2005年到2017年，大型随机对照SUCCESS A、B和C试验共招募了8190名原发性中高危乳腺癌患者。所有患者均接受了辅助化疗，并酌情接受了内分泌和/或HER2靶向治疗。采用卡普兰-梅耶法估算了无病生存期（DFS）、总生存期（OS）、乳腺癌特异性生存期（BCSS）和远处无病生存期（DDFS）等生存结果，并使用对数秩检验以及单变量和调整后多变量考克斯回归模型进行了分析。在 SUCCESS 试验中，6284 名患者接受了 NST 治疗，952 名患者接受了 ILC 治疗。中位随访时间为 64 个月。与 NST 患者相比，ILC 患者年龄更大，更有可能接受乳房切除术，肿瘤体积更大、淋巴结浸润、激素受体阳性、HER2neu 阴性和管腔 A 型肿瘤的可能性更大。在总体队列中，ILC 和 NST 在四个生存终点方面没有发现显著差异，调整后的多变量 cox 回归得出的危险比为 0.96（95% CI 0.96）。96（95% CI 0.77-1.21，p = 0.743），OS 1.13（95% CI 0.85-1.50，p = 0.414），BCSS 1.21（95% CI 0.89-1.66，p = 0.229），DDFS 0.95（95% CI 0.73-1.24，p = 0.689）。然而，我们观察到结节分期对生存率的不同影响，与NST患者相比，pN0/pN1肿瘤的ILC患者生存率更高，而pN2/pN3肿瘤的ILC患者生存率更低。我们的研究结果表明，对于因晚期淋巴结浸润而复发风险较高的患者，ILC的生存率比NST低。这些发现应在治疗决策和监测中加以考虑。
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