| 1. |
- Girma Kebede, Betlehem, et al.
(author)
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Communicative challenges among physicians, patients, and family caregivers in cancer care: An exploratory qualitative study in Ethiopia
- 2020
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:3
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Journal article (peer-reviewed)abstract
- Background: Cancer is a growing concern in Ethiopia. Though communication is essential for the treatment process, few studies have looked at communication in Ethiopian cancer care. Due to the large number of patients and scarcity of resources, it is vital to understand how to manage consultations in order to effectively help as many patients as possible in this challenging work environment. Thus, research is needed to analyze and understand the communicative challenges experienced by physicians, patients, and family caregivers, in order to successfully handle patient care in practice. Objective We explore communication in Ethiopian cancer care and present the main challenges faced by physicians, patients, and family caregivers. Methods This explorative qualitative study was conducted at the Oncology Department of the Tikur Anbessa (Black Lion) Specialized Teaching Hospital (TASH) in Addis Ababa, Ethiopia. A triangulation of data collection methods was used: 91 audio-recorded, semi-structured interviews and 21 video-recordings of authentic interactions during hospital rounds. The aim was to obtain as complete a picture as possible of communication from the perspectives of physicians, patients, and family caregivers. The interviews were analyzed using thematic content analysis and the identified themes were supported by excerpts from the transcribed recordings. Results Eight themes emerged from the data. Workload and time pressure, in combination with restricted space for privacy, limited the possibilities for physicians to deliver detailed information and provide emotional support. Furthermore, patient literacy levels, in combination with no or little cancer awareness, financial problems, reliance on traditional and religious treatments, the stigma of cancer, and a fatalistic attitude, resulted in delays in patients seeking care and participating in positive health behaviors, and, subsequently, often resulted in an unwillingness to openly discuss problems with physicians and adhere to treatment. The study also illustrates the paramount role of family in physician-patient communication in Ethiopia. Though family caregivers provide a valuable interpreting support when patients have limited language skills, they can also prevent patients from sharing information with physicians. Another important finding is that family caregivers were often responsible for making decisions about treatment and avoided telling patients about a poor prognosis, believing that conveying bad news may upset them. All of these themes have important implications for the role of ethically acceptable communication in patient-centered care. Conclusions This study has identified a number of serious challenges for successful and ethically acceptable health communication in Ethiopian cancer care. The study contributes to our understanding of the complexity around the role of family, combined with patients’ dependency on family members for communication, support, and access to care, which creates particular ethical dilemmas for the medical staff. The questions raised by this study concern how to organize consultations to achieve patient-centered health communication, while maintaining a constructive alliance with the family and not jeopardizing the patient’s continued access to care. The integration of communication training for medical students in Ethiopia, with a focus on ethical guidelines for family-centered patient consultation suitable for these circumstances, would be an essential step.
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| 2. |
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| 3. |
- Aapro, Matti, et al.
(author)
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The MAGIC survey in hormone receptor positive (HR+), HER2-negative (HER2−) breast cancer: When might multigene assays be of value?
- 2017
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In: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 33, s. 191-199
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Journal article (peer-reviewed)abstract
- © 2017 Background A modest proportion of patients with early stage hormone receptor-positive (HR+), HER2-negative (HER2−) breast cancer benefit from adjuvant chemotherapy. Traditionally, treatment recommendations are based on clinical/pathologic criteria that are not predictive of chemotherapy benefit. Multigene assays provide prognostic and predictive information that can help to make more informed treatment decisions. The MAGIC survey evaluated international differences in treatment recommendations, how traditional parameters are used for making treatment choices, and for which patients treating physicians feel most uncertain about their decisions. Methods The MAGIC survey captured respondents' demographics, practice patterns, relevance of traditional parameters for treatment decisions, and use of or interest in using multigene assays. Using this information, a predictive model was created to simulate treatment recommendations for 672 patient profiles. Results The survey was completed by 911 respondents (879 clinicians, 32 pathologists) from 52 countries. Chemo-endocrine therapy was recommended more often than endocrine therapy alone, but there was substantial heterogeneity in treatment recommendations in 52% of the patient profiles; approximately every fourth physician provided a different treatment recommendation. The majority of physicians indicated they wanted to use multigene assays clinically. Lack of reimbursement/availability were the main reasons for non-usage. Conclusions The survey reveals substantial heterogeneity in treatment recommendations. Physicians have uncertainty in treatment recommendations in a high proportion of patients with intermediate risk features using traditional parameters. In HR+, HER2− patients with early disease the findings highlight the need for additional markers that are both prognostic and predictive of chemotherapy benefit that may support more-informed treatment decisions.
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| 4. |
- Abraha, Aynalem, et al.
(author)
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Breaking bad news in cancer care: preferences of patients, family caregivers and general public in Ethiopia
- 2021
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In: International Conference on Communication in Healthcare (ICCH) 2020 Part 2, 15-16 April, 2021.
-
Conference paper (other academic/artistic)abstract
- This study explores the preferences of cancer patients, family caregivers, and the general public regarding breaking bad news in an Ethiopian oncology setting. The research was conducted at Tikur Anbessa (Black Lion) Specialized Hospital. The sample consists of patients with a confirmed cancer diagnosis, their family caregivers, and representatives from the general public with 150 subjects per cohort. A comparative cross-sectional study design and a multivariable analysis were used. The patients would like to be informed, which contradicts the perceptions of family caregivers. This creates an ethical dilemma for staff in terms of how much they involve their patients in clinical decision-making. The patients also indicate that information not to be withheld from them. In contrast, the general public prefers information about poor life expectancy to be communicated to family only, which may reflect widespread public perception of cancer as a deadly disease. The findings indicate the complexity of communication concerning breaking bad news in oncology care in Ethiopia. It requires oncologists to probe patient attitudes before information disclosure in order to find a balance between involving patients in communication at the same time as keeping a constructive alliance with family caregivers.
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| 5. |
- Abraha Woldemariam, Aynalem, et al.
(author)
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Breaking Bad News in Cancer Care: Ethiopian Patients Want More Information Than What Family and the Public Want Them to Have.
- 2021
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In: JCO global oncology. - 2687-8941. ; 7, s. 1341-1348
-
Journal article (peer-reviewed)abstract
- This study explores the preferences of patients with cancer, family caregivers, and the general public regarding breaking bad news in an Ethiopian oncology setting.The study was conducted at Tikur Anbessa (Black Lion) Specialized Hospital. The sample consists of patients with a confirmed cancer diagnosis, their family caregivers, and representatives from the general public with 150 subjects per cohort. The study used a comparative cross-sectional design and multivariable data analysis.The patients would like to be informed, which contradicts the preferences of family caregivers. This creates an ethical dilemma for staff in terms of how much they involve their patients in clinical decision making. The patients also indicate that information should not be withheld from them. By contrast, the general public prefers information about poor life expectancy to be communicated to family only, which may reflect a widespread public perception of cancer as a deadly disease.The findings indicate the complexity of communication-related preferences concerning breaking bad news in oncology care in Ethiopia. It requires oncologists to probe patient attitudes before information disclosure to find a balance between involving patients in communication at the same time as keeping a constructive alliance with family caregivers.
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| 6. |
- Andersson, Anton E, et al.
(author)
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Delta NT-proBNP predicts cardiotoxicity in HER2-positive breast cancer patients treated with trastuzumab.
- 2021
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 60:4, s. 475-481
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Journal article (peer-reviewed)abstract
- Overall survival has improved significantly in patients with human epidermal growth receptor 2 (HER2)-positive breast cancer due to the use of the monoclonal antibody trastuzumab blocking HER2. However, patients may develop trastuzumab-induced cardiotoxicity (TIC) leading to congestive heart failure. Here we assessed whether analysing NT-proBNP and assessment of electrocardiography (ECG) could detect TIC during trastuzumab therapy.One hundred thirty-six patients undergoing adjuvant, neoadjuvant or palliative chemotherapy and HER2 blockade for HER2-positive breast cancer were prospectively assessed with echocardiography, ECG and N-terminal - pro hormone B-type natriuretic peptide (NT-proBNP) testing at baseline and at 6 and 12months of trastuzumab therapy. TIC was defined as a left ventricular ejection fraction (LVEF) of less than 50% and a decline from baseline of ≥10 units.Six patients developed TIC under 12months of trastuzumab therapy (incidence 4.4%). NT-proBNP increased from 198.8±64.0pg/ml to 678.7±132.4pg/ml (p<.05) in TIC patients. With a cut-off point of 276.5pg/ml for NTproBNP and increase in NT-proBNP by 75.8pg/ml from baseline the sensitivity was 100% and the specificity 95% to detect TIC. Compared with controls, TIC patients were older (68.3±1.1years and 56.2±1.4years, respectively; p<.01), had more often diabetes mellitus (OR = 63.5, 95% CI: 5.63-915, p<.01) and atrial fibrillation (OR = 12.3; 95% CI: 1.89-74.62; p<.05) and had lower baseline LVEF (57.1±1.4% and 61.4±0.3%, respectively; p<.001). Abnormal ECGs were common in patients developing TIC.Measuring changes in NTproBNP may be used to monitor patients for TIC under trastuzumab therapy. Patients with a cardiovascular risk profile are more at risk of developing TIC.
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| 7. |
- Berbyuk Lindström, Nataliya, 1978, et al.
(author)
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Person- and Family-Centeredness in Ethiopian Cancer Care: Improving Communication, Ethics, Decision Making and Health
- 2020
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In: JMIR Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 9:5
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cancer is a major burden in Ethiopia. The Oncology Department of Tikur Anbessa (Black Lion) Specialized Hospital (TASH) in Addis Ababa is the country's sole specialist unit for cancer care. With only a handful of oncologists, a lack of resources, and a huge patient load, the work is challenging, especially in terms of achieving effective and ethical patient consultations. Patients, usually accompanied by family members, often wait for a long time to receive medical attention and frequently depart without treatment. Handling consultations effectively is essential in order to help patients as much as possible within such limitations. OBJECTIVE: The project addresses three main aims: (1) to enhance and expand the understanding of communicative and associated ethical challenges in Ethiopian cancer care; (2) to enhance and expand the understanding of the implications and use of person- and family-centered solutions to address such communicative challenges in practice, and (3) to plan and evaluate interventions in this area. METHODS: This project develops and consolidates a research collaboration to better understand and mitigate the communicative challenges in Ethiopian cancer care, with a focus on the handling and sharing of decision making, and ethical tensions between patients, staff, and family. Using theoretical models from linguistics, health communication, and health care ethics, multiple sources of data will be analyzed. Data sources currently include semi-structured interviews with the Ethiopian staff, patients, and family caregivers (91), survey data on cancer awareness (150) and attitudes to breaking bad news (450), and video-recordings of medical consultations (45). In addition, we will also develop clinical and methodological solutions to formulate educational interventions. RESULTS: The project was awarded funding by the Swedish Research Council in December 2017 for the period 2018-2021. The research ethics board in Sweden and in Ethiopia approved the conduct of the project in May 2018. The results from the studies will be published in 2020 and 2021. CONCLUSIONS: The project is a first step towards producing unique and seminal knowledge for the specific context of Ethiopia in the area of physician-patient communication research and ethics. It contributes to an understanding of the complexity around the role of family and ethical challenges in relation to patient involvement and decision making in Ethiopia. Improved knowledge in this area can provide a fundamental model for ways to improve cancer care in many other low resource settings in Africa and the Middle East, which share central cultural prerequisites (such as a strong patriarchal family structure, combined with strong and devout religiosity). The project will also serve to develop greater understanding about current challenges in Western health systems associated with greater family and patient participation in decision making. In addition, the project will also contribute to improving the education of Ethiopian health professionals working in cancer care by developing a training program to help them better understand and respond to identified challenges associated with communication.
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| 8. |
- Chamalidou, Chaido, 1972, et al.
(author)
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Compliance to adjuvant endocrine therapy and survival in breast cancer patients
- 2023
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In: Cancer Treatment and Research Communications. - 2468-2942. ; 35
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Journal article (peer-reviewed)abstract
- Background: Data on compliance to adjuvant endocrine treatment (ET) is mainly reported from prospective clinical trials or from smaller retrospective cohorts without correlation to outcome. Aims: To determine compliance to adjuvant ET and the impact on survival in a population-based series of patients with early breast cancer (BC) advised ET. Patients and methods: 1090 consecutive patients with hormone receptor positive (HR+) stage I-III BC diagnosed from 1 January 1997 to 31 December 2003 from one health care region of Sweden were included. Data on tumour, type of ET, compliance, reason for termination and outcome were collected. Statistical analyses were calculated with patients in three groups. Results: 72 patients were excluded leaving 1018 patients with a HR+ stage I to III BC for analyses. The most common ET was tamoxifen (n = 751, 73.8%). At the last follow up (31 Dec 2019) with a median follow-up of 18 years (interquartile range 16–22) 228 (22.4%) patients had a relapse. 71.1% of the included patients were compliant to endocrine therapy. Older patients ≥74 years had lower compliance, 61% compared with 75% in the other age groups (≤50 years and 51–73 years) (p < 0001), other parameters including type of ET were not associated with compliance. Low compliance remained as an independent risk factor in multivariate analyses for lower relapse-free survival, HR=1.83, 95% Confidence Interval (CI) 1.52–2.19, p < 0.001 and for time to BC death, HR=2.69, 95%CI 1.82–3.98, p < 0.001. Conclusions: Patients compliant to adjuvant ET have an improved survival.
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| 9. |
- Chamalidou, Chaido, 1972, et al.
(author)
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Survival patterns of invasive lobular and invasive ductal breast cancer in a large population-based cohort with two decades of follow up
- 2021
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In: Breast. - : Churchill Livingstone. - 0960-9776 .- 1532-3080. ; 59, s. 294-300
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Journal article (peer-reviewed)abstract
- Background: Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial. Purpose: To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort. Material and methods: From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed. Results: ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC. Conclusions: During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 10. |
- Colleoni, M., et al.
(author)
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Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00
- 2016
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 34:28, s. 3400-9
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Journal article (peer-reviewed)abstract
- Purpose To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population. (C) 2016 by American Society of Clinical Oncology.
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| 11. |
- Eiermann, W, et al.
(author)
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Triple negative breast cancer: Proposals for a pragmatic definition and implications for patient management and trial design.
- 2012
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In: Breast. - : Elsevier BV. - 1532-3080. ; 21:1, s. 20-6
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Journal article (peer-reviewed)abstract
- In trials in triple negative breast cancer (TNBC), oestrogen and progesterone receptor negativity should be defined as<1% positive cells. Negativity is a ratio of <2 between Her2 gene copy number and centromere of chromosome 17 or a copy number of 4 or less. In routine practice, immunohistochemistry is acceptable given stringent quality assurance. Triple negativity emerging after neoadjuvant treatment differs from primary TN and such patients should not enter TNBC trials. Patients relapsing with TN metastases should be eligible even if their primary was positive. Rare TN subtypes such as apocrine, adenoid-cystic and low-grade metaplastic tumours should be excluded. TN and basal-like (BL) signatures overlap but are not equivalent. Since the significance of basal cytokeratin or EGFR overexpression is not known and we lack validated assays, these features should not be used to subclassify TN tumours. Tissue collection in trials is mandatory so the effect on outcome of different tumour phenotypes and BRCA mutation can be explored. No prospective studies have established that TN tumours have particular sensitivity or resistance to any specific chemotherapy agent or radiation. TNBC patients should be treated according to tumour and clinical characteristics.
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| 12. |
- Geyer, C. E., et al.
(author)
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Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer
- 2022
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 33:12, s. 1250-1268
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Journal article (peer-reviewed)abstract
- Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.
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| 13. |
- Janeva, Slavica, et al.
(author)
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Adjuvant chemotherapy and survival in women aged 70 years and older with triple-negative breast cancer: a Swedish population-based propensity score-matched analysis
- 2020
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In: The Lancet Healthy Longevity. - 2666-7568. ; 1:3
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Journal article (peer-reviewed)abstract
- Background: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer associated with poor survival, in which adjuvant systemic treatments are limited to chemotherapy. Due to competing mortality risks and comorbidities, older patients with TNBC are often undertreated with adjuvant chemotherapy, and clinical trials on this problem are scarce, despite a growing patient population. This study aimed to assess outcomes for patients aged 70 years and older with TNBC with or without chemotherapy in a national population-based registry, to provide information that can assist in treatment decisions for these patients. Methods: In this population-based registry study, data on all patients aged 70 years and older diagnosed with primary early TNBC (larger than 5 mm in diameter and without distant metastasis) and surgically treated between Jan 1, 2009, and Dec 31, 2016, were retrieved from the Swedish National Breast Cancer Register, the Swedish Patient Register, and the Swedish Cause of Death Register. Patients with incomplete data (on oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status, surgical procedure in the breast, or information about chemotherapy) were excluded. A propensity score-matched (PSM) model was used to examine the outcomes of adjuvant chemotherapy on 5-year breast cancer-specific survival (BCSS) and 5-year overall survival (OS), adjusted for age, tumour size, tumour grade, nodal status, and comorbidities. Findings: Of 1130 women eligible for analysis, 368 (32·6%) received adjuvant chemotherapy, 45 (4·0%) received neoadjuvant treatment, and 717 (63·5%) did not receive chemotherapy. 5-year BCSS was significantly improved in patients who received adjuvant chemotherapy (85% [95% CI 81–89]) compared with patients who did not receive chemotherapy (68% [64–72]; p<0·0001). A similar benefit was observed in 5-year OS (79% [95% CI 75–84] vs 49% [45–53]; p<0·0001). In our PSM analysis, 5-year BCSS in patients treated with adjuvant chemotherapy was 83% (95% CI 78–89), versus 73% (67–80; p=0·014) in patients not treated with chemotherapy. 5-year OS in patients treated with adjuvant chemotherapy was 75% (95% CI 69–82), versus 63% (57–71; p=0·029) in patients who did not receive chemotherapy. Interpretation: In this PSM registry analysis of surgically treated female patients aged 70 years and older with TNBC without distant metastasis, we identified a significant benefit both in 5-year BCSS and 5-year OS with adjuvant chemotherapy versus no chemotherapy, which persisted when adjusting for age and comorbidities. These results underline the importance of considering adjuvant chemotherapy in older patients. Funding: Knut and Alice Wallenberg Foundation, Assar Gabrielsson Foundation.
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| 14. |
- Johansson, Henrik J, et al.
(author)
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Proteomics profiling identify CAPS as a potential predictive marker of tamoxifen resistance in estrogen receptor positive breast cancer
- 2015
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In: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 12:1, s. 8-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Despite the success of tamoxifen since its introduction, about one-third of patients with estrogen (ER) and/or progesterone receptor (PgR) - positive breast cancer (BC) do not benefit from therapy. Here, we aim to identify molecular mechanisms and protein biomarkers involved in tamoxifen resistance.RESULTS: Using iTRAQ and Immobilized pH gradient-isoelectric focusing (IPG-IEF) mass spectrometry based proteomics we compared tumors from 12 patients with early relapses (<2 years) and 12 responsive to therapy (relapse-free > 7 years). A panel of 13 proteins (TCEAL4, AZGP1, S100A10, ALDH6A1, AHNAK, FBP1, S100A4, HSP90AB1, PDXK, GFPT1, RAB21, MX1, CAPS) from the 3101 identified proteins, potentially separate relapse from non-relapse BC patients. The proteins in the panel are involved in processes such as calcium (Ca(2+)) signaling, metabolism, epithelial mesenchymal transition (EMT), metastasis and invasion. Validation of the highest expressed proteins in the relapse group identify high tumor levels of CAPS as predictive of tamoxifen response in a patient cohort receiving tamoxifen as only adjuvant therapy.CONCLUSIONS: This data implicate CAPS in tamoxifen resistance and as a potential predictive marker.
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| 15. |
- Johansson, Henrik J., et al.
(author)
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Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer
- 2013
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In: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 4:3175
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Journal article (peer-reviewed)abstract
- About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen.
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| 16. |
- Johansson, Ida, et al.
(author)
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Molecular profiling of male breast cancer - lost in translation?
- 2014
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In: The international journal of biochemistry & cell biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 53, s. 526-35
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Research review (peer-reviewed)abstract
- Breast cancer is the most common cancer form in women and it has been extensively studied on the molecular level. Male breast cancer (MBC), on the other hand, is rare and has not been thoroughly investigated in terms of transcriptional profiles or genomic aberrations. Most of our understanding of MBC has therefore been extrapolated from knowledge of female breast cancer. Although differences in addition to similarities with female breast cancer have been reported, the same prognostic and predictive markers are used to determine optimal management strategies for both men and women diagnosed with breast cancer. This review is focused on prognosis for MBC patients, prognostic and predictive factors and molecular subgrouping; comparisons are made with female breast cancer. Information was collected from relevant literature on both male and female breast cancer from the MEDLINE database between 1992 and 2014. MBC is a heterogeneous disease, and on the molecular level many differences compared to female breast cancer have recently been revealed. Two distinct subgroups of MBC, luminal M1 and luminal M2, have been identified which differ from the well-established intrinsic subtypes of breast cancer in women. These novel subgroups of breast cancer therefore appear unique to MBC. Furthermore, several studies report inferior survival for men diagnosed with breast cancer compared to women. New promising prognostic biomarkers for MBC (e.g. NAT1) deserving further attention are reviewed. Further prospective studies aimed at validating the novel subgroups and recently proposed biomarkers for MBC are warranted to provide the basis for optimal patient management in this era of personalized medicine. This article is part of a Directed Issue entitled: Rare Cancers.
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| 17. |
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| 18. |
- Kimbung, Siker, et al.
(author)
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Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer
- 2016
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In: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 22:1, s. 146-157
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Journal article (peer-reviewed)abstract
- Purpose: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. Experimental Design: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. Results: Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by down-regulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Conclusions: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. (C)2015 AACR.
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| 19. |
- Klint, L., et al.
(author)
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Real world data on adjuvant treatment of older HER2-positive breast cancer patients – A single institution experience through 8 years
- 2021
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In: Cancer Treatment and Research Communications. - : Elsevier BV. - 2468-2942. ; 28
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Journal article (peer-reviewed)abstract
- Background: The large randomized trials on trastuzumab for primary breast cancer (BC) included few old patients. With exception of endocrine treatment, trials on adjuvant therapy for the old group specifically are scarce. Aims: To compare adjuvant treatment, recurrences and survival in old and older-old patients with primary HER2 positive BC. Material and methods: Patients ≥ 70 years with diagnose of primary HER2 positive BC from 2008 through 2015 were included in this retrospective non-randomized investigation. Standard clinical and biological data (age, surgery, tumor size, nodal status, histopathological grade, vascular invasion, expression of hormone receptors, recurrences and death) were extracted from patient's charts. Comparisons were performed according to age (old; 70–74 years vs older old; ≥ 75 years) and treatment with trastuzumab or not. Patients that initiated adjuvant trastuzumab but did not complete one year (n = 8) were included in the trastuzumab group in survival analyzes. Recurrence-free survival (RFS) and overall survival (OS) were calculated in uni- and multivariate analyses. Results: A total of 115 patients were registered, eleven patients had distant metastasis and seven were omitted from all treatment including primary surgery due to serious concomitant illness and a poor general condition leaving 97 patients for analysis. There were no differences between the groups (70–74; n = 40), (≥75; n = 57) in tumor size (p = 0.86), nodal status (p = 0.10), ER (p = 0.25), PgR (p = 1.0) or vascular invasion (p = 1.0). A lower proportion of patients ≥ 75 years received adjuvant trastuzumab (21% versus 70%, p < 0.001). Adjuvant trastuzumab improved RFS (p = 0.027) and OS (p = 0.002) in univariate analyses. The corresponding figures in multivariate analysis adjusted for tumor size, nodal status and grade were RFS (p = 0.0052) and OS (p = 0.0003) respectively. Brain was the most common site of distant metastasis (15% of patients at first recurrence). Conclusions: We show a large difference in delivered adjuvant treatment between old and older old patients with a small proportion of patients aged 75 years or more receiving HER2 directed therapy that resulted in a worse survival. The vast majority can complete the planned treatment. Our results indicate that brain metastases is common also among older patients. © 2021 The Authors
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| 20. |
- Kovács, Anikó, 1961, et al.
(author)
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Spousal Cancer: A Systematic Review and Case Report of a Metachronous Presentation of Breast Cancer in a Genetically Unrelated Couple
- 2017
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In: Clinics in Oncology. - 2474-1663. ; 2
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Research review (peer-reviewed)abstract
- We present a systematic review of the literature about spousal cancer, concerning the possible cancer aetiology of synchronous and metachronous, concordant and discordant cancer types in married couples. Synchronous and metachronous breast cancer in spouses are extremely rare. We present here a married couple whom were diagnosed with metachronous breast cancer, with a 10year delay in onset in the husband. This case of spousal breast cancer may represent a coincidental phenomenon, as breast cancer is quite uncommon in men. It has been postulated that exposure to viral, nutritional and environmental / contamination factors for extended periods of time might facilitate cancer development in the same organ in spouses. However, current cancer incidence rates among cohabitants are relatively low.
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| 21. |
- Linderholm, Barbro, 1959, et al.
(author)
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Identification of intermediate risk breast cancer patients with1-3 positive lymph nodes and excellent survival after tamoxifen as only systemic adjuvant therapy by use of markers of proliferation and apoptosis
- 2013
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In: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 22:5, s. 643-649
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Journal article (peer-reviewed)abstract
- Background: According to current guidelines, patients with primary breast cancer and 1-3 lymph node metastases will in general be offered adjuvant chemotherapy. less thanbrgreater than less thanbrgreater thanAim: Our objective was to investigate the relationship between markers of proliferation and apoptosis with survival for patients subjected to adjuvant tamoxifen solely. less thanbrgreater than less thanbrgreater thanMaterial and methods: Tumour cytosol samples from 409 consecutive patients with operable oestrogen receptor positive BC, stage I-III and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase-cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival analyses were performed according to levels of ccCK18 and SPF separately, as well as combined. less thanbrgreater than less thanbrgreater thanResults: A wide range of ccCK18 protein levels was found, median 9.97, range 0.0-87.3 pg/mu gDNA. Increasing SPFs were significantly associated with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p = 0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed. Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p = 0.038) and when divided into quartiles; DRFS (p andlt; 0.001) and BCS (p = 0.0012). A similar correlation was found in patients with 1-3 lymph node metastases; DRFS (p = 0.089) and BCS (p = 0.019). A Coxs proportional hazard model including age, tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR = 0.47 (0.22-0.98), p = 0.043), and BCS (HR = 0.39 (0.16-1.00), p = 0.049), respectively. less thanbrgreater than less thanbrgreater thanConclusion: By use of a proliferation index based on markers of proliferation and apoptosis, a group of patients with 1-3 lymph node metastases with good outcome following adjuvant tamoxifen was identified; this group could possibly be spared adjuvant chemotherapy.
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| 22. |
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| 23. |
- Linderholm, Barbro, 1959, et al.
(author)
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Vascular endothelial growth factor receptor 2 and downstream p38 mitogen-activated protein kinase are possible candidate markers of intrinsic resistance to adjuvant endocrine treatment in steroid receptor positive breast cancer.
- 2011
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In: Breast cancer research and treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 125:2, s. 457-65
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Journal article (peer-reviewed)abstract
- A cross talk between tyrosine kinase receptors and mitogen-activated protein kinases (MAPKs) is proposed as involved in endocrine resistance. We wanted to investigate intratumoral levels of vascular endothelial growth factor receptor 2 (VEGFR2) and p38 MAPK in relation to relapse-free (RFS) and breast cancer corrected survival (BCCS) after adjuvant endocrine treatment, mainly tamoxifen for 2 or 5 years. We also wanted to investigate these markers in relation to early and late recurrences. VEGFR2 (n = 381) and p38 (n = 174) were determined by enzyme-linked immuno-sorbent assays in tumor homogenates from primary BC diagnosed 1993-1996. Wide ranges of VEGFR2 and p38 proteins were found; median 0.72 pg/μg DNA (range 0.0-11.66), and 0.04 pg/μg DNA (range 0.0-6.79), respectively. Detectable levels of p38 were registered in 65% and classified positive. Higher VEGFR2 were correlated to higher VEGF (P = 0.005), p38 MAPK (P = 0.018), negative ER (P = 0.008), larger tumors (P = 0.001), histopathological grade III (P = 0.018), distant metastasis (P = 0.044), shorter RFS (P = 0.013), and shorter BCCS (P = 0.017). Expression of p38 was significantly correlated with negative PgR (P = 0.044) and with early relapses (P = 0.021), while no difference was seen during the later follow-up period (P = 0.73). Higher VEGFR2 had a significant negative impact on both early (P = 0.029) and later recurrences (P = 0.018), while VEGF only predicted later relapses (P = 0.037). Our preliminary results suggest higher intratumoral levels of VEGFR2 and p38 MAPK as candidate markers of intrinsic resistance for adjuvant endocrine therapy.
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| 24. |
- Margolin, Sara, et al.
(author)
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A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer.
- 2011
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:1, s. 35-41
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Journal article (peer-reviewed)abstract
- The aim of the study was to evaluate the feasibility of tailored and dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant breast cancer therapy. Material and methods. Patients with node-positive breast cancer received either four cycles of biweekly and tailored EC (epirubicin 38-60-75-90-105-120 mg/m(2), cyclophosphamide 450-600-900-1200 mg/m(2)) followed by four cycles of docetaxel (60-75-85-100 mg/m(2)) (arm A) or the same regimen with fixed doses (E(90)C(600) + 4 → T(75) + 4) (arm B) or docetaxel, doxorubicin and cyclophosphamide (T(75)A(50)C(500)) every three weeks for six cycles (arm C). All patients received G-CSF support and prophylactic ciprofloxacin. Results. One-hundred and twenty-four patients were randomised in the study. In the A, B and C arm, 17% 19% and 3% of the patients had one or more cycles delayed due to side-effects whereas 24%, 5% and 15% experienced a grade 3 infection or febrile neutropenia. After the introduction of an extra week between the EC and T parts in the A and B arms, grade 3 hand-foot-skin reactions were reduced from 5 to 0.2%. Twenty-nine percent (A and B) and 20% (C) of the patients were hospitalised due to side-effects. Discussion. Dose-dense and tailored EC/T can be given with manageable toxicity and is after adjustment presently studied in the phase III Panther trial.
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| 25. |
- Matikas, Alexios, et al.
(author)
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Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer
- 2018
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In: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 168:2, s. 349-355
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Journal article (peer-reviewed)abstract
- Although adjuvant polychemotherapy improves outcomes for early breast cancer, the significant variability in terms of pharmacokinetics results in differences in efficacy and both short and long-term toxicities. Retrospective studies support the use of dose tailoring according to the hematologic nadirs. The SBG 2004-1 trial was a randomized feasibility phase II study which assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC regimen (group C). Women aged 18-65 years, ECOG PS 0-1 with at least one positive axillary lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term toxicity have been previously published. Here, we report safety and efficacy data after 10 years of follow-up. A total of 124 patients were included in the study. After a median follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and 63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C, respectively. There were no cases of clinically diagnosed cardiotoxicity or hematologic malignancies. No patient was lost to follow-up. In this randomized phase II trial, tailored dose adjuvant chemotherapy was feasible, without an increased risk for long-term adverse events after a median follow-up of 10 years.
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