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- Kornalijnslijper-Altena, Renske, et al.
(författare)
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PREDIX II HER2 : Improving pre-operative systemic therapy for human epidermal growth factor receptor 2 (HER2) amplified breast cancer (BC)
- 2020
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 38:15 Suppl.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neo-adjuvant systemic therapy (NAT) is the standard of care for most patients with early HER2-amplified and triple negative breast cancer (BC). Increasing the rate of pathological complete response (pCR) is highly meaningful for those patients, as pCR is strongly predictive for improved long-term disease-related outcomes. Clinical and preclinical evidence support the hypothesis that pCR-rates may be augmented by the addition of checkpoint inhibitors, such as monoclonal antibodies targeting the Programmed Death Ligand receptor 1 (PD-L1), to standard systemic NAT. Studies in different BC patient cohorts (e.g., IMPassion130, PANACEA, KATE2) have indicated that PD-L1 protein expression on tumor-infiltrating lymphocytes (TIL’s) is a predictive marker for checkpoint inhibitor efficacy.Methods: We have initiated a phase II open-label, 2:1 randomized clinical trial where women with early HER2-amplified, PD-L1+ BC (cT2-3 and/or cN+) are treated with standard NAT (composed of anti-HER2 antibodies with a chemotherapy backbone of sequentially taxanes + carboplatin and epirubicin + cyclophosphamide [EC]) +/- atezolizumab during EC. N = 190 patients will be accrued in nine centers in Sweden to be able to demonstrate a 20% increase in pCR-rate, with a power of 80% and a two-sided alpha of 10%. Firstly, a prescreening is performed to select patients with a PD-L1 expression of > 1% on TIL’s. Important exclusion criteria are significant organ dysfunction and (with some exceptions) active auto-immune diseases. Extensive translational side-studies are performed to explore predictive markers for treatment efficacy, including clinicopathologic studies, molecular imaging and microbiome analyses, as well as monitoring of acute and chronic treatment-related toxicity, objective cognitive function and quality of life. As of February 11th, 4 patients have been prescreened and 1 enrolled in the trial. The clinical trial registry number is NCT03894007.
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| 2. |
- Niemeyer Hultstrand, Jenny, et al.
(författare)
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Hormonal contraception and risk of breast cancer and breast cancer in situ among Swedish women 15-34 years of age : A nationwide register-based study
- 2022
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence on a possible association between newer hormonal contraceptives (HC) and risk of breast cancer remains inconclusive, especially as concerns progestogen-only methods.Methods: In this nationwide prospective cohort study, all Swedish women aged 15-34 at study start on January 1st 2005, or who turned 15 years during the study period, were followed until December 31st 2017. Using information from seven National Registers, we assessed the risk ratio of developing breast cancer and breast cancer in situ in relation to different HC using Poisson regression. We adjusted the analyses for several known confounders of breast cancer.Findings: This cohort included 1.5 million women providing more than 14 million person-years. During the study period, 3842 women were diagnosed with breast cancer. Compared with never users of any HC, we found no increased risk of developing breast cancer among current users of any combined HC, IRR 1.03 (0.91-1.16), whereas current users of progestogen-only methods had an increased risk of developing breast cancer, IRR 1.32 (1.20-1.45). Across all types of HC, the risk of developing breast cancer appeared to be highest the first five years of use (combined HC IRR 1.39 (1.14-1.69); progestogen-only methods IRR 1.74 (1.44-2.10). The risk disappeared ten years after the women stopped using HC. The absolute risk of breast cancer per 100,000 women-years was 22.4 for never users, 10.9 for current users of combined HC, and 29.8 for current users of progestogen-only methods.Interpretation: Current use of progestogen-only methods is associated with a small increased risk of developing breast cancer, whereas we could only detect an increased risk among users of combined HC during the first five years of use. This may partly be explained by a selective prescription of progestogen-only methods to women with risk factors for breast cancer, like smoking or obesity. As the absolute risk of breast cancer was small, the many health benefits associated with HC must also be taken into account in contraceptive counselling.
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| 3. |
- Szilcz, Máté, et al.
(författare)
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Endocrine treatment near the end of life among older women with metastatic breast cancer : a nationwide cohort study
- 2023
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: The appropriate time to discontinue chemotherapy at the end of life has been widely discussed. In contrast, few studies have investigated the patterns of endocrine treatment near death. In this study, we aimed to investigate the end-of-life endocrine treatment patterns of older women with metastatic breast cancer and explore characteristics associated with treatment.Methods: A retrospective cohort study of all older women (age ≥65 years) with hormone receptor-positive breast cancer who died in Sweden, 2016 − 2020. We used routinely collected administrative and health data with national coverage. Treatment initiation was defined as dispensing during the last three months of life with a nine-month washout period, while continuation and discontinuation were assessed by previous use during the same period. We used log-binomial models to explore factors associated with the continuation and initiation of endocrine treatments.Results: We included 3098 deceased older women with hormone receptor-positive breast cancer (median age 78). Overall, endocrine treatment was continued by 39% and initiated by 5% and of women during their last three months of life, while 31% discontinued and 24% did not use endocrine treatment during their last year of life. Endocrine treatment continuation was more likely among older and less educated women, and among women who had multi-dose drug dispensing, chemotherapy, and CDK4/6 use. Only treatment-related factors were associated with treatment initiation.Conclusion: More than a third of women with metastatic breast cancer continue endocrine treatments potentially past the point of benefit, whereas late initiation is less frequent. Further research is warranted to determine whether our results reflect overtreatment at the end of life once patients’ preferences and survival prognosis are considered.
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