Cytotoxic agents with activity in breast cancer patients previously exposed to anthracyclines: Current status and future prospects

Tamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate.

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Weight Loss in Breast Cancer Patient Management

Journal of Clinical Oncology ◽

10.1200/jco.2002.20.4.1128 ◽

2002 ◽

Vol 20 (4) ◽

pp. 1128-1143 ◽

Cited By ~ 205

Author(s):

Rowan T. Chlebowski ◽

Erin Aiello ◽

Anne McTiernan

Keyword(s):

Breast Cancer ◽

Weight Loss ◽

Clinical Outcome ◽

Cancer Patients ◽

Clinical Care ◽

Current Status ◽

Current Evidence ◽

Dietary Therapy ◽

Breast Cancer Patients ◽

Breast Cancer Outcome

PURPOSE: To systematically review and summarize evidence relevant to obesity and breast cancer clinical outcome, potential hormonal mediating mechanisms, and the current status of weight loss interventions for chronic disease management. METHODS: A comprehensive, formal literature review was conducted to identify 5,687 citations with key information from 159 references summarized in text and tables. This process included a search for all breast cancer studies exploring associations among survival or recurrence and obesity at diagnosis or weight gain after diagnosis using prospective criteria. RESULTS: On the basis of observational studies, women with breast cancer who are overweight or gain weight after diagnosis are found to be at greater risk for breast cancer recurrence and death compared with lighter women. Obesity is also associated with hormonal profiles likely to stimulate breast cancer growth. Recently, use of weight loss algorithms proven successful in other clinical settings that incorporate dietary therapy, physical activity, and ongoing behavior therapy have been endorsed by the National Institutes of Health and other health agencies. CONCLUSION: Although definitive weight loss intervention trials in breast cancer patients remain to be conducted, the current evidence relating increased body weight to adverse breast cancer outcome and the documented favorable effects of weight loss on clinical outcome in other comorbid conditions support consideration of programs for weight loss in breast cancer patients. Recommendations for the clinical care of overweight or obese breast cancer patients are offered.

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Current status of demoralization and its relationship with medical coping style, self-efficacy and perceived social support in Chinese breast cancer patients

The European Journal of Psychiatry ◽

10.1016/j.ejpsy.2020.06.007 ◽

2020 ◽

Vol 34 (4) ◽

pp. 211-218

Author(s):

J. Li ◽

X. Liu ◽

L. Xu ◽

Z. Jin

Keyword(s):

Breast Cancer ◽

Social Support ◽

Cancer Patients ◽

Self Efficacy ◽

Coping Style ◽

Perceived Social Support ◽

Current Status ◽

Breast Cancer Patients

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Cognitive impairment after cytotoxic chemotherapy

Neuro-Oncology Practice ◽

10.1093/nop/npz052 ◽

2019 ◽

Vol 7 (1) ◽

pp. 11-21 ◽

Cited By ~ 2

Author(s):

Petra Huehnchen ◽

Antonia van Kampen ◽

Wolfgang Boehmerle ◽

Matthias Endres

Keyword(s):

Breast Cancer ◽

Colon Cancer ◽

Cognitive Impairment ◽

Cancer Patients ◽

Cytotoxic Chemotherapy ◽

Cytotoxic Drugs ◽

Cytotoxic Agents ◽

Cancer Type ◽

Breast Cancer Patients ◽

The Impact

Abstract Background Neurotoxicity is a frequent side effect of cytotoxic chemotherapy and affects a large number of patients. Despite the high medical need, few research efforts have addressed the impact of cytotoxic agents on cognition (ie, postchemotherapy cognitive impairment; PCCI). One unsolved question is whether individual cytotoxic drugs have differential effects on cognition. We thus examine the current state of research regarding PCCI. Neurological symptoms after targeted therapies and immunotherapies are not part of this review. Methods A literature search was conducted in the PubMed database, and 1215 articles were reviewed for predefined inclusion and exclusion criteria. Thirty articles were included in the systematic review. Results Twenty-five of the included studies report significant cognitive impairment. Of these, 21 studies investigated patients with breast cancer. Patients mainly received combinations of 5-fluorouracil, epirubicin, cyclophosphamide, doxorubicin, and taxanes (FEC/FEC-T). Five studies found no significant cognitive impairment in chemotherapy patients. Of these, 2 studies investigated patients with colon cancer receiving 5-fluorouracil and oxaliplatin (FOLFOX). Independent risk factors for PCCI were patient age, mood alterations, cognitive reserve, and the presence of apolipoprotein E e4 alleles. Conclusions There is evidence that certain chemotherapy regimens cause PCCI more frequently than others as evidenced by 21 out of 23 studies in breast cancer patients (mainly FEC-T), whereas 2 out of 3 studies with colon cancer patients (FOLFOX) did not observe significant changes. Further studies are needed defining patient cohorts by treatment protocol in addition to cancer type to elucidate the effects of individual cytotoxic drugs on cognitive functions.

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Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review

Breast Care ◽

10.1159/000467387 ◽

2017 ◽

Vol 12 (3) ◽

pp. 168-171 ◽

Cited By ~ 12

Author(s):

Elena Laakmann ◽

Volkmar Müller ◽

Marcus Schmidt ◽

Isabell Witzel

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Cancer Patients ◽

Systemic Treatment ◽

Treatment Options ◽

Cytotoxic Agents ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Background: The incidence of brain metastases (BM) in breast cancer patients has increased. Many retrospective analyses have shown that first-line treatment with trastuzumab prolongs survival in patients with HER2-positive BM. In contrast, the evidence for other therapies targeting HER2 for patients with BM is rare. Methods: The aim of this review is to update the reader about current systemic treatment options in patients with HER2-positive metastatic breast cancer with BM who had already received trastuzumab. A literature search was performed in the PubMed database in June 2016. 30 relevant reports concerning the efficacy of trastuzumab emtansine (T-DM1), lapatinib and its combination with other cytotoxic agents, pertuzumab and novel HER2-targeting substances were identified. Results: There is limited but promising evidence for the use of T-DM1 and pertuzumab in the treatment of BM. Up to now, most reported studies used lapatinib as treatment of HER2-positive breast cancer with BM, a treatment with only a modest effect and a high toxicity profile. The combination of lapatinib with cytotoxic agents seems to result in better response rates. Conclusion: Further prospective investigations are needed to investigate the efficacy of the established and novel HER2-targeting agents on BM in HER2-positive breast cancer patients.

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