Influence of ABCB1 polymorphisms and docetaxel pharmacokinetics on pathological response to neoadjuvant chemotherapy in breast cancer patients.

We have previously reported an association between ABCB1 C3435T polymorphism and docetaxel pharmacokinetics in breast cancer patients. We therefore investigated whether these parameters could account for variations in pathological response. Five ABCB1 polymorphisms including C3435T polymorphism were analyzed in breast cancer patients receiving neoadjuvant chemotherapy with doxorubicin and docetaxel (n = 101). Pathological response was assessed using the Sataloff classification. Pharmacokinetic analysis was performed for the first course of docetaxel (n = 84). No significant association was found between ABCB1 polymorphisms or docetaxel pharmacokinetics and pathological complete response. C3435T genotype was an independent predictive factor of good response in breast (response >50 %, i.e., Sataloff T-A and T-B): OR: 4.6 (95 % CI: 1.3-16.1), p = 0.015, for TT patients versus CT and CC patients. Area under the plasma concentration-time curve (AUC) of docetaxel was the only independent predictive factor of the total absence of response in breast (Sataloff T-D): OR: 14.3, (95 % CI: 1.7-118), p = 0.015, for AUC of docetaxel <3,500 µg h/L versus ≥3,500 µg h/L. These results suggest that C3435T polymorphism and docetaxel exposure are involved in the response to neoadjuvant chemotherapy in breast cancer patients and may be useful to optimize individualized therapy.

Quality of life and impact of pain in women treated with aromatase inhibitors for breast cancer. A multicenter cohort study.

Women with hormone-dependent breast cancer are treated with aromatase inhibitors (AI) to slow disease progression by decreasing estrogen levels. However, AI have adverse effects, including pain, with potentially serious impact on quality of life (QOL) and treatment compliance. We evaluated quality of life during the first year of AI treatment, focusing particularly on the impact of pain. In a multicenter cohort study of 135 women with early-stage breast cancer, free of pain at the initiation of AI treatment, quality of life (by the EORTC QLQ-BR23), somatic and psychic symptoms, psychological characters, temperament and coping strategies were assessed at baseline and at each follow-up visit (1, 3, 6 and 12 months). The impact of treatment-induced pain on quality of life during follow-up was determined with repeated-measures regression models. These models were constructed to assess the effects of pain and pain type on quality of life during follow-up, taking into account predictors associated with quality of life at baseline. Prior ganglion resection, taxane treatment and chemotherapy, a high amplification score on the pain catastrophizing scale, and a high harm avoidance score on the personality questionnaire were associated with a significantly lower baseline QOL. Fifty-seven percent of women developed pain of five different types: upper or lower limb joint pain, diffuse pain, neuropathic pain, tendon pain and mixed pain. A significant decrease in QOL was noted in the women with pain, particularly for body image, sexual functioning and future perspectives. Moreover, the impact of pain on QOL depended on the type of pain experienced. In conclusion, women treated with aromatase inhibitors display changes in quality of life and the degree of change in quality of life depends mostly on the type of pain experienced. Oncologists and patients should be aware of painful adverse effects of AI and encouraged to provide or receive earlier and more appropriate management of these effects.

Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study.

UNLABELLED: Aromatase inhibitors (AIs) are the first-line treatment in women with breast cancer for total estrogen depletion. Half the treated women may develop pain, and this condition may therefore be seen as a clinical model of pain related to estrogen deprivation. In this prospective multicenter study, we classified AI-related pain syndromes and identified their predictors. A 1-year, prospective, multicenter cohort study, with 6 visits, was carried out on 135 women with early-stage breast cancer and no pain at the start of AI treatment. At initial assessment, we investigated clinical (demographic and psychosocial, cancer characteristics and treatment, sleep, quality of life), biological (sex hormones, vitamin D, bone biomarkers, oxidative stress, immunologic and inflammatory markers), environmental, and genetic (polymorphism for pain mechanisms) risk factors for pain. During 1 year of follow-up, 77 women (57%) developed pain, leading to AI discontinuation in 12 cases. Five pain syndromes were identified: joint pain (36%), diffuse pain (22%), tendinitis (22%), neuropathic pain (9%), and mixed pain (11%), which are mostly persistent (57%), with diffuse and joint pains the most intense. Risk factors for the development of pain included higher levels of anxiety and impaired quality of life at the initial assessment, whereas cancer characteristics, genetic background, inflammation, and immunologic and hormonal status at baseline were not significant predictors. PERSPECTIVE: This article presents a classification of AI-related pain syndromes induced by estrogen deprivation that were previously described as arthralgia, but not as neuropathic, diffuse, and mixed pain. This estrogen deprivation-related condition represents a clinical model of pain, and our study identified mostly psychological risk factors for pain development.

Prognostic factor analysis in advanced gastric cancer patients treated with hydroxyurea, leucovorin, 5-fluorouracil, and cisplatin (HLFP regimen).

This study was performed to determine the prognostic factors of 102 nonresectable locally advanced or metastatic gastric cancer patients prospectively treated with a multimodulation of 5-fluorouracil (5FU), hydroxyurea, leucovorin, and cisplatin. Response rate in 85 patients with measurable disease was 62.4% (95% confidence interval 51.9% to 72.9%). A weight increase (5% or more) was observed in 47% of patients, performance status improved in 70.6%, and symptoms disappeared in 69%. Median times for progression-free survival and overall survival were eight and 11 months, respectively. Liver metastases, more than two involved sites, and increased carcinoembryonic antigen (CEA) were found to be univariate adverse prognostic factors for survival. In a multivariate analysis, only the presence of liver metastasis was found to be an independent prognostic factor. Response rate and survival in patients with gastric linitis or diffuse forms were in the same range as in patients with intestinal forms of gastric adenocarcinoma.