Side Effects of Adjuvant Treatment of Breast Cancer

Shapiro, Charles L.; Recht, Abram

doi:10.1056/nejm200106283442607

Cited by 610 publications

(412 citation statements)

References 108 publications

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“…Conventional chemotherapy is associated with undesirable and severe side effects (Shapiro and Recht, 2001). This favors a reduction of the dose of the chemotherapeutic agent to prevent the side effects without losing its effect as anti-cancer drug.…”

Section: Regulation Of Drug Response By Mdm4mentioning

confidence: 99%

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Role of Mdm4 in drug sensitivity of breast cancer cells

et al. 2010

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The p53 tumor suppressor protein is frequently mutated in human tumors. It is thought that the p53 pathway is indirectly impaired in the remaining tumors, for example by overexpression of its important regulators Mdm2 and Mdm4, making them attractive targets for the development of anti-cancer agents. Recent studies have suggested that Mdm4 levels determine the sensitivity of tumor cells for anti-cancer therapy. To investigate this possibility, we studied the drug sensitivity of several breast cancer cell lines containing wild-type p53, but expressing different Mdm4 levels. We show that endogenous Mdm4 levels can affect the sensitivity of breast cancer cells to anti-cancer agents, but in a cell line-dependent manner and depending on an intact apoptotic response. Furthermore, treatment with the non-genotoxic agent Nutlin-3 sensitizes cells for doxorubicin, showing that activation of p53 by targeting its regulators is an efficient strategy to decrease cell viability of breast cancer cells. These results confirm a function of Mdm4 in determining the efficacy of chemotherapeutic agents to induce apoptosis of cancer cells in a p53-dependent manner, although additional undetermined factors also influence the drug response. Targeting Mdm4 to sensitize tumor cells for chemotherapeutic drugs might be a strategy to effectively treat tumors harboring wild-type p53.

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Section: Regulation Of Drug Response By Mdm4mentioning

confidence: 99%

“…However, the use of genotoxic agents in chemotherapy is associated with undesirable and severe side effects (Shapiro and Recht, 2001). Other approaches aim at disrupting the binding between Mdm2 and p53 to facilitate wild-type p53 activities.…”

Section: Introductionmentioning

confidence: 99%

Role of Mdm4 in drug sensitivity of breast cancer cells

et al. 2010

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“…3 However, concern about possible side effects is an important issue, particularly when prescribing adjuvant or chemopreventive treatments to healthy 4 or possibly cured patients after surgery. Certain side effects of chemotherapy and hormone therapy are well recognized, 5 whereas ocular toxicity is less frequently described in reports from adjuvant treatment clinical trials and is probably underestimated. 6,7 Chemotherapy-induced ocular toxicity is fairly common and not easy to prevent.…”

Section: Resultsmentioning

confidence: 99%

“…Tamoxifen-related ocular toxicity is reported uncommonly, especially in randomized trials with conventional doses (20 -40 mg per day). 5,7,8,11 Data on ocular toxicity due to selective estrogen-receptor modulators (SERMs) other than tamoxifen are even more limited. 12,13 Randomized controlled trials may underestimate the problem if side effects are not specifically assessed with clinical or instrumental examination at scheduled times.…”

Section: Resultsmentioning

confidence: 99%

Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer

Giannì

Panzini

et al. 2005

Cancer

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BACKGROUND Others have reported ocular toxicity after adjuvant chemoendocrine therapy, but this study looked at ocular toxicity in similarly treated patients from large randomized clinical trials. METHODS Information was retrieved on incidence and timing of ocular toxicity from the International Breast Cancer Study Group (IBCSG) database of 4948 eligible patients randomized to receive tamoxifen or toremifene alone or in combination with chemotherapy (either concurrently or sequentially). Case reports of patients with ocular toxicity were evaluated to determine whether ocular toxicity occurred during chemotherapy and/or hormonal therapy. Additional information was obtained from participating institutions for patients in whom ocular toxicity occurred after chemotherapy but during administration of tamoxifen or toremifene. RESULTS Ocular toxicity was reported in 538 of 4948 (10.9%) patients during adjuvant treatment, mainly during chemotherapy. Forty‐five of 4948 (0.9%) patients had ocular toxicity during hormone therapy alone, but only 30 (0.6%) patients had ocular toxicity reported either without receiving any chemotherapy or beyond 3 months after completing chemotherapy and, thus, possibly related to tamoxifen or toremifene. In 3 cases, retinal alterations, without typical aspects of tamoxifen toxicity, were reported; 4 patients had cataract (2 bilateral), 12 impaired visual acuity, 10 ocular irritation, 1 optical neuritis, and the rest had other symptoms. CONCLUSION Ocular toxicity during adjuvant therapy is a common side effect mainly represented by irritative symptoms due to chemotherapy. By contrast, ocular toxicity during hormonal therapy is rare and does not appear to justify a regular program of ocular examination. However, patients should be informed of this rare side effect so that they may seek prompt ophthalmic evaluation for ocular complaints. Cancer 2006. © 2005 American Cancer Society.

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“…ER and PR positivity correlate with better survival and response to estrogen antagonists, such as tamoxifen. 35 Endocrine therapy is effective in approximately onethird of FBCs and up to 80% of tumors expressing both ER and PR. The vast majority of MBCs are hormone receptor positive (81% in previous studies, 71% in our series), and therefore tamoxifen has become a mainstay of therapy.…”

Section: Discussionmentioning

confidence: 99%

Frequent amplification and overexpression of CCND1 in male breast cancer

Bärlund

Kuukasjärvi

Syrjäkoski

et al. 2004

Intl Journal of Cancer

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Genetic events underlying the pathogenesis of breast cancer have been studied extensively and several clinically significant markers have been identified. For example, amplification and overexpression of the ERBB2 oncogene is associated with poor prognosis in breast cancer and ERBB2 serves as a target for antibody-based therapy. Current knowledge on the pathogenesis of male breast cancer (MBC) is limited. The purpose of our study was to investigate the potential relevance of a series of genes known to be amplified in female breast cancer (FBC) in a the development and pathogenesis of MBC. To this end, we applied fluorescence in situ hybridization and immunohistochemistry to the analysis of 128 breast tumors from males. Amplification of ERBB2, MYC, PPM1D and ZNF217 was detected rarely (1-2% of tumors) indicating a considerably lower amplification frequency than in FBC. CCND1 amplification was observed in 12% of cases, being in good concordance with findings from FBC. In addition, CCND1 overexpression was detected in 63% of tumors and was associated with ER positivity (p < 0.0001). Our results indicate distinct differences in the genetic basis of MBC and FBC and suggest that marked differences exist in the pathogenesis of these diseases. The lack of ERBB2 involvement was especially unexpected and implies that ERBB2-targeted therapies are unlikely to be beneficial in MBC. Furthermore, the high frequency of hormone receptor positivity and the association between ER positivity and CCND1 overexpression supports the notion that hormonal regulation is likely to be essential for the development of MBC. © 2004 Wiley-Liss, Inc. Key words: male breast cancer; gene amplification; CCND1; tissue microarrayMale breast cancer (MBC) is a rare disease, representing Ͻ1% of all breast cancers and Ͻ1% of all cancers in men. 1,2 All histological types of breast cancer have been identified in men, with infiltrating ductal carcinoma representing about 80% of cases. Similarly to FBC, hormonal, genetic, and environmental factors are involved in the etiology of MBC. 3 Conditions associated with increased estrogen or decreased androgen levels, such as Klinefelter syndrome and testicular disorders, predispose to MBC. 1 Particularly, the Klinefelter syndrome, characterized by 47,XXY karyotype, is associated with a 50-fold increase in breast cancer risk. 4 The genetic factor most clearly associated with MBC is BRCA2 germline mutation and its frequency in men with breast cancer varies considerably (4 -40%) depending on the population investigated. 3,5 Germline BRCA1 mutations are also found in male breast cancer patients. 5 The possible role and clinical utility of oncogene alterations have been widely investigated in FBC. The most extensively studied is the ERBB2 oncogene that belongs to the epidermal growth factor receptor family. ERBB2 is amplified and overexpressed in 10 -34% of FBC and has been shown to have prognostic and predictive value. 6 Targeted therapy against ERBB2 is currently undergoing clinical trials and shows potential benefit...

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Side Effects of Adjuvant Treatment of Breast Cancer

Cited by 610 publications

References 108 publications

Role of Mdm4 in drug sensitivity of breast cancer cells

Role of Mdm4 in drug sensitivity of breast cancer cells

Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer

Frequent amplification and overexpression of CCND1 in male breast cancer

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