Sequencing of Tamoxifen and Radiotherapy After Breast-Conserving Surgery in Early-Stage Breast Cancer

Pierce, Lori J.; Hutchins, Laura F.; Green, Stephanie R.; Lew, Danika; Gralow, Julie R.; Livingston, Robert B.; Osborne, C. Kent; Albain, Kathy S.

doi:10.1200/jco.2005.01.198

Cited by 109 publications

(46 citation statements)

References 19 publications

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“…The clinical significance of concurrent tamoxifen therapy in radiotherapyrelated toxicity is controversial. Several reports have shown an increased risk of pulmonary and breast fibrosis after concurrent treatment with tamoxifen therapy and radiotherapy (18,19), whereas other reports did not show any risk (20). Furthermore, an in vitro experimental study showed that the radiosensitivity of hormone-dependent breast cancer cells might be reduced through the cytostatic effect of tamoxifen (21).…”

Section: Discussionmentioning

confidence: 94%

IL12RB2 and ABCA1 Genes Are Associated with Susceptibility to Radiation Dermatitis

Isomura

Oya

Tachiiri

et al. 2008

Clinical Cancer Research

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Purpose: Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patientoriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patient's susceptibility to severe dermatitis. To elucidate genetic polymorphisms associated with a susceptibility to radiation-induced dermatitis, a large-scale single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients with breast cancer was conducted. Experimental Design: Patients were selected from more than 3,000 female patients with early breast cancer who received radiotherapy after undergoing breast-conserving surgery.The dermatitis group was defined as patients who developed dermatitis at a National Cancer Institute CommonToxicity Criteria grade of z2. For the SNP analysis, DNA samples from each patient were subjected to the genotyping of 3,144 SNPs covering 494 genes. Results: SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with radiationinduced dermatitis. In the ABCA1 gene, one of these SNPs was a nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using polymorphisms of both genes, the probability of severe dermatitis was estimated for each combination of genotypes. These analyses showed that individuals carrying a combination of genotypes accounting for 14.7% of the Japanese population have the highest probability of developing radiation-induced dermatitis. Conclusion: Our results shed light on the mechanisms responsible for radiation-induced dermatitis. These results may also contribute to the individualization of radiotherapy.Breast-conserving therapy, consisting of breast-conserving surgery and prophylactic breast irradiation, is the standard therapy for patients with early breast cancer. In most institutions, a total dose of 45 to 50 Gy is delivered to the whole breast with a daily fraction of 1.8 to 2 Gy; this dose fractionation is regarded to be effective and safe, considering both the excellent local control rate and the low probability of severe radiation-related toxicity (1).Mild acute radiation dermatitis is commonly observed during or shortly after the completion of radiotherapy. However, large interindividual variations in the severity of dermatitis exist even when the patients have been uniformly irradiated. Approximately 5% to 10% of patients develop moderate to severe acute radiation dermatitis following whole-breast radiotherapy (2, 3).Variations in the severity of radiation dermatitis are influenced by both treatment-related and patient-related

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Section: Discussionmentioning

confidence: 94%

IL12RB2 and ABCA1 Genes Are Associated with Susceptibility to Radiation Dermatitis

Isomura

Oya

Tachiiri

et al. 2008

Clinical Cancer Research

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“…The authors, however, encourage a randomized trial to validate this finding. 26 Anastrozole is at least as effective as tamoxifen as preoperative therapy for postmenopausal women with breast cancer, and is more effective than tamoxifen in certain clinically relevant subgroups. Anastrozole represents an effective preoperative endocrine treatment option for postmenopausal patients with hormoneresponsive breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor‐positive breast cancer

Cataliotti

Buzdar

Noguchi

et al. 2006

Cancer

316

191

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Although oxytocin (OT) and oxytocin receptor (OTR) are known for roles in parturition and milk let‐down, they are not hypothalamus‐restricted. OT is important in nurturing and opposition to stress. Transcripts encoding OT and OTR have been reported in adult human gut, and OT affects intestinal motility. We tested the hypotheses that OT is endogenous to the enteric nervous system (ENS) and that OTR signaling may participate in enteric neurophysiology. Reverse transcriptase polymerase chain reaction confirmed OT and OTR transcripts in adult mouse and rat gut and in precursors of enteric neurons immunoselected from fetal rats. Enteric OT and OTR expression continued through adulthood but was developmentally regulated, peaking at postnatal day 7. Coincidence of the immunoreactivities of OTR and the neural marker Hu was 100% in the P3 and 71% in the adult myenteric plexus, when submucosal neurons were also OTR‐immunoreactive. Co‐localization with NeuN established that intrinsic primary afferent neurons are OTR‐expressing. Because OTR transcripts and protein were detected in the nodose ganglia, OT signaling might also affect extrinsic primary afferent neurons. Although OT immunoreactivity was found only in ∼1% of myenteric neurons, extensive OT‐immunoreactive varicosities surrounded many others. Villus enterocytes were OTR‐immunoreactive through postnatal day 17; however, by postnatal day 19, immunoreactivity waned to become restricted to crypts and concentrated at crypt‐villus junctions. Immunoelectron microscopy revealed plasmalemmal OTR at enterocyte adherens junctions. We suggest that OT and OTR signaling might be important in ENS development and function and might play roles in visceral sensory perception and neural modulation of epithelial biology. J. Comp. Neurol. 512:256–270, 2009. © 2008 Wiley‐Liss, Inc.

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“…Although some experimental data suggest that tamoxifen might decrease radiation sensitivity of breast cancer cells in vitro, clinical data do not substantiate this observation [63,64]. Moderately increased risks for late pulmonary damage and subcutaneous fibrosis have been reported at least for subsets of patients [65,66].…”

Section: Adjuvant Endocrine Treatmentmentioning

confidence: 85%

Radiooncological Aspects Regarding Multimodal Primary Treatment of Breast Cancer – a Review

2006

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Locoregional percutaneous radiation therapy (RT) is an integral part of a multimodal curative therapeutic concept in non-invasive and locally-limited invasive breast cancer. Large prospective randomized clinical trials and recent meta-analyses have demonstrated that RT is a major independent prognostic factor with a positive influence on local and locoregional tumor control after mastectomy and after breast-conserving surgery (BCS). RT improves local and locoregional control, independent of systemic antineoplastic therapy. Local recurrence rate is reduced by two thirds, the overall long-term reduction of local recurrence measures >20%. Rate of survival and quality of life are improved by this increased rate of tumor control. Depending upon the primary stage and related to an interval of 20 years, significant improvements achieved by RT range between 5-10%. After breast-conserving surgery, RT improves the prognosis, and long-term results are equal to those after mastectomy. Application of a total dose of 50-50.4 Gy in 1.8-2.0 Gy fractions, 5 times per week, is the considered standard therapy for irradiation of whole breast after BCS, chest wall or locoregional lymphatics, respectively. Delivery of fewer, larger fractions, reduction of target volume for RT after BCS as well as different intra- and postoperative radiation techniques (brachytherapy, electron beams and others) or more precise definition of patients who might benefit from different locoregional lymph node irradiation are currently in the focus of radiooncological investigations regarding primary treatment of breast cancer patients. Current topics concerning the application of RT are possible interactions with potentially cardiotoxic systemically administered antineoplastic drugs, questions of sequence of therapies thereby as well as the combination with oncoplastic surgery. These aspects and further developments in RT of breast cancer will be described in detail in this article.

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Sequencing of Tamoxifen and Radiotherapy After Breast-Conserving Surgery in Early-Stage Breast Cancer

Abstract: The current analysis does not suggest an adverse effect on local or systemic control with CONC versus SEQ TAM and RT in node-negative breast cancer. A randomized trial is encouraged to validate these results.

Cited by 109 publications

References 19 publications

IL12RB2 and ABCA1 Genes Are Associated with Susceptibility to Radiation Dermatitis

IL12RB2 and ABCA1 Genes Are Associated with Susceptibility to Radiation Dermatitis

Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor‐positive breast cancer

Radiooncological Aspects Regarding Multimodal Primary Treatment of Breast Cancer – a Review

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