Surgical issues surrounding use of aromatase inhibitors

Dixon, J. M.; Renshaw, Lorna; Murray, Juliette; Macaskill, E.J.; Young, Oliver; Miller, William R.

doi:10.1016/j.jsbmb.2005.04.024

Cited by 6 publications

(6 citation statements)

References 16 publications

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“…There are also limitations to the assessment of pathological response in that the pretreatment assessments (and some of the post-treatment) were performed on core biopsies, which are not guaranteed to be representative of the total tumour mass. It is also possible that assessment of ClinR/PathR at the single time point of 3 months is associated with chronological inaccuracy in that certain tumours classified as NR may go on to respond with extended treatment (Dixon et al, 2005). There is no doubt that response is not complete by 3 months and treatment up to 12 months may be associated with (a) further tumour shrinkage and (b) an increased incidence of complete ClinR.…”

Section: Discussionmentioning

confidence: 99%

Proliferation, steroid receptors and clinical/pathological response in breast cancer treated with letrozole

et al. 2006

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Sixty-three postmenopausal women with large primary breast cancers were treated with neoadjuvant letrozole (2.5 mg daily) for 3 months. Tumour samples were taken at diagnosis and after 10–14 days and 3 months treatment. Immunohistochemical staining for Ki67, oestrogen receptor (ER) and progesterone receptor (PgR) was performed and related to clinical (ClinR) and pathological responses (PathR) after 3 months treatment. ClinR was observed in 48 of 63 cases (76.2%) and PathR in 47 of 62 (75.8%). Pretreatment Ki67 scores were similar in responders (R) and non-responders (NR). Highly significant Ki67 decreases occurred in all tumour subgroups at 10–14 days ( P <0.005). A significant difference in Ki67 scores at 10–14 days ( P <0.007) was found between PathR and PathNR but not between ClinR and ClinNR. At 3 months, decreases from pretreatment Ki67 scores were highly significant in all tumour subgroups irrespective of response status. However, whereas Ki67 scores were significantly different between pathological R and NR ( P =0.009), the corresponding comparison of ClinR status was not. Significant decreases between 10–14 days and 3 months were found only in ClinR and PathR ( P =0.02 and 0.045, respectively). Treatment significantly reduced PgR expression at 14 days and 3 months (both P <0.0001), but the level of changes was not different between response status groups. In summary, letrozole produces rapid and profound decreases in expression of Ki67 and PgR but changes do not always correlate with clinical and pathological responses.

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Section: Discussionmentioning

confidence: 99%

Proliferation, steroid receptors and clinical/pathological response in breast cancer treated with letrozole

et al. 2006

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“…Unless a patient refuses surgery or is considered to have significant morbidities which limit surgical options or there is limited life expectancy, then following a satisfactory response to neoadjuvant letrozole therapy surgery should be performed followed by postoperative radiotherapy in appropriate patients. Treatment by neoadjuvant letrozole to allow breast conserving surgery is associated with good long-term disease control rates providing postoperative radiotherapy is given [28]. In patients who are not suitable for or who refuse surgery, neoadjuvant letrozole given for prolonged periods appears safe and appears to provide this small group of women with longterm disease control.…”

Section: Discussionmentioning

confidence: 99%

Increase in response rate by prolonged treatment with neoadjuvant letrozole

Dixon

Renshaw

Macaskill

et al. 2008

Breast Cancer Res Treat

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Purpose The aim of this study was to investigate the potential benefits of prolonged treatment with neoadjuvant letrozole. Patients and Methods About 182 consecutive patients have been treated in Edinburgh with neoadjuvant letrozole for 3 months or longer and 63 patients have continued on letrozole beyond 3 months. Outcomes are reported. Results Of the 63 patients who continued on letrozole, 38 patients took letrozole for more than 1 year and 23 took letrozole for more than 24 months. The median reduction in clinical volume in the first 3 months in these 63 patients was 52%. Similar reductions in median clinical volume were seen between three to 6 months (50%), 6-12 months and 12-24 months (medians 37 and 33%, respectively). At 3 months 69.8% of the 182 patients had a partial or complete response. The response rate increased to 83.5% with prolonged letrozole treatment. Continuing letrozole beyond 3 months increased the number of women who initially required mastectomy or had locally advanced breast cancer who were subsequently suitable for breast conserving surgery from 60% (81/134) at 3 months to 72% (96/134). Thirty-three women remain on letrozole alone (man age at diagnosis 83 years) and at 3 years the median time to treatment failure has not been reached. Conclusion Continuing letrozole in responding patients beyond 3-4 months achieves further clinical reduction in tumour size. For elderly women with a short life expectancy letrozole alone may provide long-term disease control.Keywords Breast conserving surgery Á Endocrine therapy Á Neoadjuvant Á Letrozole Á Large operable and locally advanced breast cancer

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“…Aromatase expression was found to be increased adjacent to tumors and in tumor-bearing breast quadrants [5,6]. These observations led to the development and clinical use of aromatase inhibitors (AI) [7][8][9][10]. These drugs not only target ER-mediated carcinogenesis, but also inhibit estrogen biosynthesis and may reduce the genotoxic effects of estrogen [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…Her-2/neu, a tyrosine kinase receptor belonging to the epidermal growth factor receptor (EGFR) family, is amplified in about 30% of advanced breast cancers [17]. Anti-estrogen drugs, such as tamoxifen, which are used in the treatment of ER-positive breast cancers, are ineffective in the treatment of Her-2/neupositive compared to Her-2/neu-negative malignancies [8]. Similarly, aromatase inhibitors (AIs), which block estrogen production, are effective in the treatment of ER-positive breast cancers, but exhibit reduced efficacy in Her-2/neupositive tumors.…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, aromatase inhibitors (AIs), which block estrogen production, are effective in the treatment of ER-positive breast cancers, but exhibit reduced efficacy in Her-2/neupositive tumors. Nonetheless, AIs are more effective in Her-2/neu-positive tumors that are positive for ER and/or progesterone receptor (PR) compared to Her-2/neu negative for these steroid receptors [8,18].…”

Section: Introductionmentioning

confidence: 99%

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Estrogen Receptor-beta Mediates the Protective Effects of Aromatase Induction in the MMTV-Her-2/neu x Aromatase Double Transgenic Mice

et al. 2011

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Breast cancers amplified for the tyrosine kinase receptor Her-2/neu constitute ~30% of advanced breast cancer cases, and are characterized by hormone independence and aggressive growth, implicating this pathway in breast oncogenesis. The induction of Her-2/neu leads to tumor development in 60% of transgenic mice. We have previously examined the effects of estrogen in the MMTV-Her-2/neu background by generating the MMTV-Her-2/neu x aromatase double transgenic mouse strain. MMTV-Her-2/neu x aromatase mice developed fewer mammary tumors than the Her-2/neu parental strain. Our present data show the induction of several estrogen-related genes, including the tumor suppressors BRCA1 and p53, and a decrease in several angiogenic factors. The phosphorylated forms of MAPK p42/44 and AKT were lower in the MMTV-Her-2/neu x aromatase double transgenic mice compared to the MMTV-Her-2/neu parental strain; conversely, phospho-p38 levels were higher in the double transgenic strain. The ERβ-selective antagonist THC reversed these changes. The regulation of these factors by ERβ was confirmed in clones of MCF7 breast cancer cells overexpressing Her-2/neu in combination with ERβ, suggesting that ERβ may play a direct role in regulating MAPK and AKT pathways. In summary, the data suggest that ERβ may play a major role in decreasing tumorigenesis and that it may affect breast cancer cell proliferation and survival by altering MAPK and AKT activation as well as modulation of tumor suppressor and angiogenesis factors. Treatment with selective ERβ agonist may provide therapeutic advantages for the treatment and prevention of breast cancer.

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Surgical issues surrounding use of aromatase inhibitors

Cited by 6 publications

References 16 publications

Proliferation, steroid receptors and clinical/pathological response in breast cancer treated with letrozole

Proliferation, steroid receptors and clinical/pathological response in breast cancer treated with letrozole

Increase in response rate by prolonged treatment with neoadjuvant letrozole

Estrogen Receptor-beta Mediates the Protective Effects of Aromatase Induction in the MMTV-Her-2/neu x Aromatase Double Transgenic Mice

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