Letrozole reduces plasma E2 and E1S levels to a significantly greater extent than anastrozole in postmenopausal women taking AIs as part of their adjuvant therapy for hormone receptor-positive breast cancer.
Genes have been identified which either change markedly or consistently in breast cancer after 14 days treatment with letrozole. These are new important data in understanding letrozole's molecular mechanism of action in breast cancers.
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.
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
BackgroundThe majority of breast conserving surgery (BCS) is performed in younger women. There is little published information about the views of women aged over 70 regarding BCS. The aim of this study was to investigate the attitudes of this age group towards BCS, and factors which may influence their treatment decision-making.MethodsA questionnaire was sent to all patients who were aged 70 or over at the time they had breast cancer surgery in NHS Lanarkshire between 1999 and 2013. This detailed surgical options and recommendations, timing of decision making, treatment expectations, psychological and cosmetic concerns and other factors which may have influenced any decision made e.g. travel for radiotherapy and potential side effects.ResultsResponses were received from 339 patients, 192 of whom had a mastectomy with the remaining undergoing BCS. In the mastectomy group 18 % (35) would have preferred to have BCS had it been an option, with 40 % (76) of group being happy to take neoadjuvant endocrine therapy to try and facilitate this. However, only 14 % (26) of patients would have considered neoadjuvant chemotherapy with the same aim. Almost half (82) of the mastectomy patients said that the risk of local recurrence following BCS was a factor which influenced their decision.ConclusionBCS is something that patients aged over 70 are interested in considering in the same way as younger patients. More than a third of patients requiring mastectomy would be willing to take neoadjuvant endocrine therapy to attempt to downstage their tumour to facilitate BCS.
Ann R Coll Surg Engl 2010; 92: 569-572 569Approximately 36,000 cases of colorectal cancer (CRC) are diagnosed per year in the UK.1 It is the third most common form of cancer among both males and females, and the second most common cause of cancer mortality in the UK. Preoperative anaemia is well recognised in patients presenting with colorectal cancer, with recent series suggesting a prevalence of iron deficiency in 60% 2 and an associated anaemia in up to 38% 3 of new presentations. Pre-operative anaemia is recognised as a predictive factor for blood transfusion, 4,5 as well as a predictor of adverse outcomes in surgical patients. Carson et al. 6 demonstrated that overall mortality increases as the haemoglobin concentration decreases, with even mild anaemia conferring an increased death risk.As well as becoming an increasingly scarce commodity, allogeneic blood transfusion confers potential risks to the recipient including immunomodulation, transfusion reaction and disease transmission. Peri-operative blood transfusion with allogeneic blood is also suggested to increase the risk of postoperative infectious complications. 7,8 A recent meta-analysis of 36 studies supports the evidence that perioperative blood transfusion has a detrimental effect on the recurrence of curable colorectal cancers although a direct causal relationship cannot be proven. 9While the benefits of long-term ferrous sulphate supplementation on iron-deficiency anaemia are well established, it is not known if short-course supplementation (2-3 weeks) impacts significantly on pre-operative haemoglobin levels
International audienceALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-four patients were randomized to receive either 12 weeks of letrozole (2.5 mg; = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg; = 42) followed by 12 weeks of letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to tamoxifen ( = 38) or continued on anastrozole or letrozole. In the beginning of the study, 42 patients had taken tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior tamoxifen therapy resulted in a significantly lower mean baseline procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior tamoxifen had significantly greater increases than patients with no prior tamoxifen. Patients treated with 3 months of tamoxifen following 6 months of an AI showed a significant decrease in markers of bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time. Anastrozole and letrozole produce similar effects on bone metabolism and turnover. Stopping tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naïve patients. Patients given tamoxifen following AI therapy showed a decrease in markers of bone resorption
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