A prospective study of aromatase inhibitor-associated musculoskeletal symptoms and abnormalities on serial high-resolution wrist ultrasonography

BACKGROUND: Nearly half of women treated with aromatase inhibitors (AI) develop AI-associated musculoskeletal symptoms (AIMSS) such as arthralgias, but to the authors' knowledge the etiology is unclear. The upper extremities are frequently affected, especially the wrists, hands, and fingers. AI use may also increase the risk of developing carpal tunnel syndrome. Tendon sheath fluid and tenosynovial changes have been demonstrated by imaging symptomatic patients who were treated with AIs. The authors hypothesized that these abnormalities are correlated with AIMSS. METHODS: Thirty consecutive patients in whom adjuvant therapy with letrozole or exemestane was initiated on a prospective clinical trial enrolled in a pilot study evaluating tendon and joint abnormalities at baseline and after 3 months of AI therapy. Patients underwent high-resolution ultrasonography of the wrists bilaterally and completed the Health Assessment Questionnaire (HAQ) and pain Visual Analog Scale (VAS). AIMSS were defined as an increase in the HAQ or VAS score during AI therapy that exceeded a predefined cutoff. RESULTS: Twenty-five patients completed both the baseline and 3-month assessments. During the first 12 months of AI therapy, 15 patients developed AIMSS, and 13 discontinued therapy because of musculoskeletal symptoms. There was a trend toward an association between the presence of tendon sheath abnormalities on wrist ultrasound at baseline and the development of AIMSS ( P = .06). CONCLUSIONS: Clinically relevant musculoskeletal symptoms develop in women treated with AIs, leading to treatment discontinuation in a substantial percentage of these patients. However, in the current study, patient-reported symptoms were not found to be associated with changes visible on wrist ultrasonography. Cancer 2010. © 2010 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78068/1/25385_ftp.pd

Treatment of Breast Cancer in Countries with Limited Resources

Early and accurate diagnosis of breast cancer is important for optimizing treatment. Local treatment of early stage breast cancer involves either mastectomy or breast-conserving surgery followed by whole-breast irradiation. The pathologic and biologic properties of a woman's breast cancer may be used to estimate her probability for recurrence of and death from breast cancer, as well as the magnitude of benefit she is likely to receive from adjuvant endocrine therapy or cytotoxic chemotherapy. Ovarian ablation or suppression with or without tamoxifen is an effective endocrine therapy in the adjuvant treatment of breast cancer in premenopausal women with estrogen receptor (ER)-positive or ER-unknown breast cancer. In postmenopausal women with ER- and/or progesterone receptor (PR)-positive or PR-unknown breast cancer, the use of tamoxifen or anastrozole is effective adjuvant endocrine therapy. The benefit of tamoxifen is additive to that of chemotherapy. Cytotoxic chemotherapy also improves recurrence rates and survival, with the magnitude of benefit decreasing with increasing age. Substantial support systems are required to optimally and safely use breast-conserving approaches to local therapy or cytotoxic chemotherapy as systemic therapy. Locally advanced breast cancer (LABC) accounts for at least half of all breast cancers in countries with limited resources and has a poor prognosis. Initial treatment of LABC with anthracycline-based chemotherapy is standard and effective. Addition of a sequential, neoadjuvant taxane thereafter increases the rate of pathologic complete responses. Neoadjuvant endocrine therapy may benefit postmenopausal women with hormone receptor-positive LABC. After an initial response to neoadjuvant chemotherapy, the use of local-regional surgery is appropriate. Most women will require a radical or modified radical mastectomy. In those women in whom mastectomy is not possible after neoadjuvant chemotherapy, the use of whole-breast and regional lymph node irradiation alone is appropriate. In those women who cannot receive neoadjuvant chemotherapy because of resource constraints, mastectomy with node dissection, when feasible, may still be considered in an attempt to achieve local-regional control. After local-regional therapy, most women should receive additional systemic chemotherapy. Women with LABC that has a positive or unknown hormone receptor status benefit from endocrine therapy with tamoxifen. The treatment of LABC requires multiple disciplines and is resource intensive. Efforts to reduce the number of breast cancers diagnosed at an advanced stage thus have the potential to improve rates of survival while decreasing the use of limited resources

Meta-analysis of trials comparing anastrozole and tamoxifen for adjuvant treatment of postmenopausal women with early breast cancer

<p>Abstract</p> <p>Objective</p> <p>It was aimed to review the literature and make a meta-analysis of the trials on both upfront, switching, and sequencing anastrozole in the adjuvant treatment of early breast cancer.</p> <p>Methods</p> <p>The PubMed, ClinicalTrials.gov and Cochrane databases were systematically reviewed for randomized-controlled trials comparing anastrozole with tamoxifen in the adjuvant treatment of early breast cancer.</p> <p>Results</p> <p>The combined hazard rate of 4 trials for event-free survival (EFS) was 0.77 (95%CI: 0.70–0.85) (<it>P </it>< 0.0001) for patients treated with anastrozole compared with tamoxifen. In the second analysis in which only ITA, ABCSG 8, and ARNO 95 trials were included and ATAC (upfront trial) was excluded, combined hazard rate for EFS was 0.64 (95%CI: 0.52–0.79) (<it>P </it>< 0.0001). In the third analysis including hazard rate for recurrence-free survival (excluding non-disease related deaths) of estrogen receptor-positive patients for ATAC trial and hazard rate for EFS of all patients for the rest of the trials, combined hazard rate was 0.73 (95%CI: 0.65–0.81) (<it>P </it>< 0.0001).</p> <p>Conclusion</p> <p>Anastrozole appears to have superior efficacy than tamoxifen in the adjuvant hormonal treatment of early breast cancer. Until further clinical evidence comes up, aromatase inhibitors should be the initial hormonal therapy in postmenopausal early breast cancer patients and switching should only be considered for patients who are currently receiving tamoxifen.</p

Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and

Five years of adjuvant tamoxifen has been the standard endocrine treatment for early-stage breast cancer for several decades. Adjuvant endocrine therapy following primary surgery for breast cancer reduces the risk of recurrence and increases overall survival beyond the period of treatment for women with estrogen receptor (ER) -positive disease ( 1 ). Mature meta-analysis data on 15-year recurrence and breast cancer mortality probabilities demonstrate substantial and persistent benefits of receiving adjuvant tamoxifen compared with no adjuvant treatment ( 1 ). Most of the effect of adjuvant tamoxifen on recurrence is seen during the first 5 years after surgery, when tamoxifen is generally still administered, with gains in recurrence-free survival of 11.4%. However, many women who are treated with 5 years of adjuvant tamoxifen still develop recurrent disease, and most of the effect of adjuvant tamoxifen on breast cancer mortality occurs after the fifth year after surgery

Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and

Five years of adjuvant tamoxifen has been the standard endocrine treatment for early-stage breast cancer for several decades. Adjuvant endocrine therapy following primary surgery for breast cancer reduces the risk of recurrence and increases overall survival beyond the period of treatment for women with estrogen receptor (ER) -positive disease ( 1 ). Mature meta-analysis data on 15-year recurrence and breast cancer mortality probabilities demonstrate substantial and persistent benefits of receiving adjuvant tamoxifen compared with no adjuvant treatment ( 1 ). Most of the effect of adjuvant tamoxifen on recurrence is seen during the first 5 years after surgery, when tamoxifen is generally still administered, with gains in recurrence-free survival of 11.4%. However, many women who are treated with 5 years of adjuvant tamoxifen still develop recurrent disease, and most of the effect of adjuvant tamoxifen on breast cancer mortality occurs after the fifth year after surgery

Minimizing early relapse and maximizing treatment outcomes in hormone-sensitive postmenopausal breast cancer: efficacy review of AI trials

Breast cancer is one of the leading causes of cancer-related deaths in women. Regardless of prognosis, all women with breast cancer are at risk for early recurrence. Nearly 50% of early recurrences occur within 5 years of surgery, and they peak at 2 years after surgery in women treated with adjuvant tamoxifen. Most early recurrences are distant metastases, which strongly correlate with increased mortality. Treatments that mitigate the risk of early distant metastases (DM) are, therefore, likely to improve overall survival in women with early breast cancer (EBC). Aromatase inhibitors (AIs)—anastrozole, letrozole, and exemestane—have been investigated as alternatives to tamoxifen for adjuvant treatment of hormone receptor-positive (HR+) EBC in postmenopausal women (PMW). AIs are better at minimizing risk of early relapse compared with tamoxifen. However, it is not clear if preferential use of AIs over tamoxifen will benefit all PMW with HR+ EBC. The ability to subtype HR+ breast cancer on the basis of biomarkers predictive of response to AIs and tamoxifen would likely be key to determining the most beneficial hormonal treatment within patient subpopulations, but this process requires thorough investigation. Until then, adjuvant therapies that provide the greatest reduction in risk of DM should be considered for all PMW with HR+ EBC. This article reviews the clinical trials of AI adjuvant therapies for hormone-sensitive breast cancer, particularly in the context of how they compare with tamoxifen in minimizing the risk of relapse, occurrence of DM, and breast cancer-related deaths

Intraoperative frozen section analysis for breast-conserving therapy in 1016 patients with breast cancer

Abstract Objective: We evaluate the number of surgical two-stage procedures after FSA during breast-conserving therapy (clinical false negative result of FSA) and investigate the influence of microcalcifications, small tumour diameter, neoadjuvant therapy and preoperative biopsy on the clinical false negative rate of FSA. Subjects: We retrospectively examined 1016 patients after intraoperative FSA during breast-conserving therapy for breast cancer operated between 1995 and 2001 at the Medical University Vienna. Results: Only 9% of all patients had to undergo a two-stage operation due to a false negative intraoperative FSA result. The annual local recurrence rate was 1.2% in all patients with no difference between one-and two-stage operated patients. In situ and pT1 lesions were similarly distributed between one-stage and two-stage operated patients. The use of neoadjuvant therapy and stereotactic biopsy (reflecting non-palpable lesions and microcalcifications) were significantly predictive for a false negative FSA result. The use of a preoperative core biopsy, however, reduced the necessity of performing a two-stage operation. Conclusion: Our study demonstrates that FSA leads to a low rate of two-stage operations. Small lesions and microcalcifications as well as the occurrence of intraductal cancer cells and neoadjuvant therapy increased while preoperative core biopsy reduced the false negative rate of FSA. Overall local recurrence rates after FSA were acceptable

Markers for the identification of late breast cancer recurrence

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited