Tamoxifen In Terms Research Articles

The need for DXA assessment of breast cancer patients following 5 years tamoxifen prior to starting an aromatase inhibitor.

Abstract Abstract #6141 Introduction: Aromatase inhibitors are increasingly being used in the adjuvant treatment of post-menopausal women with breast cancer. They are more effective than tamoxifen in terms of disease free survival and have a different side effect profile, all causing loss of bone mineral density. They can be introduced at different points in the adjuvant pathway. It has been postulated that if given in the extended setting, letrozole after 5 yrs tamoxifen, bone health may be less important. Tamoxifen is reported to increase bone mineral density so should make subsequent bone mineral density reduction with letrozole less significant. The aim of this study was to determine whether DXA scanning should be undertaken in women following 5 yrs of tamoxifen prior to starting letrozole.
 Method: 166 women who had completed 5 years of tamoxifen underwent DXA with assessment of vertebral morphometry and risk factors associated with osteoporosis and fracture rate.
 Results: Mean age was 63yrs (standard deviation [S.D] 10yrs); 154 women were post menopausal being at least 2 years after their last menstrual period; 12 women were unable to recall when they menopaused. Mean t-score and S.D was calculated at each site; spine -1.26(1.3); femoral neck -1.16(1.1) and total hip -0.91(1.1). Results were categorised by lowest t-score.
 
 Conclusion: We have demonstrated that of 166 women following completion of 5 yrs tamoxifen 26.5% have osteoporosis and 35.5% osteopenia. 28% required treatment with bisphosphonates. It cannot be assumed that Tamoxifen will cause a sufficient increase in BMD to render DXA scanning unnecessary. All patients should have DXA scanning following completion of 5 yrs tamoxifen prior to commencing letrozole. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6141.

Cost-effectiveness of anastrozole versus tamoxifen as adjuvant therapy in early breast cancer (EBC) – a German health economic analysis.

Abstract Abstract #6109 Background: The non-steroidal aromatase inhibitor (AI) anastrozole is superior to tamoxifen in terms of efficacy and safety in the adjuvant treatment of postmenopausal patients with hormone receptor-positive (HR+) early breast cancer (EBC). The aim of the current study was to evaluate the cost-effectiveness of anastrozole versus tamoxifen from the German health care perspective.
 Methods: A probabilistic Markov model was developed using data from the published literature and expert opinion to project trial outcomes to 25 years based on a cohort of 1000 postmenopausal women with HR+ EBC. Resource use data and costs were obtained from standard sources and expert opinion. Utility scores for the different heath states were obtained from a patient-based utility study using the standard gamble technique. Results were expressed as incremental cost-effectiveness ratios (ICERs) per quality adjusted life-years (QALYs) gained. Costs and benefits were discounted at 5% annually.
 Results: Total costs over the 25 year period for anastrozole and tamoxifen were €12,422 and €6,757, respectively. The cost per life year (LY) for anastrozole compared to tamoxifen was €24,822/LY gained. The ICER of anastrozole compared to tamoxifen was €21,050/QALY gained (95% CI €9,841 - €62,344). The result remained robust to all parameters tested in the sensitivity analysis. Cost-effectiveness probability curves indicated a >90% probability that the cost per QALY gained with anastrozole would be <€42,000.
 Conclusions: In this model, five years of adjuvant anastrozole is a cost-effective treatment alternative to tamoxifen in postmenopausal women with HR+ EBC from the German health care perspective. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6109.

HOXB13 protein expression predicts the benefit of tamoxifen treatment in breast cancer patients.

Abstract Abstract #6038 Background: The two-gene expression ratio HOXB13:IL17BR, originally from a microarray analysis, has been shown to be indicative of clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer, with a high ratio associated with decreased disease-free survival. Analysis of a cohort of breast cancer patients randomized to 2 or 5 years of adjuvant tamoxifen therapy showed that the two-gene ratio and expression of the HOXB13 gene alone were predictive of the benefit of prolonged tamoxifen treatment. Patients with tumors expressing HOXB13 at high levels were unresponsive to prolonged adjuvant treatment, suggesting that this gene is involved in tamoxifen resistance. It is suggested that a high two-gene ratio may indicate impaired ER signaling, which is known to predict resistance to tamoxifen. To our knowledge, there are no studies investigating the HOXB13 protein levels in breast cancer.
 Methods: We have analyzed the protein expression of HOXB13 with immunohistochemistry in tumor samples from 912 postmenopausal node negative breast cancer patients randomized to 2 years of tamoxifen or no endocrine treatment. After 2 years, recurrence-free patients were randomized to 3 more years of tamoxifen, or no further therapy. This selection enabled us to investigate the treatment predictive value of HOXB13.
 Results: Data on HOXB13 protein expression were obtained from 866 patients (see table). Tamoxifen treated patients with estrogen receptor (ER) positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival (hazard ratio (HR) 0.37, 95% CI 0.23-0.60, p=0.000048). However, for patients with a high or intermediate HOXB13 tumor expression, tamoxifen did not prolong the distant recurrence-free survival compared to the untreated patients (HR=0.83, 95% CI 0.45-1.54, p=0.55). The interaction between HOXB13 expression and benefit from tamoxifen was statistically significant (p=0.046). HOXB13 did not have any prognostic value among systemically untreated patients.
 
 Conclusions: HOXB13 protein level may be used as a predictive marker for tamoxifen treatment, but does not have any prognostic value. Patients with a high expression of HOXB13 do not seem to benefit from tamoxifen. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6038.

Breast Cancer Prevention in BRCA1/2 Mutation Carriers: A Qualitative Review

To the Editor: We recently qualitatively reviewed the literature on primary prevention strategies in BRCA 1 ⁄2 mutation carriers for chemoprevention and risk reduction surgery. The trials had to provide information on the effectiveness of primary prevention (bilateral mastectomy, bilateral salpingo-oophorectomy or tamoxifen) in terms of breast cancer risk reduction in BRCA 1 or 2 mutation carriers. This review focused on breast cancer incidence, total mortality and specific breast cancer mortality. The data from each study was descriptively summarized; a quantitative meta-analysis was not feasible in the absence of randomized controlled trials and with such heterogeneous study designs and insufficient data. Ten studies were retained. Six multi-center cohort studies evaluate the efficacy of bilateral prophylactic salpingo-oophorectomy (1‐6). They report a reduction of approximately 50% in the incidence of breast cancer and one trial reveals a mortality reduction after bilateral salpingo-oophorectomy. Three cohort studies evaluate the incidence of breast cancer after bilateral prophylactic mastectomy (7‐9). All of these studies report a significant reduction of more than 95% of the incidence of breast cancer in the BPM group. However these trials are of insufficient methodological quality and the data on the effectiveness of BPM on mortality is not available at present. One study evaluates the effectiveness of tamoxifen in healthy BRCA mutation carriers (10). This analysis shows a nonsignificant reduction of the incidence of breast cancer in BRCA 2 mutation carriers (RR: 0.38, 95% CI: 0.06‐1.56). However, this study did not highlight a reduction of the incidence of breast cancer in BRCA 1 mutation carriers (RR: 1.67, 95% CI: 0.32‐10.70). It is difficult to draw conclusions concerning the effectiveness of tamoxifen in BRCA mutation carriers given that the only study available is a (post hoc) analysis including too few cases. Primary prevention is a promising approach in the fight against breast cancer, especially for women at very high risk carrying BRCA mutations. More studies are necessary, especially to evaluate the effect of prevention on mortality.

Neo-Adjuvant Hormonal Therapy

Neo-adjuvant endocrine therapy has opened new alternatives for locally advanced breast cancer. Such therapy, which has permitted us to expand the treatment role of neo-adjuvant therapies, may be of great benefit to patient groups such as the elderly, those not suited for chemotherapy, and those whose response may not be optimal. This therapy also may be able to help us identify agents that could improve outcomes in the adjuvant setting as well as possible biologic predictors for outcome. The latest generation of endocrine therapy for breast cancer, aromatase inhibitors, has proved superior to tamoxifen in terms of toxicity and efficacy in the adjuvant setting and is currently being studied in other clinical trials. Current findings indicate that these agents are less toxic and better tolerated than neo-adjuvant chemotherapy and that third-generation anti-hormonal therapy offers improved tumor response compared with tamoxifen, which has resulted in increased breast conserving surgery. Biomarker findings of improved response in tumors that are both estrogen receptor positive and HER-2 positive as well as progesterone receptor positivity only will be important for planning future selective treatment and clinical trials.

Aromatase inhibitors in early breast-cancer treatment: The story so far

This paper describes the clinical evidence for using the aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, as adjuvant therapy for postmenopausal women with early breast cancer. Efficacy data for AIs are reviewed across different treatment strategies (initial, switched, sequenced or extended adjuvant therapy). Although trials are still ongoing, AIs have demonstrated superiority over tamoxifen in terms of disease-free survival and recurrence as initial therapy, and benefits in overall survival in switched or extended strategies. However, comparisons of efficacy data across trials are confounded by methodological differences between trials. To address this problem, mathematical models have been developed which allow for inter-trial comparisons. Results from these models indicate that initial adjuvant therapy with an AI is superior to initial therapy with tamoxifen, and suggest that initial AI therapy is better than starting tamoxifen and then switching to an AI. Further clinical trials are needed to ascertain the optimal length of treatment with an AI.

Tamoxifen in breast cancer: Not so easy to write off

For the past 30 years, tamoxifen has saved millions of lives throughout the world. The same has been proven in randomized trials and metaanalyses. Recent trials have shown clinical superiority of aromatase inhibitors over tamoxifen in terms of disease free survival and reduction in complications. However, because of the unique mechanism of tamoxifen, intrinsic advantages and low cost, this wonderdrug may still be a reasonable choice for hormonal therapy in breast cancer.

Cell growth inhibitory action of an unusual labdane diterpene, 13‐epi‐sclareol in breast and uterine cancers in vitro

In the course of our studies on the isolation of bioactive compounds from the roots of Coleus forskohlii, a traditional herb in India, rare 13-epi-sclareol has been isolated, and its structure determined by extensive 2D NMR. This is the first report of isolation from this plant. The isolated compound showed antiproliferative activity in breast and uterine cancers in vitro. The antiproliferative activity of 13-epi-sclareol is comparable to Tamoxifen in terms of IC50 and also showed concentration dependent increased apoptotic changes in the breast cancer cell line, MCF-7.

Aromatase inhibitors in post-menopausal metastatic breast carcinoma

To summarise the advances in the hormonal treatment of post-menopausal metastatic breast cancer, this paper reviews the published literature regarding the randomised trials comparing aromatase inhibitors (AIs) versus tamoxifen as a first-line therapeutic choice, or AIs versus megestrole acetate (MEG) as a second-line option. The pooled analysis of these authors on AI versus MEG as a second-line option for post-menopausal metastatic breast cancer suggested that AIs do not add any significant benefit over MEG in terms of overall response rate (ORR) and time to progression. According to the Cochrane Database, use of an AI as a second-line therapy versus any other endocrine therapy (mostly MEG) has shown a significant benefit in terms of overall survival, but not for progression-free survival, clinical benefit (CB) or ORR. Concerning the authors’ comparisons between AIs versus tamoxifen as a first-line endocrine option in post-menopausal women with metastatic breast carcinoma, AIs seem to be superior to tamoxifen, with a significant benefit in terms of ORR, CB and time to progression being observed in favour of AIs over tamoxifen with fixed effects estimates. According to the Cochrane Database, there was an advantage to the use of AIs over tamoxifen in terms of progression-free survival and CB, but not for overall survival or ORR. With regards to toxicity, AIs show similar levels of hot flushes and arthralgia, increased risks of nausea, diarrhoea and vomiting, but a decreased risk of vaginal bleeding and thromboembolic events compared with other endocrine therapies. Weight gain, dyspnoea and peripheral oedema seem to be more frequent with MEG. At present, there is no proved overall survival difference in patients who are treated first with an AI and then with tamoxifen compared with the opposite sequence. In the metastatic setting, results are limited and are based on retrospective analyses.

Place actuelle des inhibiteurs de l'aromatase dans le traitement adjuvant des cancers du sein: Reste-t-il des indications aux anti-œstrogènes de type tamoxifène ?

Adjuvant hormone therapy is indicated only in patients whose tumors express estrogen or progesterone receptors. Aromatase inhibitors (AI) are indicated only in postmenopausal patients. AI are significantly more effective than tamoxifen in terms of disease-free survival and distant recurrence-free survival; these advantages will probably result in a significant overall survival benefit after sufficient follow-up. This benefit justifies the use of AI in all postmenopausal patients in the absence of contraindications and after complete explanations of the benefit/risk ratio and potential side effects of this treatment. The benefit of AI over tamoxifen may be particularly pronounced for tumors overexpressing HER-2 and perhaps for ER+PR- tumors. Replacement of tamoxifen by AI or first-line treatment with AI is advised in patients with such tumors. Extended adjuvant treatment with AI for 5 years significantly increases survival among patients already treated with tamoxifen for 5 years; it also provides a significant overall survival benefit to patients with positive axillary nodes and should be used in this group. AI may cause several generally mild side effects, including insomnia, arthralgia, bone loss, vaginal dryness, dyspareunia and loss of libido. Tamoxifen may be appropriate for well-informed patients with these side effects, especially those with RE+ RP+ tumors and a low risk of thromboembolic or endometrial complications. The effects of AI on memory and cognition should also be investigated thoroughly before its long-term use, especially in the elderly.

Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among postmenopausal patients with early stage breast cancer

The Stockholm Breast Cancer Study Group conducted a randomized trial during 1976 through 1990 comparing adjuvant tamoxifen versus control. A total of 2 738 postmenopausal women with invasive, early stage disease were randomised between tamoxifen for 2 or 5 years, or no adjuvant endocrine therapy. Among high-risk patients the treatment was given against a background of either postoperative, locoregional radiation or CMF-type chemotherapy. The median follow up was 18 years (range 11–25 years). There was a statistically significant (p =0.001) interaction between ER status and tamoxifen with no treatment benefit among receptor negatives. PgR-status had little additional predictive value. Among ER-positive patients tamoxifen reduced locoregional recurrences by 48%, contralateral breast cancers by 54%, distant metastases by 28%, and all events by 24% (p <0.001). On the other hand, there was a substantial increase of endometrial cancer associated with tamoxifen. There was no effect of tamoxifen on intercurrent mortality whereas breast cancer deaths were reduced by 31% (p <0.001) and overall mortality by 15% (p =0.01). Tamoxifen produced long-term benefits among estrogen receptor positive patients in terms of breast cancer-related events, but also an increased incidence of endometrial cancer. Despite long-term follow-up we observed no benefit with tamoxifen in terms of cardiovascular mortality.

The Emerging Role of Aromatase Inhibitors in the Adjuvant Management of Breast Cancer

Adjuvant hormonal therapy for patients with endocrine sensitive breast cancer has been dominated for several decades by the gold standard tamoxifen. Promising data on third generation aromatase inhibitors (AI), anastrozole, letrozole and exemestane, in metastatic setting led to the development of these agents in early breast cancer. If recent results consistently show the superiority of these agents over tamoxifen, the therapeutic strategies of AIs in adjuvant setting remain discussed. Various approaches have been evaluated ranging from: 1. Front line 5 year use of AI instead of tamoxifen for newly diagnosed patients, to 2. Switching to AI after 2 or 3 years of tamoxifen for patients presently on tamoxifen (total of 5 years), or 3. Continuing with an AI after completion of 5 years of adjuvant tamoxifen. However, it is unclear today whether one of these AI strategies is superior to the other ones. The overall therapeutic index of AIs appears superior to that of tamoxifen with proven improved efficacy and better toxicity profile. AIs are all less toxic than tamoxifen in terms of thromboembolic disease and gynaecological complications while musculoskeletal disorders and joint pains are more frequent seen with AIs. This review will explore the results from the available adjuvant AIs trials and will define the present role of AIs in the adjuvant management of postmenopausal patients with breast cancer.

The study of tamoxifen and raloxifene (STAR): Initial findings from the NSABP P-2 breast cancer prevention study

LBA5 Background: The STAR trial was designed to compare raloxifene to tamoxifen in terms of relative effect on invasive breast cancer risk and on other beneficial and detrimental outcomes associated with the use of tamoxifen. Methods: The trial opened on 7-1-1999, and accrual was completed November 4, 2004, with 19,747 women enrolled. To be eligible, a woman had to be postmenopausal with a 5-year predicted breast cancer risk of 1.66% as determined by the modified Gail model. Women were randomized and treated in a double-blinded fashion to receive 5 yr of therapy with either 20 mg per day of tamoxifen or 60 mg per day of raloxifene. The protocol-defined monitoring plan called for a final analysis and release of findings when 327 invasive breast cancer cases had been diagnosed in the total population. The mean age of the population at the time of entry into this trial was 58 yr, and the mean 5-yr risk of breast cancer was 4.04%. 93.5% of the women were white; 51.5% had a hysterectomy before entry into the study; 9.2% had a history of LCIS; 71.1% had at least one first-degree relative with a history of breast cancer. The average time on the study is 47 months. Results: There was no difference between the treatment groups in terms of effect on invasive breast cancer: 163 cases in women assigned to tamoxifen and 167 in women assigned to raloxifene (RR = 1.02, 95% CI = 0.82–1.27). The risk of invasive uterine malignancies was 40% less in the raloxifene group (36 in women assigned tamoxifen and 23 in women assigned raloxifene [RR = 0.62, 95% CI = 0.35–1.08]). The risk of non invasive breast cancer was less in the tamoxifen group (57 cases in those assigned to tamoxifen and 81 in those assigned to raloxifene [RR = 1.41, 95% CI = 1.00–2.02]). There were no significant differences between the treatment groups for any of the other invasive cancer sites or for cardiac events, osteoporotic fractures, or deaths. There were fewer thromboembolic events in women taking raloxifene than in those taking tamoxifen. Conclusions: Raloxifene is an effective alternative to tamoxifen for reducing the incidence of invasive breast cancer in postmenopausal women at increased risk of developing the disease and is associated with fewer endometrial cancers, deep vein thromboses, and pulmonary emboli. [Table: see text]

Medical treatment of early breast cancer. IV: neoadjuvant treatment

The main clinical aim of neoadjuvant (also called primary or preoperative) treatment for operable breast cancer before surgery is to downstage large cancers to reduce the need for mastectomy. A...

Improved disease-free survival with epirubicin-based chemoendocrine adjuvant therapy compared with tamoxifen alone in one to three node-positive, estrogen-receptor-positive, postmenopausal breast cancer patients: results of French Adjuvant Study Group 02 and 07 trials

Background: The purpose was to compare disease-free survival (DFS) between epirubicin-based chemoendocrine therapy and tamoxifen alone in one to three node-positive (N1–3), estrogen-receptor-positive (ER+), postmenopausal early breast cancer (EBC) patients.Patients and methods: We analyzed, retrospectively, 457 patients randomized in FASG 02 and 07 trials who received: tamoxifen alone (30mg/day, 3 years); or FEC50 (fluorouracil 500mg/m2, epirubicin 50mg/m2, cyclophosphamide 500mg/m2, six cycles every 21 days) plus tamoxifen started concurrently. Radiotherapy was delivered after the third cycle in FASG 02 trial, and after the sixth in FASG 07 trial.Results: The 9-year DFS rates were 72% with tamoxifen and 84% with FEC50-tamoxifen (P = 0.008). The multivariate analysis showed that pathological tumor size >2cm was an independent prognostic factor (P = 0.002), and treatment effects remained significantly in favor of chemoendocrine therapy (P = 0.0008). The 9-year overall survival rates were 78% and 86%, respectively (P = 0.11). In the multivariate model, there was a trend in favor of chemoendocrine therapy (P = 0.07).Conclusion: The addition of FEC50 adjuvant chemotherapy to tamoxifen significantly improves long-term DFS in N1–3, ER+ and postmenopausal women. Chemoendocrine therapy seems to be more effective than tamoxifen in terms of long-term survival.

Adjuvant endocrine therapies for postmenopausal women with early breast cancer: Standards and not

Hormonal manipulations have been used for more than 100 years for the treatment of metastatic breast cancer and after definition of the concept of micro-metastases also in the adjuvant setting. In the postmenopausal population, tamoxifen has played the most important role for almost four decades. Progestins or the first generation of aromatase inhibitors (AIs) were only marginally used in the adjuvant setting due to their prohibitive toxicity. The new generation of anti-estrogen compounds, the selective estrogen receptor down-regulators (SERDs) like fulvestrant have a higher affinity for the estrogen receptor than tamoxifen, but none of its agonist activities, and have shown promising clinical activity in the treatment of advanced breast cancer. The third generation of AIs investigated in six large trials has been reported to be superior to tamoxifen in terms of disease-free survival, but not in terms of survival. These trials will be discussed in terms of results in different subpopulations and of toxicity.

Neoadjuvant Endocrine Therapy for Breast Cancer: More Questions Than Answers

Neoadjuvant endocrine therapy studies for breast cancer are a great opportunity to develop insights into the biologic basis for the efficacy of estrogen receptor–targeting agents. Neoadjuvant endocrine treatment is also appealing from the drug development perspective. Theoretically, a promising new adjuvant endocrine strategy could be first tested as a short-term neoadjuvant treatment against a standard medication. Improvements in tumor response rate, surgical outcomes, and evidence for enhanced efficacy at the cellular level, for example in terms of the effect on proliferation, would provide a sound basis for taking the new approach forward into the resource-demanding setting of a phase III adjuvant trial. The potential of randomized phase III neoadjuvant endocrine treatment trials was first emphasized by the results of a double-blind study by Eiermann et al (Letrozole P024) that compared 4 months of the aromatase inhibitor letrozole with tamoxifen as neoadjuvant treatment for women with hormone-receptor–positive tumors who were ineligible for breast-conserving surgery. Letrozole outperformed tamoxifen in terms of clinical and radiologic response rates as well as in the incidence of subsequent breast-conserving surgery. Interestingly, the advantage of letrozole appeared to be particularly evident in a subpopulation of tumors with estrogen-receptor–positive (ER ) and human epidermal growth factor receptor (HER) 1 and/or HER2-positive tumors, indicating that the comparison of endocrine agents in the neoadjuvant setting could provide insights into the molecular basis for differences in efficacy between endocrine agents. The enhanced efficacy of letrozole was also apparent at the level of the cell cycle, since letrozole suppressed tumor Ki67 immunohistochemical staining to a greater extent than tamoxifen. These results were consistent with the advantages of third generation aromatase inhibitors over tamoxifen in other disease settings. The Immediate Preoperative Anastrozole, tamoxifen or Combined with Tamoxifen study (IMPACT) is only the second phase III neoadjuvant endocrine trial to be reported in the peer-reviewed literature. The primary hypothesis focused on a drug development question: would the results of the neoadjuvant endocrine trial (IMPACT) mirror those of a much larger adjuvant study (the Arimidex, Tamoxifen, Alone or in Combination trial; ATAC)? In particular, the investigators wanted to prove that negative preliminary data for enhanced efficacy of anastrozole and tamoxifen in combination compared with tamoxifen alone in the preoperative setting would theoretically have prevented ATAC investigators from randomly assigning 3,000 women to the combination arm. With these primary aims in mind, 330 patients with ER breast cancer were randomly assigned to 3 months of treatment with either anastrozole, tamoxifen, or the combination of the two in a multicenter trial in the United Kingdom and Germany. Response was monitored by caliper measurements (“clinical response”) and by ultrasound. Final surgical outcomes were compared with the surgical approach that would have been initially chosen for the patient if she had not received primary systemic therapy. Unfortunately, none of these clinical end points showed any difference among the three arms and the efficacy of anastrozole was lower than postulated in the statistical design. Given these negative results, this editorial was solicited to consider whether the hypothesis regarding the neoadjuvant-adjuvant link is in jeopardy for neoadjuvant endocrine trials, or whether the IMPACT study was a valiant but flawed test of the postulate. A comparison of the conduct of the IMPACT trial versus the Letrozole P024 trial reveals some straightforward issues that support the latter conclusion. First is the question of sample size. Whereas the IMPACT and Letrozole P024 trial sizes were similar, the IMPACT study involved a three-way randomization. With fewer patients in each treatment group than the Letrozole JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 22 AUGUST 1 2005

Surgical issues surrounding use of aromatase inhibitors

There are important surgical issues related to the use of the third generation aromatase inhibitors in both the neoadjuvant and adjuvant settings. Neoadjuvant hormone therapy is effective at downstaging tumours, particularly large tumours initially thought to be inoperable or requiring mastectomy. Randomised trials have shown that the newer aromatase inhibitors letrozole and anastrozole increase the numbers of women who are suitable for breast-conservation compared with tamoxifen, and that letrozole is superior to tamoxifen in terms of clinical response. Aromatase inhibitors are most effective in ER-rich tumours and are clinically and biologically effective in both HER2 positive and negative tumours, whereas HER2 positive tumours show a level of resistance to tamoxifen. In neoadjuvant studies comparing aromatase inhibitors with tamoxifen, the duration of use has been 3–4 months, by which time any response is usually evident but longer treatment periods produce continued shrinkage and response. The re-excision rate following breast conservation surgery after neoadjuvant hormone therapy is favourable compared with the rates following immediate wide local excision. Local recurrence rates are acceptable in patients undergoing neoadjuvant therapy and breast-conserving surgery providing post-operative radiotherapy is given. Adjuvant aromatase inhibitors, as well as having an effect on metastatic disease and survival, reduce local and regional recurrence.

Treatment of locally advanced breast cancer

As Sunil Verma and associates note, evidence is rapidly accumulating that aromatase inhibitors offer advantages over tamoxifen in terms of efficacy and toxicity.[1][1],[2][2],[3][3] However, none of these studies has shown an overall survival advantage. At the time our guidelines[4][4] were

Aromatase inhibitors in the adjuvant setting: bringing the gold to a standard?

The death rate from breast cancer is falling rapidly in most developed countries due, at least in part, to the use of adjuvant endocrine therapy in women with endocrine responsive disease. In post-menopausal women tamoxifen has been the gold standard for nearly 20 years. More recently the aromatase inhibitors (AI) have become established in the management of advanced breast cancer and are being evaluated in the adjuvant setting in trials that include tens of thousands of women. Recently, data have emerged that provide increasingly strong evidence supporting the use of AI in the adjuvant setting. Anastrozole as initial adjuvant endocrine treatment has shown superiority over tamoxifen in terms of disease free survival, and impressive reductions in the risk of recurrence have been demonstrated in trials evaluating the switch from tamoxifen to an AI, either letrozole after 5 or exemestane after 2–3 years of tamoxifen respectively. The data from these recent publications, and the potential impact on routine care of women with post-menopausal breast cancer is discussed.