In Reply

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Value of Ki67 in breast cancer: the debate is still open.

CommentLetterSCOPUS: le.jinfo:eu-repo/semantics/publishe

Progesterone receptor testing: not the right time to be buried.

CommentLetterinfo:eu-repo/semantics/publishe

Aromatase inhibitors: a new reality for the adjuvant endocrine treatment of early-stage breast cancer in postmenopausal women.

Tamoxifen, a selective estrogen receptor modulator (SERM), has been used for many decades as the "gold standard" adjuvant treatment for patients with hormone-receptor-positive early breast cancer. This drug, when administered for 5 years, reduces the risk for recurrence, contralateral breast cancer (BC) and death. The optimal duration of tamoxifen in the adjuvant setting has not been established yet, but it has been demonstrated that 5 years are better than shorter treatment while it is still unclear if a prolongation of the treatment for more than 5 years is worthwhile. In the last few years, third generation aromatase inhibitors (AIs), either steroidal (exemestane) or non-steroidal (anastrozole, letrozole), have shown to be an effective alternative to tamoxifen in postmenopausal patients with BC regardless of its stage. These agents act by blocking the aromatase enzyme which converts androgens into estrogens. The goal of this article was to review the results of recent randomized trials comparing AIs to tamoxifen in postmenopausal women in the adjuvant setting. Two strategies have been utilized: a direct upfront comparison in which both tamoxifen and AIs were given for 5 years or an early switch in which AIs were administered after 2-3 years of tamoxifen for 3-2 years or vice versa. Both strategies have shown a superiority of AIs over tamoxifen and a different safety profile but, the optimal treatment modality has yet to be defined. Moreover, in an attempt to further reduce patients' risk of recurrence after the administration of tamoxifen for 5 years, three trials have evaluated the role of prolonging the adjuvant treatment with AIs for 5 more years in comparison to placebo (late switch). A significant improvement of disease-free survival and of overall survival in the subgroup of node-positive patients, at least in one trial, has been observed with AIs. Despite these important results several unanswered questions remain and the results of ongoing trials will hopefully clarify some of them.Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

Bringing molecular prognosis and prediction to the clinic.

In the past 30 years, important advances have been made in the knowledge of breast cancer biology and in the treatment of the disease. However, the translation of these advances into clinical practice has been slow. With the advent of molecular-based medicine, it is hoped that the bridge between the bench and the bedside will continue to be shortened. Because breast cancer is a heterogeneous disease with wide-ranging subsets of patients who have different prognoses and who respond differently to treatments, the identification of patients who need treatment and the definition of the best therapy for an individual have become the priorities in breast cancer care. This article will review the crucial role of prognostic and predictive factors in achieving these goals. A critical review of classical and newer individual molecular markers, such as hormone receptors, HER2, urokinase-type plasminogen activator and plasminogen activator inhibitor 1, cyclin E, topoisomerase II, and p53, was performed, and the preliminary results obtained using the new gene expression profiling technology are described along with their potential clinical implications.Comparative StudyJournal ArticleReviewinfo:eu-repo/semantics/publishe

Aromatase Inhibitors: A New Reality for the Adjuvant Endocrine Treatment of Early-Stage Breast Cancer in Postmenopausal Women

Tamoxifen, a selective estrogen receptor modulator (SERM), has been used for many decades as the "gold standard" adjuvant treatment for patients with hormonereceptor- positive early breast cancer. This drug, when administered for 5 years, reduces the risk for recurrence, contralateral breast cancer (BC) and death. These benefits have been observed up to 15 years and are independent of the patient's age, menopausal status, nodal status, hormonal receptor status, and the use of adjuvant chemotherapy. The optimal duration of tamoxifen in the adjuvant setting has not been established yet, but it has been demonstrated that 5 years are better than shorter treatment while it is still unclear if a prolongation of the treatment for more than 5 years is worthwhile. Tamoxifen is usually well-tolerated, but important adverse events such as endometrial cancer, cerebrovascular accidents and thromboembolic events can occur, and the increase in absolute risk of these adverse events appears to be age-correlated. In the last decade, third generation aromatase inhibitors (AIs), either steroidal (exemestane) or non-steroidal (anastrozole, letrozole), have shown to be an effective alternative to tamoxifen in postmenopausal patients with BC regardless of its stage. These agents act by blocking the aromatase enzyme which converts androgens into estrogens. Trials comparing AIs to tamoxifen in postmenopausal women with metastatic disease have shown a superiority of AIs over tamoxifen and a more favourable safety profile. In the adjuvant setting, AIs have been shown to be more effective than tamoxifen given for 5 years either in the up-front administration or after 2-3 years (early switch). Two randomised trials which have evaluated the two strategies of AIs administration have shown superimposable results in terms of efficacy with AIs given up-front or in sequence to tamoxifen. AIs seem to give benefits in comparison to placebo if given after 5 years (late switch) of tamoxifen. At the moment, therefore, the treatment decision should be based on individual factors such as risk of relapse, absolute benefit, and comorbidities.SCOPUS: ch.binfo:eu-repo/semantics/publishe

HER-2 overexpression/amplification and its interaction with taxane-based therapy in breast cancer.

Breast cancer (BC) is the most common cancer in women and it is incurable when metastases are diagnosed. Taxanes, namely docetaxel and paclitaxel, are effective chemotherapeutic agents in the metastatic, neoadjuvant and adjuvant settings. HER-2 overexpression/amplification is detected in 25-30% of BCs and confers aggressive tumor behavior as well as resistance to some systemic treatments; nevertheless, its association with response to taxane-based chemotherapy is still unclear, with conflicting results in both in vitro and in vivo preclinical studies. This review will address the impact of HER-2 overexpression/amplification in BC patients treated with taxanes. Prospective, randomized trials incorporating important biological hypotheses are either ongoing or just closed, and their results will hopefully help to shed more light on this issue.Journal ArticleResearch Support, Non-U.S. Gov'tReviewinfo:eu-repo/semantics/publishe