For decades, AstraZeneca’s Nolvadex (tamoxifen) has been the standard therapy for hormone-receptor positive breast cancer patients post-surgery. In fact, recent primary research by independent market analyst Datamonitor* has shown that nearly two-thirds of early-stage breast cancer patients receive the drug post surgery. However newer antihormonal agents called aromatase inhibitors, which lower the estrogen level in the body are increasingly being used in place of tamoxifen after clinical trials showed that aromatase inhibitors are more effective in increasing survival and minimizing disease recurrence.

Most Common

Breast cancer is the most common malignancy that afflicts women, with more than 420,000 new cases expected to be diagnosed in the seven major markets in 2005. However, it remains a disease that is highly curable if diagnosed at early stage.

Patients with early-stage breast cancer are treated- wherever possible - with surgery, the most effective form of treatment in prolonging survival.  However a significant proportion of these patients who undergo surgery experience a recurrence of the tumor, in which case, the prognosis worsens considerably, says Datamonitor senior oncology analyst Kyung Lee. “The risk of recurrence depends significantly on the characteristics and stage of breast cancer, but it can vary from 5% for local tumor to 70-80% for breast cancer with significant nodal involvement. Therefore in order to minimize the risk of recurrence, patients are treated systemically with drugs following surgery, also known as adjuvant or post-operative therapy.”

For patients with hormone-receptor positive breast cancer, antihormonal agents with or without chemotherapy are commonly used post-operatively to eradicate undetectable micrometastases of tumor cells that may have been present at the time of surgery, thereby decreasing the likelihood of relapse and increasing the cure rate.

Standard, for now

Datamonitor’s primary research has shown that even today, tamoxifen remains the most commonly used antihormonal agent in the seven major markets, with nearly two-thirds of early-stage breast cancer patients receiving the drug in the adjuvant setting, Lee says. “However newer antihormonal agents called aromatase inhibitors, which lower the estrogen level in the body are increasingly being used in place of tamoxifen.

Tamoxifen is a selective estrogen receptor modulator (SERM) that blocks the estrogen receptors and prevents cell proliferation in breast cells,

whereas clinical trials have shown that aromatase inhibitors are more effective in increasing survival and minimizing disease recurrence.

In particular, Datamonitor expects AstraZeneca’s Arimidex (anastrozole) to supersede tamoxifen and become the gold-standard adjuvant therapy for local and locally advanced breast cancer. Anastrozole is already more commonly used in the post-operative setting in the US and France compared with tamoxifen, and Datamonitor believes that other markets are likely to catch up in terms of anastrozole usage in the coming months. This is based on the latest results from the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial, published in December 2004 at the San Antonio Breast Cancer Symposium, which showed five-year anastrozole therapy to be more effective than standard five-year tamoxifen therapy in terms of survival.

There are also other aromatase inhibitors such as Novartis’ Femara (letrozole) and Pfizer’s Aromasin (exemestane) on the market, but these drugs are less commonly used than anastrozole in the seven major markets as adjuvant therapy, Lee says. “This is due to the lack of available long-term clinical data. In addition, Novartis and Pfizer do not have the experience and expertise of marketing antihormonals like AstraZeneca, which also has Faslodex (fulvestrant), Zoladex (goserelin) and Casodex (bicalutamide) in its portfolio. As a result, letrozole and exemestane are likely to remain peripheral in terms of adjuvant usage.”

However, clinical trials for letrozole and exemestane are addressing the issue of whether patients already receiving tamoxifen should switch to an aromatase inhibitor after a number of years of tamoxifen therapy. This was not investigated in the ATAC trial for anastrozole, he says. “Therefore new patients may be treated with anastrozole, but those already on tamoxifen may switch to letrozole or exemestane. Nevertheless, Datamonitor believes that if these clinical trials show positive results in switching from tamoxifen to letrozole or exemestane, it will help increase confidence in the aromatase inhibitor class as a whole and the number of patients switching from tamoxifen to anastrozole will also increase.”

(21/4/05)