Breast cancer chemoprevention in the spotlight again

Ali Conlin, M.D.
Medical oncologist
Providence Oncology and Hematology Care Clinics-Westside

Published October 2011

In 1998 the Breast Cancer Prevention Trial evaluating tamoxifen, a selective estrogen receptor modulator to prevent breast cancer, was first reported.

In this trial, more than 13,000 women were randomized to either tamoxifen or placebo for five years if they were at elevated risk for breast cancer. This study was one of the first to show we can be more proactive in preventing breast cancer. Indeed, tamoxifen provided a 49 percent risk reduction in invasive breast cancer.

Women were considered at “elevated risk” if they were older than 60, or if they were 35 or older with a history of lobular carcinoma in situ. The study’s findings generated much enthusiasm. However, the study found some statistically rare, but serious side effects among women treated with tamoxifen, including uterine cancer, deep vein thrombosis and stroke. Thus this exciting development – a drug to reduce the risk of breast cancer – was not widely accepted by primary providers.
Nearly a decade later a new class of drugs emerged to treat estrogen-receptor-positive breast cancer. Aromatase inhibitors, or AIs, work as pure anti-estrogen therapy for postmenopausal women only. (They do not work for women with functioning ovaries.)

The three AIs currently used are anastrozole (Arimidex), letrozole (Femara) and exemestane (Aromasin). Several clinical studies have shown benefit when one of these medications is incorporated into treatment for early- or late-stage estrogen-receptor-positive breast cancer in postmenopausal women. The drugs are given as either a replacement for tamoxifen, or sequentially before or after tamoxifen. Additionally, they have been noted to provide an additional 46 percent risk reduction in contra lateral breast cancers when given after tamoxifen.

The results of these earlier studies led to examination of these drugs for primary prevention as well. This past June, Paul Goss, M.D., Ph.D., et al reported findings from the NCIC CTG MAP.3 study in the New England Journal of Medicine. In this study, 4,520 women were randomized to exemestane or placebo. The women enrolled were similar to those in the earlier tamoxifen study, including women 35 or older with a history of atypical ductal hyperplasia or ductal carcinoma in situ treated with mastectomy.

The study was substantially smaller than the tamoxifen study, and the results were reported at three years. However, a 65 percent risk reduction in new invasive breast cancer with a tolerable safety profile is exciting news, and confirmation of what we all had hoped. Even more encouraging is the idea that chemoprevention for breast cancer might come to the forefront again.

It is our hope that this study will renew interest in chemoprevention, and that women with a strong family history or prior breast cancer, or women older than 60 and worried about breast cancer, can discuss this with their primary care doctors.

Clinical articles by Ali Conlin, M.D.