Breast Cancer Leads Mortality Drop in U.S., U.K.


SAN ANTONIO — Total cancer mortality among middle-aged women in the United States and United Kingdom has declined markedly since 1990—and an unprecedented drop in breast cancer mortality is the biggest reason why, Sir Richard Peto, Ph.D., said at the San Antonio Breast Cancer Symposium.

Indeed, through a series of moderate gains in survival achieved via breast screening plus incremental advances in endocrine therapy, chemotherapy, and radiotherapy, breast cancer mortality in women aged 35–69 years in the United States and United Kingdom has been almost halved since 1990.

“No other common cancer can claim such success. Hodgkin's disease, yes. Testicular cancer, yes. Childhood leukemia, yes. But this absolute gain in breast cancer survival is far bigger than the absolute gain from eliminating any of those diseases,” said Dr. Peto, professor of medical statistics and epidemiology at the University of Oxford (England).

A new analysis by Dr. Peto and colleagues at the Oxford-based Early Breast Cancer Trialists' Collaborative Group (EBCTCG) demonstrates how several advances in chemotherapy, each of only moderate impact, have together over the course of three decades added up to a massive survival benefit.

The bottom line of this analysis, based upon data on roughly 80,000 patients with early breast cancer randomized in chemotherapy trials, is: “If you give effective chemotherapy to women with or without estrogen receptor-positive disease, you'll reduce their mortality by about one-third if they're old, and by about one-half if they're young,” he said. “These are lovely results.”

The full EBCTCG database now includes 350,000 breast cancer patients in close to 400 randomized clinical trials worldwide. The world's trialists, who have met to share their updated data every 5 years since 1985, will do so next in 2010.

The first wave of chemotherapy trials compared cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) regimens with no chemotherapy. Those studies demonstrated that CMF-treated patients younger than age 50 experienced a 44% reduction in the risk of recurrence, and a 32% decrease in breast cancer mortality, during the first 4 years of follow-up. Women aged 50–69 years had a 25% reduction in recurrence and a 9% decrease in mortality.

Not enough women aged 70 years or older have been enrolled in randomized chemotherapy trials to draw conclusions about the treatment's effect in that age group.

The second wave of trials compared anthracycline-based regimens with CMF regimens. The relative risk of recurrence was reduced by a further 16% with anthracycline regimens, compared with CMF, in women younger than 50, and by 11% in those aged 50–69. Mortality resulting from breast cancer was reduced by 19% in anthracycline-treated patients younger than age 50, and by 10% in those aged 50–69.

The third wave involved 20,000 participants in randomized trials of taxane- versus anthracycline-based regimens. Taxane-based therapy in women younger than age 50 conferred a 16% reduction in recurrence risk, compared with anthracycline-based regimens, and a 14% reduction in breast cancer mortality through the first 4 years of follow-up. In 50- to 69-year-olds, taxane regimens brought an 18% decrease in recurrences and a 16% reduction in breast cancer mortality, compared with anthracycline regimens.

There haven't been trials directly comparing taxane-based regimens with no chemotherapy, but the effect can be gauged by multiplying the three event-rate ratios together. That yields a projected 62% reduction in recurrence through 4 years in women younger than age 50 who were treated with taxane regimens, compared with those getting no chemotherapy, and a 48% reduction in older patients. The reduction in breast cancer mortality works out to 54% in younger taxane-treated patients and a 33% reduction in patients aged 50–69 years, compared with those who got no chemotherapy, he continued.

Another point: The EBCTCG data convincingly show that chemotherapy is equally effective in women with estrogen receptor (ER)-positive breast cancer—the most common type of the disease—and ER-poor breast cancer. For example, women younger than age 50 who were randomized to chemotherapy had a 49% reduction in recurrence risk through 4 years if they were ER-positive, and a similar 43% reduction if they were ER-poor.

“ER status is irrelevant. The relative risk for recurrence and mortality is the same in ER-poor and ER-positive patients,” Dr. Peto noted.

That being said, the size of the absolute risk reduction depends upon prognosis. And the prognosis for ER-positive disease treated with endocrine therapy is already so good—a halving of recurrence risk through 4 years—that the further absolute gain achievable with effective chemotherapy is considerably smaller than in ER-negative disease.

Acknowledging that newer targeted therapies make chemotherapy less necessary for a growing number of patients, Dr. Peto said, “I'm not making any treatment recommendations. Look at the prognosis, discuss the side effects, discuss the costs, and decide what to do.”


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