麻豆传媒

Women with hormone receptor (HR)-positive breast cancer had a steady risk of distant recurrence for 20 years after initial diagnosis and treatment, a meta-analysis of 88 clinical trials showed.

After completing adjuvant endocrine therapy, patients with the most favorable disease status (T1N0) had <1% annual risk of distant breast cancer recurrence from years 5 to 20, resulting in a cumulative risk of 13% at year 20. The risk increased progressively with less favorable disease status, reaching a cumulative distant recurrence risk of 41% in patients with T2N4-9.

The findings might help inform discussions about the optimal duration of adjuvant endocrine therapy, which usually stops after 5 years for most patients, an international group of authors reported in the .

"Distant recurrences occurred at a steady rate for at least another 15 years after the end of the 5-year [adjuvant] treatment period," Hongchao Pan, PhD, of the Early Breast Cancer Trialists' Collaborative Group in Oxford, England, and coauthors concluded. "Throughout this time, the original nodal status and tumor diameter remained remarkably strong determinants of the annual recurrence rate."

Whether endocrine therapy should continue beyond 5 years remains an open question, awaiting an answer from meta-analyses of individual patient data from completed trials.

"When these findings are available, the likely benefits of extending therapy will have to be weighed against uncommon but potentially life-threatening side effects, such as bone fracture from aromatase inhibitors and pulmonary embolus and (for women with a uterus) endometrial cancer for tamoxifen," the authors added.

The findings confirm established knowledge about breast cancer and, along with the potential clinical implications, should be considered with the recognition that treatment has improved considerably over the past 20 years, said Jennifer Litton, MD, of the University of Texas MD Anderson Cancer Center in Houston.

"The article doesn't tell the breast cancer community anything they didn't already know, which is that cancer risk doesn't go down to zero for patients with hormone receptor-positive breast cancer," Litton, who was not involved in the analysis, told 麻豆传媒. "I wouldn't want women to panic when they see this. This is what was happening 20 years ago, and we know women are living longer, decade by decade when they are diagnosed.

"It confirms that there is a lifelong risk. We still need to do better with our chemotherapy, we need to do better with our anti-estrogen therapies. A lot of people are looking into different combinations in clinical trials, as far as the length of time that women are on these therapies."

Multiple studies demonstrated that 5 years of adjuvant endocrine therapy substantially reduced the risk of recurrence and breast cancer mortality, first with tamoxifen and subsequently with aromatase inhibitors. Some studies also showed that extending adjuvant therapy beyond 5 years can lead to further reductions in recurrence, Pan and coauthors noted.

However, endocrine therapies are associated with side effects that may not only reduce quality of life but can be serious and even life-threatening in some cases. Moreover, the toxicities associated with adjuvant endocrine therapy increase with duration of treatment.

To inform discussions about adjuvant endocrine therapy, including the optimal duration, the investigators performed a review of the literature and a meta-analysis of individual patient data for 62,923 women who participated in clinical trials of adjuvant endocrine therapy for early breast cancer. All the participants were free of breast cancer after completing 5 years of adjuvant therapy. The analysis focused on patient outcomes for years 5 to 20.

The results showed that tumor stage and nodal status at diagnosis strongly influenced the risk of distant disease recurrence. For patients with stage T1 disease, the rate of distant recurrence increased from 13% for women with no involved lymph nodes to 20% with one to three involved nodes and to 34% with four to nine involved nodes. Among women with T2 disease, the distant recurrence rate increased from 19% to 26% to 41% as nodal involvement increased from zero to four or more.

For subsets of patients with available data, tumor grade and Ki-67 (proliferation factor) status had only a moderate impact on the risk of distant recurrence. Progesterone receptor and HER2 status did not significantly affect the risk of distant recurrence.

In general, the risk of locoregional recurrence and the risk of death from breast cancer were affected by the same factors that influenced the risk of distant recurrence, the authors reported.

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