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Large tumor size, positive lymph nodes increase distant recurrence in ER-positive breast cancer

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November 8, 2017

Daniel F. Hayes

Women free from estrogen-receptor-positive breast cancer had a 40% risk for distant recurrence 15 years after the end of endocrine therapy if their original tumor size was large and cancer spread to four or more lymph nodes, according to results of a meta-analysis.

Women with small, low-grade cancers who did not have cancer spread to lymph nodes had a much lower risk of 10% for distant recurrence during the same time frame, the research showed.

“These data can be used by patients and their health care providers as they consider whether to continue taking antiestrogen therapy beyond five years, weighed against side effects and toxicity of the therapies,” Daniel F. Hayes, MD, FACP, FASCO, professor of internal medicine, Stuart B. Padnos professor in breast cancer and clinical director of the Breast Oncology Program at the University of Michigan Comprehensive Cancer Center, said in a press release.

Five years of adjuvant endocrine therapy significantly reduces the risk for locoregional and distant recurrence in estrogen-receptor-positive early-stage breast cancer. Extending adjuvant therapy can also reduce recurrence. However, endocrine therapy for 5 years can be linked to several side effects.

Whether the benefits outweigh the risks for additional side effects in the decision to extend therapy beyond 5 years has remained questionable. Absolute benefits of extended therapy depend on absolute risk for later recurrence if no further therapy is given.

Thus, Hayes, Hongchao Pan, MD, PhD, statistician and epidemiologist in the Nuffield Department of Population Health at University of Oxford in the United Kingdom, and colleagues sought to determine the influence of various characteristics of the original tumor on 20-year incidence of breast cancer outcomes in women with ER-positive early-stage breast cancer.

“As we look at extending endocrine therapy for 10 years, we wanted to determine whether there were certain subgroups of women whose risk [for] recurrence was so low they might not need to continue endocrine therapy after five years,” Hayes said.

Analyses combined individual data of 62,923 women with ER-positive early-stage breast cancer from 88 randomized clinical trials in the Early Breast Cancer Trialists’ Collaborative Group database. All patients had been scheduled to received adjuvant endocrine therapy for 5 years, then stop. In addition, all women were reported disease-free after therapy ended.

Main outcomes of the study included the rate of distant recurrence regardless of local or contralateral events, rate of any breast cancer event and mortality rate related to breast cancer.


Over the 15-year study period, a consistent number of women had their cancer spread to other parts of the body. The annual risk for distant recurrence correlated with nodal status (P < .001) and original tumor size. The 20-year risk for recurrence was 22% among women with no positive nodes, 31% with one to three nodes and 52% with four to nine nodes.

“Even though these women remained free of recurrence in the first five years, the risk [for] having their cancer recur elsewhere from years five to 20 remained constant,” Hayes said.

Patients with stage I disease and zero nodes had a 13% chance of recurrence compared with patients with one to three nodes (20%) and with four to nine nodes (34%). Patients with stage T2 disease had 19% risk for distant recurrence with no nodes, 26% risk with one to three nodes and 41% with four to nine nodes.

“It is remarkable that breast cancer can remain dormant for so long and then spread many years later with this risk remaining the same year after year and still strongly related to the size of the original cancer and whether it had spread to the nodes,” Pan said in the release.

The absolute risk for distant recurrence among patients with stage I breast cancer without nodes was 10% for low-grade disease, 13% for moderate disease and 17% for high-grade disease. Corresponding risks for any recurrence or contralateral breast cancer were 17%, 22% and 26%.

The risk for contralateral breast cancer did not appear largely dependent on tumor and nodal status.

“This finding had implications for long-term follow-up strategies and highlights the need for new approaches to reduce late recurrence,” the researchers wrote.

Disclosures: Hayes reports principle or co-investigator roles in clinical research sponsored by Eli Lilly, Janssen, Merrimack Pharmaceuticals, Pfizer, Puma Biotechnology and Veridex. Pan reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.

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