Risk of breast cancer's return continues long after treatment ends

A recent analysis has found that even 20 years after receiving a diagnosis of estrogen receptor-positive breast cancer, the risk of the cancer's return looms large. Should treatment be extended?

Estrogen receptor-positive (ER-positive) breast cancer is the most common breast cancer type, accounting for around 80 percent of all breast cancer cases.

In short, ER-positive breast cancer flourishes in response to estrogen. The standard treatments for this cancer type are tamoxifen, which blocks the effects of estrogen, or aromatase inhibitors, which stop the production of estrogen.

Even once the cancer has gone, these drugs are taken daily for 5 years. Tamoxifen reduces recurrence by half during treatment, and by almost a third in the 5 years following treatment.

Aromatase inhibitors, which will only work in women who are postmenopausal, are even better at reducing the risk of recurrence.

Should treatment be extended?

Over recent years, research has found that extending the length of time that these medications are taken could reduce risks further still. Some cancer researchers are asking whether they should be continued for 10 years.

But these drugs are not without disadvantages. Although side effects are rarely life-threatening, they can substantially impact a woman's quality of life. Side effects often mimic menopause and include hot flashes, night sweats, mood changes, and vaginal dryness. Aromatase inhibitors also carry an increased risk of osteoporosis, among other conditions.

As the authors of the current study write, "[D]ecisions about extending adjuvant endocrine therapy after 5 years without any recurrence need to balance additional benefits against additional side effects."

The analysis was carried out by researchers from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG). This group has been pooling research into a single dataset since the 1980s, looking at all aspects of breast cancer.

For this study, they took data from 88 clinical trials, including those of 62,923 women with ER-positive breast cancer. Their findings are published this week in the New England Journal of Medicine.

Long-term risk of recurrence

They found that in women who were cancer-free and in therapy for 5 years, a substantial number saw the cancer spread throughout the body over the following 15 years.

"Even though these women remained free of recurrence in the first 5 years, the risk of having their cancer recur elsewhere (for example in the bone, liver, or lung) from years 5 to 20 remained constant."

Senior study author Dr. Daniel F. Hayes

The risk was directly related to the size of the original cancer and the number of lymph nodes that it affected. Specifically, larger cancers and those that affected four or more lymph nodes carried the greatest long-term risks.

Even if the patients were recurrence-free when they stopped the endocrine therapy, they had a 40 percent risk of cancer recurrence within 15 years.

Women whose original cancers were smaller and did not involve the lymph nodes had a 10 percent risk over 15 years.

As lead study author Hongchao Pan, Ph.D. — from the University of Oxford in the United Kingdom — says, "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."

Medical News Today got the opportunity to speak to Dr. Hayes, and when asked whether or not he was surprised by the results, he replied, "There have been much smaller studies to suggest this phenomenon [...] Our results absolutely validate these and confirm the relentless risk of distant recurrence over the 2 decades after diagnosis."

What happens next?

The team now wants to understand whether there is a subset of women with ER-positive breast cancer that has a low enough risk so that extended endocrine treatment would not be needed.

Although the analysis took thousands of women into account, the researchers are quick to note that they received their diagnosis decades ago and treatment has since improved. Dr. Hayes told MNT that "it appears that prognosis is better for patients diagnosed over the last 10–15 years."

He added, "More than half of our patients were entered before 2000, and of course, we only have 20 years of follow-up on patients who were followed for 20 years — so, overall, it is possible that the data in our paper overestimate the absolute risk distant recurrence/year."

"However, we are pretty certain that they do not overestimate the concept that distant recurrences continue without abatement."

Dr. Daniel F. Hayes

MNT also asked Dr. Hayes about future research to be conducted by the EBCTCG. He said, "There are several ongoing analyses asking a number of questions. We will continue to address issues of the risks of recurrence, and the benefits of various endocrine therapy strategies as we gather more data."

It is likely that these findings and others like them will be used to advise longer treatment plans for women with more aggressive ER-positive tumors. As Dr. Hayes told us, "[O]ur data will help patients make a better-informed decision."