Long after 5 years of hormonal therapy ends, risk of recurrence may still be significant

A study published in the New England Journal of Medicine looked at women’s risk of cancer becoming metastatic and of dying from breast cancer during the 20 years after diagnosis with hormone receptor-positive breast cancer. It found that despite treatment with hormonal therapy, the risk was still significant and that tumor size and number of affected lymph nodes strongly predicted a woman’s risk of developing metastatic disease.

Background

Hormone receptor-positive breast cancer, which grows with the help of the hormones estrogen and progesterone, is the most common subtype of breast cancer. People with hormone receptor-positive breast cancer often are treated with surgery, and sometimes chemotherapy and radiation therapy. After finishing these first treatments, they go on to take hormonal therapy, a type of targeted therapy that helps block estrogen in the body from telling cancer cells to grow or multiply. The most common hormonal therapies are tamoxifen and aromatase inhibitors.

Hormonal therapies make it much less likely the cancer will return, or recur, as metastatic breast cancer. Metastatic breast cancer is breast cancer that spread outside the breast and nearby lymph nodes to distant parts of the body, like the lungs, liver, bones or brain.

Five years of daily hormonal therapy pills was standard for many years. Studies showed that compared to not taking hormonal therapy, taking 5 years of hormonal therapy lowers the risk of recurrence by 50 percent or more during those 5 years. Tamoxifen continues to lower the risk of recurrence by 30 percent in the 5 years after treatment with it ends. Five years of hormonal therapy also lowers the risk of death from breast cancer by 30 percent during treatment and for 10 years after treatment ends.

Metastatic breast cancer recurrences, especially in people with triple-negative breast cancer, often happen in the first 5 years after diagnosis. But breast cancer, especially hormone receptor-positive breast cancer, can recur at any time after treatment ends, even after the 5-year mark. Doctors don’t know why some cancers come back and some don’t, or what causes some to become metastatic quickly and others to become metastatic slowly.

More recently, researchers found that taking 10 years of tamoxifen, or 5 years of tamoxifen followed by up to 5 years of an aromatase inhibitor, lowers the risk of recurrence even more than 5 years of treatment.

Many women handle hormonal therapy well, but it can cause side effects, including menopausal symptoms and bone pain. So if they’re going to recommend women be on these treatments for a decade or more, doctors like those who worked on this study want to understand how much risk they’re helping those women avoid.

Design

This study looked at participant records from 88 studies published in the past. All of the studies were part of a database of randomized trials managed by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).

The researchers found 62,923 patient records in 88 trials that fit what they were looking for. All of the women in these records:

• Were diagnosed with breast cancer before age 75
• Had estrogen receptor-positive early-stage breast cancer. Some had cancer that was also progesterone receptor-positive, HER2-positive, or both
• Had a tumor or tumors 5 centimeters or smaller
• Had cancer in fewer than 10 lymph nodes
• Were scheduled to take hormonal therapy for 5 years, then stop
• Had no evidence the cancer had become metastatic at the end of 5 years of scheduled hormonal therapy

All women whose records were included in the study were diagnosed with early-stage breast cancer between 1976 and 2011.

The researchers’ main goals were to measure in how many of these women the cancer spread outside the breast and nearby lymph nodes and how many women died from breast cancer during the 15 years after they finished 5 years of hormonal therapy.

Results

The researchers found there was a significant risk of recurrence and of death from breast cancer during the 20 years after women were diagnosed with estrogen receptor-positive breast cancer, despite treatment with hormonal therapy. They also found that tumor size and number of affected lymph nodes strongly predicted risk of the cancer spreading outside the breast and nearby lymph nodes and of death from breast cancer, even a decade or more after diagnosis.

Risk of recurrence

The women whose records were part of this study had a 10 to 41 percent risk of recurrence in the 20 years after their diagnosis, despite standard hormonal therapy. In women with small tumors and no affected lymph nodes, tumor grade, which describes how much cancer cells look like healthy cells, was linked to risk of recurrence. Low-grade cancer looks the most like healthy cells and high-grade cancer looks the least like healthy cells. Low-grade tumors were the least likely to become metastatic, while high-grade tumors were the most likely.

In women with tumors 2 centimeters or smaller and no cancer in the lymph nodes, the risk of recurrence during the 20 years after diagnosis was:

• 10 percent in women with low-grade tumors
• 13 percent in women with moderate-grade tumors
• 17 percent In women with high-grade tumors

For women with tumors 2 centimeters or smaller who had cancer in the lymph nodes, the risk of recurrence during the 20 years after diagnosis was:

• 20 percent for women with one to three affected lymph nodes
• 34 percent for women with four to nine affected lymph nodes

For women with tumors bigger than 2 centimeters, the risk of recurrence during the 20 years after diagnosis was:

• 19 percent in women with no affected lymph nodes
• 26 percent in women with one to three affected lymph nodes
• 41 percent in women with four to nine affected lymph nodes

Risk of death from breast cancer

The women whose records were part of this study had a 7 to 29 percent risk of dying from breast cancer in the 20 years after their diagnosis, despite standard hormonal therapy.

For women with tumors 2 centimeters or smaller, the risk of death from breast cancer during the 20 years after diagnosis was:

• 7 percent in women with no affected lymph nodes
• 13 percent in women with one to three affected lymph nodes
• 22 percent in women with four to nine affected lymph nodes

For women with tumors bigger than 2 centimeters, the risk of death from breast cancer during the 20 years after diagnosis was:

• 13 percent in women with no affected lymph nodes
• 20 percent in women with one to three affected lymph nodes
• 29 percent in women with four to nine affected lymph nodes

The study found having cancer that was also progesterone receptor-positive, HER2-positive or both didn’t change a woman’s risk of the cancer spreading beyond the breast and nearby lymph nodes or of dying from breast cancer.

Limitations

Many of the women whose medical records were used in this study were diagnosed with breast cancer decades ago. Breast cancer treatment has improved since then, so women diagnosed and treated today have a lower risk of recurrence than women who were diagnosed in the past. Those improvements include taking targeted therapies for HER2-positive breast cancer and taking hormonal therapy for 10 years instead of 5. But since that’s only become common in the past few years, it hasn’t yet been possible to measure how it affects the risk of breast cancer spreading throughout the body or of death from breast cancer 20 years after diagnosis.

What this means for you

It’s common to feel conflicted about taking hormonal therapy. You may feel grateful this treatment is an option for you and that it can lower your risk of recurrence. But side effects may also impact your day-to-day life, and paying for pills for 5 to 10 years can have a strong financial impact. It may upset you to learn you may still have a significant risk of the cancer spreading outside the breast and nearby lymph nodes as many as 10 to 15 years after you stop taking hormonal therapy. But remember: This information can help you and your doctor make better treatment decisions and better understand your personal risk of recurrence.

When you finish active treatment, you and your healthcare team should create a survivorship care plan. A survivorship care plan includes recommended lifestyle changes to lower your risk of recurrence, a schedule of how often to see your cancer care and primary care providers, and what symptoms are important to tell your doctor about even as you get farther out from your diagnosis.

A better understanding of hormone receptor-positive breast cancer can help you deal with fear of recurrence. That fear may never go away completely, but it doesn’t have to stop you from living your life. LBBC has resources to help you deal with the fear.

Pan H, Gray R, Braybrooke J, et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. New England Journal of Medicine. November 9, 2017; 377:1836-46. DOI: 10.1056/NEJMoa1701830.