New research shows that long-term endocrine therapy can reduce the risk of breast cancer recurrence in the long term. But side effects keep some women from taking it.
Like many breast cancer survivors, Julie Barthels wonders if the disease will return.
“My breast cancer came silently, without my knowledge. How do I know what is silently growing inside of me now?” she asked.
According to new research, taking endocrine therapy for five years can drastically reduce the recurrence.
Taking it longer might offer continued protection.
About two of every three breast cancers are hormone receptor (HR) positive.
These are the people who can benefit from long-term endocrine therapy, such as tamoxifen.
Tamoxifen blocks the effects of estrogen.
The researchers conducted a meta-analysis of 88 trials involving 62,923 women. All had estrogen receptor (ER) positive breast cancer.
All were disease-free after five years of prescribed endocrine therapy.
The rate of recurrence was steady during a 5-year to 20-year period.
Distant recurrence was found to have a strong correlation with original tumor size and lymph node status.
Women with larger tumors and more lymph node involvement had a higher risk of recurrence, ranging from 10 to 41 percent.
The study, conducted by an international team of researchers, is published in The New England Journal of Medicine.
Dr. Paula Klein is director of cancer clinical trials at Mount Sinai Downtown-Chelsea Center as well as an associate professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai in New York.
Asked about the research, Klein told Healthline there are some caveats.
“This is a meta-analysis. They were trials of women scheduled to receive five years of therapy, but we don’t know if they completed their therapy. We know there’s not an insignificant number of patients who are noncompliant,” she said.
Klein observed that the analysis was of patients diagnosed before the year 2000.
“This paper is really not completely relevant to today’s population. We have better screening and diagnostic methods. We’re better at staging, surgery, radiation, and systemic therapy. The mortality rates of breast cancer have gone down over several decades. Patients don’t have to be extra worried,” she said.
Klein explained that patients can have one of three variations of HR-positive breast cancer.
It can be ER-positive and progesterone receptor (PR) negative, ER-negative and PR-positive, or ER-positive and PR-positive.
All three groups of HR-positive patients are treated with the same anti-estrogen therapies.
Dr. Sarah P. Cate, director of the Special Surveillance and Breast Program at Mount Sinai Downtown-Chelsea Center, told Healthline that this study won’t change current practices.
“Most practice-changing types of studies are those that are randomized and prospective. While this study is important, I don’t know that it’s presenting much different data than already presented in prior studies done in a randomized fashion,” she said.
Eileen Phillips of Colorado received her diagnosis in 1998.
She had two lumpectomies, chemotherapy, and radiation treatment.
In 2000, while still taking tamoxifen, the cancer recurred in the other breast.
This time, she had a double mastectomy but wasn’t prescribed tamoxifen.
After her diagnosis in 2010, Barthels had surgery and chemotherapy before starting on tamoxifen.
Klein said until the past few years, the standard prescription was five years of tamoxifen or an aromatase inhibitor (AI).
AIs are usually used in postmenopausal women whose ovaries no longer produce estrogen. The drugs halt production of estrogen in an enzyme called aromatase.
Klein explained that recent studies show that it’s safe and effective to take these medications for 10 years.
Who should do so?
High-risk patients who are tolerant, motivated, and compliant, according to Klein.
Who should not?
“Certainly anyone who does not have ER-positive or PR-positive breast cancer,” she said. “Or extraordinarily low-risk women who have serious contraindications to the medications.”
It’s something that must be decided on an individual basis.
“We know that 30 percent of early stage ER-positive breast cancers recur, usually somewhere other than in a breast. The question of how to identify which patients will benefit from extended treatment with estrogen is still up in the air. In general, if you have an ER-positive tumor, there’s tremendous benefit from endocrine treatment,” said Cate.
“In younger women with more aggressive disease, we always give 10 years of tamoxifen. For younger patients, the data supports tamoxifen, but we can also do ovarian suppression with drugs or ovary removal, then AI,” she added.
“Another study found there’s very little benefit in giving older patients 10 years of anti-estrogen drugs, and there’s a higher risk of complications. Older post-menopausal patients have many other options in terms of endocrine treatment with different side effect profiles,” said Cate.
Compliance is a problem when a drug has to be taken for many years, according to Cate.
And there are troublesome side effects.
Barthels’ side effects include weight gain, joint swelling, fatigue, and depression.
“All of these side effects have been difficult because I had a very active lifestyle before the cancer,” she told Healthline.
Barthels’ follow-up practices are more extensive than most. Though she hasn’t had a breast cancer recurrence, she’s since been treated for skin and renal cancer.
None of that has stopped her from taking tamoxifen, which she’ll continue until 2021, a full 10 years.
Frances Hathaway of New York was diagnosed with stage 3 breast cancer in 1998.
She had surgery and chemotherapy. But she couldn’t tolerate the side effects of tamoxifen.
“The mental effect was not good so I stopped taking it. I went to a very dark place and had thoughts of suicide, which is not my personality or nature. Uterine cancer is another risk, so what’s the point?” said Hathaway.
When it comes to better compliance, Klein said two things must be considered: quality-of-life complaints and real long-term toxicities.
“For the nagging quality-of-life issues there are non-hormonal remedies for many of them. You need to first establish that the complaints are related to the medicine. They may be age-related,” she explained.
Klein said that postmenopausal women who can’t tolerate one AI may do better with a different one. And premenopausal women who can’t tolerate tamoxifen have other options as well.
“The most serious side effects of tamoxifen are higher risk of uterine cancer and blood clots. AIs can cause accelerated bone loss. Both share all the quality of life issues: vaginal dryness, hot flashes, night sweats, and changes to mood, weight, and sexual desire. Change of life stuff,” said Klein.
Barthels’ multiple cancer diagnoses certainly warrant concern.
“I am in a place of awareness about recurrence and it can make me fearful at times,” she said.
“This can be hard for people without cancer to understand, as they may feel like treatment is over and let’s move on. It is more complicated than that. It really is about acceptance for me, and that is a process I practice on a regular basis,” she continued.
Since having a double mastectomy, Phillips said thoughts of recurrence don’t weigh too heavily.
“I’m coming up on 20 years as a survivor,” she said. “There is hope.”
For Hathaway, a nagging feeling led her to discover a lump 19 years after her first bout with breast cancer.
She had more surgery and radiation treatments, but she isn’t taking tamoxifen.
Now a patient of Klein, Hathaway is currently enrolled in a clinical trial at Mount Sinai. In the trial, patients with breast cancer are using yoga and meditation to relieve chemotherapy symptoms.
Researchers at Mount Sinai have identified a protein (PTK6) that promotes cell growth and survival in a number of cancers, including ER-positive breast cancer.
That includes those who are resistant to tamoxifen.
The discovery could be a stepping stone to new targeted therapies.
Dr. Hanna Irie is an assistant professor of medicine (hematology and medical oncology) and oncological sciences at The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and senior author of the study.
“Endocrine therapies are still the most effective medical therapy for this subtype of breast cancer, and the end goal is to inhibit growth and/or kill ER-positive breast cancer cells. However, some breast cancer patients still develop metastatic ER-positive disease despite these common endocrine therapies, so newer treatments are very important and necessary to kill endocrine therapy-resistant cancers,” she said in a press release.
Cate recommends discussing your options with your physician, but if you’re younger than 50, have lymph node involvement or late-stage disease, you should “most definitely consider taking endocrine therapy for 10 years.”
And for small tumors in postmenopausal women, it’s a case-by-case decision.
“Patients are calling now and asking if they should get another 5 years, but they’re 10 or 15 years out from diagnosis. We don’t know the answer, but it’s not standard of care because all the studies have been about continuous therapy,” said Cate.
Klein wants breast cancer survivors to know that the outlook is much brighter now.
“Regardless of what you hear, we’re doing better,” said Klein.